essay on diabetes type 2

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List

Clinical Research on Type 2 Diabetes: A Promising and Multifaceted Landscape

Type 2 diabetes constitutes an imposing epidemiological, economic, and scientific global challenge. The chronic complications of type 2 diabetes are a major cause of mortality and disability worldwide [ 1 , 2 ]. Clinical research is the main way to gain knowledge about long-term diabetic complications and reduce the burden of diabetes. This allows for designing effective programs for screening and follow-up and fine-targeted therapeutic interventions. However, new research methodologies are needed to obtain more accurate and useful insights into the biological and clinical processes involved in diabetic complication development.

During the last few years, new approaches for clinical research have incorporated digital tools to analyze the complex physiopathological background of type 2 diabetes. In this Special Issue, entitled “ Clinical Research on Type 2 Diabetes and Its Complications ” and published in the Journal of Clinical Medicine ( https://www.mdpi.com/journal/jcm/special_issues/Type_2_Diabetes_Complications ), some valuable digital methodologies were used in different studies focusing on the type 2 diabetes syndrome. Novel machine learning techniques for predicting long-term complications are one of these approaches, as the studies of Huang, Rashid, and Shin et al. depict [ 3 , 4 , 5 ]. The data presented by these authors suggest that machine learning may be more accurate in predicting diabetic microvascular complications than traditional methods. Additionally, digital tools such as artificial intelligence and machine learning can be implemented through an automated and rapid process.

Among the frequent causes of frustration for people with diabetes and the health care providers involved in their management is the delayed detection of diabetic complications. The outlook of clinical research appears promising in the near future owing to the development and implementation of advanced methods for the detection of early alterations in the micro- and macrovascular complications associated with diabetes. Two papers in this Special Issue cover the use of specific biomarkers tracing the progress of diabetic cardiovascular complications [ 6 , 7 ]. In another contribution, Lee et al. revisit the long-term glycemic variability and its relationship with end-stage kidney disease [ 8 ].

Besides the genetic approach, the application of digital techniques, including machine learning and artificial intelligence, and novel biomarkers could be crucial for individualized type 2 diabetes management, which is the backbone of precision medicine.

Two review papers address the complications that are non-traditionally linked to type 2 diabetes, although currently under exhaustive research: bone health and non-alcoholic fatty liver disease [ 9 , 10 ]. The multifaceted nature of type 2 diabetes is clearly visualized owing to the holistic angle used by these approaches.

The efficacy and safety of new type 2 diabetes pharmacological treatment are covered by three original papers [ 11 , 12 , 13 ]. The Yu-Chuan Kang et al. study includes a large population sample and an extended follow-up to evaluate the association between dipeptidyl peptidase-4 inhibitors and diabetic retinopathy [ 13 ]. This could be the first signal for a new safety risk of a pharmacological class of drugs used by millions worldwide.

The COVID-19 pandemic was first reported in China in December 2019 and continues to be a devastating condition for global health and economy. The COVID-19 disease has immediate implications for common chronic metabolic disorders such as type 2 diabetes. Both direct infection and the associated distress due to preventive measures in the general population have worsened the control of type 2 diabetes. Some factors indicate that COVID-19 or other coronavirus-caused diseases can be seasonal or persistent in the future. Type 2 diabetes has a strong negative effect on the prognosis of patients with COVID-19. Three papers in this Special Issue review the implications of this disease in relation to diabetes [ 14 , 15 , 16 ].

Finally, the aim of researchers in this field should be to make all these remarkable advances accessible to those populations experiencing more difficulties due to sociodemographic factors such as cultural deprivation, sex discrimination, or limited income [ 17 , 18 , 19 ].

Acknowledgments

The authors acknowledge the continuous editorial assistance of Nicole Quinn, Always English S.L.

Funding Statement

This research received no external funding.

Author Contributions

Conceptualization, writing—original draft preparation, writing—review and editing were equally done by F.G.-P. and C.A. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

HYPOTHESIS AND THEORY article

Type 2 diabetes mellitus: a pathophysiologic perspective.

• Department of Medicine, Duke University, Durham, NC, United States

Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood glucose concentration is 100 milligrams/deciliter the bloodstream of an average adult contains about 5–10 grams of glucose. Carbohydrate-restricted diets have been used effectively to treat obesity and T2DM for over 100 years, and their effectiveness may simply be due to lowering the dietary contribution to glucose and insulin levels, which then leads to improvements in hyperglycemia and hyperinsulinemia. Treatments for T2DM that lead to improvements in glycemic control and reductions in blood insulin levels are sensible based on this pathophysiologic perspective. In this article, a pathophysiological argument for using carbohydrate restriction to treat T2DM will be made.

Introduction

Type 2 Diabetes Mellitus (T2DM) is characterized by a persistently elevated blood glucose, or an elevation of blood glucose after a meal containing carbohydrate ( 1 ) ( Table 1 ). Unlike Type 1 Diabetes which is characterized by a deficiency of insulin, most individuals affected by T2DM have elevated insulin levels (fasting and/or post glucose ingestion), unless there has been beta cell failure ( 2 , 3 ). The term “insulin resistance” (IR) has been used to explain why the glucose levels remain elevated even though there is no deficiency of insulin ( 3 , 4 ). Attempts to determine the etiology of IR have involved detailed examinations of molecular and intracellular pathways, with attribution of cause to fatty acid flux, but the root cause has been elusive to experts ( 5 – 7 ).

Table 1 . Definition of type 2 diabetes mellitus.

How Much Glucose Is in the Blood?

Keeping in mind that T2DM involves an elevation of blood glucose, it is important to understand how much glucose is in the blood stream to begin with, and then the factors that influence the blood glucose—both exogenous and endogenous factors. The amount of glucose in the bloodstream is carefully controlled—approximately 5–10 grams in the bloodstream at any given moment, depending upon the size of the person. To calculate this, multiply 100 milligrams/deciliter × 1 gram/1,000 milligrams × 10 deciliters/1 liter × 5 liters of blood. The “zeros cancel” and you are left with 5 grams of glucose if the individual has 5 liters of blood. Since red blood cells represent about 40% of the blood volume, and the glucose is in equilibrium, there may be an extra 40% glucose because of the red blood cell reserve ( 8 ). Adding the glucose from the serum and red blood cells totals about 5–10 grams of glucose in the entire bloodstream.

Major Exogenous Factors That Raise the Blood Glucose

Dietary carbohydrate is the major exogenous factor that raises the blood glucose. When one considers that it is common for an American in 2021 to consume 200–300 grams of carbohydrate daily, and most of this carbohydrate is digested and absorbed as glucose, the body absorbs and delivers this glucose via the bloodstream to the cells while attempting to maintain a normal blood glucose level. Thinking of it in this way, if 200–300 grams of carbohydrates is consumed in a day, the bloodstream that holds 5–10 grams of glucose and has a concentration of 100 milligrams/deciliter, is the conduit through which 200,000–300,000 milligrams (200 grams = 200,000 milligrams) passes over the course of a day.

Major Endogenous Factors That Raise the Blood Glucose

There are many endogenous contributors that raise the blood glucose. There are at least 3 different hormones that increase glucose levels: glucagon, epinephrine, and cortisol. These hormones increase glucose levels by increasing glycogenolysis and gluconeogenesis ( 9 ). Without any dietary carbohydrate, the normal human body can generate sufficient glucose though the mechanism of glucagon secretion, gluconeogenesis, glycogen storage and glycogenolysis ( 10 ).

Major Exogenous Factors That Lower the Blood Glucose

A reduction in dietary carbohydrate intake can lower the blood glucose. An increase in activity or exercise usually lowers the blood glucose ( 11 ). There are many different medications, employing many mechanisms to lower the blood glucose. Medications can delay sucrose and starch absorption (alpha-glucosidase inhibitors), slow gastric emptying (GLP-1 agonists, DPP-4 inhibitors) enhance insulin secretion (sulfonylureas, meglitinides, GLP-1 agonists, DPP-4 inhibitors), reduce gluconeogenesis (biguanides), reduce insulin resistance (biguanides, thiazolidinediones), and increase urinary glucose excretion (SGLT-2 inhibitors). The use of medications will also have possible side effects.

Major Endogenous Factors That Lower the Blood Glucose

The major endogenous mechanism to lower the blood glucose is to deliver glucose into the cells (all cells can use glucose). If the blood glucose exceeds about 180 milligrams/deciliter, then loss of glucose into the urine can occur. The blood glucose is reduced by cellular uptake using glut transporters ( 12 ). Some cells have transporters that are responsive to the presence of insulin to activate (glut4), others have transporters that do not require insulin for activation. Insulin-responsive glucose transporters in muscle cells and adipose cells lead to a reduction in glucose levels—especially after carbohydrate-containing meals ( 13 ). Exercise can increase the glucose utilization in muscle, which then increases glucose cellular uptake and reduce the blood glucose levels. During exercise, when the metabolic demands of skeletal muscle can increase more than 100-fold, and during the absorptive period (after a meal), the insulin-responsive glut4 transporters facilitate the rapid entry of glucose into muscle and adipose tissue, thereby preventing large fluctuations in blood glucose levels ( 13 ).

Which Cells Use Glucose?

Glucose can used by all cells. A limited number of cells can only use glucose, and are “glucose-dependent.” It is generally accepted that the glucose-dependent cells include red blood cells, white blood cells, and cells of the renal papilla. Red blood cells have no mitochondria for beta-oxidation, so they are dependent upon glucose and glycolysis. White blood cells require glucose for the respiratory burst when fighting infections. The cells of the inner renal medulla (papilla) are under very low oxygen tension, so therefore must predominantly use glucose and glycolysis. The low oxygen tension is a result of the countercurrent mechanism of urinary concentration ( 14 ). These glucose-dependent cells have glut transporters that do not require insulin for activation—i.e., they do not need insulin to get glucose into the cells. Some cells can use glucose and ketones, but not fatty acids. The central nervous system is believed to be able to use glucose and ketones for fuel ( 15 ). Other cells can use glucose, ketones, and fatty acids for fuel. Muscle, even cardiac muscle, functions well on fatty acids and ketones ( 16 ). Muscle cells have both non-insulin-responsive and insulin-responsive (glut4) transporters ( 12 ).

Possible Dual Role of an Insulin-Dependent Glucose-Transporter (glut4)

A common metaphor is to think of the insulin/glut transporter system as a key/lock mechanism. Common wisdom states that the purpose of insulin-responsive glut4 transporters is to facilitate glucose uptake when blood insulin levels are elevated. But, a lock serves two purposes: to let someone in and/or to keep someone out . So, one of the consequences of the insulin-responsive glut4 transporter is to keep glucose out of the muscle and adipose cells, too, when insulin levels are low. The cells that require glucose (“glucose-dependent”) do not need insulin to facilitate glucose entry into the cell (non-insulin-responsive transporters). In a teleological way, it would “make no sense” for cells that require glucose to have insulin-responsive glut4 transporters. Cells that require glucose have glut1, glut2, glut3, glut5 transporters—none of which are insulin-responsive (Back to the key/lock metaphor, it makes no sense to have a lock on a door that you want people to go through). At basal (low insulin) conditions, most glucose is used by the brain and transported by non-insulin-responsive glut1 and glut3. So, perhaps one of the functions of the insulin-responsive glucose uptake in muscle and adipose to keep glucose OUT of the these cells at basal (low insulin) conditions, so that the glucose supply can be reserved for the tissue that is glucose-dependent (blood cells, renal medulla).

What Causes IR and T2DM?

The current commonly espoused view is that “Type 2 diabetes develops when beta-cells fail to secrete sufficient insulin to keep up with demand, usually in the context of increased insulin resistance.” ( 17 ). Somehow, the beta cells have failed in the face of insulin resistance. But what causes insulin resistance? When including the possibility that the environment may be part of the problem, is it possible that IR is an adaptive (protective) response to excess glucose availability? From the perspective that carbohydrate is not an essential nutrient and the change in foods in recent years has increased the consumption of refined sugar and flour, maybe hyperinsulinemia is the cause of IR and T2DM, as cells protect themselves from excessive glucose and insulin levels.

Insulin Is Already Elevated in IR and T2DM

Clinical experience of most physicians using insulin to treat T2DM over time informs us that an escalation of insulin dose is commonly needed to achieve glycemic control (when carbohydrate is consumed). When more insulin is given to someone with IR, the IR seems to get worse and higher levels of insulin are needed. I have the clinical experience of treating many individuals affected by T2DM and de-prescribing insulin as it is no longer needed after consuming a diet without carbohydrate ( 18 ).

Diets Without Carbohydrate Reverse IR and T2DM

When dietary manipulation was the only therapy for T2DM, before medications were available, a carbohydrate-restricted diet was used to treat T2DM ( 19 – 21 ). Clinical experience of obesity medicine physicians and a growing number of recent studies have demonstrated that carbohydrate-restricted diets reverse IR and T2DM ( 18 , 22 , 23 ). Other methods to achieve caloric restriction also have these effects, like calorie-restricted diets and bariatric surgery ( 24 , 25 ). There may be many mechanisms by which these approaches may work: a reduction in glucose, a reduction in insulin, nutritional ketosis, a reduction in metabolic syndrome, or a reduction in inflammation ( 26 ). Though there may be many possible mechanisms, let's focus on an obvious one: a reduction in blood glucose. Let's assume for a moment that the excessive glucose and insulin leads to hyperinsulinemia and this is the cause of IR. On a carbohydrate-restricted diet, the reduction in blood glucose leads to a reduction in insulin. The reduction in insulin leads to a reduction in insulin resistance. The reduction in insulin leads to lipolysis. The resulting lowering of blood glucose, insulin and body weight reverses IR, T2DM, AND obesity. These clinical observations strongly suggest that hyperinsulinemia is a cause of IR and T2DM—not the other way around.

What Causes Atherosclerosis?

For many years, the metabolic syndrome has been described as a possible cause of atherosclerosis, but there are no RCTs directly targeting metabolic syndrome, and the current drug treatment focuses on LDL reduction, so its importance remains controversial. A recent paper compared the relative importance of many risk factors in the prediction of the first cardiac event in women, and the most powerful predictors were diabetes, metabolic syndrome, smoking, hypertension and BMI ( 27 ). The connection between dietary carbohydrate and fatty liver is well-described ( 28 ). The connection between fatty liver and atherosclerosis is well-described ( 29 ). It is very possible that the transport of excess glucose to the adipose tissue via lipoproteins creates the particles that cause the atherosclerotic damage (small LDL) ( Figure 1 ) ( 30 – 32 ). This entire process of dietary carbohydrate leading to fatty liver, leading to small LDL, is reversed by a diet without carbohydrate ( 26 , 33 , 34 ).

Figure 1 . Key aspects of the interconnection between glucose and lipoprotein metabolism.

Reducing dietary carbohydrate in the context of a low carbohydrate, ketogenic diet reduces hyperglycemia and hyperinsulinemia, IR and T2DM. In the evaluation of an individual for a glucose abnormality, measure the blood glucose and insulin levels. If the insulin level (fasting or after a glucose-containing meal) is high, do not give MORE insulin—instead, use an intervention to lower the insulin levels. Effective ways to reduce insulin resistance include lifestyle, medication, and surgical therapies ( 23 , 35 ).

The search for a single cause of a complex problem is fraught with difficulty and controversy. I am not hypothesizing that excessive dietary carbohydrate is the only cause of IR and T2DM, but that it is a cause, and quite possibly the major cause. How did such a simple explanation get overlooked? I believe it is very possible that the reductionistic search for intracellular molecular mechanisms of IR and T2DM, the emphasis on finding pharmaceutical (rather than lifestyle) treatments, the emphasis on the treatment of high total and LDL cholesterol, and the fear of eating saturated fat may have misguided a generation of researchers and clinicians from the simple answer that dietary carbohydrate, when consumed chronically in amounts that exceeds an individual's ability to metabolize them, is the most common cause of IR, T2DM and perhaps even atherosclerosis.

While there has historically been a concern about the role of saturated fat in the diet as a cause of heart disease, most nutritional experts now cite the lack of evidence implicating dietary saturated fat as the reason for lack of concern of it in the diet ( 36 ).

The concept of comparing medications that treat IR by insulin-sensitizers or by providing insulin itself was tested in the Bari-2D study ( 37 ). Presumably in the context of consuming a standard American diet, this study found no significant difference in death rates or major cardiovascular events between strategies of insulin sensitization or insulin provision.

While lifestyle modification may be ideal to prevent or cure IR and T2DM, for many people these changes are difficult to learn and/or maintain. Future research should be directed toward improving adherence to all effective lifestyle or medication treatments. Future research is also needed to assess the effect of carbohydrate restriction on primary or secondary prevention of outcomes of cardiovascular disease.

Data Availability Statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

Author Contributions

The author confirms being the sole contributor of this work and has approved it for publication.

Conflict of Interest

EW receives royalties from popular diet books and is founder of a company based on low-carbohydrate diet principles (Adapt Your Life, Inc.).

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

1. American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care . (2016) 39 (Suppl. 1):S13–22. doi: 10.2337/dc16-S005

PubMed Abstract | CrossRef Full Text | Google Scholar

2. Bogardus C, Lillioja S, Howard BV, Reaven G, Mott D. Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects. J Clin Invest. (1984) 74:1238–46. doi: 10.1172/JCI111533

3. Reaven GM. Compensatory hyperinsulinemia and the development of an atherogenic lipoprotein profile: the price paid to maintain glucose homeostasis in insulin-resistant individuals. Endocrinol Metab Clin North Am. (2005) 34:49–62. doi: 10.1016/j.ecl.2004.12.001

4. DeFronzo RA, Ferrannini E. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care. (1991) 14:173–94. doi: 10.2337/diacare.14.3.173

5. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. (2005) 365:1415–28. doi: 10.1016/S0140-6736(05)66378-7

6. Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: review of the underlying molecular mechanisms. J Cell Physiol. (2019) 234:8152–61. doi: 10.1002/jcp.27603

7. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. (2000) 106:171–6. doi: 10.1172/JCI10583

8. Guizouarn H, Allegrini B. Erythroid glucose transport in health and disease. Pflugers Arch. (2020) 472:1371–83. doi: 10.1007/s00424-020-02406-0

9. Petersen MC, Vatner DF, Shulman GI. Regulation of hepatic glucose metabolism in health and disease. Nat Rev Endocrinol. (2017) 13:572–87. doi: 10.1038/nrendo.2017.80

10. Tondt J, Yancy WS, Westman EC. Application of nutrient essentiality criteria to dietary carbohydrates. Nutr Res Rev. (2020) 33:260–70. doi: 10.1017/S0954422420000050

11. Colberg SR, Hernandez MJ, Shahzad F. Blood glucose responses to type, intensity, duration, and timing of exercise. Diabetes Care. (2013) 36:e177. doi: 10.2337/dc13-0965

12. Mueckler M, Thorens B. The SLC2 (GLUT) family of membrane transporters. Mol Aspects Med. (2013) 34:121–38. doi: 10.1016/j.mam.2012.07.001

13. Bryant NJ, Govers R, James DE. Regulated transport of the glucose transporter GLUT4. Nat Rev Mol Cell Biol. (2002) 3:267–77. doi: 10.1038/nrm782

14. Epstein FH. Oxygen and renal metabolism. Kidney Int. (1997) 51:381–5. doi: 10.1038/ki.1997.50

15. Cahill GF. Fuel metabolism in starvation. Annu Rev Nutr. (2006) 26:1–22. doi: 10.1146/annurev.nutr.26.061505.111258

16. Murashige D, Jang C, Neinast M, Edwards JJ, Cowan A, Hyman MC, et al. Comprehensive quantification of fuel use by the failing and nonfailing human heart. Science. (2020) 370:364–8. doi: 10.1126/science.abc8861

17. Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes. (2017) 66:241–55. doi: 10.2337/db16-0806

18. Westman EC, Yancy WS, Mavropoulos JC, Marquart M, McDuffie JR. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab. (2008) 5:36. doi: 10.1186/1743-7075-5-36

CrossRef Full Text | Google Scholar

19. Allen F. The treatment of diabetes. Boston Med Surg J. (1915) 172:241–7. doi: 10.1056/NEJM191502181720702

20. Osler W, McCrae T. The Principles and Practice of Medicine . 9th ed. New York and London: Appleton & Company (1923).

21. Lennerz BS, Koutnik AP, Azova S, Wolfsdorf JI, Ludwig DS. Carbohydrate restriction for diabetes: rediscovering centuries-old wisdom. J Clin Invest. (2021) 131:e142246. doi: 10.1172/JCI142246

22. Steelman GM, Westman EC. Obesity: Evaluation and Treatment Essentials . 2nd ed. Boca Raton: CRC Press, Taylor & Francis Group (2016). 340 p.

23. Athinarayanan SJ, Adams RN, Hallberg SJ, McKenzie AL, Bhanpuri NH, Campbell WW, et al. Long-term effects of a novel continuous remote care intervention including nutritional ketosis for the management of type 2 diabetes: a 2-year non-randomized clinical trial. Front Endocrinol. (2019) 10:348. doi: 10.3389/fendo.2019.00348

24. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. (2011) 54:2506–14. doi: 10.1007/s00125-011-2204-7

25. Isbell JM, Tamboli RA, Hansen EN, Saliba J, Dunn JP, Phillips SE, et al. The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery. Diabetes Care. (2010) 33:1438–42. doi: 10.2337/dc09-2107

26. Bhanpuri NH, Hallberg SJ, Williams PT, McKenzie AL, Ballard KD, Campbell WW, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol. (2018) 17:56. doi: 10.1186/s12933-018-0698-8

27. Dugani SB, Moorthy MV, Li C, Demler OV, Alsheikh-Ali AA, Ridker PM, et al. Association of lipid, inflammatory, and metabolic biomarkers with age at onset for incident coronary heart disease in women. JAMA Cardiol. (2021) 6:437–47. doi: 10.1001/jamacardio.2020.7073

28. Duwaerts CC, Maher JJ. Macronutrients and the adipose-liver axis in obesity and fatty liver. Cell Mol Gastroenterol Hepatol. (2019) 7:749–61. doi: 10.1016/j.jcmgh.2019.02.001

29. Zhang L, She Z-G, Li H, Zhang X-J. Non-alcoholic fatty liver disease: a metabolic burden promoting atherosclerosis. Clin Sci Lond Engl. (1979) 134:1775–99. doi: 10.1042/CS20200446

30. Horton TJ, Drougas H, Brachey A, Reed GW, Peters JC, Hill JO. Fat and carbohydrate overfeeding in humans: different effects on energy storage. Am J Clin Nutr. (1995) 62:19–29. doi: 10.1093/ajcn/62.1.19

31. Packard C, Caslake M, Shepherd J. The role of small, dense low density lipoprotein (LDL): a new look. Int J Cardiol. (2000) 74 (Suppl. 1):S17–22. doi: 10.1016/S0167-5273(99)00107-2

32. Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. (2020) 41:2313–30. doi: 10.1093/eurheartj/ehz962

33. Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. (2004) 140:769. doi: 10.7326/0003-4819-140-10-200405180-00006

34. Tendler D, Lin S, Yancy WS, Mavropoulos J, Sylvestre P, Rockey DC, et al. The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study. Dig Dis Sci. (2007) 52:589–93. doi: 10.1007/s10620-006-9433-5

35. Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg. (1995) 222:339–50. doi: 10.1097/00000658-199509000-00011

36. Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, et al. Saturated fats and health: a reassessment and proposal for food-based recommendations: JACC state-of-the-art review. J Am Coll Cardiol. (2020) 76:844–57. doi: 10.1016/j.jacc.2020.05.077

37. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med . (2009) 360:2503–15. doi: 10.1056/NEJMoa0805796

Keywords: type 2 diabetes, insulin resistance, pre-diabetes, carbohydrate-restricted diets, hyperinsulinemia, hyperglycemia

Citation: Westman EC (2021) Type 2 Diabetes Mellitus: A Pathophysiologic Perspective. Front. Nutr. 8:707371. doi: 10.3389/fnut.2021.707371

Received: 09 May 2021; Accepted: 20 July 2021; Published: 10 August 2021.

Reviewed by:

Copyright © 2021 Westman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Eric C. Westman, ewestman@duke.edu

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Type 2 Diabetes Mellitus Essays

Evidence-based nursing practice, increased coffee intake and the risk of type 2 diabetes mellitus, popular essay topics.

• American Dream
• Artificial Intelligence
• Black Lives Matter
• Bullying Essay
• Career Goals Essay
• Causes of the Civil War
• Child Abusing
• Civil Rights Movement
• Community Service
• Cultural Identity
• Cyber Bullying
• Death Penalty
• Depression Essay
• Domestic Violence
• Freedom of Speech
• Global Warming
• Gun Control
• Human Trafficking
• I Believe Essay
• Immigration
• Importance of Education
• Israel and Palestine Conflict
• Leadership Essay
• Legalizing Marijuanas
• Mental Health
• National Honor Society
• Police Brutality
• Pollution Essay
• Racism Essay
• Romeo and Juliet
• Same Sex Marriages
• Social Media
• The Great Gatsby
• The Yellow Wallpaper
• Time Management
• To Kill a Mockingbird
• Violent Video Games
• What Makes You Unique
• Why I Want to Be a Nurse
• Send us an e-mail

Home — Essay Samples — Nursing & Health — Other Diseases & Conditions — Diabetes

Essays About Diabetes

The burden of diabetes, the dangers of diabetes and the proper management of the disease, made-to-order essay as fast as you need it.

Each essay is customized to cater to your unique preferences

+ experts online

Diabetes: Type 1 and Type 2

Overview of diabetes mellitus, research on diabetes and its effects on people, a research on the management of type 2 diabetes mellitus, let us write you an essay from scratch.

• 450+ experts on 30 subjects ready to help
• Custom essay delivered in as few as 3 hours

Types, Causes and Treatment of Diabetes

Diabetes mellitus: definition, types, effects and causes, results of diabetes mellitus type 2 progressing, the types of diabetes, get a personalized essay in under 3 hours.

Expert-written essays crafted with your exact needs in mind

The Type 1 and Type 2 Diabetes

Overview of diabetes mellitus: symptoms, types and treatment, what is gestational diabetes, critically analyse the effect of physical activity on type 2 diabetes, home remedies for diabetes, a study on diabetes, the risks of amputation, and life after amputation, the need for special diabetes program in america, insulin therapy in type 2 diabetes mellitus, medications for blood glucose and pressure control during diabetes, diabetes in children: definition of diabetes burnout and how peer pressure contributes to diabetes, recommendations to delay the onset of diabetes and control of diabetes, the np influence and diabetes, the types of diabetes mellitus, review of the consequences of diabetes mellitus, current methods of treating diabetic foot ulcer, the role and responsibilities of a registered nurse when treating diabetic patients, methods of improvement in the awareness & treatment of insulin abuse, diabetes: how to eat healthy and maintain good levels, behavioral interventions to improve glycemic control in african americans with t2dm, diabetes mellitus: analysis of the types, strategies and treatments.

Diabetes mellitus, commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time.

Symptoms often include frequent urination, increased thirst and increased appetite.

There are three main types of diabetes mellitus: Type 1 diabetes, Type 2 diabetes, and Gestational diabetes.

Family history, obesity, lack of exercise, genetics, air pollution, etc.

More than 37 million people in the United States have diabetes, and 1 in 5 of them don’t know they have it. Diabetes is the 7th leading cause of death in the United States. In the last 20 years, the number of adults diagnosed with diabetes has more than doubled as the American population has aged and become more overweight or obese.

Relevant topics

• Eating Disorders

By clicking “Check Writers’ Offers”, you agree to our terms of service and privacy policy . We’ll occasionally send you promo and account related email

No need to pay just yet!

We use cookies to personalyze your web-site experience. By continuing we’ll assume you board with our cookie policy .

• Instructions Followed To The Letter
• Deadlines Met At Every Stage
• Unique And Plagiarism Free

Essay on Diabetes

Introduction

Diabetes is a healthcare condition that has continued to affect so many people, both young and old. Understanding more about Diabetes will help people live a healthy lifestyle by avoiding all the possible things that might cause it. In this assignment, I will assess why Diabetes is a significant health issue to individuals and the world. I will discuss the background of Diabetes, its definitions, and the types of Diabetes. Besides, I will discuss what is needed to promote individual and group health for people who have Diabetes. By the end of the assignment, one will have better knowledge about Diabetes since I will also discuss the causes and preventive measures that can be undertaken to prevent the disease. Towards the end of the assignment, I will describe three achievable health promotion goals, hence helping fight against Diabetes. I will also describe some of the interventions and roles that different people, groups, and organizations play to reduce the high cases of Diabetes in the world.

During the medieval ages, being diagnosed with Diabetes was like a death sentence. The pioneers of diabetes treatment were Thomas Willis, Sushruta, and Arataeus (Mandal, 2021). The three were Greek physicians who encouraged people to exercise on horsebacks to prevent excess urination. They also described other therapies like overfeeding and taking wine to reduce starvation and excessive loss of fluids (Mandal, 2021). On the other hand, the ancient Indians would test for Diabetes by taking ants near a person’s urine. If the human urine attracted the ants, then the person would be diagnosed with urine (Mandal, 2021). Diabetes is a disease that is the leading cause of high blood sugar levels. People who have Diabetes have bodies that cannot make enough insulin, or their bodies cannot use the insulin they have effectively (Healthline, 2021). Insulin is the hormone that moves sugars from the blood to the body cells. There are several types of Diabetes, including type 1 diabetes, type 2 diabetes, gestational diabetes, prediabetes, and Diabetes insipidus (Healthine, 2021). All these types affect our bodies differently, and they all have different effects, hence different coping strategies.

The rationale for Choosing Diabetes

Diabetes is among the most severe health issues in the world. This is the reason why I chose to discuss it to create awareness about it. The bad thing with Diabetes is that one can get it and not know that they have it. By the time they realize that they have Diabetes, the condition is worse, and the person is highly affected. According to Genesis Medical Associates (2015), one out of three adults have higher blood sugar levels; a condition referred to as prediabetes. If the persons do not change their lifestyles, the sugar levels increase, leading to other types of Diabetes (Genesis Medical Associates, 2015). Learning about Diabetes will allow people to support each other in the fight against Diabetes. This includes eating healthy meals and maintaining a healthy lifestyle through exercising (Dowshen, 2021). Another reason why I chose to discuss Diabetes is to learn more about the causes and how to manage the disease. Since most people do not know about the condition, it is crucial to educate them so that in case they feel any symptoms, and they can get the treatment as early as possible (Dowshen, 2021). It is easy to deal with Diabetes as long as the signs are detected early enough and the patient follows the given guidelines on healthy living.

Epidemiology

Diabetes is a significant health concern since it affects so many people in the world. Diabetes can affect any person. However, some ethnic groups are affected more than others. The Alaska Natives and the American Indians are more affected by Diabetes as compared to all other ethnic groups. In terms of age, more than sixty-five years are more prone to getting diabetes than young people. According to Shaikh (2021), % of the people who are more than 65 years have diabetes. However, the young people are also affected but at a meager percentage compared to the older people.

The risk factors for Type 1 diabetes are hereditary, hence easily transferred from parents to children. Type 1 diabetes primarily affects young children and teenagers. Also, white Americans are at a higher risk of getting the disease than African Americans and Latino Americans (Shaikh, 2021). Type 2 diabetes affects middle and old age persons. Also, other risk factors for type 2 diabetes include genes, being overweight, a history of gestational pregnancy, and giving birth to a baby that is more than 9lbs (Shaikh, 2021).

It is important to note that diabetes is more prone in rural areas where people do not have access to health services and education. In the United Kingdom, 28% of the people with diabetes have issues obtaining medication due to a lack of health services and knowledge on how to go about diabetes treatment (Whicher et al., 2019 p.243). Besides, most of the people who are in the rural do not go for annual health checkups; hence their conditions get worse daily.

Assessment and assessment tools for Diabetes

Different tools are used during the assessment of diabetes. Assessing diabetes is very important as it helps differentiate between different types of diabetes and the extent of the condition. The Diabetes Prevention Screening Tool helps identify the persons at risk of getting diabetes (Diabetes Education Services, 2021). Such people are encouraged to join the CDC prevention program. There is also the Risk Test for Pre Diabetes patients to understand the risks they face as pre-diabetics (Diabetes Education Services, 2021).

The Diabetes Risk calculator is a tool that is used to detect undiagnosed diabetes and prediabetes. The social Support Assessment Tool helps diabetic patients to have a support system (Diabetes Initiative, 2020). Patients who have Diabetes need a lot of support from family and friends. The support shown will help them adhere to the doctor’s instructions, hence improving the chances of being better. Another assessment is the Mental Health Progress Report. The report is filled up during the patient’s follow-up visits. The assessment involves questions determining if the patient is affected by the condition mentally (Diabetes Initiative, 2020). It helps the doctors to guide the patient on how they can cope mentally with Diabetes.

Health Promotion Goals that you will like to Achieve

One of the goals that I would like to achieve is to reduce the high number of people diagnosed with Diabetes. I will encourage people to ensure they exercise at least thirty minutes a day to become physically fit. To make this goal achievable, I will create small groups that will act as support systems. This will help push people towards healthy living, preventing them from being diagnosed with the condition (Cecelia Health, 2021). My goal is realistic since it is easy to adopt a good eating habit and exercise at least thirty minutes daily. Still, it becomes easier when these activities are done in groups so that members feel motivated. To ensure that the goal is achieved, I will set a time frame of three months. Each member must have dropped at least 10 pounds within three months and managed to exercise at least 30 minutes daily, consistently.

The second goal is to enhance a better diabetes management program. Most people who have diabetes do not know what they should avoid, while others ignore the advice given to them by the doctors. In this case, I will form a group of people of different ages who are diabetic. The group formed will be a support system that will help each other cope with Diabetes. I will encourage the group members to remain healthy by eating the right food and exercising daily (McDermott, 2020). For those that are older, they can do simple exercises like jogging and walking a few kilometers daily. After five months, I will assess each patient’s changes in sugar levels and the general healthcare status (McDermott, 2020). I expect the sugar levels to be expected or close to normal for most patients within this period. Besides, the patients will have adapted to the new lifestyle since they got used to it.

Interventions for your health promotion goals

As indicated above, the first goal is to reduce the high numbers of people diagnosed with diabetes. The first health intervention is by ensuring that people are engaging in vigorous activities and exercises. Before one retires to bed, they must ensure that they have done a bit of practice to increase the metabolic activities of their bodies (Harvard T.H CHAN, 2021). Exercising helps maintain a moderate weight; hence, the high obesity and overweight people will reduce significantly. Besides, exercise helps increase insulin sensitivity in the body. As a result, the body cells can consume the sugars that are in the bloodstream.

For this intervention to work, both individuals and groups work together. A person must know that they have a personal responsibility to ensure that they maintain healthy body weight. Besides, organizations can play a significant role by ensuring that they create team-building activities (Harvard T.H CHAN, 2021). Organizations can set a day or two per month whereby all the employees and employers are involved in various team-building activities. This will help to ensure that at least all members keep fit, even if some of the members might not be keeping fit at a personal level. Since young people are also at a very high risk of getting diabetes, schools should develop a schedule to see all the students engage in exercise activities (John Muir Health, 2021). For example, the school can decide to have a physical exercise lesson after every two days.

Another intervention that will see few people being diagnosed with diabetes is maintaining a healthy eating lifestyle. Most people, especially teenagers, eat food that is full of calories. First, one should ensure they increase the fiber intake (Science Daily, 2018). Fiber is essential as it helps to slow down the digestion of carbs and sugars. Foods that contain more fibers include legumes, vegetables, and whole grains. Too many carbs place a person at a very high risk of getting diabetes. Another healthy eating habit is taking plenty of water to stay hydrated at all times (John Muir Health, 2021). When one takes a lot of water, it also helps the kidney eliminate excess sugars through the urine (Science Daily, 2018). A well-hydrated person is at a lower risk of getting diabetes. However, one should avoid sugar-sweetened drinks as they raise the level of glucose in the blood.

Both individuals and organizations have a role to play when it comes to maintaining a healthy eating lifestyle. Families should ensure that they prepare meals that are balanced diet. As an individual, one has a choice to eat whatever they want. Following this, one should avoid taking foods with high carb content instead of increasing the intake of high fiber meals. Organizations should also participate in this intervention by preparing healthy meals for their employees (Science Daily, 2018). Communities should be encouraged to grow more fibers and take the origin foods rather than rely on ready-made foods with high calories. Also, schools can be involved by ensuring that they have a reasonable timetable for all the meals, and the fiber intake for each student should be higher than the carb intake.

The second goal is enhancing better management for people who are living with diabetes. Individuals have a tremendous responsibility to ensure that they follow the given guidelines to stabilize sugar levels efficiently. As a diabetic patient, one should know the type of diabetes they are suffering from and the measures they are supposed to take to become better (NIH, 2021). The first step that a diabetic person should take is to ensure that they are not stressed. Stress triggers sugar levels, hence raising them. To reduce stress triggers, one can listen to their favorite music, take a walk, breathing in and out, or doing their favorite activities (Diabetes UK, 2021). Also, a person needs to have a support system to reach out in case they feel stressed.

The second step that one can take to deal with diabetes is ensuring that they eat well. After being assessed by the doctor, a health care team should help the sick person come up with a meal plan (Diabetes UK, 2021). The meal plan should contain fewer calories, fewer sugars and salt, and high saturated fats. Also, a diabetic person should eat foods that have high fiber, like rice and bread. Instead of drinking sweetened juices, a diabetic person should ensure that they take plenty of clean drinking water. This helps to keep the body hydrated at all times.

Both individuals and groups have a significant role in ensuring that diabetic persons are taken care of. They have the necessary things needed for them to reduce sugar levels. Health facilities should make sure that they do follow-ups so that if a patient has forgotten to go for checkups, they can go upon being reminded. Besides, other organizations like NGOs should develop fiber for needy people who might not afford such things.

Evaluation of your Health Promotion Care

Maintaining a healthy lifestyle through exercise is not hard to achieve as long as the people involved know the benefits of exercising. Exercising is an effective strategy that will help prevent diabetes and prevent other diseases like heart attack and stroke (Diabetes UK, 2021). However, people should be allowed to choose the kind of exercise that they want to do. Instead of going for a run, one can engage in other activities like playing football, netball, or swimming (Harvard T.H CHAN, 2021). Since people are not the same, one should not be forced to go for a morning jog, yet they like swimming. If this is done, the exercises will be more effective since people will be doing them willingly. I would recommend that the government makes it paramount for organizations to have different days from engaging in other activities like swimming, running, jogging, etc. Also, schools should ensure that there are various exercises for all the students to have one or two activities that they can engage in easily.

The second promotion of care was encouraging people to eat healthy meals. From the above discussion, it is evident that people need to engage in healthy lifestyles. Whether a person has diabetes or not, engaging in a healthy lifestyle is very important (Science Daily, 2018. Following this, one should ensure that they avoid high calories and have high fibers. This healthcare plan can be effective only if the government and other non-governmental organizations are willing to provide the proper meals for the people in need. Some diabetic people do not have access to medical care; hence they cannot do follow-ups about their conditions. As a result, the health care plan will become hard to achieve if the doctors and health care workers do not follow up on their patients to ensure they have taken the right medicines and that the sugar levels are not increasing (John Muir Health, 2021. For this, I would recommend that treatment of diabetes becomes free of charge in all public healthcare institutions. This will make it easy for the poor diabetic people to go for checkups since they know they will not be asked for any money to get the services they need. During the Diabetes Awareness week in the country, the government led by the health care sector should ensure that people are educated about diabetes. This will help people learn more about it and engage in activities that will help reduce diseases.

Tannahill Health Promotion Model

The Tannahill Health Promotion Model helps in the prevention of diabetes and protection of people who have diabetes. As discussed above, diabetes can be prevented through eating the right foods and ensuring that one is physically fit. The Tannahill Health promotion strategy also suggests a good communication flow between the patient and the health care providers (Queens University Belfast, 2021). In this case, the healthcare providers should do the follow up’s for their patients. The third aspect of the Tannahill Health promotion program is that the citizens should be given health protection through the legislature, social measures, and financial measures (Queens University Belfast, 2021). This includes helping needy people eat healthy meals and ensuring that organizations and companies give their employees the proper meals. Besides, Companies, organizations, and schools should set aside specific days where each person is engaged in other activities like swimming, ring, and playing their favorite games.

Diabetes is indeed one of the most severe diseases in the world. Diabetes affects both the young and the old and people of all ages. Although people at the age of 65 and older are more prone to being diagnosed with diabetes, other factors also determine if a person is prone to getting diabetes (Healthline, 2021). For example, a child can get diabetes from their parents; hence they get hereditary diabetes. Women who have experienced gestational diabetes are also at a very high risk of contracting the disease again (Shaikh, 2021). People who are not physically fit are also prone to getting diabetes. Following this, it is evident that although some people are more prone to getting diabetes, several other factors play a significant role.

Although diabetes is a severe condition worldwide, it can be controlled and the high rates reduced. This can be achieved through two maintaining it; exercising and eating suitable meals. Since some people cannot afford the healthy diet recommended for diabetic people, the government and other non-governmental organizations can provide such meals to the people (Whicher et al., 2019 p.243. Also, ensuring that the medication services are accessible at the public hospitals will encourage most people to go for follow-ups. Exercising is easy since there are so many activities that help burn calories (Shaikh, 2021). That is why it is essential to let the person choose activities they are good at and concentrate on them. Generally, although diabetes is a serious condition, it is easy to prevent and manage it if all resources are available.

Cecelia Health, 2021.  How to Set and Achieve SMART Goals — in Life and Diabetes – Cecelia Health . [online] Cecelia Health. Available at: <https://www.ceceliahealth.com/how-to-set-and-achieve-smart-goals-in-life-and-diabetes/> [Accessed 1 June 2021].

Diabetes Education Services, 2021.  Screening Tools for Diabetes – Diabetes Education Services . [online] Diabetes Education Services. Available at: <https://diabetesed.net/screening-tools-for-diabetes/> [Accessed 1 June 2021].

Diabetes Initiative, 2020.  Tools: Assessment Instruments . [online] Diabetesinitiative.org. Available at: <http://www.diabetesinitiative.org/resources/type/assessmentInstruments.html> [Accessed 1 June 2021].

Diabetes UK, 2021.  10 Tips for Healthy Eating with Diabetes . [online] Diabetes UK. Available at: <https://www.diabetes.org.uk/guide-to-diabetes/enjoy-food/eating-with-diabetes/10-ways-to-eat-well-with-diabetes> [Accessed 1 June 2021].

Dowshen, S., 2021.  Diabetes Control: Why It’s Important (for Teens) – Nemours KidsHealth . [online] Kidshealth.org. Available at: <https://kidshealth.org/en/teens/diabetes-control.html> [Accessed 1 June 2021].

Genesis Medical Associates, 2015.  The Importance Of Understanding And Preventing Diabetes – Genesis Medical Associates, Inc . [online] Genesismedical.org. Available at: <https://www.genesismedical.org/blog/the-importance-of-understanding-and-preventing-diabetes> [Accessed 1 June 2021].

Harvard T.H CHAN, 2021.  Simple Steps to Preventing Diabetes . [online] The Nutrition Source. Available at: <https://www.hsph.harvard.edu/nutritionsource/disease-prevention/diabetes-prevention/preventing-diabetes-full-story/> [Accessed 1 June 2021].

Healthline, 2021.  Everything You Need to Know About Diabetes . [online] Healthline. Available at: <https://www.healthline.com/health/diabetes#:~:text=Diabetes%20mellitus%2C%20commonly%                                                                                 20known%20as,the%20insulin%20it%20does%20make.> [Accessed 1 June 2021].

John Muir Health, 2021.  Preventing Diabetes . [online] Johnmuirhealth.com. Available at: <https://www.johnmuirhealth.com/health-education/conditions-treatments/diabetes-articles/preventing-diabetes.html> [Accessed 1 June 2021].

Mandal, A., 2021.  History of Diabetes . [online] News Medical. Available at: <https://www.news-medical.net/health/History-of-Diabetes.aspx#:~:text=The%20term%20diabetes%20was%20probably,sweet%20taste%20of%20the%20urine.> [Accessed 1 June 2021].

McDermott, A., 2020.  7 Long-Term Goals for Better Diabetes Management . [online] Healthline. Available at: <https://www.healthline.com/health/type-2-diabetes/living-better-with-type-2-diabetes/long-term-goals-everyone-with-type-2-diabetes-should-make> [Accessed 1 June 2021].

NIH, 2021.  4 Steps to Manage Your Diabetes for Life | NIDDK . [online] National Institute of Diabetes and Digestive and Kidney Diseases. Available at: <https://www.niddk.nih.gov/health-information/diabetes/overview/managing-diabetes/4-steps> [Accessed 1 June 2021].

Queens University Belfast, 2021.  Health Promotion.  [online] Queens University Belfast. Available at  https://www.qub.ac.uk/elearning/public/HealthyEating/HealthPromotion/  [Accessed 1 June 2021]

Science Daily, 2018.  Physical exercise reduces the risk of developing diabetes, study shows . [online] ScienceDaily. Available at: <https://www.sciencedaily.com/releases/2018/02/180220102420.htm> [Accessed 1 June 2021].

Shaikh, J., 2021.  What Population Is Most Affected by Diabetes? . [online] MedicineNet. Available at: <https://www.medicinenet.com/what_population_is_most_affected_by_diabetes/article.htm> [Accessed 1 June 2021].

Whicher, C., O’Neill, S., and Holt, R., 2019. Diabetes in the UK: 2019.  Diabetic Medicine , [online] 37(2), pp.242-247. Available at: <https://onlinelibrary.wiley.com/doi/epdf/10.1111/dme.14225> [Accessed 1 June 2021].

Cite this page

Similar essay samples.

• Essay on Compare and Contrast Two Mental Health Theories
• Essay on Freedom of Expression
• Essay on Human Resource (HR) as a Strategic Business Partner
• Resources to Support Science in the Foundation Stage
• Neisseria meningitidis
• Essay on Performance Appraisal

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 23 July 2015

Type 2 diabetes mellitus

• Ralph A. DeFronzo 1 ,
• Ele Ferrannini 2 ,
• Leif Groop 3 ,
• Robert R. Henry 4 ,
• William H. Herman 5 ,
• Jens Juul Holst 6 ,
• Frank B. Hu 7 ,
• C. Ronald Kahn 8 ,
• Itamar Raz 9 ,
• Gerald I. Shulman 10 ,
• Donald C. Simonson 11 ,
• Marcia A. Testa 12 &
• Ram Weiss 13  

Nature Reviews Disease Primers volume  1 , Article number:  15019 ( 2015 ) Cite this article

50k Accesses

1055 Citations

131 Altmetric

Metrics details

• Diabetes complications
• Type 2 diabetes

Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 1 digital issues and online access to articles

111,21 € per year

only 111,21 € per issue

Buy this article

• Purchase on SpringerLink
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors

Novel therapies with precision mechanisms for type 2 diabetes mellitus

Heterogeneity and endotypes in type 1 diabetes mellitus

DeFronzo, R. A. Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58 , 773–795 (2009). A classic review of the aetiology of T2DM, with a therapeutic approach based on its pathophysiology.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Abdul-Ghani, M. A., Tripathy, D. & DeFronzo, R. A. Contributions of β-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 29 , 1130–1139 (2006).

Article   CAS   PubMed   Google Scholar  

Gerstein, H. C. et al . Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res. Clin. Pract. 78 , 305–312 (2007).

Article   PubMed   Google Scholar  

Hawa, M. I. et al . Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: action LADA 7. Diabetes Care 36 , 908–913 (2013).

Article   PubMed   PubMed Central   Google Scholar  

Gardner, D. S. & Tai, E. S. Clinical features and treatment of maturity onset diabetes of the young (MODY). Diabetes. Metab. Syndr. Obes. 5 , 101–108 (2012).

American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 37 , S14–S80 (2014). A comprehensive overview of the standards of medical care published by the ADA.

Article   Google Scholar  

DeFronzo, R. A. & Abdul-Ghani, M. A. Preservation of β-cell function: the key to diabetes prevention. J. Clin. Endocrinol. Metab. 96 , 2354–2366 (2011).

Ferrannini, E., Gastaldelli, A. & Iozzo, P. Pathophysiology of prediabetes. Med. Clin. North Am. 95 , 327–339 (2011).

Garvey, W. T. et al . Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release. Diabetes Care 37 , 912–921 (2014).

Nathan, D. M. et al . Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care 30 , 753–759 (2007).

DeFronzo, R. A. et al . Pioglitazone for diabetes prevention in impaired glucose tolerance. N. Engl. J. Med. 364 , 1104–1115 (2011). A large prospective study demonstrating the efficacy of thiazolidinediones in preventing the progression of IGT to T2DM.

Zinman, B. et al . Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet 376 , 103–111 (2010).

Dansinger, M. L., Tatsioni, A., Wong, J. B., Chung, M. & Balk, E. M. Meta-analysis: the effect of dietary counseling for weight loss. Ann. Intern. Med. 147 , 41–50 (2007).

Purcell, K. et al . The effect of rate of weight loss on long-term weight management: a randomised controlled trial. Lancet Diabetes Endocrinol. 2 , 954–962 (2014).

Ali, M. K., Echouffo-Tcheugui, J. & Williamson, D. F. How effective were lifestyle interventions in real-world settings that were modeled on the Diabetes Prevention Program? Health Aff. (Millwood) 31 , 67–75 (2012).

Tuomilehto, J. et al . Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 344 , 1343–1350 (2001).

Inzucchi, S. E. et al . Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 35 , 1364–1379 (2012). ADA position statement on the treatment of T2DM, advocating a stepped care approach starting with metformin.

American Association of Clinical Endocrinologists. AACE Comprehensive Diabetes Algorithm 2013 Consensus Statement. Endocr. Pract. Suppl. 1 , 1–87 (2015). AACE position statement on the treatment of T2DM, advocating initial monotherapy or combination therapy based upon the starting HbA1c, and recommending various antidiabetic medications as initial therapy.

Google Scholar  

Pozzilli, P. et al . The A1C and ABCD of glycaemia management in type 2 diabetes: a physician's personalized approach. Diabetes Metab. Res. Rev. 26 , 239–244 (2010). The first published report by key opinion leaders recommending individualized therapy based on the age and body weight of patients, the presence or absence of complications, and duration and aetiology of disease.

International Diabetes Federation. IDF Diabetes Atlas 6th Edition. IDF [online] , (2013).

Hu, F. B. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care 34 , 1249–1257 (2011). An important study emphasizing the role of diet, physical activity and genes — beyond obesity — in the diabetes epidemic that is engulfing Asian countries as they are exposed to westernization.

Chan, J. C. et al . Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 301 , 2129–2140 (2009).

Ley, S. H., Hamdy, O., Mohan, V. & Hu, F. B. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. Lancet 383 , 1999–2007 (2014).

Grøntved, A., Rimm, E. B., Willett, W. C., Andersen, L. B. & Hu, F. B. A prospective study of weight training and risk of type 2 diabetes mellitus in men. Arch. Intern. Med. 172 , 1306–1312 (2012).

Grøntved, A. & Hu, F. B. Television viewing and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis. JAMA 305 , 2448–2455 (2011).

Cappuccio, F. P., D'Elia, L., Strazzullo, P. & Miller, M. A. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 33 , 414–420 (2009).

Pan, A., Schernhammer, E. S., Sun, Q. & Hu, F. B. Rotating night shift work and risk of type 2 diabetes: two prospective cohort studies in women. PLoS Med. 8 , e1001141 (2011).

Barnett, A. H., Eff, C., Leslie, R. D. & Pyke, D. A. Diabetes in identical twins. A study of 200 pairs. Diabetologia 20 , 87–93 (1981).

Wang, Y. C., McPherson, K., Marsh, T., Gortmaker, S. L. & Brown, M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet 378 , 815–825 (2011).

Wang, X. et al . Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 36 , 166–175 (2013).

Li, S., Shin, H. J., Ding, E. L. & van Dam, R. M. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 302 , 179–188 (2009).

Ding, E. L. et al . Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N. Engl. J. Med. 361 , 1152–1163 (2009).

Wang, T. J. et al . Metabolite profiles and the risk of developing diabetes. Nat. Med. 17 , 448–453 (2011).

Esteve, E., Ricart, W. & Fernández-Real, J.-M. Gut microbiota interactions with obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve with insulin resistance? Curr. Opin. Clin. Nutr. Metab. Care 14 , 483–490 (2011).

Hu, F. B. et al . Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N. Engl. J. Med. 345 , 790–797 (2001).

Schellenberg, E. S., Dryden, D. M., Vandermeer, B., Ha, C. & Korownyk, C. Lifestyle interventions for patients with and at risk for type 2 diabetes. Ann. Intern. Med. 159 , 543–551 (2013). A comprehensive review of the effectiveness of lifestyle intervention in the treatment of T2DM, emphasizing that, although initially successful, most subjects with diabetes regain the majority of lost weight over the subsequent 3–5 years.

DeFronzo, R. A. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53 , 1270–1287 (2010). A comprehensive review describing the role of excess tissue lipid deposition in the development of insulin resistance, β-cell failure and atherosclerotic cardiovascular disease: that is, lipotoxicity.

Hemminki, K., Li, X., Sundquist, K. & Sundquist, J. Familial risks for type 2 diabetes in Sweden. Diabetes Care 33 , 293–297 (2010).

Groop, L. et al . Metabolic consequences of a family history of NIDDM (the Botnia study): evidence for sex-specific parental effects. Diabetes 45 , 1585–1593 (1996).

Lyssenko, V. et al . Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes 54 , 166–174 (2005).

Grant, S. F. et al . Variant of transcription factor 7-like 2 ( TCF7L2 ) gene confers risk of type 2 diabetes. Nat. Genet. 38 , 320–323 (2006).

Lyssenko, V. et al . Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes. J. Clin. Invest. 117 , 2155–2163 (2007).

Sladek, R. et al . A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445 , 881–885 (2007).

Saxena, R. et al . Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316 , 1331–1336 (2007).

Morris, A. P. et al . Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 44 , 981–990 (2012).

Flannick, J. et al . Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat. Genet. 46 , 357–363 (2014).

Lyssenko, V. et al . Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat. Genet. 41 , 82–88 (2009).

Rosengren, A. H. et al . Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science 327 , 217–220 (2010).

Tang, Y. et al . Genotype-based treatment of type 2 diabetes with an α2A-adrenergic receptor antagonist. Sci. Transl Med. 6 , 257ra139 (2014). These paper provides an example in which a genetic finding in an animal model of diabetes has been translated into a drug target in humans, the ADRA2A gene.

De Jesus, D. F. & Kulkarni, R. N. Epigenetic modifiers of islet function and mass. Trends Endocrinol. Metab. 25 , 628–636 (2014).

Ozcan, S. Minireview: microRNA function in pancreatic β cells. Mol. Endocrinol. 28 , 1922–1933 (2014).

Lyssenko, V. et al . Clinical risk factors, DNA variants, and the development of type 2 diabetes. N. Engl. J. Med. 359 , 2220–2232 (2008). This paper presents a genetic explanation for the development of T2DM.

Travers, M. E. et al . Insights into the molecular mechanism for type 2 diabetes susceptibility at the KCNQ1 locus from temporal changes in imprinting status in human islets. Diabetes 62 , 987–992 (2013).

Gulli, G., Ferrannini, E., Stern, M., Haffner, S. & DeFronzo, R. A. The metabolic profile of NIDDM is fully established in glucose-tolerant offspring of two Mexican-American NIDDM parents. Diabetes 41 , 1575–1586 (1992).

Martin, B. C. et al . Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 340 , 925–929 (1992).

Ferrannini, E. & Mari, A. β-cell function in type 2 diabetes. Metabolism 63 , 1217–1227 (2014).

Kahn, S. E., Cooper, M. E. & Del Prato, S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383 , 1068–1083 (2014).

Muller, D. C., Elahi, D., Tobin, J. D. & Andres, R. Insulin response during the oral glucose tolerance test: the role of age, sex, body fat and the pattern of fat distribution. Aging (Milano) 8 , 13–21 (1996).

CAS   Google Scholar  

Nauck, M. A., Vardarli, I., Deacon, C. F., Holst, J. J. & Meier, J. J. Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down? Diabetologia 54 , 10–18 (2011).

Madsbad, S. The role of glucagon-like peptide-1 impairment in obesity and potential therapeutic implications. Diabetes Obes. Metab. 16 , 9–21 (2014).

Bays, H., Mandarino, L. & DeFronzo, R. A. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J. Clin. Endocrinol. Metab. 89 , 463–478 (2004).

Perry, R. J., Samuel, V. T., Petersen, K. F. & Shulman, G. I. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510 , 84–91 (2014). An excellent review of the specific lipid varieties and the molecular events through which they cause insulin resistance in the liver.

Bensellam, M., Laybutt, D. R. & Jonas, J.-C. The molecular mechanisms of pancreatic β-cell glucotoxicity: recent findings and future research directions. Mol. Cell. Endocrinol. 364 , 1–27 (2012).

Ritzel, R. A., Meier, J. J., Lin, C.-Y., Veldhuis, J. D. & Butler, P. C. Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets. Diabetes 56 , 65–71 (2007).

Collins, S., Pi, J. & Yehuda-Shnaidman, E. Uncoupling and reactive oxygen species (ROS) — a double-edged sword for β-cell function? “Moderation in all things”. Best Pract. Res. Clin. Endocrinol. Metab. 26 , 753–758 (2012).

Cabrera, O. et al . The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc. Natl Acad. Sci. USA 103 , 2334–2339 (2006).

Hodson, D. J. et al . Lipotoxicity disrupts incretin-regulated human β cell connectivity. J. Clin. Invest. 123 , 4182–4194 (2013).

Brandhorst, H., Brandhorst, D., Brendel, M. D., Hering, B. J. & Bretzel, R. G. Assessment of intracellular insulin content during all steps of human islet isolation procedure. Cell Transplant. 7 , 489–495 (1998).

Rahier, J., Guiot, Y., Goebbels, R. M., Sempoux, C. & Henquin, J. C. Pancreatic β-cell mass in European subjects with type 2 diabetes. Diabetes Obes. Metab. 10 (Suppl. 4), 32–42 (2008). A post-mortem study demonstrating a decline in β-cell mass with preservation of α-cell mass in individuals with T2DM.

Marselli, L. et al . Are we overestimating the loss of beta cells in type 2 diabetes? Diabetologia 57 , 362–365 (2014).

Marchetti, P. et al . The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia 50 , 2486–2494 (2007).

Marchetti, P. & Masini, M. Autophagy and the pancreatic beta-cell in human type 2 diabetes. Autophagy 5 , 1055–1056 (2009).

Gupta, D. & Leahy, J. L. Islet amyloid and type 2 diabetes: overproduction or inadequate clearance and detoxification? J. Clin. Invest. 124 , 3292–3294 (2014).

Mezza, T. et al . Insulin resistance alters islet morphology in nondiabetic humans. Diabetes 63 , 994–1007 (2014). This work in human islets describes the impact of insulin resistance on the relative proportion of α-cells and β-cells, and the functional consequences — in terms of insulin and glucagon secretion — of this chronic adaptation.

Deng, S. et al . Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 53 , 624–632 (2004).

Igoillo-Esteve, M. et al . Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes. Diabetologia 53 , 1395–1405 (2010).

Giacca, A., Xiao, C., Oprescu, A. I., Carpentier, A. C. & Lewis, G. F. Lipid-induced pancreatic β-cell dysfunction: focus on in vivo studies. Am. J. Physiol. Endocrinol. Metab. 300 , E255–E262 (2010).

Halban, P. A. et al . β-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. J. Clin. Endocrinol. Metab. 99 , 1983–1992 (2014).

Ferrannini, E. et al . Natural history and physiological determinants of changes in glucose tolerance in a non-diabetic population: the RISC Study. Diabetologia 54 , 1507–1516 (2011). This longitudinal study of non-diabetic subjects identifies baseline insulin resistance and β-cell dysfunction as predictors of future dysglycaemia.

Michaliszyn, S. F. et al . β-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes. Diabetes 63 , 3846–3855 (2014).

Mari, A. et al . Mechanisms of the incretin effect in subjects with normal glucose tolerance and patients with type 2 diabetes. PLoS ONE 8 , e73154 (2013).

Holst, J. J., Knop, F. K., Vilsbøll, T., Krarup, T. & Madsbad, S. Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care 34 , S251–S257 (2011).

Camastra, S. et al . Long-term effects of bariatric surgery on meal disposal and β-cell function in diabetic and nondiabetic patients. Diabetes 62 , 3709–3717 (2013).

Ferrannini, E. The stunned β cell: a brief history. Cell Metab. 11 , 349–352 (2010).

Shulman, G. I. et al . Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N. Engl. J. Med. 322 , 223–228 (1990). This study demonstrated that defects in insulin-stimulated muscle glycogen synthesis was the major factor responsible for whole-body insulin resistance in patients with T2DM.

Groop, L. C. et al . Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. J. Clin. Invest. 84 , 205–213 (1989).

Guilherme, A., Virbasius, J. V., Puri, V. & Czech, M. P. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat. Rev. Mol. Cell Biol. 9 , 367–377 (2008).

Gerich, J. E., Meyer, C., Woerle, H. J. & Stumvoll, M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care 24 , 382–391 (2001).

Honka, H. et al . Validation of [ 18 F]fluorodeoxyglucose and positron emission tomography (PET) for the measurement of intestinal metabolism in pigs, and evidence of intestinal insulin resistance in patients with morbid obesity. Diabetologia 56 , 893–900 (2013).

Meijer, R. I. et al . Insulin-induced microvascular recruitment in skin and muscle are related and both are associated with whole-body glucose uptake. Microcirculation 19 , 494–500 (2012).

Blázquez, E., Velázquez, E., Hurtado-Carneiro, V. & Ruiz-Albusac, J. M. Insulin in the brain: its pathophysiological implications for states related with central insulin resistance, type 2 diabetes and Alzheimer's disease. Front. Endocrinol. (Lausanne) 5 , 161 (2014).

Kleinridders, A., Ferris, H. A., Cai, W. & Kahn, C. R. Insulin action in brain regulates systemic metabolism and brain function. Diabetes 63 , 2232–2243 (2014).

Kulkarni, R. N. et al . Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96 , 329–339 (1999). An insightful study documenting that β-cell-specific insulin receptor knockout results in markedly impaired insulin secretion and overt diabetes, thereby providing a unifying mechanism whereby insulin resistance explains both the defects in insulin-stimulated tissue glucose uptake and decreased insulin secretion.

Oliveira, J. M., Rebuffat, S. A., Gasa, R. & Gomis, R. Targeting type 2 diabetes: lessons from a knockout model of insulin receptor substrate 2. Can. J. Physiol. Pharmacol. 92 , 613–620 (2014).

Samuel, V. T. & Shulman, G. I. Mechanisms for insulin resistance: common threads and missing links. Cell 148 , 852–871 (2012). An excellent review of the molecular mechanism responsible for insulin resistance in T2DM and obesity.

Magnusson, I., Rothman, D. L., Katz, L. D., Shulman, R. G. & Shulman, G. I. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J. Clin. Invest. 90 , 1323–1327 (1992). This study demonstrated that increased rates of hepatic glucose production in patients with poorly controlled T2DM could entirely be attributed to increased rates of gluconeogenesis.

Matsuda, M. et al . Glucagon dose-response curve for hepatic glucose production and glucose disposal in type 2 diabetic patients and normal individuals. Metabolism 51 , 1111–1119 (2002).

Samuel, V. T. et al . Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with type 2 diabetes. Proc. Natl Acad. Sci. USA 106 , 12121–12126 (2009).

Baron, A. D., Schaeffer, L., Shragg, P. & Kolterman, O. G. Role of hyperglucagonemia in maintenance of increased rates of hepatic glucose output in type II diabetics. Diabetes 36 , 274–283 (1987).

DeFronzo, R. A., Ferrannini, E., Hendler, R., Wahren, J. & Felig, P. Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange. Proc. Natl Acad. Sci. USA 75 , 5173–5177 (1978).

Ferrannini, E. et al . The disposal of an oral glucose load in patients with non-insulin-dependent diabetes. Metabolism 37 , 79–85 (1988).

DeFronzo, R. A. et al . Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care 36 , 3169–3176 (2013).

Barrett, E. J., Wang, H., Upchurch, C. T. & Liu, Z. Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am. J. Physiol. Endocrinol. Metab. 301 , E252–E263 (2011).

Baron, A. D. Hemodynamic actions of insulin. Am. J. Physiol. 267 , E187–E202 (1994).

CAS   PubMed   Google Scholar  

Krüger, M. et al . Dissection of the insulin signaling pathway via quantitative phosphoproteomics. Proc. Natl Acad. Sci. USA 105 , 2451–2456 (2008).

Cusi, K. et al . Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J. Clin. Invest. 105 , 311–320 (2000). The first study in humans with T2DM to demonstrate impaired insulin signal transduction through the IRS1–PI3K pathway in muscle, with normal to increased insulin signalling through the MAPK pathway.

Krook, A. et al . Characterization of signal transduction and glucose transport in skeletal muscle from type 2 diabetic patients. Diabetes 49 , 284–292 (2000).

Copps, K. D. & White, M. F. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia 55 , 2565–2582 (2012).

Bouzakri, K. et al . IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas transplant recipients. Diabetes 55 , 785–791 (2006).

Hiratani, K. et al . Roles of mTOR and JNK in serine phosphorylation, translocation, and degradation of IRS-1. Biochem. Biophys. Res. Commun. 335 , 836–842 (2005).

Krssak, M. et al . Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 42 , 113–116 (1999).

Petersen, K. F. et al . Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J. Clin. Invest. 109 , 1345–1350 (2002).

Petersen, K. F. et al . Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 54 , 603–608 (2005).

Lara-Castro, C. & Garvey, W. T. Intracellular lipid accumulation in liver and muscle and the insulin resistance syndrome. Endocrinol. Metab. Clin. North Am. 37 , 841–856 (2008).

Yu, C. et al . Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J. Biol. Chem. 277 , 50230–50236 (2002).

Bezy, O. et al . PKCδ regulates hepatic insulin sensitivity and hepatosteatosis in mice and humans. J. Clin. Invest. 121 , 2504–2517 (2011).

Samuel, V. T. et al . Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J. Biol. Chem. 279 , 32345–32353 (2004).

Samuel, V. T. et al . Inhibition of protein kinase Cε prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J. Clin. Invest. 117 , 739–745 (2007).

Choi, C. S. et al . Suppression of diacylglycerol acyltransferase-2 ( DGAT2 ), but not DGAT1 , with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance. J. Biol. Chem. 282 , 22678–22688 (2007).

Morino, K. et al . Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J. Clin. Invest. 115 , 3587–3593 (2005).

Szendroedi, J. et al . Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans. Proc. Natl Acad. Sci. USA 111 , 9597–9602 (2014).

Larsen, P. J. & Tennagels, N. On ceramides, other sphingolipids and impaired glucose homeostasis. Mol. Metab. 3 , 252–260 (2014).

Turpin, S. M. et al . Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metab. 20 , 678–686 (2014).

Cantley, J. L. et al . CGI-58 knockdown sequesters diacylglycerols in lipid droplets/ER-preventing diacylglycerol-mediated hepatic insulin resistance. Proc. Natl Acad. Sci. USA 110 , 1869–1874 (2013).

Patti, M.-E. & Corvera, S. The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr. Rev. 31 , 364–395 (2010). Mitochondrial dysfunction as a causative factor in the development of insulin resistance in T2DM is reviewed.

Ritov, V. B. et al . Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes 54 , 8–14 (2005).

Petersen, K. F. et al . Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300 , 1140–1142 (2003).

Petersen, K. F., Dufour, S., Befroy, D., Garcia, R. & Shulman, G. I. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N. Engl. J. Med. 350 , 664–671 (2004).

Mogensen, M. et al . Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 56 , 1592–1599 (2007).

Petersen, K. F., Dufour, S. & Shulman, G. I. Decreased insulin-stimulated ATP synthesis and phosphate transport in muscle of insulin-resistant offspring of type 2 diabetic parents. PLoS Med. 2 , e233 (2005).

Wang, C.-H., Wang, C.-C., Huang, H.-C. & Wei, Y.-H. Mitochondrial dysfunction leads to impairment of insulin sensitivity and adiponectin secretion in adipocytes. FEBS J. 280 , 1039–1050 (2013).

Rains, J. L. & Jain, S. K. Oxidative stress, insulin signaling, and diabetes. Free Radic. Biol. Med. 50 , 567–575 (2011).

Morino, K. et al . Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes. Diabetes 61 , 877–887 (2012).

Romeo, G. R., Lee, J. & Shoelson, S. E. Metabolic syndrome, insulin resistance, and roles of inflammation — mechanisms and therapeutic targets. Arterioscler. Thromb. Vasc. Biol. 32 , 1771–1776 (2012).

Arkan, M. C. et al . IKK-β links inflammation to obesity-induced insulin resistance. Nat. Med. 11 , 191–198 (2005).

De Alvaro, C., Teruel, T., Hernandez, R. & Lorenzo, M. Tumor necrosis factor α produces insulin resistance in skeletal muscle by activation of inhibitor κB kinase in a p38 MAPK-dependent manner. J. Biol. Chem. 279 , 17070–17078 (2004).

Howard, J. K. & Flier, J. S. Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol. Metab. 17 , 365–371 (2006).

Lebrun, P. & Van Obberghen, E. SOCS proteins causing trouble in insulin action. Acta Physiol. (Oxf.) 192 , 29–36 (2008).

Article   CAS   Google Scholar  

Uysal, K. T., Wiesbrock, S. M. & Hotamisligil, G. S. Functional analysis of tumor necrosis factor (TNF) receptors in TNF-α-mediated insulin resistance in genetic obesity. Endocrinology 139 , 4832–4838 (1998).

Ofei, F., Hurel, S., Newkirk, J., Sopwith, M. & Taylor, R. Effects of an engineered human anti-TNF-α antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45 , 881–885 (1996).

Kim, J. K. et al . Prevention of fat-induced insulin resistance by salicylate. J. Clin. Invest. 108 , 437–446 (2001).

Yuan, M. et al . Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKK β. Science 293 , 1673–1677 (2001).

Goldfine, A. B. et al . The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann. Intern. Med. 152 , 346–357 (2010).

Lumeng, C. N. & Saltiel, A. R. Inflammatory links between obesity and metabolic disease. J. Clin. Invest. 121 , 2111–2117 (2011).

Nishimura, S. et al . CD8 + effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat. Med. 15 , 914–920 (2009).

Feuerer, M. et al . Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat. Med. 15 , 930–939 (2009).

Bertola, A. et al . Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61 , 2238–2247 (2012).

Cai, D. et al . Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat. Med. 11 , 183–190 (2005).

Perry, R. J. et al . Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell 160 , 745–758 (2015).

Mori, M. A. et al . A systems biology approach identifies inflammatory abnormalities between mouse strains prior to development of metabolic disease. Diabetes 59 , 2960–2971 (2010).

Mauer, J. et al . Myeloid cell-restricted insulin receptor deficiency protects against obesity-induced inflammation and systemic insulin resistance. PLoS Genet. 6 , e1000938 (2010).

Shi, H. et al . TLR4 links innate immunity and fatty acid-induced insulin resistance. J. Clin. Invest. 116 , 3015–3025 (2006).

Ron, D. & Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 8 , 519–529 (2007).

Boden, G. et al . Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals. Diabetes 57 , 2438–2444 (2008).

Eizirik, D. L., Cardozo, A. K. & Cnop, M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr. Rev. 29 , 42–61 (2008). A comprehensive review of ER stress and the UPR in the development of insulin resistance and obesity.

Gregor, M. F. et al . Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss. Diabetes 58 , 693–700 (2009).

Ozawa, K. et al . The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes 54 , 657–663 (2005).

Herschkovitz, A. et al . Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance. J. Biol. Chem. 282 , 18018–18027 (2007).

Boden, G. Endoplasmic reticulum stress: another link between obesity and insulin resistance/inflammation? Diabetes 58 , 518–519 (2009).

Sengupta, S., Peterson, T. R. & Sabatini, D. M. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol. Cell 40 , 310–322 (2010).

Shah, O. J., Wang, Z. & Hunter, T. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr. Biol. 14 , 1650–1656 (2004).

Ozcan, U. et al . Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol. Cell 29 , 541–551 (2008).

Park, S. W. et al . The regulatory subunits of PI3K, p85α and p85β, interact with XBP-1 and increase its nuclear translocation. Nat. Med. 16 , 429–437 (2010).

Stratton, I. M. et al . Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321 , 405–412 (2000). A seminal UK Prospective Diabetes Study study unequivocally demonstrating that improved glycaemic control reduced the incidence of microvascular, and to a lesser extent, macrovascular complications in patients with T2DM.

Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R. & Neil, H. A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 359 , 1577–1589 (2008). A long-term follow-up of the UK Prospective Diabetes Study showing that early intensive glycaemic control has a persistent impact on preventing both microvascular and macrovascular complications long after initiation of the intensified antidiabetic regimen has been discontinued: that is, the ‘legacy effect’.

Brownlee, M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54 , 1615–1625 (2005). A lucid discussion of the molecular pathways involved in the development of diabetic microvascular complications.

Giacco, F. & Brownlee, M. Oxidative stress and diabetic complications. Circ. Res. 107 , 1058–1070 (2010).

Coutinho, M., Gerstein, H. C., Wang, Y. & Yusuf, S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 22 , 233–240 (1999).

Taskinen, M.-R. & Borén, J. New insights into the pathophysiology of dyslipidemia in type 2 diabetes. Atherosclerosis 239 , 483–495 (2015). An up-to-date review of the pathogenesis of diabetic dyslipidaemia and its treatment.

Isomaa, B. et al . Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24 , 683–689 (2001).

Adler, A. I. et al . Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ 321 , 412–419 (2000).

Williams, B. Treating hypertension in patients with diabetes: when to start and how low to go? JAMA 313 , 573–574 (2015). The optimal blood pressure goal in hypertensive patients with T2DM is discussed in light of the controversial results observed in the blood pressure arm of the ACCORD trial.

Lastra, G., Syed, S., Kurukulasuriya, L. R., Manrique, C. & Sowers, J. R. Type 2 diabetes mellitus and hypertension: an update. Endocrinol. Metab. Clin. North Am. 43 , 103–122 (2014).

International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32 , 1327–1334 (2009).

[No authors listed.] Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20 , 1183–1197 (1997). A reference publication by the ADA on the diagnosis and classification of diabetes mellitus.

Herman, W. H. Diabetes epidemiology: guiding clinical and public health practice: the Kelly West Award Lecture, 2006. Diabetes Care 30 , 1912–1919 (2007). A landmark lecture providing a comprehensive overview of the epidemiology of T2DM and the public health implications for diabetes prevention.

DECODE Study Group, European Diabetes Epidemiology Group. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases? Diabetes Care 26 , 688–696 (2003).

Engelgau, M. M., Narayan, K. M. & Herman, W. H. Screening for type 2 diabetes. Diabetes Care 23 , 1563–1580 (2000).

LeFevre, M. L. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: U.S. Preventive Services Task Force Recommendation Statement. Ann. Intern. Med. 161 , 587–593 (2014).

Lindström, J. & Tuomilehto, J. The diabetes risk score: a practical tool to predict type 2 diabetes risk. Diabetes Care 26 , 725–731 (2003).

Tabaei, B. P. & Herman, W. H. A multivariate logistic regression equation to screen for diabetes: development and validation. Diabetes Care 25 , 1999–2003 (2002).

World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus (WHO, 1999).

Pan, X. R. et al . Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT Diabetes Study. Diabetes Care 20 , 537–544 (1997).

Knowler, W. C. et al . Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N. Engl. J. Med. 346 , 393–403 (2002).

Ramachandran, A. et al . The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia 49 , 289–297 (2006).

Chiasson, J.-L. et al . Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359 , 2072–2077 (2002).

Kawamori, R. et al . Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet 373 , 1607–1614 (2009).

Knowler, W. C. et al . Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. Diabetes 54 , 1150–1156 (2005).

Gerstein, H. C. et al . Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368 , 1096–1105 (2006).

Li, G. et al . The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet 371 , 1783–1789 (2008).

Lindström, J. et al . Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 368 , 1673–1679 (2006).

Knowler, W. C. et al . 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 374 , 1677–1686 (2009). Long-term follow-up of body weight regain and diabetes incidence in patients with IGT in the Diabetes Prevention Program treated with lifestyle heavy, lifestyle light and metformin, showing that gradual weight regain is the norm and that 40–50% of patients with IGT develop diabetes despite successful weight loss.

DeFronzo, R. A., Eldor, R. & Abdul-Ghani, M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care 36 , S127–S138 (2013). A rational approach to the treatment of T2DM is presented based on its pathophysiology.

Raz, I. et al . Personalized management of hyperglycemia in type 2 diabetes: reflections from a Diabetes Care Editors’ Expert Forum. Diabetes Care 36 , 1779–1788 (2013).

Nakagami, T., Kawahara, R., Hori, S. & Omori, Y. Glycemic control and prevention of retinopathy in Japanese NIDDM patients. A 10-year follow-up study. Diabetes Care 20 , 621–622 (1997).

Lim, E. L. et al . Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 54 , 2506–2514 (2011).

Jazet, I. M. et al . Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients. Diabetologia 51 , 309–319 (2008).

Abdul-Ghani, M. A. et al . Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes. Metab. 17 , 268–275 (2015). This prospective randomized trial using a combination of antidiabetic agents proven to reverse known pathophysiological abnormalities in T2DM demonstrated superiority of glycaemic control compared with the stepped approach of metformin followed by a sulfonylurea and then basal insulin recommended by most national diabetes organizations.

Harrison, L. B., Adams-Huet, B., Raskin, P. & Lingvay, I. β-cell function preservation after 3.5 years of intensive diabetes therapy. Diabetes Care 35 , 1406–1412 (2012).

Gram, J. et al . Pharmacological treatment of the pathogenetic defects in type 2 diabetes: the randomized multicenter South Danish Diabetes Study. Diabetes Care 34 , 27–33 (2011).

DeFronzo, R. A. et al . Combination of empagliflozin and linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin. Diabetes Care 38 , 384–393 (2015).

Weng, J. et al . Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 371 , 1753–1760 (2008).

Hu, Y. et al . Short-term intensive therapy in newly diagnosed type 2 diabetes partially restores both insulin sensitivity and β-cell function in subjects with long-term remission. Diabetes Care 34 , 1848–1853 (2011). One of several recent studies demonstrating that intensive insulin therapy to correct the decompensated metabolic state in newly diagnosed patients with T2DM can lead to durable glycaemic control without or with a marked reduction in antidiabetic medications.

Xiang, A. H. et al . Effect of pioglitazone on pancreatic β-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes 55 , 517–522 (2006).

Astrup, A. et al . Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int. J. Obes. (Lond.) 36 , 843–854 (2012).

Cusi, K., Consoli, A. & DeFronzo, R. A. Metabolic effects of metformin on glucose and lactate metabolism in noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab. 81 , 4059–4067 (1996).

Turner, R. C., Cull, C. A., Frighi, V. & Holman, R. R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 281 , 2005–2012 (1999). A landmark UK Prospective Diabetes Study documenting the need for progressive add-on therapies in newly diagnosed patients with T2DM receiving initial therapy with metformin or with a sulfonylurea.

Brown, J. B., Conner, C. & Nichols, G. A. Secondary failure of metformin monotherapy in clinical practice. Diabetes Care 33 , 501–506 (2010).

Kahn, S. E. et al . Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N. Engl. J. Med. 355 , 2427–2443 (2006). A 5-year ADOPT study demonstrating long-term durable HbA1c reduction with rosiglitazone compared with a progressive rise in HbA1c observed with metformin and sulfonylureas, and a more rapid deterioration of glycaemic control with sulfonylureas compared with metformin.

Madiraju, A. K. et al . Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature 510 , 542–546 (2014).

Ferrannini, E. The target of metformin in type 2 diabetes. N. Engl. J. Med. 371 , 1547–1548 (2014).

[No authors listed.] Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 352 , 854–865 (1998).

Maedler, K. et al . Sulfonylurea induced β-cell apoptosis in cultured human islets. J. Clin. Endocrinol. Metab. 90 , 501–506 (2005).

Roumie, C. L. et al . Comparative effectiveness of sulfonylurea and metformin monotherapy on cardiovascular events in type 2 diabetes mellitus: a cohort study. Ann. Intern. Med. 157 , 601–610 (2012).

Simpson, S. H., Majumdar, S. R., Tsuyuki, R. T., Eurich, D. T. & Johnson, J. A. Dose–response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ 174 , 169–174 (2006).

Simpson, S. H. et al . Mortality risk among sulfonylureas: a systematic review and network meta-analysis. Lancet Diabetes Endocrinol. 3 , 43–51 (2015). A review of the published literature that examines the relationship between sulfonylurea therapy and the development of adverse cardiovascular events.

Yki-Järvinen, H. Thiazolidinediones. N. Engl. J. Med. 351 , 1106–1118 (2004).

Eldor, R., DeFronzo, R. A. & Abdul-Ghani, M. In vivo actions of peroxisome proliferator-activated receptors: glycemic control, insulin sensitivity, and insulin secretion. Diabetes Care 36 , S162–S174 (2013). An exhaustive review of the mechanism of action, efficacy and side-effect profile of the thiazolidinedione class of antidiabetic medications.

Miyazaki, Y., He, H., Mandarino, L. J. & DeFronzo, R. A. Rosiglitazone improves downstream insulin receptor signaling in type 2 diabetic patients. Diabetes 52 , 1943–1950 (2003).

Gastaldelli, A. et al . Thiazolidinediones improve β-cell function in type 2 diabetic patients. Am. J. Physiol. Endocrinol. Metab. 292 , E871–E883 (2007).

DeFronzo, R. A. et al . Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates. Diabetes 62 , 3920–3926 (2013).

Kahn, S. E. et al . Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT. Diabetes 60 , 1552–1560 (2011).

Dormandy, J. A. et al . Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366 , 1279–1289 (2005). A large prospective study (PROactive) demonstrating that pioglitazone significantly reduced the second principal end point of myocardial infarction, stroke and cardiovascular death; the primary end point did not reach statistical significance because of the inclusion of peripheral arterial disease and leg revascularization, which is known to be refractory to medical intervention, including statin therapy.

Aronoff, S. et al . Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care 23 , 1605–1611 (2000).

Erdmann, E., Song, E., Spanheimer, R., van Troostenburg de Bruyn, A.-R. & Perez, A. Observational follow-up of the PROactive study: a 6-year update. Diabetes Obes. Metab. 16 , 63–74 (2014).

[No authors listed.] Takeda announces completion of the post-marketing commitment to submit data to the FDA, the EMA and the PMDA for pioglitazone containing medicines including ACTOS. Takeda [online] , (2014).

Levin, D. et al . Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis. Diabetologia 58 , 493–504 (2015).

Kjems, L. L., Holst, J. J., Vølund, A. & Madsbad, S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on β-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 52 , 380–386 (2003).

Vilsbøll, T., Krarup, T., Madsbad, S. & Holst, J. J. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 45 , 1111–1119 (2002).

Aroda, V. R. et al . Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin. Ther. 34 , 1247–1258.e22 (2012).

Deacon, C. F. Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: a comparative review. Diabetes Obes. Metab. 13 , 7–18 (2011).

Balas, B. et al . The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J. Clin. Endocrinol. Metab. 92 , 1249–1255 (2007).

Drucker, D. J. Incretin action in the pancreas: potential promise, possible perils, and pathological pitfalls. Diabetes 62 , 3316–3323 (2013). A comprehensive review of the effect of incretin hormones on pancreatic hormone secretion and pathology by one of the world's leading authorities.

White, W. B. et al . Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369 , 1327–1335 (2013).

Scirica, B. M. et al . Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369 , 1317–1326 (2013).

Cervera, A. et al . Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. Am. J. Physiol. Endocrinol. Metab. 294 , E846–E852 (2008).

Bunck, M. C. et al . Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care 34 , 2041–2047 (2011). A landmark 3-year prospective study demonstrating the marked and durable improvement in β-cell function using the combined hyperglycaemic and euglycaemic insulin clamp techniques following exenatide treatment in patients with T2DM.

Klonoff, D. C. et al . Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr. Med. Res. Opin. 24 , 275–286 (2008).

Schwartz, S. & Kohl, B. A. Type 2 diabetes mellitus and the cardiometabolic syndrome: impact of incretin-based therapies. Diabetes Metab. Syndr. Obes. 3 , 227–242 (2010).

Eng, C., Kramer, C. K., Zinman, B. & Retnakaran, R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet 384 , 2228–2234 (2014).

Egan, A. G. et al . Pancreatic safety of incretin-based drugs — FDA and EMA assessment. N. Engl. J. Med. 370 , 794–797 (2014).

Van de Laar, F. A. et al . Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst. Rev. 2 , CD003639 (2005).

Esposito, K. et al . Dipeptidyl peptidase-4 inhibitors and HbA1c target of &lt;7% in type 2 diabetes: meta-analysis of randomized controlled trials. Diabetes Obes. Metab. 13 , 594–603 (2011).

Richter, B., Bandeira-Echtler, E., Bergerhoff, K. & Lerch, C. L. Dipeptidyl peptidase-4 (DPP-4) inhibitors for type 2 diabetes mellitus. Cochrane Database Syst. Rev. 2 , CD006739 (2008).

Abdul-Ghani, M. A., Norton, L. & DeFronzo, R. A. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr. Rev. 32 , 515–531 (2011). An excellent review of the mechanism of action, efficacy and safety of the recently approved SGLT2 inhibitor class of antidiabetic medications.

Wright, E. M., Loo, D. D. & Hirayama, B. A. Biology of human sodium glucose transporters. Physiol. Rev. 91 , 733–794 (2011).

Merovci, A. et al . Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J. Clin. Invest. 124 , 509–514 (2014).

Ferrannini, E. et al . Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J. Clin. Invest. 124 , 499–508 (2014).

Abdul-Ghani, M. A., DeFronzo, R. A. & Norton, L. Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30–50% of filtered glucose load in humans. Diabetes 62 , 3324–3328 (2013).

Cherney, D. Z. I. et al . Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 129 , 587–597 (2014).

Holman, R. R. et al . Three-year efficacy of complex insulin regimens in type 2 diabetes. N. Engl. J. Med. 361 , 1736–1747 (2009). A comparison of the efficacy and side-effect profile of commonly used complex insulin regimens for the treatment of patients with T2DM.

Gough, S. C. L. et al . Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2 , 885–893 (2014).

Wilding, J. P. et al . Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial. Ann. Intern. Med. 156 , 405–415 (2012).

Anderson, M., Powell, J., Campbell, K. M. & Taylor, J. R. Optimal management of type 2 diabetes in patients with increased risk of hypoglycemia. Diabetes Metab. Syndr. Obes. 7 , 85–94 (2014).

PubMed   PubMed Central   Google Scholar  

Schopman, J. E. et al . The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis. Diabetes Metab. Res. Rev. 30 , 11–22 (2014).

Desouza, C., Salazar, H., Cheong, B., Murgo, J. & Fonseca, V. Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring. Diabetes Care 26 , 1485–1489 (2003).

Gerstein, H. C. et al . Effects of intensive glucose lowering in type 2 diabetes. N. Engl. J. Med. 358 , 2545–2559 (2008). The ORIGIN trial demonstrated that physiological insulin replacement doses (30–40 units per day) in newly diagnosed patients with T2DM could control HbA1c without an increased risk of cardiovascular events; however, the risk of hypoglycaemia was significantly increased, and the study did not examine the effect of higher doses of insulin, which are usually required to normalize glycaemia in more long-standing diabetes, on cardiovascular risk or other potential side effects of insulin therapy.

Cushman, W. C. et al . Effects of intensive blood-pressure control in type 2 diabetes mellitus. N. Engl. J. Med. 362 , 1575–1585 (2010).

James, P. A. et al . 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311 , 507–520 (2014).

Emdin, C. et al . Association of cardiovascular trial registration with positive study findings: Epidemiological Study of Randomized Trials (ESORT). JAMA Intern. Med. 175 , 304–307 (2015).

Testa, M. A. & Simonson, D. C. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled, double-blind trial. JAMA 280 , 1490–1496 (1998). This was the first randomized trial to demonstrate that better glucose control improves QOL, cognitive function and general perceived health, and reduces symptom distress and absenteeism from work.

Testa, M. A. & Simonson, D. C. Assesment of quality-of-life outcomes. N. Engl. J. Med. 334 , 835–840 (1996).

Testa, M. A., Simonson, D. C. & Turner, R. R. Valuing quality of life and improvements in glycemic control in people with type 2 diabetes. Diabetes Care 21 , C44–C52 (1998).

Bode, B. W. et al . Patient-reported outcomes following treatment with the human GLP-1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. Diabetes Obes. Metab. 12 , 604–612 (2010).

Testa, M. A. et al . Comparative effectiveness of basal-bolus versus premix analog insulin on glycemic variability and patient-centered outcomes during insulin intensification in type 1 and type 2 diabetes: a randomized, controlled, crossover trial. J. Clin. Endocrinol. Metab. 97 , 3504–3514 (2012). This randomized trial demonstrated that patient satisfaction with treatment was more positively affected by improved QOL, reduced glucose variability and better glycaemic control with a basal-bolus regimen than negatively affected by the burden of additional injections.

Cotter, A. P., Durant, N., Agne, A. A. & Cherrington, A. L. Internet interventions to support lifestyle modification for diabetes management: a systematic review of the evidence. J. Diabetes Complications 28 , 243–251 (2014).

Rose, M. et al . The PROMIS Physical Function item bank was calibrated to a standardized metric and shown to improve measurement efficiency. J. Clin. Epidemiol. 67 , 516–526 (2014).

DeFronzo, R. A. & Triplitt, C. Novel agents for T2DM. Diabetes Spectr. 27 , 100–112 (2014). This article presents a more detailed review of novel antidiabetic agents that currently are being investigated in animals and humans for the treatment of T2DM.

Wong, A. K., Howie, J., Petrie, J. R. & Lang, C. C. AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. Clin. Sci. (Lond.) 116 , 607–620 (2009).

Agrawal, N. K. & Kant, S. Targeting inflammation in diabetes: newer therapeutic options. World J. Diabetes 5 , 697–710 (2014). Inflammation in insulin target tissues and β-cells is a now well-established pathogenetic abnormality T2DM. This article reviews the mechanism by which inflammation contributes to glucose intolerance in T2DM and potential interventions to suppress inflammation and improve insulin sensitivity and β-cell function.

Poy, M. N. et al . miR-375 maintains normal pancreatic α- and β-cell mass. Proc. Natl Acad. Sci. USA 106 , 5813–5818 (2009).

Burant, C. F. et al . TAK-875 versus placebo or glimepiride in type 2 diabetes mellitus: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 379 , 1403–1411 (2012).

Assmann, A., Hinault, C. & Kulkarni, R. N. Growth factor control of pancreatic islet regeneration and function. Pediatr. Diabetes 10 , 14–32 (2009).

Vasavada, R. C. et al . Protein kinase C-ζ activation markedly enhances β-cell proliferation: an essential role in growth factor mediated β-cell mitogenesis. Diabetes 56 , 2732–2743 (2007).

Wiederkehr, A. & Wollheim, C. B. Mitochondrial signals drive insulin secretion in the pancreatic β-cell. Mol. Cell. Endocrinol. 353 , 128–137 (2012).

Wang, C. et al . Deficiency of APPL1 in mice impairs glucose-stimulated insulin secretion through inhibition of pancreatic beta cell mitochondrial function. Diabetologia 56 , 1999–2009 (2013).

Sivitz, W. I. & Yorek, M. A. Mitochondrial dysfunction in diabetes: from molecular mechanisms to functional significance and therapeutic opportunities. Antioxid. Redox Signal. 12 , 537–577 (2010).

Li, N., Stojanovski, S. & Maechler, P. Mitochondrial hormesis in pancreatic β cells: does uncoupling protein 2 play a role? Oxid. Med. Cell. Longev. 2012 , 740849 (2012).

Aquilano, K., Baldelli, S., Pagliei, B. & Ciriolo, M. R. Extranuclear localization of SIRT1 and PGC-1α: an insight into possible roles in diseases associated with mitochondrial dysfunction. Curr. Mol. Med. 13 , 140–154 (2013).

Matschinsky, F. M. et al . Glucokinase activators for diabetes therapy: May 2010 status report. Diabetes Care 34 , S236–S243 (2011).

Engel, S. S. Glycemic and lipid effects of the short-acting glucagon receptor antagonist MK-3577 in patients with type 2 diabetes. Diabetes Abstr. 61 , A266 (2012).

Gumbiner, B. Pronounced glucose (G) reduction in poorly controlled T2DM with MB07803, a novel fructose-1, 6-biphosphatase inhibitor (FBPasel) with reduced potential for acid-base disturbance versus the 1st generation FBPasel CS-917. Diabetes Abstr. 58 , LB4 (2009).

Kumashiro, N. et al . Targeting pyruvate carboxylase reduces gluconeogenesis and adiposity and improves insulin resistance. Diabetes 62 , 2183–2194 (2013).

Stark, R. et al . A role for mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M) in the regulation of hepatic gluconeogenesis. J. Biol. Chem. 289 , 7257–7263 (2014).

Harlan, D. M., Kenyon, N. S., Korsgren, O. & Roep, B. O. Current advances and travails in islet transplantation. Diabetes 58 , 2175–2184 (2009).

Motté, E. et al . Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts. Am. J. Physiol. Endocrinol. Metab. 307 , E838–E846 (2014).

Pagliuca, F. W. et al . Generation of functional human pancreatic β cells in vitro . Cell 159 , 428–439 (2014).

Blum, B. et al . Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway. eLife 3 , e02809 (2014).

Pickup, J. C. Banting Memorial Lecture 2014* Technology and diabetes care: appropriate and personalized. Diabet. Med. 32 , 3–13 (2015).

Peyser, T., Dassau, E., Breton, M. & Skyler, J. S. The artificial pancreas: current status and future prospects in the management of diabetes. Ann. NY Acad. Sci. 1311 , 102–123 (2014). This article presents an up-to-to-date status report on progress with the artificial pancreas (closed-loop system).

Klonoff, D. C. Afrezza inhaled insulin: the fastest-acting FDA-approved insulin on the market has favorable properties. J. Diabetes Sci. Technol. 8 , 1071–1073 (2014).

Eldor, R., Arbit, E., Corcos, A. & Kidron, M. Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study. PLoS ONE 8 , e59524 (2013).

DeFronzo, R. A. Dissociation between metformin plasma exposure and its glucose-lowering effect: a novel gut-mediated mechanism of action. Diabetes 62 , a281 (2013).

DePaoli, A. M., Higgins, L. S., Henry, R. R., Mantzoros, C. & Dunn, F. L. Can a selective PPARγ modulator improve glycemic control in patients with type 2 diabetes with fewer side effects compared with pioglitazone? Diabetes Care 37 , 1918–1923 (2014).

Colca, J. R., Tanis, S. P., McDonald, W. G. & Kletzien, R. F. Insulin sensitizers in 2013: new insights for the development of novel therapeutic agents to treat metabolic diseases. Expert Opin. Investig. Drugs 23 , 1–7 (2014).

Suh, J. M. et al . Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature 513 , 436–439 (2014).

Gaich, G. et al . The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 18 , 333–340 (2013).

Jeoung, N. H. & Harris, R. A. Role of pyruvate dehydrogenase kinase 4 in regulation of blood glucose levels. Korean Diabetes J. 34 , 274–283 (2010).

Povel, C. M. et al . Metabolic syndrome model definitions predicting type 2 diabetes and cardiovascular disease. Diabetes Care 36 , 362–368 (2013).

Pacini, G., Mari, A., Fouqueray, P., Bolze, S. & Roden, M. Imeglimin increases glucose-dependent insulin secretion and improves β-cell function in patients with type 2 diabetes. Diabetes Obes. Metab. 17 , 541–545 (2015).

Birch, A. M., Buckett, L. K. & Turnbull, A. V. DGAT1 inhibitors as anti-obesity and anti-diabetic agents. Curr. Opin. Drug Discov. Devel. 13 , 489–496 (2010).

Liu, L. et al . Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J. Clin. Invest. 117 , 1679–1689 (2007).

Harrima, G., Greenwood, J. & Bhar, S. Acetyl-CoA carboxylase inhibition by NDI-630 inhibits fatty acid synthesis stimulates fatty acid oxidative, reduces body weight, improvise insulin sensitivity, and modulates dyslipidemia in rats. Diabetes Abstr. 62 , A161 (2013).

Tao, H., Zhang, Y., Zeng, X., Shulman, G. I. & Jin, S. Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat. Med. 20 , 1263–1269 (2014).

Perry, R. J. et al . Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. Cell Metab. 18 , 740–748 (2013).

Garvey, W. T. et al . Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am. J. Clin. Nutr. 95 , 297–308 (2012).

Carlsson, L. M. et al . Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N. Engl. J. Med. 367 , 695–704 (2012). The effectiveness and safety of bariatric surgery in the treatment of obesity and T2DM is reviewed in this longest ongoing study on surgical intervention.

Neuschwander-Tetri, B. A. et al . Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet 385 , 956–965 (2014).

Out, C., Groen, A. K. & Brufau, G. Bile acid sequestrants: more than simple resins. Curr. Opin. Lipidol. 23 , 43–55 (2012).

Cellitti, S. A novel GLP-1-FGF21 fusion protein for the treatment of diabetes and obesity. Keystone Symp. Obes. (2014).

Thareja, S., Aggarwal, S., Bhardwaj, T. R. & Kumar, M. Protein tyrosine phosphatase 1B inhibitors: a molecular level legitimate approach for the management of diabetes mellitus. Med. Res. Rev. 32 , 459–517 (2012).

Chakraborty, C., Doss, C. G., Bandyopadhyay, S. & Agoramoorthy, G. Influence of miRNA in insulin signaling pathway and insulin resistance: micro-molecules with a major role in type-2 diabetes. Wiley Interdiscip. Rev. RNA 5 , 697–712 (2014).

Tilg, H. & Moschen, A. R. Microbiota and diabetes: an evolving relationship. Gut 63 , 1513–1521 (2014).

Patel, S. R., Hakim, D., Mason, J. & Hakim, N. The duodenal–jejunal bypass sleeve (EndoBarrier Gastrointestinal Liner) for weight loss and treatment of type 2 diabetes. Surg. Obes. Relat. Dis. 9 , 482–484 (2013).

Bhatt, M. P., Lim, Y.-C. & Ha, K.-S. C-peptide replacement therapy as an emerging strategy for preventing diabetic vasculopathy. Cardiovasc. Res. 104 , 234–244 (2014).

Bhat, M., Pouliot, M., Couture, R. & Vaucher, E. The kallikrein–kinin system in diabetic retinopathy. Prog. Drug Res. 69 , 111–143 (2014).

PubMed   Google Scholar  

Hajhosseiny, R. et al . Have we reached the limits for the treatment of diabetic nephropathy? Expert Opin. Investig. Drugs 23 , 511–522 (2014).

Williams, M. E. et al . Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am. J. Nephrol. 27 , 605–614 (2007).

De Zeeuw, D. et al . The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2 diabetic nephropathy. J. Am. Soc. Nephrol. 25 , 1083–1093 (2014).

Boussageon, R. et al . Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343 , d4169 (2011).

Colditz, G. A., Willett, W. C., Rotnitzky, A. & Manson, J. E. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann. Intern. Med. 122 , 481–486 (1995).

Chan, J. M., Rimm, E. B., Colditz, G. A., Stampfer, M. J. & Willett, W. C. Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care 17 , 961–969 (1994).

Download references

Acknowledgements

The authors acknowledge grants from: the South Texas Veterans Healthcare System to R.A.D.; the National Institutes of Health (grants R01DK24092 to R.A.D.; DK58845 and P30 DK46200 to F.B.H.; R01 DK-040936, R01 DK-049230, R24 DK-085836, UL1 RR-045935, R01 DK-082659 and R24 DK085610 to G.I.S.; P30 DK036836 to C.R.K. Novo Nordisk Foundation for Basic Metabolic Research and the University of Copenhagen to G.I.S. and C.R.K.; DVA-Merit Review grant and VA San Diego Healthcare System to R.H.; National Institute for Diabetes and Digestive and Kidney Disease (grant P30DK092926) to W.H.; the Swedish Research Council (grants 2010–3490 and 2008–6589) and European Council (grants GA269045) to L.G.; Italian Ministry of University & Research (MIUR 2010329EKE) to E.F.; the Patient-Centered Outcomes Research Institute (PCORI) Program Award (CE1304-6756) to D.C.S. and M.A.T.; NovoNordisk Foundation to the NNF Center for Basic Metabolic Research to J.H. W.H. acknowledges the Michigan Center for Diabetes Translational Research and I.R. thanks R. Sprung for editorial assistance.

Author information

Authors and affiliations.

Diabetes Division, Department of Medicine, University of Texas Health Science Center, South Texas Veterans Health Care System and Texas Diabetes Institute, 701 S. Zarzamoro, San Antonio, 78207, Texas, USA

Ralph A. DeFronzo

CNR Institute of Clinical Physiology, Pisa, Italy

Ele Ferrannini

Department of Clinical Science Malmoe, Diabetes & Endocrinology, Lund University Diabetes Centre, Lund, Sweden

University of California, San Diego, Section of Diabetes, Endocrinology & Metabolism, Center for Metabolic Research, VA San Diego Healthcare System, San Diego, California, USA

Robert R. Henry

University of Michigan, Ann Arbor, Michigan, USA

William H. Herman

University of Copenhagen, Kobenhavn, Denmark

Jens Juul Holst

Department of Nutrition, Harvard T.H. Chan School of Public Health and Department of Epidemiology, Harvard T.H. Chan School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Frank B. Hu

Harvard Medical School and Joslin Diabetes Center, Boston, Massachusetts, USA

C. Ronald Kahn

Division of Internal Medicine, Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel

Howard Hughes Medical Institute and the Departments of Internal Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA

Gerald I. Shulman

Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Donald C. Simonson

Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA

Marcia A. Testa

Department of Human Metabolism and Nutrition, Braun School of Public Health, Hebrew University, Jerusalem, Israel

You can also search for this author in PubMed   Google Scholar

Contributions

Introduction (R.R.H.); Epidemiology (F.B.H.); Mechanisms/pathophysiology (L.C.G., C.R.K., E.F., G.I.S. and R.A.D.); Diagnosis, screening and prevention (W.H.H.); Management (R.A.D.); Quality of life (D.C.S. and M.A.T.); Outlook (I.R., J.J.H. and R.W.); overview of Primer (R.A.D.).

Corresponding author

Correspondence to Ralph A. DeFronzo .

Ethics declarations

Competing interests.

The authors declare the following potential COI: (1) R.A.D.: Research Grant Support - AstraZeneca, Bristol Myers Squibb, Janssen; Speaker's Bureau - AstraZeneca, Novo Nordisk, Advisory Board/Consultant - AstraZeneca, Janssen, Novo Nordisk, Boehringer Ingelheim, Lexicon, Intarcia; (2) E.F.: Research Grant Support - Boehringer Ingelheim, Eli Lilly; Consultant/Speaker Bureau-Boehringer Ingelheim, Eli Lilly, Sanofi, Novo Nordisk, Janssen, AstraZeneca, Takeda, Medtronic, Intarcia; (3) C.R.K. serves as a consultant for Medimmune, Merck, Five Prime Therapeutics, CohBar, Antriabio, and Catabasis; (4) L.G. has no conflict of interest; (5) R.H. has received grant support from Hitachi, Janssen, Eli Lilly, Sanofi-Aventis and Viacyte and is a consultant/advisory board member for Alere, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Clin Met, Eisai, Elcelyx, Gilead, Intarcia, Isis, Janssen, Merck, Novo Nordisk, Sanofi-Aventis, and Vivus; (6) W.H.H. has no conflict of interest; (7) J.J.H. has received grant support from Novartis and Merck and is a consultant/advisory board member for Glaxo, Smith, Kline, Novo Nordisk, and Zealand Pharmaceuticals; (8) M.A.T. has no conflict of interest; (9) R.W. serves as a consultant for Medtronics and Kamada and is on the speaker's bureau for Medtronics and Novo Nordisk; (10) F.H. has received research support from California Walnut Commission and Metegenics; (11) G.I.S. serves on scientific advisory boards for Merck and Novartis and he has received research grant support from Gilead Pharmaceuticals; (12) D.C.S. has no conflict of interest; (13) I.R. – Advisory Board: Novo Nordisk, Astra Zeneca/BMS, MSD, Eli Lilly, Sanofi, Medscape Cardiology; Consultant: Astra Zeneca/BMS, Insuline; Speaker's Bureau: Eli Lilly, Novo Nordisk, Astra Zeneca/BMS, J&J, Sanofi, MSD, Novartis, Teva; Shareholder: Insuline, Labstyle.

PowerPoint slides

Powerpoint slide for fig. 1, powerpoint slide for fig. 2, powerpoint slide for fig. 3, powerpoint slide for fig. 4, powerpoint slide for fig. 5, powerpoint slide for fig. 6, powerpoint slide for fig. 7, powerpoint slide for fig. 8, rights and permissions.

Reprints and permissions

About this article

Cite this article.

DeFronzo, R., Ferrannini, E., Groop, L. et al. Type 2 diabetes mellitus. Nat Rev Dis Primers 1 , 15019 (2015). https://doi.org/10.1038/nrdp.2015.19

Download citation

Published : 23 July 2015

DOI : https://doi.org/10.1038/nrdp.2015.19

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Essay on Diabetes

Students are often asked to write an essay on Diabetes in their schools and colleges. And if you’re also looking for the same, we have created 100-word, 250-word, and 500-word essays on the topic.

Let’s take a look…

100 Words Essay on Diabetes

What is diabetes.

Diabetes is a chronic disease where the body can’t control blood sugar levels. This happens because the body either doesn’t make enough insulin or can’t use it properly.

Types of Diabetes

There are two main types: Type 1 and Type 2. Type 1 is when the body doesn’t produce insulin. Type 2 is when the body doesn’t use insulin well.

Managing Diabetes

Diabetes can be managed through a healthy diet, regular exercise, and medication. Regular check-ups are also important to monitor blood sugar levels.

The Impact of Diabetes

If not managed, diabetes can lead to serious health problems like heart disease, kidney disease, and vision loss.

250 Words Essay on Diabetes

Introduction.

Diabetes, a chronic metabolic disorder, is characterized by an increased level of glucose in the blood. It arises due to the body’s inability to produce or effectively utilize insulin, a hormone responsible for glucose regulation.

Etiology of Diabetes

Diabetes is classified into two major types: Type 1 and Type 2. Type 1 diabetes, an autoimmune disorder, is a result of the body’s immune system attacking insulin-producing cells in the pancreas. On the other hand, Type 2 diabetes, the more prevalent form, is primarily associated with insulin resistance and often linked to obesity and sedentary lifestyle.

Impact and Management

Diabetes can lead to severe complications like heart disease, kidney failure, and blindness if left unmanaged. Management involves lifestyle modifications, including a healthy diet, regular physical activity, and medication or insulin therapy as needed.

Prevention and Future Research

Prevention strategies for Type 2 diabetes involve promoting healthier lifestyles and early detection. For Type 1 diabetes, research is still ongoing to understand its triggers. Advances in technology and medicine, such as artificial pancreas systems and islet cell transplantation, show promise for future diabetes management.

Diabetes, a global health crisis, requires comprehensive understanding and management strategies. With ongoing research and advancements, the future holds potential for improved diabetes care and prevention.

500 Words Essay on Diabetes

Introduction to diabetes.

There are primarily two types of diabetes: Type 1 and Type 2. Type 1 diabetes is an autoimmune condition where the body’s immune system attacks the insulin-producing cells in the pancreas. This type is less common and usually develops early in life. Type 2 diabetes, on the other hand, is more prevalent and typically develops in adulthood. It occurs when the body becomes resistant to insulin or doesn’t produce enough to maintain a normal glucose level.

Risk Factors and Symptoms

Several factors increase the risk of developing diabetes, including genetics, obesity, lack of physical activity, and poor diet. Additionally, certain ethnic groups are at a higher risk.

Management and Treatment

While there is currently no cure for diabetes, it can be effectively managed with a combination of lifestyle changes and medication. Regular exercise, a balanced diet, and maintaining a healthy weight are crucial for managing both types of diabetes.

For Type 1 diabetes, insulin injections or use of an insulin pump are necessary. Type 2 diabetes can often be managed with lifestyle changes and oral medication, but insulin may be required as the disease progresses.

Complications and Prevention

Prevention strategies for Type 2 diabetes include regular physical activity, a healthy diet, maintaining a normal body weight, and avoiding tobacco use. Early detection through regular health screenings is also critical, as early treatment can prevent or delay the onset of complications.

Diabetes is a significant global health concern that requires concerted efforts for effective management and prevention. Understanding the disease, its risk factors, and the importance of early detection can go a long way in reducing the impact of this chronic condition. Through lifestyle changes and medical intervention, individuals with diabetes can lead healthy and fulfilling lives.

That’s it! I hope the essay helped you.

If you’re looking for more, here are essays on other interesting topics:

Happy studying!

Leave a Reply Cancel reply

Your email address will not be published. Required fields are marked *

• Patient Care & Health Information
• Diseases & Conditions
• Type 2 diabetes

Type 2 diabetes is a condition that happens because of a problem in the way the body regulates and uses sugar as a fuel. That sugar also is called glucose. This long-term condition results in too much sugar circulating in the blood. Eventually, high blood sugar levels can lead to disorders of the circulatory, nervous and immune systems.

In type 2 diabetes, there are primarily two problems. The pancreas does not produce enough insulin — a hormone that regulates the movement of sugar into the cells. And cells respond poorly to insulin and take in less sugar.

Type 2 diabetes used to be known as adult-onset diabetes, but both type 1 and type 2 diabetes can begin during childhood and adulthood. Type 2 is more common in older adults. But the increase in the number of children with obesity has led to more cases of type 2 diabetes in younger people.

There's no cure for type 2 diabetes. Losing weight, eating well and exercising can help manage the disease. If diet and exercise aren't enough to control blood sugar, diabetes medications or insulin therapy may be recommended.

Products & Services

• A Book: The Essential Diabetes Book
• A Book: The Mayo Clinic Diabetes Diet
• Assortment of Health Products from Mayo Clinic Store

Symptoms of type 2 diabetes often develop slowly. In fact, you can be living with type 2 diabetes for years and not know it. When symptoms are present, they may include:

• Increased thirst.
• Frequent urination.
• Increased hunger.
• Unintended weight loss.
• Blurred vision.
• Slow-healing sores.
• Frequent infections.
• Numbness or tingling in the hands or feet.
• Areas of darkened skin, usually in the armpits and neck.

When to see a doctor

See your health care provider if you notice any symptoms of type 2 diabetes.

There is a problem with information submitted for this request. Review/update the information highlighted below and resubmit the form.

From Mayo Clinic to your inbox

Sign up for free and stay up to date on research advancements, health tips, current health topics, and expertise on managing health. Click here for an email preview.

Error Email field is required

Error Include a valid email address

To provide you with the most relevant and helpful information, and understand which information is beneficial, we may combine your email and website usage information with other information we have about you. If you are a Mayo Clinic patient, this could include protected health information. If we combine this information with your protected health information, we will treat all of that information as protected health information and will only use or disclose that information as set forth in our notice of privacy practices. You may opt-out of email communications at any time by clicking on the unsubscribe link in the e-mail.

Thank you for subscribing!

You'll soon start receiving the latest Mayo Clinic health information you requested in your inbox.

Sorry something went wrong with your subscription

Please, try again in a couple of minutes

Type 2 diabetes is mainly the result of two problems:

• Cells in muscle, fat and the liver become resistant to insulin As a result, the cells don't take in enough sugar.
• The pancreas can't make enough insulin to keep blood sugar levels within a healthy range.

Exactly why this happens is not known. Being overweight and inactive are key contributing factors.

How insulin works

Insulin is a hormone that comes from the pancreas — a gland located behind and below the stomach. Insulin controls how the body uses sugar in the following ways:

• Sugar in the bloodstream triggers the pancreas to release insulin.
• Insulin circulates in the bloodstream, enabling sugar to enter the cells.
• The amount of sugar in the bloodstream drops.
• In response to this drop, the pancreas releases less insulin.

The role of glucose

Glucose — a sugar — is a main source of energy for the cells that make up muscles and other tissues. The use and regulation of glucose includes the following:

• Glucose comes from two major sources: food and the liver.
• Glucose is absorbed into the bloodstream, where it enters cells with the help of insulin.
• The liver stores and makes glucose.
• When glucose levels are low, the liver breaks down stored glycogen into glucose to keep the body's glucose level within a healthy range.

In type 2 diabetes, this process doesn't work well. Instead of moving into the cells, sugar builds up in the blood. As blood sugar levels rise, the pancreas releases more insulin. Eventually the cells in the pancreas that make insulin become damaged and can't make enough insulin to meet the body's needs.

Risk factors

Factors that may increase the risk of type 2 diabetes include:

• Weight. Being overweight or obese is a main risk.
• Fat distribution. Storing fat mainly in the abdomen — rather than the hips and thighs — indicates a greater risk. The risk of type 2 diabetes is higher in men with a waist circumference above 40 inches (101.6 centimeters) and in women with a waist measurement above 35 inches (88.9 centimeters).
• Inactivity. The less active a person is, the greater the risk. Physical activity helps control weight, uses up glucose as energy and makes cells more sensitive to insulin.
• Family history. An individual's risk of type 2 diabetes increases if a parent or sibling has type 2 diabetes.
• Race and ethnicity. Although it's unclear why, people of certain races and ethnicities — including Black, Hispanic, Native American and Asian people, and Pacific Islanders — are more likely to develop type 2 diabetes than white people are.
• Blood lipid levels. An increased risk is associated with low levels of high-density lipoprotein (HDL) cholesterol — the "good" cholesterol — and high levels of triglycerides.
• Age. The risk of type 2 diabetes increases with age, especially after age 35.
• Prediabetes. Prediabetes is a condition in which the blood sugar level is higher than normal, but not high enough to be classified as diabetes. Left untreated, prediabetes often progresses to type 2 diabetes.
• Pregnancy-related risks. The risk of developing type 2 diabetes is higher in people who had gestational diabetes when they were pregnant and in those who gave birth to a baby weighing more than 9 pounds (4 kilograms).
• Polycystic ovary syndrome. Having polycystic ovary syndrome — a condition characterized by irregular menstrual periods, excess hair growth and obesity — increases the risk of diabetes.

Complications

Type 2 diabetes affects many major organs, including the heart, blood vessels, nerves, eyes and kidneys. Also, factors that increase the risk of diabetes are risk factors for other serious diseases. Managing diabetes and controlling blood sugar can lower the risk for these complications and other medical conditions, including:

• Heart and blood vessel disease. Diabetes is associated with an increased risk of heart disease, stroke, high blood pressure and narrowing of blood vessels, a condition called atherosclerosis.
• Nerve damage in limbs. This condition is called neuropathy. High blood sugar over time can damage or destroy nerves. That may result in tingling, numbness, burning, pain or eventual loss of feeling that usually begins at the tips of the toes or fingers and gradually spreads upward.
• Other nerve damage. Damage to nerves of the heart can contribute to irregular heart rhythms. Nerve damage in the digestive system can cause problems with nausea, vomiting, diarrhea or constipation. Nerve damage also may cause erectile dysfunction.
• Kidney disease. Diabetes may lead to chronic kidney disease or end-stage kidney disease that can't be reversed. That may require dialysis or a kidney transplant.
• Eye damage. Diabetes increases the risk of serious eye diseases, such as cataracts and glaucoma, and may damage the blood vessels of the retina, potentially leading to blindness.
• Skin conditions. Diabetes may raise the risk of some skin problems, including bacterial and fungal infections.
• Slow healing. Left untreated, cuts and blisters can become serious infections, which may heal poorly. Severe damage might require toe, foot or leg amputation.
• Hearing impairment. Hearing problems are more common in people with diabetes.
• Sleep apnea. Obstructive sleep apnea is common in people living with type 2 diabetes. Obesity may be the main contributing factor to both conditions.
• Dementia. Type 2 diabetes seems to increase the risk of Alzheimer's disease and other disorders that cause dementia. Poor control of blood sugar is linked to a more rapid decline in memory and other thinking skills.

Healthy lifestyle choices can help prevent type 2 diabetes. If you've received a diagnosis of prediabetes, lifestyle changes may slow or stop the progression to diabetes.

A healthy lifestyle includes:

• Eating healthy foods. Choose foods lower in fat and calories and higher in fiber. Focus on fruits, vegetables and whole grains.
• Getting active. Aim for 150 or more minutes a week of moderate to vigorous aerobic activity, such as a brisk walk, bicycling, running or swimming.
• Losing weight. If you are overweight, losing a modest amount of weight and keeping it off may delay the progression from prediabetes to type 2 diabetes. If you have prediabetes, losing 7% to 10% of your body weight may reduce the risk of diabetes.
• Avoiding long stretches of inactivity. Sitting still for long periods of time can increase the risk of type 2 diabetes. Try to get up every 30 minutes and move around for at least a few minutes.

For people with prediabetes, metformin (Fortamet, Glumetza, others), a diabetes medication, may be prescribed to reduce the risk of type 2 diabetes. This is usually prescribed for older adults who are obese and unable to lower blood sugar levels with lifestyle changes.

More Information

• Diabetes prevention: 5 tips for taking control
• Professional Practice Committee: Standards of Medical Care in Diabetes — 2020. Diabetes Care. 2020; doi:10.2337/dc20-Sppc.
• Diabetes mellitus. Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetes-mellitus-dm. Accessed Dec. 7, 2020.
• Melmed S, et al. Williams Textbook of Endocrinology. 14th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed Dec. 3, 2020.
• Diabetes overview. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/all-content. Accessed Dec. 4, 2020.
• AskMayoExpert. Type 2 diabetes. Mayo Clinic; 2018.
• Feldman M, et al., eds. Surgical and endoscopic treatment of obesity. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 11th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed Oct. 20, 2020.
• Hypersmolar hyperglycemic state (HHS). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hyperosmolar-hyperglycemic-state-hhs. Accessed Dec. 11, 2020.
• Diabetic ketoacidosis (DKA). Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetic-ketoacidosis-dka. Accessed Dec. 11, 2020.
• Hypoglycemia. Merck Manual Professional Version. https://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hypoglycemia. Accessed Dec. 11, 2020.
• 6 things to know about diabetes and dietary supplements. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/tips/things-to-know-about-type-diabetes-and-dietary-supplements. Accessed Dec. 11, 2020.
• Type 2 diabetes and dietary supplements: What the science says. National Center for Complementary and Integrative Health. https://www.nccih.nih.gov/health/providers/digest/type-2-diabetes-and-dietary-supplements-science. Accessed Dec. 11, 2020.
• Preventing diabetes problems. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/diabetes/overview/preventing-problems/all-content. Accessed Dec. 3, 2020.
• Schillie S, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recommendations and Reports. 2018; doi:10.15585/mmwr.rr6701a1.
• Caffeine: Does it affect blood sugar?
• GLP-1 agonists: Diabetes drugs and weight loss
• Hyperinsulinemia: Is it diabetes?
• Medications for type 2 diabetes

Associated Procedures

• Bariatric surgery
• Endoscopic sleeve gastroplasty
• Gastric bypass (Roux-en-Y)
• Glucose tolerance test

News from Mayo Clinic

• Mayo study uses electronic health record data to assess metformin failure risk, optimize care Feb. 10, 2023, 02:30 p.m. CDT
• Mayo Clinic Minute: Strategies to break the heart disease and diabetes link Nov. 28, 2022, 05:15 p.m. CDT
• Mayo Clinic Q and A: Diabetes risk in Hispanic people Oct. 20, 2022, 12:15 p.m. CDT
• The importance of diagnosing, treating diabetes in the Hispanic population in the US Sept. 28, 2022, 04:00 p.m. CDT
• Mayo Clinic Minute: Managing Type 2 diabetes Sept. 28, 2022, 02:30 p.m. CDT
• Symptoms & causes
• Diagnosis & treatment
• Doctors & departments

Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission.

• Opportunities

Mayo Clinic Press

Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press .

• Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence
• The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book
• Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance
• FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment
• Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book

5X Challenge

Thanks to generous benefactors, your gift today can have 5X the impact to advance AI innovation at Mayo Clinic.

Diabetes: Types and Management Essay

• To find inspiration for your paper and overcome writer’s block
• As a source of information (ensure proper referencing)
• As a template for you assignment

Diabetes is a chronic disease that undermines the body’s metabolizing of food into energy. Upon consumption, food eaten is mostly digested into glucose that is then released into the blood. This raises the level of glucose in the blood, which stimulates insulin release from the pancreas. Insulin triggers the cells to take in blood sugar to be used as energy. Diabetes is when the body fails to manufacture adequate insulin or use it as it should. Diabetes is a serious disease that impacts the body’s metabolism and can lead to adverse health outcomes if unaddressed.

Without adequate insulin or when cells fail to react to the presence of insulin, glucose accumulates in the bloodstream, which can cause serious health conditions. Insulin is only one of the hormones related to glucose usage. The others include glucagon, cortisol, epinephrine, growth hormone, amylin, GLP-1, and glucose-dependent insulinotropic peptide (GIP) (Lutz et al., 2014). These hormones are meant to keep the concentration of blood sugar at a narrow range that allows for optimal functioning.

Diabetes falls into three main classes: type 1, type 2, and gestational diabetes. Type 1 diabetes is when the body attacks itself, keeping it from manufacturing insulin and there is no known cure (CDC, 2021). Type 2 diabetes occurs when the body fails to consume insulin as needed and blood glucose rises to abnormal levels. Gestational diabetes affects pregnant women that do not have a history of diabetes. This type usually goes away after birth but it increases the risk of the affected individual developing type 2 diabetes later in life.

There is no known cure for diabetes but it can be managed in several ways including exercising, eating healthy food, maintaining a healthy weight and taking insulin and medication. However, acute diabetes complications like hypoglycaemia, hyperosmolar hyperglycemic nonketotic coma, and diabetic ketoacidosis can stand in the way of these interventions. These complications limit movement, diet, activity intensity, and generally the implementation of the interventions meant to manage the condition.

Diabetes is one of the most prevalent diseases in the United States caused when the body fails to optimally metabolize food into energy. The condition falls into three main classifications, type 1, type 2, and gestational diabetes. There is no known cure for diabetes but there are several interventions to manage it including exercising, eating healthy food, and staying active. However, acute complication can stand in the way of effective intervention implementation.

CDC. (2021). What is Diabetes? Centers for Disease Control and Prevention.

Lutz, C. A., Mazur, E., & Litch, N. (2014). Nutrition and diet therapy . FA Davis.

• Advanced Glycation End Products and Mortality Among Diabetic Patients
• Diabetes: Symptoms and Risk Factors
• Stocking Epinephrine in Schools
• Cause and Diagnosis of Type 2 diabetes
• Biot- Management Laboratory: Rat GLP
• Epidemiology of Diabetes and Forecasted Trends
• The Aboriginal Diabetes Initiative in Canada
• Vitamin D and Dyslipidemia in Metabolic Syndrome
• Communicating the Issue of Diabetes
• The Prevention of Diabetes and Its Consequences on the Population
• Chicago (A-D)
• Chicago (N-B)

IvyPanda. (2023, August 15). Diabetes: Types and Management. https://ivypanda.com/essays/diabetes-types-and-management/

"Diabetes: Types and Management." IvyPanda , 15 Aug. 2023, ivypanda.com/essays/diabetes-types-and-management/.

IvyPanda . (2023) 'Diabetes: Types and Management'. 15 August.

IvyPanda . 2023. "Diabetes: Types and Management." August 15, 2023. https://ivypanda.com/essays/diabetes-types-and-management/.

1. IvyPanda . "Diabetes: Types and Management." August 15, 2023. https://ivypanda.com/essays/diabetes-types-and-management/.

Bibliography

IvyPanda . "Diabetes: Types and Management." August 15, 2023. https://ivypanda.com/essays/diabetes-types-and-management/.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• My Bibliography
• Collections
• Citation manager

Save citation to file

Email citation, add to collections.

• Create a new collection
• Add to an existing collection

Add to My Bibliography

Your saved search, create a file for external citation management software, your rss feed.

• Search in PubMed
• Search in NLM Catalog
• Add to Search

Type 2 diabetes

Affiliations.

• 1 Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK.
• 2 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
• 3 Family Medicine Department, Korle Bu Teaching Hospital, Accra Ghana and Community Health Department, University of Ghana Medical School, Accra, Ghana.
• 4 Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK. Electronic address: [email protected].
• PMID: 36332637
• DOI: 10.1016/S0140-6736(22)01655-5

Type 2 diabetes accounts for nearly 90% of the approximately 537 million cases of diabetes worldwide. The number affected is increasing rapidly with alarming trends in children and young adults (up to age 40 years). Early detection and proactive management are crucial for prevention and mitigation of microvascular and macrovascular complications and mortality burden. Access to novel therapies improves person-centred outcomes beyond glycaemic control. Precision medicine, including multiomics and pharmacogenomics, hold promise to enhance understanding of disease heterogeneity, leading to targeted therapies. Technology might improve outcomes, but its potential is yet to be realised. Despite advances, substantial barriers to changing the course of the epidemic remain. This Seminar offers a clinically focused review of the recent developments in type 2 diabetes care including controversies and future directions.

Copyright © 2022 Elsevier Ltd. All rights reserved.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests EA has received fellowship funding from AstraZeneca. SL has been a member on advisory boards or has consulted with Merck Sharp & Dohme, and NovoNordisk. He has received grant support from AstraZeneca, Merck Sharp & Dohme, and Astellas. He has also served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co, Merck Sharp & Dohme, Chong Kun Dang Pharmaceutical, and Novo Nordisk. RL has received a research grant from Novo Nordisk. She has also received funds for serving on an advisory board for Sanofi and consultancy fees from Sanofi, AstraZeneca, Novo Nordisk, and Boehringer Ingelheim. DRW has received honoraria as a speaker for AstraZeneca, Sanofi-Aventis, and Lilly, and received research funding support from Novo Nordisk. MJD has acted as consultant, advisory board member, and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk, and Sanofi; an advisory board member and speaker for AstraZeneca; an advisory board member for Janssen, Lexicon, Pfizer, and ShouTi Pharma; and as a speaker for Napp Pharmaceuticals, Novartis, and Takeda Pharmaceuticals International. She has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, AstraZeneca, and Janssen.

• Cancer is becoming the leading cause of death in diabetes. Wang M, Sperrin M, Rutter MK, Renehan AG. Wang M, et al. Lancet. 2023 Jun 3;401(10391):1849. doi: 10.1016/S0140-6736(23)00445-2. Lancet. 2023. PMID: 37270233 No abstract available.

Similar articles

• Type 2 diabetes. Chatterjee S, Khunti K, Davies MJ. Chatterjee S, et al. Lancet. 2017 Jun 3;389(10085):2239-2251. doi: 10.1016/S0140-6736(17)30058-2. Epub 2017 Feb 10. Lancet. 2017. PMID: 28190580 Review.
• Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool? Florez JC. Florez JC. Diabetologia. 2017 May;60(5):800-807. doi: 10.1007/s00125-017-4227-1. Epub 2017 Mar 10. Diabetologia. 2017. PMID: 28283684 Review.
• Precision medicine: The future in diabetes care? Scheen AJ. Scheen AJ. Diabetes Res Clin Pract. 2016 Jul;117:12-21. doi: 10.1016/j.diabres.2016.04.033. Epub 2016 Apr 26. Diabetes Res Clin Pract. 2016. PMID: 27329017 Review.
• Psychological interventions to improve self-management of type 1 and type 2 diabetes: a systematic review. Winkley K, Upsher R, Stahl D, Pollard D, Kasera A, Brennan A, Heller S, Ismail K. Winkley K, et al. Health Technol Assess. 2020 Jun;24(28):1-232. doi: 10.3310/hta24280. Health Technol Assess. 2020. PMID: 32568666 Free PMC article.
• Care of diabetes in children and adolescents: controversies, changes, and consensus. Cameron FJ, Wherrett DK. Cameron FJ, et al. Lancet. 2015 May 23;385(9982):2096-106. doi: 10.1016/S0140-6736(15)60971-0. Lancet. 2015. PMID: 26009230 Review.
• Laminaria japonica Polysaccharide Regulates Fatty Hepatosis Through Bile Acids and Gut Microbiota in Diabetes Rat. Zhang B, Wang J, Chen X, Xue T, Xin J, Liu Y, Wang X, Li X. Zhang B, et al. Mar Biotechnol (NY). 2024 Aug 29. doi: 10.1007/s10126-024-10365-1. Online ahead of print. Mar Biotechnol (NY). 2024. PMID: 39207652
• Oral Semaglutide in Type 2 Diabetes: Clinical-Metabolic Outcomes and Quality of Life in Real-World Practice. Pantanetti P, Ronconi V, Sguanci M, Palomares SM, Mancin S, Tartaglia FC, Cangelosi G, Petrelli F. Pantanetti P, et al. J Clin Med. 2024 Aug 13;13(16):4752. doi: 10.3390/jcm13164752. J Clin Med. 2024. PMID: 39200893 Free PMC article.
• Single and mixed associations of composite antioxidant diet on triglyceride-glucose index. Xu Y, Zhuang Y, Zhang H. Xu Y, et al. Lipids Health Dis. 2024 Aug 19;23(1):254. doi: 10.1186/s12944-024-02233-7. Lipids Health Dis. 2024. PMID: 39160518 Free PMC article.
• Prevalence of diabetic retinopathy and its risk factors in rural patients with type 2 diabetes referring to Beijing Huairou Hospital, China. Wang J, Zhang H. Wang J, et al. BMC Ophthalmol. 2024 Aug 12;24(1):336. doi: 10.1186/s12886-024-03606-3. BMC Ophthalmol. 2024. PMID: 39128998 Free PMC article.
• Predictive Factors for Altered Quality of Life in Patients with Type 2 Diabetes Mellitus. Albai O, Braha A, Timar B, Timar R. Albai O, et al. J Clin Med. 2024 Jul 26;13(15):4389. doi: 10.3390/jcm13154389. J Clin Med. 2024. PMID: 39124656 Free PMC article.

Publication types

• Search in MeSH

Related information

Linkout - more resources, full text sources.

• Elsevier Science
• Genetic Alliance
• MedlinePlus Health Information
• Citation Manager

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.