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Thank you for visiting nature. 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. 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. The clinical presentation, underlying pathophysiology and disease progression in patients with diabetes can vary considerably among individuals and, on occasion, atypical presentation of symptoms can make clear-cut classification of T2DM difficult.

At the time of diagnosis, many patients with T2DM are asymptomatic, whereas others present with severe hyperglycaemia or even diabetic ketoacidosis. Latent autoimmune diabetes in adults 4 and maturity-onset diabetes of the young 5 can masquerade as T2DM. In asymptomatic individuals, the timing and frequency of testing for prediabetes or T2DM are based on the presence or absence of risk factors 6.

Prevention of diabetes requires identification of individuals who have prediabetes and intervention with lifestyle modifications weight loss and exercise plus antidiabetic and anti-obesity medications 7 — 9.

Pioglitazone 11 and combined low-dose metformin and rosiglitazone 12 also are very effective in preventing the conversion of prediabetes to diabetes. Lifestyle intervention weight loss and exercise alone, although initially effective, is associated with weight regain in most individuals 13 — However, those individuals with prediabetes who successfully lose weight and maintain a physical activity programme can be expected to benefit from decreased conversion to diabetes 16 , an improved lipid profile and reduced cardiovascular risk, including a reduced risk of developing hypertension.

Your institute does not have access to this article. DeFronzo, R. Banting lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58 , — A classic review of the aetiology of T2DM, with a therapeutic approach based on its pathophysiology. Abdul-Ghani, M.

Diabetes Care 29 , — Gerstein, H. 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. Article PubMed Google Scholar. Hawa, M. Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: action LADA 7.

Diabetes Care 36 , — Gardner, D. Clinical features and treatment of maturity onset diabetes of the young MODY. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 37 , S14—S80 A comprehensive overview of the standards of medical care published by the ADA. Article Google Scholar. Ferrannini, E. Pathophysiology of prediabetes. North Am.

Garvey, W. Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome treated with phentermine and topiramate extended release.

Diabetes Care 37 , — Nathan, D. Impaired fasting glucose and impaired glucose tolerance: implications for care. Diabetes Care 30 , — Pioglitazone for diabetes prevention in impaired glucose tolerance. A large prospective study demonstrating the efficacy of thiazolidinediones in preventing the progression of IGT to T2DM. Zinman, B. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus CANOE trial : a double-blind randomised controlled study.

Lancet , — Dansinger, M. Meta-analysis: the effect of dietary counseling for weight loss. Purcell, K. The effect of rate of weight loss on long-term weight management: a randomised controlled trial. Lancet Diabetes Endocrinol.

Ali, M. How effective were lifestyle interventions in real-world settings that were modeled on the Diabetes Prevention Program?

Health Aff. Millwood 31 , 67—75 Tuomilehto, J. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.

Inzucchi, S. Diabetes Care 35 , — ADA position statement on the treatment of T2DM, advocating a stepped care approach starting with metformin. American Association of Clinical Endocrinologists. 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. Diabetes Metab. 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 [online] , Hu, F. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care 34 , — 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. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA , — Ley, S. Prevention and management of type 2 diabetes: dietary components and nutritional strategies. A prospective study of weight training and risk of type 2 diabetes mellitus in men. Television viewing and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a meta-analysis.

Cappuccio, F. Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care 33 , — Pan, A. Rotating night shift work and risk of type 2 diabetes: two prospective cohort studies in women.

PLoS Med. Barnett, A. Diabetes in identical twins. A study of pairs. Diabetologia 20 , 87—93 Wang, Y. Wang, X.

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