The British Journal of Diabetes & Vascular Disease

The prevalence of diabetes is increasing worldwide, bringing personal and economic burdens. Impaired glucose tolerance (IGT) generally precedes type 2 diabetes and strategies which target IGT and delay or prevent the onset of type 2 diabetes are being explored. IGT and type 2 diabetes are characterised by insulin resistance. Lifestyle and pharmacological approaches which ameliorate insulin resistance are being investigated as methods of diabetes prevention.

The substantial burden of morbidity and mortality associated with type 2 diabetes and the high costs associated with the management of diabetic complications highlight the need for the development of strategies for the prevention of diabetes. Impaired glucose tolerance is a pre-diabetic state which may present an opportunity for intervention to prevent the onset of clinical diabetes. Four recent clinical trials, the DPP, the FDPS, the STOP-NIDDM and the Da Qing study, have evaluated interventions based on diet and exercise and/or pharmacotherapy in pre-diabetic subjects. In all these trials the intervention strategies significantly reduced the incidence of diabetes. A worldwide epidemic of type 2 diabetes will occur over the coming decades and translating the results of these studies into practical and effective initiatives for diabetes prevention is an urgent clinical priority.Br J Diabetes Vasc Dis 2003;3(suppl 1):S6—S11

It is well established that the incidences of type 2 diabetes and impaired glucose tolerance are very low at ideal body weight (body mass index [BMI] 21—22 kg/m2) but increases with increasing body fat and BMI. Adipose tissue is an active endocrine organ which secretes many hormones involved in the regulation of body weight and appetite, including leptin and tumour necrosis factor-alpha, which are related to diabetes development. Weight loss is an important goal within the overall management of diabetes, and recent intervention trials have established that the benefits of weight loss may extend to the prevention of diabetes itself. Weight loss associated with diet and exercise in the DPP and the FDPS, by the anti-obesity drug orlistat in the XENDOS trial, and by gastric surgery in the SOS study all significantly reduced the incidence of diabetes compared with controls. The prevention or reversal of obesity is therefore an increasingly important therapeutic target in the prevention of type 2 diabetes.

Physical activity improves insulin sensitivity and glucose metabolism, although such effects are short-lasting and regular exercise is needed to sustain them. Weight loss, especially loss of visceral fat, appears to be especially important in improving metabolic function and clinical outcomes. The most important consequences of exercise are probably promotion of weight loss and prevention of weight gain. Substantial weight losses, associated with significant improvements in glycaemic control and reductions in the incidence of type 2 diabetes, have been observed in intervention studies in overweight or obese subjects. These benefits were achieved using intensive lifestyle interventions, pharmacotherapy or surgery. Thus, programmes of diet and exercise aimed at achieving control of body weight should play a central role in strategies for diabetes prevention.

Lifestyle intervention prevents or delays the conversion from impaired glucose tolerance (IGT) to type 2 diabetes. However, many subjects fail to achieve and/or maintain long-term weight loss and to follow a regular exercise regimen may require pharmacologic therapy. Insulin resistance in liver, muscle and fat, along with impaired beta-cell function, plays a central role in the pathogenesis of type 2 diabetes. Insulin sensitising drugs, including metformin and the thiazolidinediones, have significantly reduced the conversion rate of IGT to type 2 diabetes in subjects in several large, well designed clinical trials. Insulin-sensitising drugs are likely to play an important role in future strategies for diabetes prevention.