Diabetes
Summary
The prevalence of diabetes, in particular type 2 diabetes, is increasing worldwide. Type 2 diabetes increases with age, but recently has been affecting much younger individuals. In the UK, diabetes prevalence has doubled over the last 12-15 years, and is set to double again over a similar timeframe. The prevalence of diabetes in the UK is now, on average, 3.3%, though many patients are undiagnosed.The prevalence of diabetes, in particular type 2 diabetes, is increasing worldwide. Type 2 diabetes increases with age, but recently has been affecting much younger individuals. In the UK, diabetes prevalence has doubled over the last 12–15 years, and is set to double again over a similar timeframe. The prevalence of diabetes in the UK is now, on average, 3.3%, though many patients are undiagnosed. Increasingly sedentary lifestyles and greater adiposity are of concern. UK rates of obesity (body mass index >30 kg/m2) of 20–25% are similar to levels in the USA, and higher than in most European countries. Obesity, inactivity and poor diet contribute to worsening glucose tolerance, insulin resistance, hypertension, mixed dyslipidaemia, haemorheological and clotting abnormalities, increased levels of inflammatory markers and hyperuricaemia.
Type 1 and type 2 diabetes cause microvascular and macrovascular complications as well as acute glycaemic symptoms. Substantial morbidity and premature mortality reduce life expectancy by about 30% at any age of diabetes onset. Microvascular risk (e.g. neuropathy, nephropathy and retinopathy) is associated with diabetes duration, blood pressure and glycaemic control. The risk of macrovascular (e.g. coronary, cerebrovascular and peripheral vascular) disease is increased by diabetes itself (partly through changes in lipoprotein and triglyceride profile).
Previously the Diabetes Control and Complications Trial demonstrated substantially reduced microvascular risk with glycaemic control in type 1 diabetes, though macrovascular events were too few to assess accurately. The more recent United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes demonstrated the benefits of tighter control of glycaemia and blood pressure. Trial targets were not that strict by current ideals, and there were difficulties maintaining improvements. A 0.9% HbA1C difference was maintained, but patients deteriorated over a decade despite increasing treatment. The use of metformin in UKPDS was associated with a significant decrease in macrovascular disease, although the sample size was quite small, whilst a slightly smaller group of patients who were given metformin and sulphonylurea in combination actually had the worst prognosis. To achieve 10/5 mmHg blood pressure difference often required two or three (or more) antihypertensives. Epidemiological results (actual achieved glucose and blood pressure) suggested that there was no lower blood pressure threshold below which improvement did not occur. These studies did not control cholesterol, but 20,500 (~6,000 diabetic) patients in the Heart Protection Study (HPS) showed major reductions in mortality and vascular events with simvastatin in patients with coronary heart disease, treated hypertension or diabetes and total cholesterol levels greater than 3.5 mmol/L.
Diet and lifestyle changes are the mainstay of diabetes management, particularly for patients with adiposity. Glucose, blood pressure and lipids all improve with weight loss. However, motivation and the ability of most patients to achieve, and importantly maintain, fitness and long-term weight loss is limited.
In practice, many diabetic patients need pharmacological treatments for glycaemic control. In metabolic syndrome, insulin-resistant, obese patients, insulin sensitisers (metformin, thiazolidenediones [glitazones]) are appropriate. Metformin is often used, and is not associated with weight increase as glycaemia improves, though it is often associated with gastrointestinal effects. In the Diabetes Prevention Program (DPP) in the USA, metformin was shown to be effective in reducing the risk of developing diabetes, though it was not as effective as intensive dietary and lifestyle modification in this regard. However, the intensive lifestyle interventions that took place in the DPP required substantial input from nutritionists, at a level that would not likely be achieved in countries outside the USA. Glitazones tend to increase abdominal fat. For thinner patients, less likely to have insulin resistance, sulphonylureas are appropriate. Inhibition of starch digestion with a-glucosidase inhibitors (e.g. acarbose) can improve glycaemia, as can weight reduction with orlistat or sibutramine. With insulin resistance and relative lack of insulin, metabolic handling of postprandial glucose and fats is poor, and control of glucose and triglyceride excursions is difficult. In these cases postprandial glucose regulators need to be considered, and perhaps fibrates for hypertriglyceridaemia. Many patients need multiple antidiabetic agents, and many eventually come to need insulin. In addition, statins impart the greatest macrovascular benefit, whilst glycaemic and blood pressure pharmacotherapies can help to prevent microvascular complications.
The challenges for both patient and doctor in diabetes management are major: one or more antidiabetic agent, a statin, perhaps a fibrate, aspirin and one or more antihypertensive agents may be required. Thus, patient education may prove necessary to gain their concordance and improve treatment persistence. The increasing prevalence of diabetes, and its resulting comorbidities, result in excess hospital admissions for people with diabetes but with diabetes not being the primary diagnosis. Diabetic patients consume 3–4-fold increased healthcare resource, and it is essential to manage their condition actively.
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This Editorial has been written by the specialist opinion leader, Dr John PD Reckless, Consultant Endocrinologist and Honorary Reader in Medicine and Biochemistry at the University of Bath and Royal United Hospital, Bath and published in the latest issue of the serial publication, Drugs in Context.
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