reduces life expectancy by five to 10 years. from eight Western

reduces life expectancy by five to 10 years. from eight Western studies-72% experienced at least one complication and 24% experienced both (microvascular and macrovascular) complications.w2 Over six months 13 of the individuals were admitted to hospital for any mean of 23 days. The estimated average yearly cost per individual was €2834 (￡1934 $3585); 55% of this cost was attributable to hospital admissions and only 7% to the cost of insulin and oral drugs for decreasing glucose.1 Who evolves complications? The risk of developing complications is variable (table 1). For nephropathy in particular a strong but unknown genetic influence exists. The duration of diabetes glycaemic control and hypertension are the strongest risk factors for microvascular disease; smoking blood pressure lipids and albuminuria are the strongest risk factors for NSC 105823 macrovascular disease. Table 1 Risk factors and markers for the development of complications of diabetes Macrovascular disease Extra mortality from cardiovascular disease is seen in all age groups particularly in young people with type 1 diabetes (package 2) and is exacerbated by interpersonal deprivation (table).w3 Premenopausal ladies with diabetes lose their safety against macrovascular disease (fig A on bmj.com).2 w4 w5 In type 2 diabetes the risk of myocardial infarction and stroke is two to NSC 105823 five occasions higher than in the general population. Summary points Individuals with diabetes have an average reduction in life expectancy of five to 10 years mainly because of premature cardiovascular disease The microvascular complications specific to diabetes (retinopathy nephropathy neuropathy) also contribute to premature mortality and morbidity The risk of vascular complications can be greatly reduced by limited control of glucose and blood pressure and by aggressive management of cardiovascular risk factors Early detection of complications by systematic annual screening allows prompt treatment that may prevent or delay the emergence of end stage disease A multifactorial approach to tightening the management of risk factors reduces the progression of microvascular and macrovascular complications Retinopathy The World Health Organization estimations that diabetic retinopathy is the cause of blindness in 5% of NSC 105823 blind people worldwide.3 Almost everyone with diabetes offers some degree of retinopathy after 20 years (observe appendix on bmj.com for the grading of diabetic retinopathy) but only 20-50% of individuals develop sight threatening disease. In some centres the cumulative incidence of sight threatening retinopathy is falling.4 w6 w7 Nephropathy About half of individuals with diabetes develop microalbuminuria at some point. Approximately one third will progress to proteinuria one third will remain microalbuminuric and one third will revert to normal albumin excretion (fig 1).w8 Microalbuminuria and proteinuria are more common in ethnic minorities worldwide.w9 w10 Once proteinuria is present progression to end stage renal disease is inevitable. From 20% to 50% of individuals who start renal alternative therapy have diabetes.5 w11 The rapid increase in the numbers of individuals with diabetes requiring renal replacement in Europe NSC 105823 in recent years is due mainly to Akt1 the rise in the number of individuals with type 2 diabetes (fig B on bmj.com).6 Fig 1 Development of nephropathy NSC 105823 Package 1: Long term vascular complications of diabetes Microvascular complications Retinopathy Nephropathy Neuropathy Macrovascular complications Cerebrovascular disease Ischaemic heart disease Peripheral arterial disease Neuropathy Individuals with diabetes have a 30-50% lifetime risk of developing chronic peripheral neuropathy (package 3) and 10-20% of individuals develop severe symptoms.7 w12 w13 Peripheral neuropathy contributes to foot ulceration and amputation of lower limbs.8 Erectile dysfunction happens in up to 50% of men over 50 years compared with 15-20% of men without diabetes. Additional neuropathies are rare but have a major impact on quality of life and life expectancy. Pathophysiology Both the metabolic and haemodynamic abnormalities of diabetes contribute to the development of complications. Intracellular hyperglycaemia evolves in cells that cannot.