Microvasculature in diabetes

Most of the so-called long-term complications of diabetes mellitus stem from malfunction of the microvasculature. It has long been recognized that microvascular disease underlies diabetic retinopathy as well as nephropathy. More recently, damage to the microvasculature has been implicated in diabetic cardiopathy l as well as the pathogenesis of diabetic neuropathy 2. The focus of this review will be on diabetic microangiopathy as it relates to the retinal renal and peripheral microvasculature. The clinical consequences of this microangiopathic process are formidable 3. Diabetic retinopathy remains the major cause of blindness in people aged between 30 and 60 years in the UK; diabetic nephropathy is the single major cause of commencement on renal support programmes in many western countries. Large-scale population studies have examined the lifetime risks of renal and retinal disease. In young people with diabetes 97.5% will develop evidence of some retinopathy after a disease duration of 15 years. A survey in 1983 defined a blindness prevalence of 8.5% in diabetic patients. Various studies have suggested that between 30% and 40% of patients with insulin-dependent diabetes go on to develop diabetic nephropathy. In contrast to retinopathy, this particular complication only appears to afflict a proportion of the diabetic population. However, the patient who develops nephropathy or its precursor albuminuria contends not only with the prospect of renal failure but also an increased expression of all the other complications of diabetes, as well as a mortality rate many times that of his or her counterpart who avoids this particular complication. The true prevalence of diabetic neuropathy is difficult to quantitate because of variations in diagnostic criteria. It has been termed the commonest complication of diabetes and although it may be clinically silent in many patients, peripheral sensory neuropathy is a major cause of diabetic foot ulceration which results in frequent hospitalization and contributes to the fact that 40% of non-traumatic lower limb amputations occur in people with diabetes. It is not surprising that the personal impact of this clinical burden is considerable. The fear of blindness remains the major anxiety faced by people with diabetes and quality of life studies have documented the personal toll of living under the shadow of the prospect of microangiopathic complications 4. In financial terms diabetes is a major strain on healthcare resources and the direct and indirect cost attributable to the microangiopathic complications comprise a substantial proportion of the overall cost 1.51. Despite the fact that it is more than 70 years since insulin therapy was introduced to provide a means to sustain the life of people with insulin-dependent diabetes, relatively little progress has been made in the development of preventative therapy for microangiopathic complications. A variety of retrospective and short-term prospective studies pointed to a relationship between the development of microangiopathic complications and glycaemic control. The strength of this relationship was confirmed by the Diabetes Control and Complication Trial 6, a definitive prospective study confirming that long-term good glycaemic control in young people with insulin-dependent diabetes is associated with a retardation of the development of retinopathy, nephropathy and evidence of neural disease. This achievement was not without cost however; the intensively controlled group who achieved better glycaemic control experienced a three-fold risk of hypogly-