Vascular complications of diabetes

British Medical Journal, April 15, 2000 by Richard Donnelly, Alistair M Emslie-Smith, Iain D Gardner, Andrew D Morris

Adults with diabetes have an annual mortality of about 5.4% (double the rate for non-diabetic adults), and their life expectancy is decreased on average by 5-10 years. Although the increased death rate is mainly due to cardiovascular disease, deaths from non-cardiovascular causes are also increased. A diagnosis of diabetes immediately increases the risk of developing various clinical complications that are largely irreversible and due to microvascular or macrovascular disease. Duration of diabetes is an important factor in the pathogenesis of complications, but other risk factors--for example, hypertension, cigarette smoking, and hypercholesterolaemia--interact with diabetes to affect the clinical course of microangiopathy and macroangiopathy.

Microvascular complications

A continuous relation exists between glycaemic control and the incidence and progression of microvascular complications. Hypertension and smoking also have an adverse effect on microvascular outcomes. In the diabetes control and complications trial--a landmark study in type 1 diabetes--the number of clinically important microvascular endpoints was reduced by 34-76% in patients allocated to intensive insulin (that is, a 10% mean reduction in glycated haemoglobin ([Hb.sub.A1c]) concentration from 8.0% to 7.2%). However, these patients also had more hypoglycaemic episodes. Similarly, in the UK prospective diabetes study of patients with type 2 diabetes, an intensive glucose control policy that lowered glycated haemoglobin concentrations by an average of 0.9% compared with conventional treatment (median [Hb.sub.A1c] 7.0% v 7.9%) resulted in a 25% reduction in the overall microvascular complication rate. It was estimated that for every 1% reduction in [Hb.sub.A1c] concentration there is a 35% reduction in microvascular disease.

Retinopathy

Diabetic retinopathy is a progressive disorder classified according to the presence of various clinical abnormalities. It is the commonest cause of blindness in people aged 30-69 years. Damage to the retina arises from a combination of microvascular leakage and microvascular occlusion; these changes can be visualised in detail by fluorescein angiography. A fifth of patients with newly discovered type 2 diabetes have retinopathy at the time of diagnosis. In type 1 diabetes, vision threatening retinopathy almost never occurs in the first five years after diagnosis or before puberty. After 15 years, however, almost all patients with type 1 diabetes and two thirds of those with type 2 diabetes have background retinopathy.

Vision threatening retinopathy is usually due to neovascularisation in type 1 diabetes and maculopathy in type 2 diabetes. Depending on the relative contribution of leakage or capillary occlusion, maculopathy is divided into three types: exudative maculopathy (when hard exudates appear in the region of the macula), ischaemic maculopathy (characterised by) a predominance of capillary occlusion which results in clusters of haemorrhages), and oedematous maculopathy (extensive leakage gives rise to macular oedema). Treatment of maculopathy and proliferative retinopathy with laser photocoagulation prevents further loss of vision rather than restores diminished visual acuity.

Nephropathy

Diabetic nephropathy is characterised by proteinuria [is greater than] 300 mg/24 h, increased blood pressure, and a progressive decline in renal function. At its most severe, diabetic nephropathy results in end stage renal disease requiring dialysis or transplantation, but in the early stages overt disease is preceded by a phase known as incipient nephropathy (or microalbuminuria), in which the urine contains trace quantities of protein (not detectable by traditional dipstick testing). Microalbuminuria is defined as an albumin excretion rate of 20-300 mg/24 h or 20-200 [micro]g/min in a timed collection and is highly predictive of overt diabetic nephropathy, especially in type 1 diabetes.

The rate of decline in glomerular filtration rate varies widely) between individuals, but antihypertensive treatment greatly slows the decline in renal function and improves survival in patients with diabetic nephropathy.

In patients with type 1 diabetes complicated by diabetic nephropathy, angiotensin converting enzyme inhibitors have renoprotective effects above those that can be attributed to reduced blood pressure; they are beneficial even in normotensive patients and ameliorate other associated microvascular complications such as retinopathy. In patients with type 2 diabetes, achieving good blood pressure control (which often requires combination therapy) is more important than the choice of antihypertensive drug, although angiotensin converting enzyme inhibitors are the preferred first line treatment

The development of proteinuria is a marker of widespread vascular damage and signifies an increased risk of subsequent end stage renal disease and macrovascular complications, especially coronary heart disease. Microproteinuria and proteinuria are strongly associated with decreased survival in both type 1 and type 2 diabetes.