ABC of arterial and venous disease Vascular complications of diabetes

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 (HbA1c) 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 HbA1c 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 HbA1c 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,

Background retinopathy showing microaneurysms and small blot haemorrhages

Risk of morbidity associated with all types of diabetes mellitus

Complication Relative risk*

Blindness 20

End stage renal disease 25

Amputation 40

Myocardial infarction 2-5

Stroke 2-3 *Compared with non-diabetic patients

Vascular complications of diabetes

Microvascular Macrovascular

Retinopathy Ischaemic heart disease

Nephropathy Stroke

Neuropathy Peripheral vascular disease

Relation between glycaemic control (HbA1c) and risk of progression of microvascular complications (retinopathy) and severe hypoglycaemia in patients with type 1 diabetes. Data from the diabetes control and complications trial. Dotted lines represent 95% confidence intervals

Classification and features of diabetic retinopathy

Grade

Examination features

Symptoms

I Background retinopathy

II Background with maculopathy

III Preproliferative retinopathy

IV Proliferative retinopathy

V Advanced diabetic eye disease

Background retinopathy showing microaneurysms and small blot haemorrhages

Microaneurysms

Small blot haemorrhages

Hard exudates

Not affecting macula

Leakage in macular region

Capillary occlusion

Hard exudates

Cotton wool spots

Venous abnormalities

Large blot haemorrhages

Intraretinal microvascular abnormalities

New vessels on disc or elsewhere on retina

Extensive fibrovascular proliferation Retinal detachment Vitreous haemorrhage Thrombotic glaucoma

None

Central visual loss (such as reading difficulty) None

None, but complications cause visual loss Severe visual loss 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 > 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 ^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.

Neuropathy

The diabetic neuropathies present in several ways. The commonest form is a diffuse progressive polyneuropathy affecting mainly the feet. It is predominantly sensory, often asymptomatic, and affects 40-50% of all patients with diabetes. Reduced sensation can be detected with a monofilament, and patients with sensory neuropathy as well as other high risk features need advice on foot care to minimise the risk of ulceration. Neuropathic foot ulcers can be distinguished from vascular ulcers, although a mixed aetiology is common.

Macrovascular complications

Atherosclerotic disease accounts for most of the excess mortality in patients with diabetes. In the UK prospective diabetes study, fatal cardiovascular events were 70 times more common than deaths from microvascular complications. The

Diabetic maculopathy

- Statt of antihypertensive treatment

- Statt of antihypertensive treatment

Change in glomerular filtration rate

11.3 ml/min/year

Change in glomerular filtration rate

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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