Diabetes

ABC of Diabetes
by Peter J. Watkins

Diabetic complications: cause and prevention

Introduction

Patients with long-standing diabetes may develop complications affecting the eyes, kidneys or nerves (microvascular complications) or major arteries. The major arteries are affected in people with diabetes, causing a substantial increase in both in coronary artery disease and strokes as well as peripheral vascular disease. The greatest risk of large vessel disease occurs in those diabetic patients who develop proteinuria or microalbuminuria, which are associated with widespread vascular damage. These complications are often discovered at presentation in Type 2 diabetic patients who must have had diabetes for many years before it has been diagnosed. Issues concerning macrovascular complications are described in chapter 17.

During the last two decades, there has been a considerable increase in understanding the mechanisms underlying the development of the long-term diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) and macrovascular disease, accompanied by major developments in preventing them. The United Kingdom Prospective Diabetes Survey (UKPDS) in particular demonstrated quantitatively the long-term harmful effects of hyperglycaemia and hypertension in the development of both microvascular and macrovascular complications in Type 2 diabetes. Both UKPDS and the Diabetes Complications and Control Trial (DCCT) of Type 1 diabetes demonstrated the benefits of optimal control.

Causes and prevention of complications

Major advances in recent years have resulted in an actual decrease of some complications, notably nephropathy. Primary prevention of diabetic complications, together with retardation of their progression, is now possible, chiefly by tight control of the diabetes and of hypertension, together with reduction of other “risk factors” detailed in chapter 17. Even when the complications are established, their progression leading to serious damage can be delayed.

Although many attempts have been made to develop specific pharmacological agents to alter the course of diabetic complications, and although many trials are in progress at the present time, none have proved unequivocally successful and none are licensed. There is at present intense interest in and optimism for the use of protein kinase-C inhibitors.

Two major studies

DCCT: a multicentre study of 1441 Type 1 diabetic patients in the United States examining the effects of tight control on the development of microvascular complications, terminated after nine years because of highly significant benefits reported in 1993. The benefits on the microvascular complications were considerable.

UKPDS: a multicentre study of 5102 Type 2 diabetic patients co-ordinated from Oxford, assessed both the harmful effects of persistent hyperglycaemia and hypertension on the development of microvascular and macrovascular complications, and also demonstrated the benefits of 10 years of better, compared with less satisfactory, control of both glycaemia and blood pressure reported in 1998. Benefits were achieved regardless of the drugs used to reach the required standards of either blood glucose or blood pressure control.

The long-term effects of treatment in the two studies are shown in the two figures demonstrating the stable control in Type 1 diabetes (DCCT) compared with the deteriorating control in Type 2 diabetes as the disease progresses (UKPDS).

Persistent hyperglycaemia

Over many years this is the principal underlying cause of the microvascular complications of diabetes. It is also an independent risk factor for the development of macrovascular coronary artery disease and cataract formation. The UKPDS showed precisely the increasing hazard in relation to continuously rising HbA1c levels, without any specific threshold point, and then demonstrated the benefits of tight control. Once complications are established additional factors, notably hypertension, may accelerate their progression (for further details see chapters on specific complications).

Note: The rest of the chapter is omitted.