Diabetes complications constitute a growing healthcare threat

The health complications of diabetes looms so large in the total perspective of diabetes management that it is difficult to overstate their impact on quality of life and even survival.  Put in simple terms, the importance of diabetic complications may be assessed from the fact that diabetic patients are generally accepted to have twice the normal incidence of cardiovascular disease and stroke; 25 times the normal incidence of blindness; 20 times the normal incidence of gangrene, and a significantly increased risk of developing neurological and renal disease.

(See Report #D510, “Diabetes Management Worldwide, 2009-2018.”)

With the global prevalence of diabetes expected to rise 54% by 2030, accelerated in part by a commensurate rise in obesity, the significance of the risk of complications becomes clear.

Patients with longstanding diabetes may develop complications affecting the eyes or kidneys (microvascular complications), nerves, or major arteries. The major arteries are affected by diabetes in two ways. Coronary artery disease is commoner in diabetic people than in non-diabetic people. The greatest risk of large vessel disease occurs in those diabetic patients who develop proteinuria or microalbuminuria, suggesting widespread vascular damage. The distribution of arterial narrowing tends to be more distal than in non-diabetic people, whether in the coronary arteries or in the peripheral arteries affecting feet and legs. The cause of the microvascular complications is not understood, but the most important influence is probably the quality of diabetic control over many years. There may also be a genetic influence, which can be detected in identical twins. Fortunately not all diabetic patients develop these complications, and probably as many as one-fifth are spared altogether even after 40 or 50 years of diabetes. Curiously, both retinopathy and neuropathy may occur in isolation, but serious nephropathy is always accompanied by retinopathy and usually by neuropathy as well.


After 30 years of diabetes over 80% of patients will have retinopathy. In many cases this is a mild background retinopathy that changes little over the years. Unpredictably, however, changes may develop which threaten vision, generally from macular disease or vitreous hemorrhage. Since treatment is now available which can prevent blindness, it is essential to identify the lesions which are amenable to treatment before vision deteriorates.


Diabetic neuropathies constitute a diverse group of conditions. The commonest is a diffuse polyneuropathy which damages distal peripheral nerves (affecting chiefly the feet), together with the autonomic nervous system. It is a classic diabetic complication, gradually progressing (although at very variable rates) as the duration of diabetes lengthens and often, but not always, associated with other long-term diabetic complications. In contrast, mononeuropathies and acute painful neuropathies run a well defined cause from a relatively acute onset to a more or less complete recovery in 6 to 18 months. These reversible neuropathies, which may be the reason for initial presentation, occur at any stage of diabetes, are more common in non-insulin dependent men, and are not necessarily associated with other diabetic complications.

Neuropathy is usually symptomless and is therefore a hazard to the unwary patient. In more advanced neuropathies the patient is aware of sensory loss: numbness (and in some a sensation of coldness) may progressively worsen until there is almost complete anesthesia below the knee, but this is not common. Reduced sensation in the feet may result in unnoticed trauma from ill fitting shoes, nails or stones, walking barefoot, or burns from hot water bottles or sitting too close to a fire. Self-inflicted wounds from crude attempts at chiropody are dangerous because they often become infected.


In 30%–40% of all patients with insulin-dependent diabetes, proteinuria, the hallmark of diabetic nephropathy, develops within 30 years of diagnosis. It usually begins after 15–20 years, rarely occurring before 5 years or after 30 years. The prevalence of nephropathy has decreased during the past 50 years. White non-insulin dependent diabetic patients are less likely to develop nephropathy than Afro-Caribbean and Asian diabetics, in whom the incidence of nephropathy is much higher. In non-insulin dependent diabetes proteinuria from nephropathy may be present at the time of diagnosis of diabetes. End- stage renal failure still develops in about 20% of insulin-dependent patients diagnosed when less than 30 years old. With the development of transplantation and chronic ambulatory peritoneal dialysis for end-stage renal failure the outlook for these patients is relatively good, although problems from coronary artery disease at all stages of nephropathy remains very serious.

At the onset of insulin-dependent diabetes there is evidence of hyperfiltration with increased glomerular filtration rate, large kidneys, and large glomeruli. These defects can be reversed by meticulous diabetic control; there is some limited evidence that these changes predispose to the subsequent development of nephropathy.

Individuals who develop type 2 diabetes in middle life are often thought to be at less risk of complications than type 1 diabetics, whose condition has been present since childhood. However it must be remembered that many type 2 diabetics have already had their condition, although in relatively mild form, for 10 or more years before diagnosis. As far as complications are concerned, the clock may already have been running for several years.

Metabolic Syndrome

The term metabolic syndrome refers to a clustering of specific cardiovascular disease (CVD) risk factors whose underlying pathophysiology is thought to be related to insulin resistance. The metabolic syndrome is characterized by a group of metabolic risk factors including abdominal obesity, atherogenic dyslipidemia (high triglycerides, low HDL cholesterol and high LDL cholesterol), elevated blood pressure and insulin resistance or glucose intolerance.

People with the metabolic syndrome are at increased risk of coronary heart disease and other diseases including stroke and peripheral vascular disease, as well as type 2 diabetes. The American Heart Association estimates that over 50 million Americans have the metabolic syndrome.

Some people are genetically predisposed to insulin resistance. Acquired factors, such as excess body fat and physical inactivity, can elicit insulin resistance and the metabolic syndrome in these people.

The AHA also points out that there are no well-accepted criteria for diagnosing the metabolic syndrome. The American Heart Association and the National Heart, Lung, and Blood Institute recommend that the metabolic syndrome be identified as the presence of three or more of these components:

  • Elevated waist circumference: Men—Equal to or greater than 40 inches (102 cm); Women—Equal to or greater than 35 inches (88 cm)
  • Elevated triglycerides: Equal to or greater than 150 mg/dL
  • Reduced HDL (“good”) cholesterol: Men—Less than 40 mg/dL; Women—Less than 50 mg/dL
  • Elevated blood pressure: Equal to or greater than 130/85 mm Hg
  • Elevated fasting glucose: Equal to or greater than 100 mg/dL

However, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) released a joint statement questioning the utility of the term “metabolic syndrome” and discouraging doctors from using it. They say that this is not a discrete disease in itself, but merely a clustering of cardiovascular risk factors, and have asked doctors to stop “labeling millions of people with a presumed disease that does not stand on firm ground.” Doctors, they say, should not try to treat this presumed disease as a whole, but should simply address each one of the risk factors encompassed by metabolic syndrome individually. They especially object to the use of metabolic syndrome as a specific target of therapy in clinical trials.