What is Diabetes?

Diabetes is recognized as a group of heterogeneous disorders with the common elements of hyperglycaemia and glucose intolerance, due to insulin deficiency, impaired effectiveness of insulin action, or both 1 . Diabetes mellitus is classified on the basis of aetiology and clinical presentation of the disorder into four types.

  • type 1 diabetes,
  • type 2 diabetes,
  • gestational diabetes mellitus (GDM), and
  • other specific types.


Type 1 diabetes

Type 1 diabetes is sometimes called insulin-dependent, immune-mediated or juvenile-onset diabetes. It is caused by destruction of the insulin-producing cells of the pancreas, typically due to an auto-immune reaction, where they are attacked by the body's defense system. The beta cells of the pancreas therefore produce little or no insulin, the hormone that allows glucose to enter body cells. The reason why this occurs is not fully understood.

The disease can affect people of any age, but usually occurs in children or young adults. Type 1 diabetes is one of the most common endocrine and metabolic conditions in childhood. People with type 1 diabetes need injections of insulin every day in order to control the levels of glucose in their blood. Without insulin, people with type 1 diabetes will die.

The onset of type 1 diabetes is often sudden and dramatic and can include symptoms such as:

  • abnormal thirst and a dry mouth
  • frequent urination
  • extreme tiredness/lack of energy
  • constant hunger
  • sudden weight loss
  • slow-healing wounds
  • recurrent infections
  • blurred vision

The incidence of type 1 diabetes is increasing, the reasons for which are unclear but are likely to be mainly due to changes in environmental risk factors. Environmental risk factors, increased height and weight development, increased maternal age at delivery, and possibly some aspects of diet and exposure to some viral infections may initiate autoimmunity or accelerate an already ongoing beta cell destruction.

Type 2 diabetes

Type 2 diabetes is characterized by insulin resistance and relative insulin deficiency, either of which may be present at the time that diabetes becomes clinically manifest. The diagnosis of type 2 diabetes usually occurs after the age of 40 years but could occur earlier, especially in populations with high diabetes prevalence. There are increasing reports of children developing type 2 diabetes. Type 2 diabetes can remain undetected, i.e. asymptomatic, for many years and the diagnosis is often made from associated complications or incidentally through an abnormal blood or urine glucose test.

Type 2 diabetes is often, but not always, associated with obesity, which itself can cause insulin resistance and lead to elevated blood glucose levels. It is strongly familial, but major susceptibility genes have not yet been identified. There are several possible factors in the development of type 2 diabetes. These include:

  • Obesity, diet and physical inactivity
  • Increasing age
  • Insulin resistance
  • Family history of diabetes
  • Less than optimum intrauterine environment
  • Ethnicity

In contrast to type 1 diabetes, people with type 2 diabetes are not dependent on exogenous insulin and are not ketosis-prone, but may require insulin for control of hyperglycaemia if this is not achieved with diet alone or with oral hypoglycaemic agents.

The rising prevalence of type 2 diabetes is associated with rapid cultural and social changes, ageing populations, increasing urbanization, dietary changes, reduced physical activity and other unhealthy lifestyle and behavioural patterns 2 .

Gestational diabetes

Gestational diabetes mellitus (GDM) is a glucose intolerance of varying degrees of severity which starts or is first recognized during pregnancy. The definition applies regardless of whether insulin is used for treatment or if the condition persists after pregnancy.

Maintaining control of blood glucose levels significantly reduces the risk to the baby as an increased maternal glucose level could result in complications in the baby including large size at birth, birth trauma, hypoglycaemia and jaundice. Women who have had GDM have an increased risk of developing type 2 diabetes in later years. GDM is also associated with increased risk of obesity and abnormal glucose metabolism during childhood and adult life in the offspring.

Diabetes complications

In virtually every high-income country, diabetes is ranked among the leading causes of blindness, renal failure and lower limb amputation. Diabetes is also now one of the leading causes of death, largely because of a markedly increased risk of coronary heart disease and stroke (cardiovascular disease). In addition to the human suffering that diabetes-related complications cause, to those with diabetes but also to their carers, their economic costs are huge. Costs include those for healthcare, loss of earnings, and economic costs to the wider society in loss of productivity and associated lost opportunities for economic development. 

Chronic elevation of blood glucose, even when no symptoms are present to alert the individual to the presence of diabetes, will eventually lead to tissue damage, with consequent, and often serious, disease. Whilst evidence of tissue damage can be found in many organ systems, it is the kidneys, eyes, peripheral nerves and vascular tree, which manifest the most significant, and sometimes fatal, diabetes complications (see Figure 1.1).

Unsatisfactory metabolic control in children can result in stunted growth, and exposure to both severe hypoglycaemia and chronic hyperglycaemia can adversely affect neurological development. Children are more sensitive to a lack of insulin than adults and are at a higher risk of a rapid and dramatic development of diabetic ketoacidosis (diabetic coma).

The mechanism by which diabetes leads to these complications is complex, and not yet fully understood, but involves the direct toxic effects of high glucose levels, along with the impact of elevated blood pressure, abnormal lipid levels and both functional and structural abnormalities of small blood vessels.

The major chronic complications of diabetes are:

  • cardiovascular disease (CVD);
  • nephropathy;
  • neuropathy;
  • amputation; and
  • retinopathy.

Cardiovascular disease
Cardiovascular disease is the major cause of death in diabetes, accounting in most populations for 50% or more of all diabetes fatalities, and much disability. The kinds of CVD that accompany diabetes include angina, myocardial infarction (heart attack), stroke, peripheral artery disease, and congestive heart failure (CHF).

Nephropathy
Diabetes is an increasingly important cause of renal failure, and indeed has now become the single most common cause of end stage renal disease, i.e. that which requires either dialysis or kidney transplantation, in the USA 3 , and in other countries.

Neuropathy
When blood glucose and blood pressure are not controlled, diabetes can harm the nerves. Problems with digestion and urination, impotence, and many other functions can result, but the most commonly affected area is the feet and legs. Nerve damage in these areas is called peripheral neuropathy and could manifest in many ways including loss of feeling in the feet and toes. Loss of feeling is a particular risk because it can allow foot injuries to escape notice and treatment, leading to major infections and amputation.

Amputation
Through effects on peripheral nerves and arteries, diabetes can lead to foot ulceration, infection and the need for amputation. People with diabetes carry a risk of amputation that may be more than 25 times greater than that seen in those without diabetes 4 .

Retinopathy
Diabetes can harm sight and cause blindness in several ways. The most common cause of blindness in diabetes is macular oedema, caused by fluid build-up behind the retina of the eye. A more common complication is background and proliferative retinopathy, which can cause blindness as a result of repeated haemorrhages at the back of the eye. Diabetes also increases the risk of cataracts and glaucoma.

The major diabetes complications

Impaired glucose tolerance

Impaired glucose tolerance (IGT) is an asymptomatic condition defined by elevated (though not diabetic) levels of blood glucose two hours after a 75g oral glucose challenge. Along with impaired fasting glucose (IFG), it is now recognized as being a stage in the transition from normality to diabetes. Not surprisingly, IGT shares many characteristics with type 2 diabetes, being associated with obesity, advancing age, insulin resistance and an insulin secretory defect.

Insulin

Insulin is the internal secretion of the pancreas formed by groups of cells called the islets of Langerhans. It is the hormone needed to enable glucose to enter the cells and provide energy. Insulin is also important in keeping blood glucose levels within acceptable limits.

Insulin is injected into the body by people with type 1 diabetes in whom the cells that produce insulin have been destroyed. This is the most common form of diabetes in children and young adults, and they depend on insulin for survival. Insulin may also be used by people with type 2 diabetes. In type 2 diabetes, the body needs more insulin than it can produce.

Since the landmark discovery of insulin by Frederick Banting and Charles Best in 1921, huge steps forward have been made in research and development in creating genetically engineered human insulin. Until relatively recently insulin was derived from a limited resource of the pancreas of cattle and pigs.

 

Insulin production and action

1: Harris M, Zimmet P. Classification of diabetes mellitus and other categories of glucose intolerance. In Alberti K, Zimmet P, Defronzo R, editors. International Textbook of Diabetes Mellitus. Second Edition. Chichester: John Wiley and Sons Ltd; 1997. p9-23.

2: World Health Organization. Prevention of diabetes mellitus. Report of a WHO Study Group. Geneva: World Health Organization; 1994. No. 844.

3: United States Renal Data System. Annual Data Report. 2002. http://www.usrds.org/adr.htm

4: Davis TM, Stratton IM, Fox CJ, et al. U.K. Prospective Diabetes Study 22. Effect of age at diagnosis on diabetic tissue damage during the first 6 years of NIDDM. Diabetes Care 1997; 20 (9): 1435-1441.