Diabetes mellitus

Diabetes mellitus is defined by the World Health Organization as "a chronic disease that occurs when the pancreas does not produce enough insulin, or alternatively, when the body cannot effectively use the insulin it produces."

A conservative analysis estimated that in the year 2000, 2.8% of the global population had diabetes mellitus and this was projected to rise to 4.4% in 2030. It is expected that by 2030 at least 366 million people will have diabetes; that is one in every 23 people. Diabetes is the fourth leading cause of global death by disease and at least 50% of all people with diabetes are unaware of their condition. In some countries, this figure may reach 80%.

The disease is characterised by increased levels of glucose (a form of sugar) in the blood.

Regulation of blood glucose

Main article blood glucose regulation

A healthy individual maintains blood glucose levels between 3.5 – 8 mmol/L (63-144 mg/dL) despite wide fluctuations in both glucose intake from meals and glucose utilisation to meet energy demands. When blood glucose levels are outside this range, the body experiences adverse effects.

If blood glucose levels are low (hypoglycaemia), the brain is unable to function correctly. This is because oxidation of glucose provides the energy for brain cell activity. As the brain cannot store glucose, it requires a constant supply of glucose in its blood supply.

A persistently high glucose level (hyperglycaemia) is the main indicator of diabetes mellitus.

Diabetes mellitus is caused by an imbalance between insulin secretion and insulin resistance

Main articles: Insulin

The hormone, insulin is the key regulator of blood glucose levels. It is released from the beta cells of the pancreas in response to a range of neural, nutrient, hormonal and chemical stimuli. Insulin secretion is increased by high blood glucose levels and inhibited by falling glucose levels. The actions of insulin lower blood glucose levels.

Insulin’s actions include:

• Stimulation of:
• *Glucose uptake by fat and muscle cells,
• *Glucose oxidation within cells to release energy, cellular respiration,
• *Glucose storage as glycogen in liver and muscle cells, glycogenesis,
  • Manufacture of triglycerides by fat cells using glucose as a substrate, and
• Inhibition of glucose production from the intermediaries of fat and protein metabolism, gluconeogenesis.

 Maintaining normal blood glucose levels therefore requires a balance between the secretion of insulin and the sensitivity of liver, muscle, fat and other cells to the action of insulin. The sensitivity of these cells to the action of insulin is impaired by obesity, genetic, hormonal and a range of other factors. This impaired sensitivity is termed insulin resistance.

Normally insulin resistance can be compensated for by increased insulin secretion. The elevated blood glucose levels that are characteristic of diabetes mellitus result from either absolute insulin deficiency or insulin resistance accompanied by impaired ability to compensate by increased insulin secretion.

Other hormones influencing blood glucose levels

The hormone glucagon opposes many of the actions of insulin. In particular, it stimulates the release of glucose stored as glycogen in the liver and if these stores are depleted, promotes gluconeogenesis.

Other hormones influencing blood glucose levels include adrenalin (epinephrine), corticosteroids, growth hormone and thyroid hormones.

Causes of diabetes mellitus

Diabetes mellitus is usefully classified into three primary types. They have different causes but share symptoms and adverse effects related to persistently raised blood glucose.

Diabetes mellitus type 1

Main article Diabetes mellitus type 1

Type 1 diabetes is caused by selective destruction of the insulin-producing cells of the pancreas. It is usually initiated by an immune response, triggered by an interaction of genes and environmental factors. Eventually autoantibodies to the islet cells of the pancreas are produced resulting in destruction of the islet cells and consequent loss of insulin production.

There is a prolonged prodromal phase preceding the onset of symptoms, but when they do occur, onset is usually abrupt. Blood sugar rises rapidly with associated thirst, hunger, excessive urination, weight loss and fatigue.

Type 1 diabetes usually occurs before the age of 30 years with a peak age of onset between 10 and 14 years. Insulin therapy is required for survival.

Type 1 diabetes has previously been called 'Juvenile Diabetes' and 'Insulin Dependent Diabetes Mellitus (IDDM)'. These terms have been abandoned. Although type 1 diabetes is predominantly a disease of young people and people with this disorder require insulin therapy, it can occur at any age and insulin may be beneficial in the treatment of people with any type of diabetes mellitus.

Diabetes mellitus type 2

Main article Diabetes mellitus type 2

Type 2 diabetes represents a group of metabolic disorders which include variable degrees of reduced sensitivity of body tissues to the action of insulin (insulin resistance), decreased insulin secretion and increased hepatic glucose production. Onset is usually gradual and it is frequently preceded by a period of impaired glucose tolerance or the metabolic syndrome.

Type 2 diabetes is the most frequently occurring form of diabetes mellitus and the rate of onset increases with increasing age. Although type 2 diabetes is predominantly a disease of older people, it is increasingly occurring in young obese people.

There is a strong genetic component to type 2 diabetes, people who have two parents with type 2 diabetes have an approximately 40% risk of developing it themselves. Risk of developing type 2 diabetes is increased by obesity and physical inactivity.

In the past, type 2 diabetes has been called 'Maturity onset diabetes' and 'Non insulin dependent diabetes mellitus (NIDDM)'. These terms have been abandoned. Type 2 diabetes can occur in children and some people with this form of diabetes benefit from insulin therapy.

Gestational diabetes mellitus

Main article Gestational diabetes

Gestational diabetes is caused by the development of insulin resistance during late pregnancy related to the metabolic changes that occur. Gestational diabetes usually settles after the baby has been born but women who have experienced gestational diabetes are left with an approximately 50% chance of developing diabetes.

Other specific types of diabetes mellitus

There are other less common types of diabetes mellitus.

These are associated with:

• Genetic beta-cell secretory defects;
• Genetic defects in insulin action;
• Diseases of the exocrine pancreas, such as pancreatitis or pancreatic cancer;
• Endocrine disorders, such as Cushing syndrome, acromegaly and phaeochromocytoma;
• Drugs or chemicals, such as corticosteroids and thiazide diuretics;
• Infections, such as rubella and cytomegalovirus;
• Uncommon forms of immune-related diabetes, such as the type associated with insulin-receptor antibodies;
• Genetic syndromes associated with diabetes, such as Klinefelter syndrome and Down syndrome.