Diabetes Mellitus and Insulin

Diabetes Mellitus and Insulin

Diabetes

Diabetes mellitus is a clinical condition characterized by impairment of carbohydrate metabolism caused by an absolute or relative deficiency of insulin or insulin responsiveness, which leads to hyperglycemia and glucosuria.

Insulin

Insulin is a small protein produced by the β cells of the islets of Langerhans in the pancreas. Insulin has multiple and complex interactions with lipid, protein, and glucose metabolism. Normal production in the adult human is approximately 40 to 50 U/day. Insulin acts through receptor sites on cells. The half-life of insulin in the circulation is only a few minutes. In patients with hepatic dysfunction, the loss of gluconeogenesis (production of glucose in the liver from protein and fat) and a prolongation of insulin effect increase the risk of hypoglycemia. Renal disease may prolong the action of insulin, is another risk factor for hypoglycemia, and is an important consideration in managing the use of exogenous insulin in diabetic patients.

The most fundamental action of insulin is to stimulate increased cellular uptake of glucose. This is particularly important in skeletal muscle cells, where muscle activity also increases glucose uptake and is an important variable in the management of the physically active diabetic patient. The brain and liver are exceptions where insulin does not affect glucose transport. Hence, the diabetic patient has hyperglycemia because of inadequate cellular uptake of glucose. Along with glucose, potassium enters the cells under the influence of insulin, so the diabetic patient is also likely to have an imbalance of potassium concentrations across cell membranes. Other important metabolic functions of insulin include the stimulation of glycogen formation, as well as the suppression of gluconeogenesis and lipolysis. The patient with insulin deficiency has low glycogen stores and active gluconeogenesis. This implies that in the diabetic patient, due to an absence of glycogen, protein must be broken down to make glucose. Fat metabolism is also abnormal in the diabetic state, with acceleration of lipid catabolism and increased formation of ketone bodies. A deficiency of insulin leads to increased fatty acid liberation from adipose tissue.

Glucagon

Glucagon is a polypeptide released from the α cells of the pancreas, and acts both to stimulate the release of insulin and oppose some of the effects of insulin. Glucagon release is stimulated by hypoglycemia, as well as by epinephrine and cortisol, and is suppressed by glucose ingestion. The metabolic effects of stress are intricately involved with the same pathways as those involved in DM. During stress, elevations in the circulating levels of cortisol, glucagon, catecholamines, and growth hormone all act to cause hyperglycemia. In addition, glucagon and α-adrenergic stimulation exert a suppressive effect on insulin release. Mild hyperglycemia may occur in the stressed patient who does not have DM. In the diabetic patient, stress makes the diabetes more difficult to control. In a patient with minimal or subclinical DM before the stressful episode, the glucose balance may become difficult to manage during the stress-related event.

The Symptoms and Signs of Diabetes Mellitus

• Polyphagia (excessive hunger)
• Polyuria (excessive urine output)
• Polydipsia (excessive thirst)
• Presence of Ketone in urine. An excessive accumulation of ketones causes the patient to develop a metabolic acidosis (or ketosis). This is associated with dehydration and electrolyte imbalance. The patient with uncontrolled diabetes may present with collapse and coma due to metabolic acidosis (ketosis).

Table 5.1 Classification of Diabetes Mellitus