Diabetes- The Disease

Diabetes is a condition that occurs because of a lack of insulin or because of the presence of factors opposing the actions of insulin. The result of insufficient action of insulin is an increase in blood glucose concentration (hyperglycaemia). Many other metabolic abnormalities occur, notably an increase in ketone bodies in the blood when there is a severe lack of insulin.

Click here to find out about hyperglycaemia and ketoacidosis

Patients can show a wide range of symptoms, Which are summarised below.

Excessive thirst & appetite (polydypsia)
Polyuria (excessive urination)
Pruritus or balanitis
Weight loss
Lethargy
Nausea
Blurred vision
In Women - Frequent vaginal infections e.g. Candida infections
In Men - Impotence

Diabetes is normally diagnosed on the basis of the patient's clinical symptoms (listed above) in combination with a high fasting blood glucose concentration. In some cases, however, clinical symptoms may be absent and the diagnosis depends upon demonstrating hyperglycaemia. A positive diagnosis may be made when:

Symptoms are present with a capillary whole blood glucose concentration greater than 11.1mmol/L (ref. range 3 - 5.7mmol/L),

Symptoms are absent, but there have been two separate blood glucose measurements each of greater than 11.1mmol/L.

The individual shows a positive glucose tolerance test, i.e., when a baseline blood glucose is greater than 6.7mmol/L and increases to above 11.1mmol/L two hours after a 75g load of glucose monohydrate.

Insulin is the major hormone secreted by the pancreas. Insulin is a small protein comprising 51 amino acids residues and is synthesised in the beta cells of the Islets of Langerhans via its precursor, proinsulin. One molecule of proinsulin is cleaved by enzymes to give one molecule of insulin and one molecule of C-peptide (this is physiologically inert). C-peptide can be measured in some diabetic patients to show that insulin production has occurred.

Below is a diagram to show insulin packaged into granules within a normal subject.

Figure 1 A cell of the Islets of Langerhans, showing secretory granules (red)

Insulin acts in several ways to reduce circulating blood glucose levels. It enhances cellular uptake of glucose from the blood in many tissues, particularly skeletal muscle and adipose tissue. It also stimulates glycogen production and inhibits glycogen breakdown in muscles and hepatocytes.

Action	Tissue/Organ
*Effect on carbohydrate metabolism*
Enhances glucose uptake into cells	Adipose and muscle
Increases glycolysis	Adipose and muscle
Increases glycogen synthesis	Muscle and liver
Reduces glycogen breakdown	Muscle and liver
Reduces gluconeogenesis	Liver
*Effects on lipid metabolism*
Reduces fat breakdown	Adipose
Increases fatty acid synthesis	Adipose
Increases low density lipoprotein synthesis	Liver
Increases cholesterol synthesis	Liver
Effects on protein metabolism
Increases amino acid transport	Many tissues
Increases protein synthesis	Muscle and others
Reduces protein breakdown	Muscle and others

Table 1 Metabolic effects of insulin

It can be seen from table 1 that insulin is a potent anabolic agent. Insulin enhances body mass by promoting muscle and fat deposition and inhibiting the breakdown of these tissues. For this reason insulin has recently been the subject of drug misuse.