Diabetes mellitus is a disorder of carbohydrate metabolism in which the action of insulin is diminished or absent through altered secretion, decreased insulin activity, or a combination of both factors. There are two principal classes of diabetes (and many sub types not listed here):
Type I diabetes: Type I diabetes, also referred to as insulin dependent diabetes mellitus (IDDM), is due to a deficiency of insulin following autoimmune destruction of pancreatic beta cells. Patients with type I diabetes require administration of insulin.
Type II diabetes: Type II diabetes, also referred to as non-insulin dependent diabetes (NIDDM), is due to reduced secretion of insulin or to peripheral resistance to the action of insulin. Although patients may be controlled on diet alone, many require administration of oral antidiabetic drugs or insulin to maintain satisfactory control.
The aim of treatment is to achieve the best possible control of plasma glucose concentration and prevent or minimize complications including microvascular complications (retinopathy, albuminuria, neuropathy).
Diabetes mellitus is a strong risk factor for cardiovascular disease. Other risk factors such as smoking, hypertension, obesity and hyperlipidaemia should also be addressed.
Insulin: Insulin plays a great role in the regulation of carbohydrate, fat and protein metabolism. It is a polypeptide hormone of complex structure. There are differences in the amino acid sequence of animal insulin's, human insulin's and the human insulin analogues.
Insulin may be of beef or pork origin or it may be human insulin produced by gene technology or by modification of porcine insulin.
All insulin preparations are to a greater or lesser extent immunogenic in man but immunological resistance to insulin action is uncommon. Human and Porcine insulin are less immunogenic than bovine insulin and where possible most newly diagnosed IDDM patients are now given human insulin.
Insulin is inactivated by gastro-intestinal enzymes, and must therefore be given by injection; the subcutaneous route is ideal in most circumstances. It is usually injected in to the upper arms, thighs, buttocks, or abdomen; there may be increased absorption from a limb site if the limb is used in strenuous exercise following the injection. Generally subcutaneous insulin injections cause few problems; fat hypertrophy does however occur but can be minimized by rotating the injection site. Local allergic reactions are now rare. The various types of insulin may also be given intramuscularly when the onset of action is faster than with the subcutaneous route. An even faster onset may be achieved with intravenous administration, but this route is only suitable for fast-acting or soluble insulin.
Most patients can and should monitor their own blood glucose concentrations using blood glucose strips. Since blood glucose levels vary throughout the day, it is best to recommend that patients should maintain blood glucose concentrations of between 4 and 10 mmol/litre for most of the day while accepting that on occasions levels will be higher; strenuous efforts should be made to prevent blood glucose concentrations falling below 4 mmol/litre. Patients should be advised to look for troughs and peaks of blood glucose and to adjust their insulin dosage only once or twice a week. Insulin doses are determined on an individual basis, by gradually increasing the dose but avoiding hypoglycemic reactions.
In the absence of blood glucose monitoring strips, urine glucose can be tested to ensure glucose levels are not too high. It is the method of personal choice for many patients with type II diabetes mellitus. It is less reliable than blood glucose but is easier and costs much less. All patients should monitor either blood or urine glucose level daily.
Hypoglycemia: The most frequent complications of insulin therapy is hypoglycemia and patients taking insulin should be educated about its cause, symptoms, and treatment. Most patients can recognize the early warning signs of hypoglycemic and by taking sugar immediately they can prevent more serious symptoms developing. Comatose patients should be given intravenous glucose or, if this is not practicable, subcutaneous or intramuscular glucagons. Hypoglycemia can also develop in patients taking oral hypoglycemic, notably the sulphonylureas. Some patients may no longer be able to recognize the warning signs of hypoglycemia after transferring from animal to human insulin and these patients, if appropriate, should be transferred back to porcine insulin.
Car drivers need to be particularly careful to avoid hypoglycemia. They should check their blood glucose concentrations before driving and, on long journeys, at intervals of approximately two hours; they should ensure that a supply of sugar is always readily available. If hypoglycemia occurs the driver should switch off the ignition until recovery is complete (may be 15 minutes or longer). Driving is not permitted when hypoglycemic awareness has been lost. For sporadic physical activity departing from the patients usual daily routine extra carbohydrate may need to be taken to avert hypoglycemia. Blood glucose should be monitored before, during and after exercise.
Diabetic Ketoacidosis. Diabetic ketoacidosis results from a lack of insulin due to a number of factors and the onset may be over hours or days. It is characterized by hyperglycemia, hyperketonaemia, and acidaemia and is a medical emergency which should be treated promptly with fluid and electrolyte replacement and insulin. However, over vigorous fluid replacement without severe dehydration carries the risk of precipitating cerebral oedema.
Isophane/NPH insulin (HPB)*
Injection 100units/ml in 10ml vial
* HPB stands for Human, porcine, and Bovine
Indications: - diabetes mellitus
Cautions: -see notes above; reduce dose in renal impairment; occasionally insulin resistance necessitating large doses; pregnancy and breastfeeding; see also interactions.
Drug interactions: - analgesics, antibacterials, antifungals, uricosurics.
Side effects: -hypoglycaemia in overdose; localized and rarely generalized, allergic reactions; lipoatrophy at injection site; insulin resistance. Protamine may cause allergic reactions
Dose and Administrations
By subcutaneous injection, according to requirements.
Intravenous injection is contraindicated.
Storage: - unopened vials of insulin should be stored at 2°C to 8°C and should not be subjected to freezing. The vial in use may be stored at room temperature; exposure to extremes in temperature or direct sunlight should be avoided.
Insulin Zinc suspension/Insulin Lente (HPB)*
Injection 100 units/ml in 10ml vial
* HPB stands for Human, porcine, and Bovine
Indications: -diabetes mellitus (long acting)
Cautions, Drug interactions, Side effects: see notes above and under Isophane insulin.
Dose and Administrations
By subcutaneous injection, according to requirements
Storage: -store between 2°C and 8°C protect from freezing.
Oral antidiabetic drugs. If patients with NIDDM have not achieved suitable control after about 3 months old dietary modification and increased physical activity, then oral hypoglycemic may be tried.
The two major classes of oral hypoglycemic agents are the sulphonylureas and the biguanides.
Sulphonylureas act mainly by augmenting insulin secretion and therefore only effective if there is some residual pancreatic beta-cell activity. They may occasionally lead to hypoglycaemia 4 hours or more after food. This may be dose related and usually indicates excessive dose and it occurs more frequently with long-acting sulfonylureas such as Glibenclamide and occurs particularly in the elderly. The sulphonylureas have the disadvantage that they may encourage weight gain. They should not be used during breast-feeding and caution is required in the elderly and those with renal or hepatic insufficiency because of the risk of hypoglycaemia. Insulin therapy is generally required during intercurrent illness, during surgery and also during pregnancy.
Indications: type II diabetes mellitus
Cautions: -renal impairment, hepatic impairment, elderly, substitute insulin during severe infection, trauma, surgery.
Drug interactions: - Analgesics (azapropazone, phenylbutazone and possibly other NSAIDs enhance effect of sulphonylureas), Antibacterial, Antifungals, uricosurics.
Side effects: - mild and infrequent, including gastrointestinal disturbances and headache; hypersensitivity reactions; hypoglycaemia, particularly in the elderly.
Contraindications: -ketoacidosis; porphyria; pregnancy; breastfeeding.
Dose and Administrations: -Initially 5mg daily with or immediately after break fast (Elderly 2.5mg, but avoid - see notes above), adjusted according to response, maximum 15mg daily.