Selection Oftherapy For Diabetes

Patients are treated with:

• Diet plus insulin

• Diet plus oral agent (metformin) plus insulin

• For ketoacidosis: soluble insulin, urgently.

Diabetic patients under 30 years: almost all need insulin; the exception is the rare single-gene disorder of Maturity Onset Diabetes of the Young (MODY) due usually to mutations in the glucoki-nase gene.

Diabetic patients over 30 years: approximately one-third need insulin, one-third oral agents and one-third diet only.

Type 1 diabetes: human insulin is preferred for new patients (for regimen see below).

Type 2 diabetes: careful trial is the only sure way of deciding who can be maintained on oral therapy rather than on insulin. About 30% of patients will be adequately managed without oral therapy. When diet alone has failed to control Type 2 diabetes, it is necessary to add an oral agent; the choice should fall first on

• metformin for the obese patient: the usual regimen is metformin 500 mg once or twice daily after meals, increasing at 2-4-weekly intervals to a maximum of 3 g daily.

• a sulphonylurea for the nonobese: an example regimen would be gliclazide 80 mg orally (or

40 mg in the small or aged) before the main meal of the day. The dose is adjusted, according to response, at 2-4-weekly intervals by increments of 40-80 mg, to a maximum of 320 mg. If control is incomplete, metformin may be added.

Insulin treatment in Type 2 diabetes. When oral therapy fails, insulin treatment should be used alone or in combination with metformin. There is little advantage from adding insulin to a sulphonylurea. The advent of thiazolidinediones offers an alternative to combining metformin with insulin, but more experience of these drugs is required before their combination with metformin can be routinely recommended. It is important to stop the thiazo-lidinedione, if not effective, before progressing to insulin. Definitive evidence that institution of insulin will reduce complications is lacking; however, there is an improvement in quality of life, with few patients requesting to stop insulin once they have started, and the improved glycaemic control can be assumed also to improve outcome. Initial treatment with a single injection of intermediate-acting insulin (see Fig. 35.1) at night, or twice daily, may control hyperglycaemia. Fluctuations in blood glucose levels may be controlled with twice daily mixed insulin or by multiple injections.

Re-evaluation of the requirement for drugs can be made after the patient has been controlled and stable for 3-6 months, but complete withdrawal of oral agents is unusual.

Monitoring of patients taking oral agents should be as close as those on insulin. The prognosis of poorly controlled type 2 diabetes is serious.

Prevention of complications in Type 2 diabetes:

the United Kingdom Prospective Diabetes Study (UKPDS)9'10 This landmark study in Type 2 diabetes confirmed that good glycaemic control and aggressive blood pressure reduction independently improve outcome. For every 1% reduction in HbAlc there was a 21% reduction in diabetes related deaths, and 37% reduction in microvascular disease. The study disproved concerns about long-term safety of sulphonylureas, but suggested that metformin might be the preferred first-line pharmacological therapy in obese patients. Of highest importance was the finding that effective blood pressure control — regardless of type of antihypertensive drug — was more influential than glycaemic control in preventing macrovascular complications. Reduction of blood pressure in 758 patients to a mean of 144/82 mmHg achieved 32% reduction in deaths related to diabetes and 37% reduction in microvascular end points, compared to 390 patients treated to a blood pressure of 154/87 mmHg.

Type 1 treatment. The range of insulin formulations available allows flexible adjustment of the

9 UK Prospective Diabetes Study (UKPDS) Group 1998 Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352: 854-865.

10 UK Prospective Diabetes Study (UKPDS) Group 1998 Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. British Medical Journal 317: 703-713.

regimen to the patient's way of life. No single regimen suits all patients but one of the following regimens can suit most patients (see Fig. 35.1):

• Three doses of soluble insulin (before the main meals) plus an intermediate-acting insulin at bedtime

• A biphasic or intermediate-acting insulin (see Fig. 35.1) twice a day before morning and evening meals

• A single morning dose of a biphasic or intermediate-acting insulin before breakfast may suffice for some patients.

Injection technique has pharmacokinetic consequences according to whether the insulin is delivered into the subcutaneous tissue or (inadvertently) into muscle. The introduction of a range of appropriate length needles and pen-shaped injectors has enabled patients to inject perpendicularly to the skin without risk of intramuscular injection. The absorption of insulin is as much as 50% more rapid from shallow i.m. injection. Clearly factors such as heat or exercise which alter skin or muscle blood flow can markedly alter the rate of insulin absorption.

Patients should standardise their technique to ensure injection is s.c. Inadvertent i.m. injection of an overnight dose of an extended duration insulin can lead to inadequate early morning control of blood glucose. Sites of injection should be rotated to minimise the now rare local complications (lipodystrophy). Absorption is faster from arm and abdomen than it is from the thigh and buttock.

Complications of diabetes. A well-controlled diabetic is less liable to ketosis and infections. It is now certain that good control of glycaemia mitigates the serious microvascular complications, retinopathy, nephropathy, neuropathy and cataract. Too tight control of glycaemia can increase the frequency of attacks of hypoglycaemia.

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