[Insulin therapy]

Abstract

Large randomised, controlled clinical trials have clearly shown that, both in type 1 (DCCT) and in type 2 (UKPDS, Kumamoto Study), micro and macrovascular complications are largely preventable with intensive insulin or oral hypoglycemic therapy and optimal metabolic control. Intensive insulin therapy can be performed in selected cases through continuous subcutaneous insulin infusion with a pump. However, almost equally good results can be obtained with a regimen of multiple injections based on a rational association of fast acting and slow acting insulin preparations. The present availability of fast acting insulin analogues (lispro and aspart insulin), characterised by aminoacid substitutions in the C-terminal portion of B-chain and a fast absorption rate from the subcutaneous tissue, is of great advantage in this context. Fast-acting analogues restore prandial insulin peaks while multiple doses of NPH restore basal insulin levels for the control of fasting blood glucose levels. New protracted acting insulin analogues and premixed preparations of fast acting analogues and NPH will soon be available. Pharmcokinetics of the protracted - acting analogue glargine seems particularly satisfactory. Glargine is present in vials in acid solution and has a neutral isoelectric point. Therefore, when injected, glargine precipitated in the subcutaneous tissue and is reabsorbed very slowly in the following 20-24 hours. Moreover, new fatty acid derivatives of insulin analogues are now under experimentation. The protraction of action of this kind of insulin is due to its binding with serum and interstitial albumin and subsequent slow release. Multiple insulin regimens are available for different types of diabetes, different degrees of insulin deficiency and peculiar clinical features of individual patients. However, in any case, insulin therapy should aim to near - normalise not only mean blood glucose and glycated hemoglobin values but also postprandial blood glucose level which represent an independent risk factor an for diabetic complications.