ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 ME2

Rational for using insulin analogues in the treatment of diabetes mellitus

Geremia Bolli

University of Perugia, Perugia, Italy.

In both Type 1 and Type 2 diabetes mellitus (T1, T2DM) there is stringent need to maintain A1C<7.0% since clinical diagnosis all life long. Large, prospective, intervention trials have proven that A1C<7.0% is the most (and the only!) effective mean to prevent onset of vascular complications of diabetes and/or delay its progression.

In T1DM, it is mandatory to use basal+meal-time insulin. The gold standard is the continuous s.c. insulin infusion (CSII) with rapid-acting insulin analogues. As compared to multiple daily injections (MDI) based on rapid- and long-acting insulin analogues, CSII provides the highest flexibility in life-style, although A1C and risk of hypoglycaemia are no superior vs MDI. With MDI, the basal insulin need should be replaced with a long-acting analogue, either glargine once daily, or detemir twice daily (in the majority of subjects). NPH should no longer be in use in T1DM (including children and elderly people) because of the risk for nocturnal hypoglycaemia and hypoglycaemia unawareness. Rapid-acting analogues (lispro, or aspart or glulisine), not human regular insulin, should be given at each meal, including snacks in children, adults and elderly people with T1DM. The dual advantage of rapid-acting analogues vs human regular insulin, is lower post-prandial hypoglycaemia and lower A1C, with less risk for hypoglycaemia and greater flexibility (improved life-style).

In T2DM, the present recommendation is aggressive treatment of hyperglycaemia to lower A1C to below 7.0%, initially with life-style changes+metformin, but immediately after with early initiation of basal insulin and/or additional oral drugs whenever A1C is not at target within three months (ADA/EASD consensus, 2006). Insulin in T2DM should be initiated as evening administration of either the cheap NPH insulin, or the more sophisticated (and expensive) long-acting insulin analogues glargine (once daily), or detemir (once or twice daily in more than 50% of T2DM subjects). All basal insulins NPH, glargine and detemir keep A1C<7.0% in T2DM failing to oral drugs, but the risk of hypoglycaemia is about 50% less using glargine or detemir versus NPH. Because prevention of hypoglycaemia is at least as important as it is reduction in A1C, the basal insulin of choice is a long-acting insulin analogue. When starting basal insulin in T2DM, it is important that the evening insulin dose is titrated to fasting normoglycaemia (100 mg/dl, 5.5 mmol/l). The titration may require weeks of time and large dose in subjects who are insulin resistant due to obesity, primarily visceral obesity (fatty liver). The modern view is that a large insulin dose should not worry neither the doctor not the patient because insulin is healthy. When meal-time insulin is needed, rapid-acting insulin analogues (lispro, or aspart or glulisine) should be used in T2DM, not human regular insulin.

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