The quest for physiologic insulin replacement.
Historically, the objective of insulin replacement has been to simulate the 2 major components of insulin secretion in individuals without diabetes mellitus: the low-level basal secretion during the night and periods of fasting, and the prandial secretion in response to food intake. The variable pharmacokinetic and pharmacodynamic characteristics of conventional insulin preparations have made mimicking these physiologic profiles virtually impossible. Balancing the effects of diet, exercise, and the numerous factors contributing to intra- and inter-individual variations in insulin absorption and action, such as type, site of injection, and dosage of insulin, while avoiding the very serious side effect of hypoglycemia in seeking normoglycemia, presents a further challenge. Recently, these limitations have been addressed by recombinant DNA-mediated development of insulin analogues, such as rapid-acting insulin lispro, aspart and glulisine, and the long-acting insulin preparations, insulin glargine and detemir. The molecular structures of these analogues have produced time-action profiles that better approach prandial and basal insulin secretion, thus allowing for easier, safer, and more flexible treatment regimens.
Owens
David R
DR
Diabetes Research Unit, Llandough Hospital, Penarth, Vale of Glamorgan, Cardiff, Wales CF64 2XX, United Kingdom. owensdr@cf.ac.uk
D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D007328:Insulin