The demonstrated role of the tight control of hyperglycaemia for the prevention of long-term
diabetic complications has reoriented the goals of
insulin supply toward the search for restoration of the effects of physiological insulin secretion rather than the simple survival of
insulin deficient patients and the reduction in the number of daily
insulin injections to be performed. Normal
blood glucose control requires the availability of a fast-acting
insulin therapy at meal time in order to reduce hyperglycaemic excursions and a basal
insulin therapy able to stabilize
blood glucose between meals. Reduction of induced hypoglycaemic risk represents the secondary objective beside the main goal of avoiding hyperglycaemia. Fast-acting analogues, by a faster dissociation of their hexameric conformation after their injection or infusion in subcutaneous tissue, reduce post-meal hyperglycaemia, while their shortened duration of action versus
regular insulin minimizes late post-absorptive risk of hypoglycaemia. Long-acting analogues, by their precipitation in subcutaneous tissue or their slowly reversible binding to
albumin, provide a benefit on
blood glucose stability versus NPH or
zinc insulins. Continuous
insulin therapy using pumps offers both a better
blood glucose stability than multiple daily
injections and a broader flexibility in life mode. Using the peritoneal route by implantable pumps is a mean to improve
blood glucose stability in poorly controlled patients in spite of optimized subcutaneous
insulin therapy. The development of
glucose sensors provides reinforced information on
blood glucose, versus self-monitoring by capillary blood measurements, that contributes to a better adaptation of
insulin therapy. First trials of connections between
blood glucose data and
insulin delivery open a perspective toward
glucose-modulated
insulin therapy, at least in periods outside meals, leading to first models of semi-automated
artificial endocrine pancreas. The alternative of a cellular
insulin supply by pancreas or
islet transplantation looked promising during recent years, but lack of transplants and adverse events related to immune suppression limit their use to very specific cases where benefit/risk ratio is positive.