Minimizing Hypoglycemia While Maintaining Glycemic Control in Diabetes

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Abstract
N an accompanying Perspectives article, Cryer (1) identifies a number of different areas where thera- peutic interventions have the potential to reduce hypoglycemia without compromising glycemic con- trol. Some approaches provide well-defined clinical bene- fits, a few offer dramatic reductions in hypoglycemia but remain out of reach for most people, and others, although promising, have yet to be properly evaluated (Table 1). In this Perspectives article, I examine the evidence that underpins these interventions. It is beyond the scope of this article to review the data for each potential interven- tion in detail, but the reader is directed to the source where appropriate. The focus of this article is treatment of type 1 diabetes, as most of the specific potential therapies have been evaluated in this group, although included are comments in relation to recent trials of intensive therapy in type 2 diabetes. PREVENTING ABSOLUTE OR RELATIVE INSULIN EXCESS Education and skills training in self-management. Long before the benefits of tight glucose control had been established (2), the belief that insulin therapy should be designed to replace insulin "physiologically" had been advocated by a small number of enthusiastic clinicians. The advent of blood glucose monitoring in the late 1970s had a major impact, since background and meal-related insulin could be given separately and adjusted according to self-monitored blood glucose measurements. Partici- pants were encouraged to eat freely, calculating their insulin dose according to their chosen amount of carbohydrate. Integrating these components was a complex task, probably beyond that of many physicians, let alone pa- tients. If this was to be undertaken every day, then patients needed to acquire the skill of flexible insulin self-manage- ment and apply it successfully. The therapeutic education approach was pioneered by Assal et al. (3), and Berger and Muhlhauser (4) went on to develop a residential training course (Insulin Treatment and Training program (ITTP)) evaluating the intervention in a series of studies, including randomized controlled trials. Their group highlighted the major differences between rates of severe hypoglycemia in different centers in the Diabetes Control and Complica-