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In an attempt to differentiate the effect of fenfluramine hydrochloride from that of caloric restriction on carbohydrate tolerance in patients with lipodystrophy, parameters of carbohydrate homeostasis were studied in patients with lipodystrophy during periods offenfluramine treatment and during periods of caloric restriction. Although carbohydrate tolerance appeared to improve initially in one patient when treated with fenfluramine, this improvement did not persist. No beneficial influence of fenfluramine on carbohydrate tolerance could be identified in the other patients studied. By contrast, all patients demonstrated an improvement in carbohydrate tolerance in response to caloric restriction. These data suggest that caloric restriction improves carbohydrate tolerance in patients with lipodystrophy whereas fenfluramine, in the absence of caloric restriction, has no long-term beneficial effect.

Normalization of plasma glucose concentration with subcutaneous injections of insulin has been difficult. With intravenous insulin delivery, normalization of plasma glucose concentration in adult-onset diabetic patients has been achieved when their plasma insulin concentration was normalized. In juvenile-onset diabetic subjects totally lacking endogenous insulin, the effect of normalization of the plasma insulin concentration has not yet been reported. In the present studies, the plasma insulin profile was normalized in four brittle, insulin-dependent diabetic subjects throughout three meals (breakfast, lunch, and supper). Plasma free insulin concentration was assayed after precipitation of endogenous insulin antibodies with polyethylene glycol. Acute meal-related increases in plasma free insulin concentration were achieved with a programmable intravenous insulin delivery system. When plasma insulin profiles were normalized in insulin-dependent diabetic subjects lacking endogenous insulin secretion, an improvement in meal-related glucose excursions was observed. However, complete normalization of plasma glucose concentration was not achieved, suggesting that factors other than plasma insulin concentration modulate carbohydrate homeostasis in brittle diabetes. These factors may include portal vein hypoinsulinemia during peripheral vein insulin infusion, stress hormone concentrations, and tissue insulin resistance.

Newer concepts regarding the management of diabetes favor a diet that is more liberal in carbohydrate content and more personalized for the patient. Ideally, the end result will be improved glycemic control and fewer complications. Allowing more flexibility in the diet is a way of fostering better patient compliance. Alcohol, for example, which is frequently disallowed, can safely be included in the diet of many diabetic patients who desire a drink with meals, provided that certain guidelines are followed. Dietary substitutions can be made with relative ease. Although there are contraindications to its use by certain people, alcohol in moderation does not appear to compromise carbohydrate homeostasis in most individuals and, if early studies are confirmed, could possibly have some beneficial side-effects. More open discussion of alcohol use with patients is needed to give them the know-how to alter their diets and to inform them of the necessary precautions.