Ten patients with insulin-dependent diabetes mellitus between the ages of 10-28 years and with diabetes less than 10 years will be randomized into two treatment groups. Patients in Group A (conventional therapy) will be managed by diet and insulin, the latter, using a combination of regular and intermediate insulins, will be delivered by intermittent subcutaneous bolus injection at least two times daily. Patients in Group B (rigid control therapy) will be managed by diet and regular insulin, the latter delivered by continuous subcutaneous insulin infusion (CSII) supplemented by intermittent pre-prandial bolus injections of insulin. Baseline studies obtained during initial regulation of the diabetic state in a clinical research unit will be identical for both groups and include a 24 hour analysis of appropriate metabolic and hormonal parameters. Followup outpatient care and monitoring of the diabetic control will be similar for patients in both groups. These will include measurements of plasma glucose, lipids, glycosylated hemoglobin levels and analysis of results of home blood glucose and urine glucose measurements. Ancillary protocols have been developed to study the morphologic and functional aspects of platelets in both groups at baseline and in progress. Bone analysis employing photon absorptiometry and renal function studies employing measurements of protein excretion after exercise and urinary kallikrein levels will be compared in all patients. Retinal studies including fluorescein angiography will be performed at baseline and annually thereafter. Nerve conduction studies will be done similarly. Analyses of these data will provide insight into the effects of therapy in the conventional and rigid control groups. In Group A, the goal will be metabolic control appropriate to the usual and customary practice of clinical diabetology in 1981. Goals of therapy of patients in Group B will be normalization of all biochemical abnormalities. The purpose of Phase II of this study will be to test the feasibility of achieving these goals.
