This application is a response to RFA NIAMDD 80-01 which is a multicenter prospective randomized clinical trial of the effect of blood glucose control on vascular complications of insulin-dependent diabetes mellitus. The first 6 months (phase I) constitutes a period of planning wherein principal investigators and coinvestigators from the participating centers will meet regularly to develop detailed protocols for the 2 years feasibility study (phase II). Based on the guidelines in the RFA our proposal for phase II is as follows: Ten ketosisprone, insulin-dependent, C-peptide deficient diabetics, ages 10-28 years, with diabetes of 2 years' duration at each participating center will be randomly assigned to either continuation of conventional insulin therapy or to a program of intensive insulin therapy. Conventional insulin therapy will be no more complex than a split-mixed insulin program. Intensive insulin therapy may be multiple injections of short-acting insulin daily or what we intend to use, continuous subcutaneous insulin infusion by a portable insulin infusion pump. Determination of infusion rates for the pump will be done from a 24-hour period of glucose control using an artificial endocrine pancreas, BIOSTATOR. All patients will undergo assessment of glucose, lipid and amino acid metabolism and assessment of retinal status by visual acuity, fundal photographs, fluorescein angiography and quantitative vitreous flurophotometry at entry and at 6 and 12 months. Dirunal plasma glucose, amino acid, free fatty acid and ketone body concentrations will be measured at 3 and 9 months as well. Patients using the insulin pump will be instructed in home blood glucose monitoring whereas patients using conventional treatment will not. Patients on insulin pump treatment will telephone the home blood glucose monitoring results at regular intervals to the patient coordinator, who, with a coinvestigator, will assest in making changes in insulin infusion rates if necessary. Patients will bring home blood glucose reagent strips at regular visits for verification of reading by the nurse practitioner.
