This application is in response to RFA NIAMDD 81-01 for participation as a clinical center in a Collaborative Clinical Trial on the relationship between blood glucose control and vascular complications of insulin dependent diabetes mellitus. A research plan is presented for a feasibility study to determine whether random assignment to strict control treatment regimens can result in clinically and statistically meaningful improvements in metabolic control as compared to a group randomly assigned to """"""""standard therapy"""""""" drawn from the same patient pool. The strict control regimens (Intensive Therapy) proposed are multiple-premeal insulin injection, and open-loop infusion pumps, each in association with appropriate home blood glucose monitoring, dietary, exercise, and activity guidelines and training. The importance of age stratification is discussed. Groups will be compared metabolically by assessing changes and differences in HgbA1C, fuel oxidation by indirect calorimetry, glucose response to standard meal, and 24 hour glucose profile. Adherence to protocol will be monitored, as well as patient safety including psychosocial impact of therapy. An additional randomization within the strict control (Intensive Therapy) groups is proposed to assess the value of the artificial endocrine pancreas (Biostator R) in implementing these regimens. Ophthalmologic and other endpoints for future phases of the study are discussed as well as presenting information on the willingness and capability of the Joslin Diabetes Center to participate in all four phases of the proposed study.
