Long Term Objective: to determine whether early interventional therapies candelay, prevent, or reverse the development of Type 1 diabetes.
Specific Aims :intervention trials for subjects with pre-diabetes and new onset diabetesThe Diabetes Prevention Trial - Type 1 (DPT-1): to determine whether the earlyintervention use of insulin in nondiabetic relatives of persons with Type 1diabetes can delay their development of Type 1 diabetes as a clinical disease.Insulin is used for this purpose since it is a well characterized antigenspecifically produced by beta cells. Research design: the parenteral antigenprotocol enrolled subjects found to be at high risk (greater than 50 percent)for development of diabetes in the next 5 years. Subjects randomized to theinsulin-treated group received insulin intravenously for 4 days each year andtwo injections of Ultralente each day (before breakfast and before bedtime).The oral antigen protocol enrolls subjects found to be at intermediate risk(25-50 percent) for the development of Type 1 diabetes in the next 5 years.This is a double-blind study and all subjects take 1 capsule daily, with halfreceiving the antigen and the others receiving a placebo. Levels of antibodies,insulin, C-peptide, HbA1C and glucose are followed. The main study endpoint istwo ?diabetic? oral glucose tolerance tests (OGTT) performed on different days.Immunotherapy Trial in New Onset Type 1 Diabetes: to test the hypothesis thatmycophenolate mofetil (MMF alone or with daclizumab (DZB) will prolong theperiod of C-peptide production in subjects with new onset Type 1 diabetes. Asecondary aim is to provide the clinical material for the validation ofsurrogate markers for immunity to islet beta-cells. This study is innovative inthat these agents have not been previously evaluated but are rational choicesfor intervention in an autoimmune disorder.Research design: Levels of autoantibodies and T cell reactivity to isletautoantigens, both of which are surrogate immunological parameters specific forType 1 diabetes will be followed. Measures of immune modulation will includeserologic and T cell reactivity to recall antigens. The metabolic end-points ofthis study will be fasting and stimulated C-peptide, hemoglobin A1C, and totalinsulin dose. If this study has a positive outcome, then we would propose asimilar study in people at high risk for developing Type 1 diabetes.
| Writing Committee for the Type 1 Diabetes TrialNet Oral Insulin Study Group; Krischer, Jeffrey P; Schatz, Desmond A et al. (2017) Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA 318:1891-1902 |
| Ismail, Heba M; White, Kama S; Krischer, Jeffrey P et al. (2015) First test effect in intravenous glucose tolerance testing. Pediatr Diabetes 16:129-37 |
