This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Type 1 diabetes is a very common disorder affecting 1/400 persons by the age of 18 years in the United States alone. It is responsible for a disproportionate percentage of the morbidity and mortality associated with diabetes because of its typically young age of onset and difficulty achieving good glycemic control. Although exogenous administration of insulin allows for normal growth and development in children with this condition, it is not a cure. Studies which have attempted to modify the autoimmune process which underlies the development of hyperglycemia in patients with type 1 diabetes have focused on the preservation of the innate insulin secretory capacity of the endocrine pancreas as the primary outcome variable. Interventions that might preserve residual beta-cell function and thereby improve glycemic control have the potential to have significant effects on long-term morbidity and mortality.In recent years, a number of insulin analogs have been developed which have varying time-action profiles due to varying mechanisms of absorption. In comparison to children on the moderate-acting analog NPH, we have retrospective data to suggest that children placed on the long-acting analog glargine achieve significantly better average glycemic control for at least the first nine months after diagnosis of type 1 diabetes. This contrasts to children with long-standing diabetes who are switched from NPH to glargine, who show no significant change in average glycemic control as measured by Hemoglobin A1c values. Therefore, we propose a randomized trial of insulins glargine and NPH in patients aged 6-18 years newly diagnosed with type 1 diabetes to address whether this difference is due to better preservation of the innate insulin secretory capacity of the pancreas. In order to evaluate whether there is a differnece in insulin reserve between patients treated with glargine vs NPH, we will perform mixed meal tolerance tests at study entry and again at 6 and 12 months, with C-peptide secretion as the primary outcome variable. If a difference is found, this could have significant implications for future intervention studies in patients with type 1 diabetes, as failing to control for insulin regimen could be a potential confounding variable in such studies.
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