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Natural History of ß-Cell Function in Type 1 Diabetes

From the Naomi Berrie Diabetes Center and the Departments of Pediatrics and Medicine, College of Physicians and Surgeons, Columbia University, New York, New York

Despite extensive and ongoing investigations of the immune mechanisms of autoimmune diabetes in humans and animal models, there is much less information about the natural history of insulin secretion before and after the clinical presentation of type 1 diabetes and the factors that may affect its course. Studies of insulin production previously published and from the Diabetes Prevention Trial (DPT)-1 suggest that there is progressive impairment in insulin secretory responses but the reserve in response to physiological stimuli may be significant at the time of diagnosis, although maximal responses are more significantly impaired. Other factors, including insulin resistance, may play a role in the timing of clinical presentation along this continuum. The factors that predict the occurrence and rapidity of decline in ß-cell function are still largely unknown, but most studies have identified islet cell autoantibodies as predictors of future decline and age as a determinant of residual insulin production at diagnosis. Historical as well as recent clinical experience has emphasized the importance of residual insulin production for glycemic control and prevention of end-organ complications. Understanding the modifiers and predictors of ß-cell function would allow targeting immunological approaches to those individuals most likely to benefit from therapy.

Key Words: DCCT, Diabetes Control and Complications Trial • DPT, Diabetes Prevention Trial • FPIR, first-phase insulin response • ICA, islet cell antibody • ISR, insulin secretory rate • IVGTT, intravenous glucose tolerance test • MMTT, mixed-meal tolerance test

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