Dysregulation of glucose metabolism in preclinical type 1 diabetes.

Long-term prospective studies have provided valuable information about preclinical type 1 diabetes (T1D). Children who have seroconverted to positive for islet autoantibodies have also, in follow-up, had metabolic tests to understand the timing and development of abnormal glucose tolerance and declining insulin secretion before the clinical diagnosis of T1D. First phase insulin response (FPIR) in the intravenous glucose tolerance test (IVGTT) is lower in the progressors positive for multiple islet autoantibodies in all age groups and as early as 4-6 years before the diagnosis when compared with the non-progressors positive for only islet cell antibodies (ICA). An accelerated decline in FPIR is seen in the progressors during the last 1.5 years before the diagnosis. These results indicate that the progressors may have an early intrinsic defect in beta cell development or function. In the oral glucose tolerance test (OGTT) the peak C-peptide response is delayed in the progressors at least 2 years before diagnosis. Glucose levels and HbA1c are increasing about 2 years before clinical diagnosis. An increase in HbA1c and detection of abnormal glucose tolerance in OGTT are useful in the prediction of the timing of clinical onset of T1D. Continuous glucose monitoring (CGM) may be useful in the prediction of T1D as an early indicator of increased glycemic variability but more data from larger series are needed for confirmation. Children followed in the prospective studies are diagnosed earlier and have a decreased frequency of ketoacidosis at the diagnosis of T1D when compared with age-matched cases from the population.