Fasting hypoglycemia is associated with disease progression in presymptomatic early stage type 1 diabetes

Objective In children with presymptomatic type 1 diabetes, intermittent hyperglycemia and rising hemoglobin A1c levels are a known signal of progression toward insulin-dependency. Episodes of hypoglycemia, however, have also been reported in one published case. We investigated the prevalence of hypoglycemia and its association with disease progression in children with presymptomatic type 1 diabetes. Methods We compared the frequency of hypoglycemic fasting blood glucose levels (<60mg/dL) in 48 autoantibody negative and 167 multiple beta-cell autoantibody positive children aged 2 to 5years. We classified the autoantibody positive children into three categories based on their glucose levels in fasting state (hypoglycemic [<60mg/dL], normoglycemic [60-99mg/dL] or hyperglycemic [100mg/dL]). We then compared the glucose levels under challenge during oral glucose tolerance tests (OGTTs) between the three categories. Results In the autoantibody positive children, 5.1% of the fasting samples were hypoglycemic, while in the autoantibody negative children no hypoglycemia was observed. Hypoglycemia occurred more often in autoantibody positive children who had already entered stage 2 or stage 3 of type 1 diabetes than in stage 1 patients (P = 0.02). Children who had hypoglycemic compared to normoglycemic fasting blood glucose values had higher 120-minute blood glucose values under OGTT challenge, and a higher rate of pathological OGTTs (P = 0.04). Conclusions Fasting hypoglycemia seems to be an indicator of disease progression in presymptomatic type 1 diabetes and may therefore represent a novel marker for the identification of children who should be monitored more closely for progression toward insulin-dependent type 1 diabetes.