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 (<60 mg/dL) in 48 autoantibody negative and 167 multiple β‐cell autoantibody positive children aged 2 to 5 years. We classified the autoantibody positive children into three categories based on their glucose levels in fasting state (hypoglycemic [<60 mg/dL], normoglycemic [60‐99 mg/dL] or hyperglycemic [≥100 mg/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.