Melanie Heinrich1, Nicole Maison1, Peter Achenbach1, Robin Assfalg1, Sonja Braig2, Dominik Böcker3, Desiree Dunstheimer4, Uwe Ermer5, Antonia Gavazzeni6, Eva-Maria Gerstl7, Sandra Hummel1, Kerstin Kick1, Herbert Müller8, Nicole Nellen-Hellmuth9, Christian Ockert10, Marina Sindichakis11, Stefanie Tretter12, Katharina Warncke1,13, Anette-Gabriele Ziegler1, Andreas Beyerlein1. 1. Institute of Diabetes Research, Helmholtz Zentrum München, Munich, Germany, and Forschergruppe Diabetes der Technischen Universität München, Munich, Germany. 2. Department of Pediatrics, Klinikum Bayreuth, Bayreuth, Germany. 3. Department of Pediatrics, Klinikum Nürnberg Nord, Nuremberg, Germany. 4. Department of Pediatrics, Klinikum Augsburg, Augsburg, Germany. 5. Department of Pediatrics, Kliniken St Elisabeth, Neuburg an der Donau, Germany. 6. Pediatric Practice Bogenhausen, Munich, Germany. 7. Department of Pediatric Diabetology, Pediatric Hospital Dritter Orden Passau, Passau, Germany. 8. Department of Pediatrics, Klinikum Kempten, Kempten, Germany. 9. Family Practice Dr Med Hans-Jörg Hellmuth, Würzburg, Germany. 10. Department of Pediatrics, RoMed Kliniken, Rosenheim, Germany. 11. Department of Pediatrics, Kliniken Südostbayern, Traunstein, Germany. 12. Department of Pediatrics, Kliniken Nordoberpfalz, Weiden, Germany. 13. Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Abstract
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.
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.