Hypothalamic Glucose Concentrations Are Higher in Subjects with Type 1 Diabetes (T1D) and Impaired Awareness of Glycemia (IAH) than in T1D without IAH

Abstract

IAH occurs commonly in patients with T1D but its pathogenesis remains uncertain. Previous investigation has suggested that recurrent hypoglycemia leads to an upregulation of brain glucose transport thereby assuring that the brain will have better fuel delivery during subsequent episodes of hypoglycemia. If so, subjects with T1D and IAH should have higher hypothalamic brain glucose concentrations than subjects with T1D without IHA when studied at the same level of glycemia. Here we used 1H-magnetic resonance spectroscopy at 7 T to measure (Glucose+Taurine)/ total Creatine in a 13x12x10 mm3 hypothalamic voxel in such patient groups while they were maintained at euglycemia and then hypoglycemia using a glucose clamp. Since taurine and creatine do not change with glycemia, this is a valid measure of brain glucose concentrations. IAH was defined using the Clarke questionnaire with subjects found indeterminate further classified using the Gold questionnaire. We found that hypothalamic (Glucose+Taurine)/ total Creatine was significantly higher in T1D with IAH at both euglycemia and hypoglycemia when compared to T1D without IAH. These data support the hypothesis that a change in glucose transport may contribute to the pathogenesis of IAH. T1D with IAH (n=9)T1D without IAH (n=9)Age (years)47.6 ± 1729.2 ± 8Hemoglobin A1c (%)7.3 ± 0.97.3 ± 0.7Glycemia at euglycemia (mg/dl)98 ± 495 ± 7Glycemia during hypoglycemia (mg/dl)48 ± 348 ± 5Epinephrine during hypoglycemia (pg/ml)250 ± 155711±442*Symptom score during hypoglycemia8 ± 936 ± 14**Hypothalamic glucose at euglycemia (Glucose+Taurine)/ total Creatine (mM)0.43 ± 0.110.27 ± 0.08**Hypothalamic glucose at hypoglycemia (Glucose+Taurine)/ total Creatine (mM)0.23 ± 0.040.15 ± 0.02***p=0.03, **p < 0.001. Disclosure A. Moheet: None. D. Deelchand: None. A. Kumar: None. G. Oz: Research Support; Self; Takeda Pharmaceuticals U.S.A., Inc. E.R. Seaquist: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company, Sanofi, Zucera, InfoMed, 360 consulting. Other Relationship; Self; Novo Nordisk Inc..