Glial acetate metabolism is increased following a 72-h fast in metabolically healthy men and correlates with susceptibility to hypoglycemia

AIMS: Prior exposure to insulin-induced hypoglycemia was shown to increase glial acetate metabolism (GAM) during subsequent exposure to hypoglycemia in diabetic individuals. However, it remained unclear whether this effect was dependent on the disease state or the antecedent cause of hypoglycemia. We aimed to establish whether exposure to fasting-induced hypoglycemia was sufficient to produce alterations in GAM in non-diabetic individuals. METHODS: GAM was measured via carbon-13 magnetic resonance spectroscopy during infusion of [1-(13)C] acetate before and after a 72-h fast in six metabolically healthy men. All participants were male, aged 18–40 years, with a Body Mass Index of 20.0–27.9 kg/m(2), who consented to reside at Pennington Biomedical Research Center for 4 days. The main outcome measure was the percent enhancement of cerebral [1-(13)C] bicarbonate (the primary metabolic byproduct of glial oxidation of [1-(13)C] acetate). Continuous glucose monitoring was used to measure hypoglycemic episodes during the 72-h fast. RESULTS: As expected, 72 h of fasting significantly reduced blood glucose levels and resulted in a high frequency of hypoglycemic episodes. Steady-state GAM increased from 53.5 ± 3.7 to 61.9 ± 1.7% following the 72-h fast (p = 0.005). This increase correlated with greater duration of hypoglycemia experienced during the fast (r = 0.967). In addition, subjects with greater GAM at baseline experienced a greater increase in the duration of hypoglycemia experienced during the 72-h fast (r = 0.979). CONCLUSIONS: GAM has potential as a biomarker for susceptibility to hypoglycemic episodes. TRAIL REGISTRATION: Clinicaltrials.gov ID: NCT02690168. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00592-018-1180-5) contains supplementary material, which is available to authorized users.