18 F-fluorodeoxyglucose uptake in brown adipose tissue during insulin-induced hypoglycemia and mild cold exposure in non-diabetic adults

Abstract

ObjectiveHypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue 18F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography. MethodsIn nine healthy adults 18F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17°C) during euglycemia (blood glucose 4.5mmol/L) and hypoglycemia (2.5mmol/L) using a hyperinsulinemic glucose clamp. ResultsBrown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of 18F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0–7.7) versus 3.1 (2.2–12.5) g/mL (p=0.7). Similarly there were no differences in mean standardized 18F-fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6°C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of 18F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones. ConclusionsThis study shows that there is a similar amount of 18F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase.