Regional brain glucose uptake following gastric bypass surgery during normo- and hypoglycemic clamp: a pilot FDG-PET study.

Purpose: We aimed to characterize the RYGB-induced changes in the dynamics of brain glucose uptake. We addressed heterogeneity between brain regions during experimental normo- and hypoglycemia and explored associations with anthropometric and metabolic outcomes of RYGB.

Methods: Analyses of regional brain glucose uptake were performed on 9 individuals with obesity and no diabetes, investigated with combined brain ¹⁸F-FDG-PET and fMRI during hyperinsulinemic normo- and hypoglycemic clamp, one month before and four months after RYGB. FDG clearance, reflecting glucose uptake rate, was assessed in 38 brain regions, covering all cortical areas and subcortical nuclei, during hyperinsulinemic normo- and hypoglycemia. Correlation analyses were performed to identify associations with other outcomes of RYGB.

Results: FDG uptake rate during hypoglycemia was higher than during normoglycemia in all brain regions, both before and after RYGB. Moreover, in most regions and especially in cortical areas involved in inhibitory behavioral control, FDG uptake rate tended to be reduced after surgery during normoglycemia but elevated during hypoglycemia. However, these post-surgical changes in FDG uptake rate were opposite in the hypothalamus. Thus, the hypo-to-normoglycemia FDG clearance ratio tended to increase in all brain regions following RYGB, but not in the amygdala and the hypothalamus. Changes in regional FDG uptake rate after RYGB during normoglycemia were associated with weight loss and improved systemic insulin sensitivity.

Conclusion: Using dynamic FDG-PET, we show region-specific patterns of changes in glucose utilization following RYGB. In the hypothalamus, glucose uptake during normoglycemia tended to rise after RYGB while it was reduced in cortical regions involved in behavioral control. Following RYGB, the hypothalamus and amygdala, in contrast to other regions, displayed trends of reduced glucose uptake during hypoglycemia. These pilot results highlight the brain effects of RYGB and suggest behavioral and neuroendocrine adaptations which contribute to its antidiabetic effects.