1817-P: Metabolic Surgery Affects Brain Glucose Metabolism, Cognitive Function, and Neuroplasticity in Humans

Abstract

Risk of neurodegenerative disorders, cognitive dysfunction and impaired neuroplasticity (NP) is increased in obesity. We evaluated the effect of metabolic surgery (RYGB) on insulin sensitivity, brain glucose utilization, cognitive function and NP. Thirteen obese subjects (BMI 46±4.9 kg/m2; HbA1c 40.1±5.9 mmol/mol; age 42.4±9.8 years) with no history of psychiatric illness and psychoactive drug use and major brain disorders were recruited. Subjects underwent a 75 gr OGTT during a 60 min FDG dynamic brain PET study, standardized neurocognitive tests and NP by psychophysical technique at baseline and 6-months after RYGB. Plasma glucose, insulin, GLP-1, GIP, VIP, BDNF and leptin were measured during OGTT. After RYGB, BMI declined (45.7±1.6 to 34.3±1.6 kg/m2; p<0.001) and insulin sensitivity improved (HOMA-IR 4.7±0.9 to 1.6±0.4; P=0.006). Cerebral glucose metabolic rate (CMRg; by voxel-wise paired analysis) declined in several brain regions (p=0.005, kE>50). Token and Trail Making Test score change correlated with CMRg change in orbitofrontal (r=0.6, r=-0.81), parietal (r=0.64, r=-0.77), temporal (r=0.6, r=-0.78) and visual cortex (r=0.64, r=-0.75), hippocampus (r=0.6, r=-0.71) and caudate/putamen (r=0.64, r=-0.80; all p=0.03 or less), respectively. After RYGB, NP increased (0.01± 0.03 to 0.11±0.04; p=0.008) and correlated with CMRg change in orbitofrontal cortex (r=0.59; p=0.03) and hippocampus (r=0.58; p=0.03). CMRg of several cortical and subcortical areas correlated with HOMA-IR (p<0.001) but not with BMI. GLP-1/GIP levels increased (P<0.002) with no correlation with CMRg, VIP or BDNF levels. Fasting leptin decreased (73.8±45.5 to 14.3±5.9 pmol/l; p<0.008) and correlated with CMRg change in hippocampus (r=0.6; r=0.03). These results show that metabolic surgery modulates CMRg in brain areas involved in cognitive function and neuroplasticity, suggesting reduction of brain glucose utilization decrease may contribute to brain neuroprotection. Disclosure G. Daniele: None. A. Dardano: None. D. Volterrani: None. A. Ciccarone: None. L. Giusti: None. G. Aghakhanyan: None. G. Ceccarini: None. F. Santini: None. C. Moretto: None. P. Binda: None. C. Lunghi: None. M. Morrone: None. S. Del Prato: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, GlaxoSmithKline plc., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Board Member; Self; AstraZeneca. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited.

Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort

“…Even though the relevance of our findings under clamp conditions may be criticized because of their experimental nature, systemic insulin levels achieved during euglycemic hyperinsulinemic clamps were those typically seen in the postprandial state. Information about brain glucose metabolism in more physiologic conditions is scanty, but Daniele et al ( 32 ) found that after bariatric surgery, BGU during the oral glucose tolerance test decreased, a finding which is solidly in line with our current findings.…”