Relation of Insulin Resistance to Brain Glucose Metabolism in Fasting and Hyperinsulinemic States: A Systematic Review and Meta-analysis

Abstract

Context: Abnormal brain glucose metabolism may cause cognitive disease in type 2 diabetes, yet the relation between insulin resistance and brain glucose metabolism has not been systematically described. Objective: We evaluated the impact of metabolic condition (fasting vs insulin stimulation, eg, from hyperinsulinemic clamp) on the association between insulin resistance of different etiologies and brain glucose metabolism. Data Sources: PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception until February 2022. Study Selection. Of 656 unique records, we deemed 31 eligible. Criteria were studies assessing brain glucose metabolism (uptake or metabolic rate) by 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography in individuals characterized by measures of or clinical proxies for insulin resistance (eg, type 2 diabetes and obesity). Data Extraction: Two independent investigators extracted data and assessed study quality. Data Synthesis: We applied random-effects models to pool Hedge's g standardized mean differences. Insulin resistance was associated with decreased brain glucose metabolism during fasting [−0.47 SD, 95% confidence interval (CI): −0.73 to −0.22, P < .001, I2 = 71%] and increased metabolism during insulin stimulation (1.44 SD, 95% CI 0.79 to 2.09, P = .002, I2 = 43%). Contrary to type 2 diabetes and other insulin resistance-related conditions, obesity was not associated with brain hypometabolism in fasting states (0.29 SD, 95% CI −.81 to 1.39). Conclusion: Metabolic conditions modify associations between insulin resistance and brain glucose metabolism; ie, most individuals with insulin resistance display hypometabolism during fasting and hypermetabolism during insulin stimulation.