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

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, e.g., 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 thirty-one eligible. Criteria were studies assessing brain glucose metabolism (uptake or metabolic rate) by 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography ([18F]-FDG-PET) in individuals characterized by measures of or clinical proxies for insulin resistance (e.g., 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 (-0.47SD, 95%CI: -0.73 to -0.22, p<0.001, I2=71%) and increased metabolism during insulin stimulation (1.44SD, 95%CI: 0.79 to 2.09, p=0.002, I2=43%). Contrary to type 2 diabetes and other insulin resistance-related conditions, obesity was not associated with brain hypometabolism in fasting states (0.29SD, 95%CI: -0.81 to 1.39).

CONCLUSIONS: Metabolic conditions modify associations between insulin resistance and brain glucose metabolism, i.e. most individuals with insulin resistance display hypometabolism during fasting and hypermetabolism during insulin stimulation.