The Effect of Insulin Resistance on Brain Glucose Uptake-A Systematic Review and Metaanalysis

Objective: We investigated the association between peripheral insulin resistance (IR) and brain glucose uptake (BGU) and further determined if testing condition (fasting vs. hyperinsulinemic-euglycemic clamp) was a moderator of the association. Methods: A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science, studies assessing an association between measures of or clinical proxies for IR (e.g. diabetes and obesity) and BGU were included. Effect sizes were standardized and transformed into correlation coefficients and a random effect meta-analysis performed. Further, a subgroup analysis on testing condition was conducted. Results: Twenty-one studies (n = 3,620) were included in the meta-analysis. The pooled correlation (-0.13 [95% CI: -0.37; 0.12], p=0.3) showed a substantial heterogeneity (I2 = 98%). Subgroup analysis revealed that IR negatively correlated with BGU when subjects were examined at fasting conditions (-0.42 [95% CI: -0.59; -0.21], I2 = 99%) and positively correlated when subjects were examined during a hyperinsulinemic-euglycemic clamp (0.53 [ 0.38; 0.66], I2 = 47%)(figure 1). Test condition significantly moderated the association (p <0.01) and explained 55% of the heterogeneity. Conclusion: Across the studies IR results in abnormal BGU in both fasting and hyperinsulinemic states, clamp conditions reverse the low BGU in IR. Disclosure N.J.Jensen: None. A.J.Porse: None. H.Speyer: None. J.Krogh: None. M.Gejl: None. A.H.Gjedde: None. J.Rungby: Advisory Panel; Abbott, Consultant; Novo Nordisk, Speaker's Bureau; Boehringer-Ingelheim, AstraZeneca.