Relation of Insulin Resistance to Brain Glucose Metabolism in Fasting and Hyperinsulinemic States

Nicole J Jensen, Ane J Porse, Helena Z Wodschow, Helene Speyer, Jesper Krogh, Lisbeth Marner, Michael Gejl, Albert Gjedde, Jørgen Rungby
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 2, February 2025, Pages e525–e537
https://doi.org/10.1210/clinem/dgae570

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, 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 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.

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