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

Nicole J. Jensen; Ane J. Porse; Helena Z. Wodschow; Helene Speyer; Jesper Krogh; Lisbeth Marner; Michael Gejl; Albert Gjedde; Jørgen Rungby

doi:10.1210/clinem/dgae570

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

Nicole J. Jensen^*, Ane J. Porse, Helena Z. Wodschow, Helene Speyer, Jesper Krogh, Lisbeth Marner, Michael Gejl, Albert Gjedde, Jørgen Rungby

^*Corresponding author for this work

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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.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	110
Issue	2
Pages (from-to)	e525-e537
ISSN	0021-972X
DOIs	https://doi.org/10.1210/clinem/dgae570
Publication status	Published - 1 Feb 2025

Keywords

brain glucose metabolism
brain glucose uptake
insulin resistance
obesity
type 2 diabetes

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10.1210/clinem/dgae570

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title = "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.",

keywords = "brain glucose metabolism, brain glucose uptake, insulin resistance, obesity, type 2 diabetes",

author = "Jensen, {Nicole J.} and Porse, {Ane J.} and Wodschow, {Helena Z.} and Helene Speyer and Jesper Krogh and Lisbeth Marner and Michael Gejl and Albert Gjedde and J{\o}rgen Rungby",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.",

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Relation of Insulin Resistance to Brain Glucose Metabolism in Fasting and Hyperinsulinemic States: A Systematic Review and Meta-analysis. / Jensen, Nicole J.; Porse, Ane J.; Wodschow, Helena Z. et al.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 110, No. 2, 01.02.2025, p. e525-e537.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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T1 - Relation of Insulin Resistance to Brain Glucose Metabolism in Fasting and Hyperinsulinemic States

T2 - A Systematic Review and Meta-analysis

AU - Jensen, Nicole J.

AU - Porse, Ane J.

AU - Wodschow, Helena Z.

AU - Speyer, Helene

AU - Krogh, Jesper

AU - Marner, Lisbeth

AU - Gejl, Michael

AU - Gjedde, Albert

AU - Rungby, Jørgen

N1 - Publisher Copyright: © The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.

PY - 2025/2/1

Y1 - 2025/2/1

N2 - 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.

AB - 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.

KW - brain glucose metabolism

KW - brain glucose uptake

KW - insulin resistance

KW - obesity

KW - type 2 diabetes

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DO - 10.1210/clinem/dgae570

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SN - 0021-972X

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JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

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ER -

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

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