Evidence mapPaperPMID 42210415Full record

ArticleCardiovascular diabetology. Endocrinology reports2026

Sex-specific roles of insulin-like growth factor-1, lean mass and fat mass in type 2 diabetes prevention: Mendelian randomization studies in Western and East Asian populations.

Man Ki Kwok, Parco Ming Fai Siu, Shan Luo, Shiu Lun Au Yeung, Gabriel M Leung, Catherine Mary Schooling

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Article in Cardiovascular diabetology. Endocrinology reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Man Ki KwokSchool of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong, China. mmkkwok@hkmu.edu.hk.
Parco Ming Fai SiuSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Shan LuoSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Shiu Lun Au YeungSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Gabriel M LeungSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Catherine Mary SchoolingSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Funding

Health and Medical Research Fund 18192191
6 · The paper itself

Abstract

backgroundSex-specific effects of body composition and its drivers, including insulin-like growth factor-1 (IGF-1), on type 2 diabetes mellitus (T2DM) are understudied across ethnicity. We assessed the role of IGF-1 in T2DM and mediation by lean or fat mass, by sex in Western and East Asian populations, using Mendelian randomization (MR).

methodsGenetic predictors of exposure (IGF-1) and mediators (fat or lean mass) were applied to genetic associations with T2DM in Europeans (n = 898,130) and East Asians (n = 433,540). Univariable and multivariable MR (MVMR) were used to obtain total and direct effects of IGF-1 and fat or lean mass on T2DM. Mediation analyses were conducted to obtain indirect effects.

resultsIn the Western population, genetically predicted higher IGF-1 was positively associated with T2DM in women [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.11 to 1.32] but not men, and in both sexes with lean mass but not fat mass. Lean mass in both sexes decreased and fat mass in women increased T2DM risk. In the East Asian population, genetically predicted higher IGF-1 was positively associated with T2DM in both sexes (1.07, 95% CI 1.02 to 1.12), and with lean mass and fat mass in men. Lean and fat mass were unrelated to T2DM. The association of IGF-1 with T2DM was not mediated by lean or fat mass.

conclusionsIGF-1 may directly increase T2DM risk, independent of body composition, in Western women and East Asians. Fat mass in women and less lean mass in both sexes may also increase T2DM risk in Western populations.

Indexed as

Fat massInsulin-like growth factor-1Lean massMendelian randomizationType 2 diabetes

Identifiers

PMID42210415
PMCPMC13220589

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.