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Updated: Oct 20, 2025

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
Published on: February 17, 2023
Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function
Kira Zhi Hua Lai1, Zhila Semnani-Azad1, Ravi Retnakaran2
1Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Canada.
Background And Aims:
To examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function.
Methods And Results:
Adults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (β = 11.0, 95%CI 5.43-17.0), ISI (β = 10.4, 95%CI 4.35-16.8), IGI/HOMA-IR (β = 7.12, 95%CI 0.98-13.6) and ISSI-2 (β = 4.38, 95%CI 1.05-7.80), all p < 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77-1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p < 0.01).
Conclusion:
In a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.
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