Sex Differences in the Effects of Diet on Metabolic Health: Role of Vegetable Protein and Alcohol Intake

Background: /Objective: Aging is associated with a decline in metabolic health, including impaired glucose regulation. Both diet and biological sex impact metabolic health, yet sexual heterogeneity in diet response is understudied. We report on sex-specific associations between diet and insulin sensitivity, insulin resistance, and android and intermuscular fat composition in older adults. Methods: This secondary analysis uses baseline data from a previously completed clinical trial (n=96), MASTERS study. An oral glucose tolerance test (OGTT) was used to calculate insulin resistance and insulin sensitivity as measures of metabolic function, while dual-energy x-ray absorptiometry and computed tomography were used to assess body composition. Univariate analyses were used to identify sex-specific associations between metabolic health and single nutrients and other dietary components. Multiple regression modeling was employed to identify dietary patterns that best predicted metabolic health. Results: In men, greater intake of vegetable protein (p<0.0001) and whole grains (p=0.001) were associated with higher insulin sensitivity, while refined grains (p=0.003) and conjugated linoleic acids (p<0.001) were negatively associated. In women, insulin sensitivity was positively associated with alcohol (p<0.001) and xylitol (p=0.007). In multiple regression models, diets rich in whole grains, nuts, and seeds predicted higher insulin sensitivity in men, while alcohol remained the strongest predictor in women. Conclusions: Men showed better metabolic health with plant-based diets, while alcohol intake was the strongest dietary factor linked to insulin sensitivity in women. These findings support the need for sex-specific clinical trials and dietary guidance for aging populations.