Adiposity-Independent Effects of Aging on Insulin Sensitivity and Clearance in Mice and Humans

UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes

Publication Date


Document Type



Cellular and Molecular Physiology | Endocrinology | Hormones, Hormone Substitutes, and Hormone Antagonists | Lipids | Nutritional and Metabolic Diseases


OBJECTIVE: Aging is associated with impaired insulin sensitivity and increased prevalence of type 2 diabetes. However, it remains unclear whether aging-associated insulin resistance is due to increased adiposity or other age-related factors. To address this question, the impact of aging on insulin sensitivity was investigated independently of changes in body composition.

METHODS: Cohorts of mice aged 4 to 8 months ("young") and 18 to 27 months ("aged") exhibiting similar body composition were characterized for glucose metabolism on chow and high-fat diets. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analyses. The relationship between aging and insulin resistance in humans was investigated in 1,250 nondiabetic Mexican Americans who underwent hyperinsulinemic-euglycemic clamps.

RESULTS: In mice with similar body composition, age had no detrimental effect on plasma glucose and insulin levels. While aging did not diminish glucose tolerance, hyperinsulinemic-euglycemic clamps demonstrated impaired insulin sensitivity and reduced insulin clearance in aged mice on chow and high-fat diets. Consistent with results in the mouse, age remained an independent determinant of insulin resistance after adjustment for body composition in Mexican American males.

CONCLUSIONS: This study demonstrates that in addition to altered body composition, adiposity-independent mechanisms also contribute to aging-associated insulin resistance in mice and humans.

DOI of Published Version



Obesity (Silver Spring). 2019 Mar;27(3):434-443. doi: 10.1002/oby.22418. Link to article on publisher's site

Journal/Book/Conference Title

Obesity (Silver Spring, Md.)

Related Resources

Link to Article in PubMed

PubMed ID