Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men

Nelly Pitteloud, Vamsi K. Mootha, Andrew A. Dwyer, Megan Hardin, Hang Lee, Karl Fredrik Eriksson, Devjit Tripathy, Maria Yialamas, Leif Groop, Dariush Elahi, Frances J. Hayes

Research output: Contribution to journalArticlepeer-review

345 Scopus citations


OBJECTIVE - The goal of this study was to examine the relationship between serum testosterone levels and insulin sensitivity and mitochondrial function in men. RESEARCH DESIGN AND METHODS - A total of 60 men (mean age 60.5 ± 1.2 years) had a detailed hormonal and metabolic evaluation. Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp. Mitochondrial function was assessed by measuring maximal aerobic capacity (Vo2max) and expression of oxidative phosphorylation genes in skeletal muscle. RESULTS - A total of 45% of subjects had normal glucose tolerance, 20% had impaired glucose tolerance, and 35% had type 2 diabetes. Testosterone levels were positively correlated with insulin sensitivity (r = 0.4, P < 0.005). Subjects with hypogonadal testosterone levels (n = 10) had a BMI > 25 kg/m2 and a threefold higher prevalence of the metabolic syndrome than their eugonadal counterparts (n = 50); this relationship held true after adjusting for age and sex hormone-binding globulin but not BMI. Testosterone levels also correlated with Vo2max (r = 0.43, P < 0.05) and oxidative phosphorylation gene expression (r = 0.57, P < 0.0001). CONCLUSIONS - These data indicate that low serum testosterone levels are associated with an adverse metabolic profile and suggest a novel unifying mechanism for the previously independent observations that low testosterone levels and impaired mitochondrial function promote insulin resistance in men.

Original languageEnglish (US)
Pages (from-to)1636-1642
Number of pages7
JournalDiabetes care
Issue number7
StatePublished - Jul 2005
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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