Effects of Two Years of Testosterone Replacement on Insulin Secretion, Insulin Action, Glucose Effectiveness, Hepatic Insulin Clearance and Postprandial Glucose Turnover in Elderly Men

  1. Rita Basu, MD1,
  2. Chiara Dalla Man, PhD3,
  3. Marco Campioni, PhD3,
  4. Ananda Basu, MD1,
  5. K. Sreekumaran Nair, MD, PhD1,
  6. Michael D. Jensen, MD1,
  7. Sundeep Khosla, MD1,
  8. George Klee, MD, PhD2,
  9. Gianna Toffolo, PhD3,
  10. Claudio Cobelli, PhD3 and
  11. Robert A Rizza, MD (rizza.robert{at}mayo.edu)1
  1. Division of Endocrinology, Diabetes, Metabolism & Nutrition,1
  2. Laboratory Medicine & Pathology,2
  3. Mayo Clinic College Of Medicine, Rochester, MN; University of Padova, Padova, Italy.3

    Abstract

    Objective: To determine if, and if so the mechanism by which, testosterone replacement improves carbohydrate tolerance.

    Research Design and Methods: Fifty-five elderly men with relative testosterone deficiency ingested a labeled mixed meal and underwent a frequently sampled labeled IVGTT before and after treatment with either placebo or testosterone patch (5 mg/day) for two years.

    Results: Despite restoring bioavailable testosterone to values observed in young men, the change (24 month minus baseline values) in fasting and postprandial glucose, insulin, C-peptide concentrations, meal appearance, glucose disposal and endogenous glucose production were virtually identical to those observed after two years of placebo. The change over time in insulin and C-peptide concentrations post intravenous glucose injection also did not differ. Furthermore, the change over time in insulin action and glucose effectiveness (measured with the unlabeled and labeled “oral” and “intravenous” minimal models), as well as insulin secretion and hepatic insulin clearance (measured with the C-peptide model) did not differ in the testosterone and placebo groups.

    Conclusions: We conclude that two years of treatment of elderly men with testosterone does not improve carbohydrate tolerance nor does it alter insulin secretion, insulin action, glucose effectiveness, hepatic insulin clearance or the pattern of postprandial glucose metabolism. Thus testosterone deficiency is unlikely to be the cause of the age associated deterioration in glucose tolerance commonly observed in elderly men.

    Footnotes

      • Received February 20, 2007.
      • Accepted May 3, 2007.