The prevalence of diabetes mellitus increases with age. While the mechanism by which age increases the risk of diabetes remain to be fully elucidate, the development of insulin resistance coupled with an inability to appropriately increase insulin secretion appears to play an important role. The present experiments will seek to determine whether the age associated decrease in circulating androgens contributes to the alterations in carbohydrate metabolism that are commonly observed in the elderly. To do so, the major determinants of glucose tolerance (e.g. insulin action, insulin secretion and glucose effectiveness) will be measured prior to and following one year of treatment with either gonadal (testosterone in men) or adrenal (dihydroepinadosterone in men and women) androgens in amounts designed to restore plasma levels to those typically observed in young (e.g. 20-30 years) healthy individuals. Results will be compared to those observed in a) matched elderly individuals treated with placebo for one year to control for time dependent changes; and b) gender matched young health subjects. Insulin action and glucose effectiveness will be measured using a modification of the insulin suppression test combined with the """"""""cold"""""""" and """"""""hot"""""""" minimal models. Insulin secretion will be measured following ingestion of a mixed meal from C-peptide data using a deconvolution approach. The postprandial pattern of carbohydrate metabolism will be measured using the dual isotope radio-labeled meal technique H13/C02 bicarbonate infusion and indirect calorimetry. Results will be interpreted in light of concomitant measures of body composition (percent body fat, visceral obesity, lean body mass), levels of fitness (V02 max, strength), fat metabolism (in collaboration with Dr. Jensen project 4) and protein metabolism (in collaboration with Dr. Nair in project 1). It is anticipated that the proposed studies, by defining the effects of androgen replacement on carbohydrate metabolism, will provide new insights regarding the potential benefits and risks of using these agents in the treatment of age related sarcopenia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG014383-05
Application #
6600404
Study Section
Project Start
2002-06-15
Project End
2003-05-31
Budget Start
Budget End
Support Year
5
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Espinosa De Ycaza, Ana E; Rizza, Robert A; Nair, K Sreekumaran et al. (2016) Effect of Dehydroepiandrosterone and Testosterone Supplementation on Systemic Lipolysis. J Clin Endocrinol Metab 101:1719-28
Du, S; Rajjo, T; Santosa, S et al. (2014) The thermic effect of food is reduced in older adults. Horm Metab Res 46:365-9
Dalla Man, Chiara; Piccinini, Francesca; Basu, Rita et al. (2013) Modeling hepatic insulin sensitivity during a meal: validation against the euglycemic hyperinsulinemic clamp. Am J Physiol Endocrinol Metab 304:E819-25
Manesso, Erica; Toffolo, Gianna M; Basu, Rita et al. (2011) Modeling nonsteady-state metabolism from arteriovenous data. IEEE Trans Biomed Eng 58:1253-9
Koutsari, Christina; Ali, Asem H; Nair, K Sreekumaran et al. (2009) Fatty acid metabolism in the elderly: effects of dehydroepiandrosterone and testosterone replacement in hormonally deficient men and women. J Clin Endocrinol Metab 94:3414-23
Clarke, Bart L; Khosla, Sundeep (2009) New selective estrogen and androgen receptor modulators. Curr Opin Rheumatol 21:374-9
Man, Chiara Dalla; Toffolo, Gianna; Basu, Rita et al. (2008) Use of labeled oral minimal model to measure hepatic insulin sensitivity. Am J Physiol Endocrinol Metab 295:E1152-9
Dhatariya, Ketan K; Greenlund, Laura J S; Bigelow, Maureen L et al. (2008) Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function. Mayo Clin Proc 83:1218-25
Basu, Rita; Dalla Man, Chiara; Campioni, Marco et al. (2007) Two years of treatment with dehydroepiandrosterone does not improve insulin secretion, insulin action, or postprandial glucose turnover in elderly men or women. Diabetes 56:753-66
Cobelli, Claudio; Toffolo, Gianna Maria; Dalla Man, Chiara et al. (2007) Assessment of beta-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am J Physiol Endocrinol Metab 293:E1-E15

Showing the most recent 10 out of 20 publications