OR48-2 Testosterone Supplementation Improves Carbohydrate and Lipid Metabolism in Some Older Obese Men

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR48-Insulin Resistance & Metabolic Syndrome: From Clinical Physiology to Clinical Care
Translational
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 9:30 AM
Room 304 (Moscone Center)
Jiaxiu He*1, Jeffrey Chukwuneke2, Hee Won Kim3, Patrick Colletti4, Thomas Allen Buchanan4, Kevin Edward Yarasheski5 and Fred R Sattler6
1University of Southern California, Los Angeles, CA, 2Rutgers University, 3University Southern California, 4University of Southern California, 5Washington Univ Med Sch, Saint Louis, MO, 6Univ of Southern CA, Granada Hills, CA
Purpose: Testosterone (T) may benefit cardiometabolics (obesity, insulin resistance [IR], lipids). We aimed to determine if topical T (10/d) given to obese (waist >100cm), older men with low AM T (<400ng/dL, LC-MSMS) and IR (HOMA-IR ≥3.0, HgbA1C ≥5.5%, or fasting insulin ≥18μU/mL) for 20 weeks reduces fat mass and whether changes in insulin sensitivity (Si) would be primarily central (liver) or peripheral (muscle).    

Methods: We measured fat and lean body mass (LBM) by DEXA; fasting FFA and lipids in a CTSA lab; central and peripheral Si using a 2-stage, hyperinsulinemic euglycemic clamp (whole body [WB] Si, HGO, Rd); liver and intramyocellular (IMCL, soleus) lipid by 1H-MR spectroscopy.

Results: 20 men (68 years old, range=62-78) weighing 105kg (85-137) lost a median of 1.4kg (-7.4 to 2.0; p=0.002) total fat, 0.9kg (-4.6 to 0.2; p=0.0007) trunk fat and 0.7kg (-3.0 to 2.3, p=0.01) extremity (ext) fat, and gained 1.4kg of total LBM (-0.8 to 7.1; p=0.0002) and 1.2kg of ext LBM (-1.1 to 4.8; p=0.0006) during T treatment (Rx). WB Si improved by 1.05 (-2.44 to 3.73; dL/min per μU/mL, p=0.04) and Rd by 1.16 (-3.08 to 3.85, p=0.03). Ds in WB Si and Rd only occurred with declines in trunk and ext fat larger than the median declines, whereby Si WB improved (+1.59, p=0.04; +1.56, p=0.06, respectively) as did Rd (+2.08, p=0.04; +2.11, p=0.05). At wk20, HGO was related to trunk fat (ρ=-0.57, p=0.009) and % total fat (ρ=-0.65, p=0.002) but not to D in fat. Liver fat/H2O declined in 14 (by 44%) of 19 persons with associated Ds in Si WB (+1.36, p=0.09) and Rd (+1.23, p=0.08). IMCL/Cr declined in 12 (by 41%) of 15 with Ds in Si WB (+0.57, p=0.06) and Rd (+0.61, p=0.04). In these subjects, baseline FFA correlated with WB Si, HGO, and Rd (ρ=-0.63, -0.58, -0.59, p≤0.02). By multi-linear regression, Ds in total fat and FFA during the clamp (wk20-wk0) accounted for 55% and 15% of D in WB Si (p≤0.03), and 74% (p<0.0001) and 8% (p=0.06) of D in Rd. Triglycerides decreased by 35mg/dL (-239 to 38; p=0.02), LDL-C by 14mg/dL (-56 to 27; p=0.02), and HDL-C by 5mg/dL (-23 to 2; p=0.004). No serious AEs occurred.

Conclusions: In older obese men with IR, T Rx significantly reduced fat mass and improved WB Si and glucose disposal if there were large reductions in regional adiposity. T improved LDL-C and triglycerides but reduced HDL-C. Physiologic factors (e.g. D in fat, FFA, tissue lipid) that predict the most favorable cardiometabolic responses to T in older men should be confirmed.

Disclosure: FRS: Study Investigator, Solvay Pharmaceuticals. Nothing to Disclose: JH, JC, HWK, PC, TAB, KEY

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: R01 AG18169 NCRR M01 RR00043