title: Testosterone, Dihydrotestosterone, Sex Hormone-Binding Globulin, and Incident Diabetes Among Older Men: The Cardiovascular Health Study.
abstract: Although sex hormone-binding globulin (SHBG) and testosterone (T) have been inversely associated with risk of diabetes, few studies have examined dihydrotestosterone (DHT), a more potent androgen than T, in older adults, whose glycemic pathophysiology differs from younger adults.
  
  
  
  To determine the associations of SHBG, T, and DHT with insulin resistance and incident diabetes in older adult men.
  
  
  
  In a prospective cohort study, we evaluated baseline levels of SHBG, T, and DHT using liquid chromatography-tandem mass spectrometry among 852 men free of diabetes and cardiovascular disease in the Cardiovascular Health Study in 1994.
  
  
  
  Insulin resistance estimated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and insulin sensitivity estimated by the Gutt index in 1996, and incident diabetes (n = 112) ascertained over a mean follow-up of 9.8 years.
  
  
  
  In linear regression models adjusted for demographics, alcohol consumption, current smoking, body mass index, and other androgens, SHBG [HOMA-IR 0.30 units lower per doubling; 95% confidence interval (CI), 0.08 to 0.52; P = 0.01] and total DHT (HOMA-IR 0.18 units lower per doubling; 95% CI, 0.06 to 0.30; P = 0.01), but not free T (P = 0.33), were inversely associated with insulin resistance. In corresponding Cox proportional hazards models, total DHT was again inversely associated with risk of diabetes (adjusted hazard ratio per doubling, 0.69; 95% CI, 0.52 to 0.92; P = 0.01), but SHBG (hazard ratio, 1.09; 95% CI, 0.74 to 1.59; P = 0.66) and free T (hazard ratio, 1.15; 95% CI, 0.92 to 1.43; P = 0.23) were not.
  
  
  
  Among older men, higher levels of DHT were inversely associated with insulin resistance and risk of diabetes over the ensuing 10 years, whereas levels of T were not. Future studies are still needed to clarify the role of SHBG in risk of diabetes in this population.
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Joyce
authors.affiliation: Departments of Biostatistics.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Biggs
authors.affiliation: Division on Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Luc
authors.initials: L
authors.lastname: Djoussé
authors.affiliation: Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California 92093.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Departments of Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Kizer
authors.affiliation: New York Academy of Medicine, New York, New York 10029; and.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Psychiatry and Behavioral Sciences, and.|VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Shores
authors.affiliation: Medicine, University of Washington, Seattle, Washington 98115.|Geriatric Research, Education and Clinical Center.|VA Puget Sound Health Care System, Seattle, Washington 98108.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Matsumoto
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology*; D013196:Dihydrotestosterone / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis*; D013739:Testosterone / Q000097:blood*
chemical_list: D015415:Biomarkers; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone