Daniele Massera1, Mary L Biggs2, Marcella D Walker3, Kenneth J Mukamal4, Joachim H Ix5, Luc Djousse6, Rodrigo J Valderrábano7, David S Siscovick8, Russell P Tracy9, Xiaonan Xue1, Jorge R Kizer10. 1. Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY. 2. University of Washington, Seattle, WA. 3. Columbia University Vagelos College of Physicians and Surgeons, New York, NY. 4. Beth Israel Deaconess Medical Center, Boston, MA. 5. University of California San Diego, San Diego, CA. 6. Brigham and Women's Hospital, Boston, MA. 7. University of Miami, Miami, FL. 8. The New York Academy of Medicine, New York, NY. 9. University of Vermont, Burlington, VT. 10. Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY jorge.kizer@einstein.yu.edu.
Abstract
OBJECTIVE: To investigate the relationship of osteocalcin (OC), a marker of bone formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a marker of bone resorption, with incident diabetes in older women. RESEARCH DESIGN AND METHODS: The analysis included 1,455 female participants from the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0] years). The cross-sectional association of serum total OC and CTX levels with insulin resistance (HOMA-IR) was examined using multiple linear regression. The longitudinal association of both markers with incident diabetes, defined by follow-up glucose measurements, medications, and ICD-9 codes, was examined using multivariable Cox proportional hazards models. RESULTS: OC and CTX were strongly correlated (r = 0.80). In cross-sectional analyses, significant or near-significant inverse associations with HOMA-IR were observed for continuous levels of OC (β = -0.12 per SD increment; P = 0.004) and CTX (β = -0.08 per SD; P = 0.051) after full adjustment for demographic, lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196 cases of incident diabetes occurred. After full adjustment, both biomarkers exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per SD [95% CI 0.71-1.02; P = 0.075]; CTX: 0.82 per SD [0.69-0.98; P = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. CONCLUSIONS: In late postmenopausal women, lower OC and CTX levels were associated with similarly increased risks of insulin resistance at baseline and incident diabetes over long-term follow-up. Further research to delineate the mechanisms linking abnormal bone homeostasis and energy metabolism could uncover new approaches for the prevention of these age-related disorders.
OBJECTIVE: To investigate the relationship of osteocalcin (OC), a marker of bone formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a marker of bone resorption, with incident diabetes in older women. RESEARCH DESIGN AND METHODS: The analysis included 1,455 female participants from the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0] years). The cross-sectional association of serum total OC and CTX levels with insulin resistance (HOMA-IR) was examined using multiple linear regression. The longitudinal association of both markers with incident diabetes, defined by follow-up glucose measurements, medications, and ICD-9 codes, was examined using multivariable Cox proportional hazards models. RESULTS: OC and CTX were strongly correlated (r = 0.80). In cross-sectional analyses, significant or near-significant inverse associations with HOMA-IR were observed for continuous levels of OC (β = -0.12 per SD increment; P = 0.004) and CTX (β = -0.08 per SD; P = 0.051) after full adjustment for demographic, lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196 cases of incident diabetes occurred. After full adjustment, both biomarkers exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per SD [95% CI 0.71-1.02; P = 0.075]; CTX: 0.82 per SD [0.69-0.98; P = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. CONCLUSIONS: In late postmenopausal women, lower OC and CTX levels were associated with similarly increased risks of insulin resistance at baseline and incident diabetes over long-term follow-up. Further research to delineate the mechanisms linking abnormal bone homeostasis and energy metabolism could uncover new approaches for the prevention of these age-related disorders.
Authors: Russel Burge; Bess Dawson-Hughes; Daniel H Solomon; John B Wong; Alison King; Anna Tosteson Journal: J Bone Miner Res Date: 2007-03 Impact factor: 6.741
Authors: Lesley A Inker; Christopher H Schmid; Hocine Tighiouart; John H Eckfeldt; Harold I Feldman; Tom Greene; John W Kusek; Jane Manzi; Frederick Van Lente; Yaping Lucy Zhang; Josef Coresh; Andrew S Levey Journal: N Engl J Med Date: 2012-07-05 Impact factor: 91.245
Authors: Ann V Schwartz; Anne L Schafer; Andrew Grey; Eric Vittinghoff; Lisa Palermo; Li-Yung L Lui; Robert B Wallace; Steven R Cummings; Dennis M Black; Douglas C Bauer; Ian R Reid Journal: J Bone Miner Res Date: 2013-06 Impact factor: 6.741
Authors: Maria G Karas; Laura M Yee; Mary L Biggs; Luc Djoussé; Kenneth J Mukamal; Joachim H Ix; Susan J Zieman; David S Siscovick; John S Gottdiener; Michael A Rosenberg; Richard A Kronmal; Susan R Heckbert; Jorge R Kizer Journal: Am J Epidemiol Date: 2016-05-05 Impact factor: 4.897