Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study
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. The analysis included 1,455 female participants from the population-based Cardiovascu...
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| Published in | Diabetes care Vol. 41; no. 9; pp. 1901 - 1908 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Diabetes Association
01.09.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0149-5992 1935-5548 1935-5548 |
| DOI | 10.2337/dc18-0849 |
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| Abstract | 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.
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.
OC and CTX were strongly correlated (
= 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;
= 0.004) and CTX (β = -0.08 per SD;
= 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;
= 0.075]; CTX: 0.82 per SD [0.69-0.98;
= 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance.
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. |
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| AbstractList | 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. 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. 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. OC and CTX were strongly correlated ( = 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; = 0.004) and CTX (β = -0.08 per SD; = 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; = 0.075]; CTX: 0.82 per SD [0.69-0.98; = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. 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. 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.OBJECTIVETo 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.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.RESEARCH DESIGN AND METHODSThe 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.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.RESULTSOC 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.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.CONCLUSIONSIn 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. |
| Author | Biggs, Mary L. Djousse, Luc Siscovick, David S. Xue, Xiaonan Walker, Marcella D. Valderrábano, Rodrigo J. Kizer, Jorge R. Mukamal, Kenneth J. Massera, Daniele Tracy, Russell P. Ix, Joachim H. |
| Author_xml | – sequence: 1 givenname: Daniele orcidid: 0000-0002-9499-6456 surname: Massera fullname: Massera, Daniele organization: Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY – sequence: 2 givenname: Mary L. surname: Biggs fullname: Biggs, Mary L. organization: University of Washington, Seattle, WA – sequence: 3 givenname: Marcella D. surname: Walker fullname: Walker, Marcella D. organization: Columbia University Vagelos College of Physicians and Surgeons, New York, NY – sequence: 4 givenname: Kenneth J. surname: Mukamal fullname: Mukamal, Kenneth J. organization: Beth Israel Deaconess Medical Center, Boston, MA – sequence: 5 givenname: Joachim H. surname: Ix fullname: Ix, Joachim H. organization: University of California San Diego, San Diego, CA – sequence: 6 givenname: Luc surname: Djousse fullname: Djousse, Luc organization: Brigham and Women’s Hospital, Boston, MA – sequence: 7 givenname: Rodrigo J. surname: Valderrábano fullname: Valderrábano, Rodrigo J. organization: University of Miami, Miami, FL – sequence: 8 givenname: David S. surname: Siscovick fullname: Siscovick, David S. organization: The New York Academy of Medicine, New York, NY – sequence: 9 givenname: Russell P. surname: Tracy fullname: Tracy, Russell P. organization: University of Vermont, Burlington, VT – sequence: 10 givenname: Xiaonan surname: Xue fullname: Xue, Xiaonan organization: Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY – sequence: 11 givenname: Jorge R. orcidid: 0000-0001-9936-7803 surname: Kizer fullname: Kizer, Jorge R. organization: Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30002202$$D View this record in MEDLINE/PubMed |
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| Snippet | 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... 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... |
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| SubjectTerms | Age Aged Aged, 80 and over Biochemical markers Biocompatibility Biomarkers Biomarkers - analysis Biomarkers - blood Biomedical materials Bone and Bones - metabolism Bone growth Bone Remodeling - physiology Bone resorption Bone Resorption - blood Bone Resorption - epidemiology Bone turnover Cardiovascular disease Cardiovascular System - physiopathology Collagen (type I) Collagen Type I - blood Cross-Sectional Studies Crosslinking Demographics Diabetes Diabetes mellitus Diabetes Mellitus - blood Diabetes Mellitus - epidemiology Energy metabolism Epidemiology/Health Services Research Female Hazards Health risks Homeostasis Humans Incidence Insulin Metabolism Older people Osteocalcin Osteocalcin - blood Osteogenesis Osteoporosis Population (statistical) Population studies Post-menopause Regression analysis Research design Risk Factors Statistical analysis Statistical models Womens health |
| Title | Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study |
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