Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study

Daniele Massera, Mary L. Biggs, Marcella D. Walker, Kenneth J. Mukamal, Joachim H. Ix, Luc Djousse, Rodrigo J. Valderrábano, David S. Siscovick, Russell P. Tracy, Xiaonan (Nan) Xue, Jorge Kizer

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1901-1908
Number of pages8
JournalDiabetes Care
Volume41
Issue number9
DOIs
StatePublished - Sep 1 2018

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Bone Remodeling
Osteocalcin
Biomarkers
Health
International Classification of Diseases
Insulin Resistance
Social Adjustment
Bone Resorption
Collagen Type I
Proportional Hazards Models
Osteogenesis
Energy Metabolism
Life Style
Linear Models
Homeostasis
Cross-Sectional Studies
Demography
Bone and Bones
Glucose
Serum

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Massera, D., Biggs, M. L., Walker, M. D., Mukamal, K. J., Ix, J. H., Djousse, L., ... Kizer, J. (2018). Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study. Diabetes Care, 41(9), 1901-1908. https://doi.org/10.2337/dc18-0849

Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women : The Cardiovascular Health Study. / Massera, Daniele; Biggs, Mary L.; Walker, Marcella D.; Mukamal, Kenneth J.; Ix, Joachim H.; Djousse, Luc; Valderrábano, Rodrigo J.; Siscovick, David S.; Tracy, Russell P.; Xue, Xiaonan (Nan); Kizer, Jorge.

In: Diabetes Care, Vol. 41, No. 9, 01.09.2018, p. 1901-1908.

Research output: Contribution to journalArticle

Massera, D, Biggs, ML, Walker, MD, Mukamal, KJ, Ix, JH, Djousse, L, Valderrábano, RJ, Siscovick, DS, Tracy, RP, Xue, XN & Kizer, J 2018, 'Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women: The Cardiovascular Health Study', Diabetes Care, vol. 41, no. 9, pp. 1901-1908. https://doi.org/10.2337/dc18-0849
Massera, Daniele ; Biggs, Mary L. ; Walker, Marcella D. ; Mukamal, Kenneth J. ; Ix, Joachim H. ; Djousse, Luc ; Valderrábano, Rodrigo J. ; Siscovick, David S. ; Tracy, Russell P. ; Xue, Xiaonan (Nan) ; Kizer, Jorge. / Biochemical Markers of Bone Turnover and Risk of Incident Diabetes in Older Women : The Cardiovascular Health Study. In: Diabetes Care. 2018 ; Vol. 41, No. 9. pp. 1901-1908.
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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.",
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AU - Mukamal, Kenneth J.

AU - Ix, Joachim H.

AU - Djousse, Luc

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N2 - 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.

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