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. 2018 Sep;41(9):1901-1908.
doi: 10.2337/dc18-0849. Epub 2018 Jul 12.

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

Daniele Massera  1 , Mary L Biggs  2 , Marcella D Walker  3 , Kenneth J Mukamal  4 , Joachim H Ix  5 , Luc Djousse  6 , Rodrigo J Valderrábano  7 , David S Siscovick  8 , Russell P Tracy  9 , Xiaonan Xue  1 , Jorge R Kizer  10
Affiliations

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

Daniele Massera et al. Diabetes Care. 2018 Sep.

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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Figures

Figure 1
Figure 1
Distribution of OC (A) and CTX (B) in the study sample.
Figure 2
Figure 2
Sensitivity analyses examining the associations of serum OC and CTX with incident diabetes in selected subgroups of the study sample. Model 1 is adjusted for age, race, and field center. Model 2 is additionally adjusted for BMI; systolic blood pressure; antihypertensive therapy; smoking status; alcohol consumption; physical activity; HRT; prevalent CHD, CHF, stroke, and AF; LDL; and eGFR. Model 3 is adjusted for 25-OHD levels in participants with available data.
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