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. 2010 Dec;33(12):2561-6.
doi: 10.2337/dc10-0858. Epub 2010 Oct 7.

Osteoprotegerin and mortality in type 2 diabetic patients

Henrik Reinhard  1 , Maria Lajer, Mari-Anne Gall, Lise Tarnow, Hans-Henrik Parving, Lars M Rasmussen, Peter Rossing
Affiliations

Osteoprotegerin and mortality in type 2 diabetic patients

Henrik Reinhard et al. Diabetes Care. 2010 Dec.

Abstract

Objective: Plasma osteoprotegerin (OPG) is an emerging strong and independent predictor of cardiovascular disease (CVD) in high-risk populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells, and increased plasma OPG levels may reflect arterial vascular damage. We aimed to investigate the prognostic value of OPG in relation to all-cause and cardiovascular mortality in a cohort of type 2 diabetic patients.

Research design and methods: In a prospective observational follow-up study, 283 type 2 diabetic patients (172 men; aged 53.9 ± 8.8 years) were followed for a median of 16.8 years (range 0.2-23.0). Baseline plasma OPG concentrations were determined by immunoassay.

Results: During follow-up, 193 (68%) patients died. High versus low levels of OPG predicted all-cause mortality (covariate-adjusted for urinary albumin excretion rate [UAER], estimated glomerular filtration rate, and conventional risk factors); hazard ratio (HR) 1.81 [95% CI 1.21-2.69]. The all-cause predictive effect of OPG was independent of NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) and was also useful within groups divided according to level of UAER. In total, 103 (73%) patients died because of CVD. High and medium versus low levels of OPG predicted cardiovascular mortality (unadjusted HR 1.86 [95% CI 1.07-3.23] and 3.51 [2.10-5.85], respectively). However, after adjustment for the covariates, HRs were no longer significant.

Conclusions: Elevated plasma OPG is a strong predictor of all-cause mortality in type 2 diabetic patients. The effect of OPG on all-cause mortality was independent of conventional cardiovascular risk factors, UAER, and NT-proBNP levels.

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Figures

Figure 1
Figure 1
Kaplan-Meier curves of all-cause mortality in 283 type 2 diabetic patients according to tertiles of plasma OPG. Bottom line, 1st tertile (OPG <1,691 pg/ml); center line, 2nd tertile (OPG 1,691–2,219 pg/ml); top line 3rd tertile (OPG >2,219 pg/ml). Log-rank test for overall difference, P < 0.0001.
Figure 2
Figure 2
Kaplan-Meier curves of cardiovascular mortality in 283 type 2 diabetic patients according to tertiles of plasma OPG. Bottom line, 1st tertile (OPG <1,691 pg/ml); center line, 2nd tertile (OPG 1,691–2,219 pg/ml); top line, 3rd tertile (OPG >2,219 pg/ml). Log-rank test for overall difference, P < 0.0001.
Figure 3
Figure 3
Kaplan-Meier curves of all-cause mortality in 283 type 2 diabetic patients according to UAER and median plasma OPG (1,963 pg/ml). Patients with normoalbuminuria and OPG <1,963 pg/ml (blue line) or OPG >1,963 pg/ml (green line); patients with microalbuminuria and OPG <1,963 pg/ml (gray line) or OPG >1,963 pg/ml (purple line); and patients with macroalbuminuria and OPG <1,963 pg/ml (yellow line) or OPG >1,963 pg/ml (red line). Log-rank test for overall difference, P < 0.0001.
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