A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D3 and parathyroid hormone levels in patients with type 2 diabetes

Pär Jennersjö, Hans Guldbrand, Stefan Björne, Toste Länne, Mats Fredrikson, Torbjörn Lindström, Magnus Wijkman, Carl Johan Östgren, Fredrik H Nystrom, Pär Jennersjö, Hans Guldbrand, Stefan Björne, Toste Länne, Mats Fredrikson, Torbjörn Lindström, Magnus Wijkman, Carl Johan Östgren, Fredrik H Nystrom

Abstract

Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes.

Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry.

Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p >0.9).

Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV.

Trial registration: ClinicalTrials.gov: NCT01049737.

Keywords: Arteriosclerosis; Calcium; Mortality; Parathyroid hormone; Type 2 diabetes; Vitamin D.

Figures

Fig. 1
Fig. 1
Cox regression analysis of total mortality in male patients with type 2 diabetes in relation to vitamin D tertiles. Data are shown for upper (dashed line) and lower tertiles (continuous line) of levels of vitamin D adjusted for parathyroid hormone levels, HbA1c, waist circumference, age, 24-h systolic ambulatory blood pressure, serum-apoB, carotid-femoral PWV and carotid IMT
Fig. 2
Fig. 2
Cox regression analysis of total mortality in women with type 2 diabetes in relation to levels of parathyroid hormone levels. The dashed line represents upper tertile and the continuous line the risk in patients with levels in the lower tertile of parathyroid hormone levels after adjustments for levels of vitamin D, HbA1c, waist circumference, age, 24-h systolic ambulatory blood pressure, serum-apoB, carotid-femoral PWV and carotid IMT

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