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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.

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.

SUBMITTER: Jennersjo P

PROVIDER: S-EPMC4466811 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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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.

Jennersjö Pär P Guldbrand Hans H Björne Stefan S Länne Toste T Fredrikson Mats M Lindström Torbjörn T Wijkman Magnus M Östgren Carl Johan CJ Nystrom Fredrik H FH

Diabetology & metabolic syndrome 20150612

<h4>Background</h4>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.<h4>Methods</h4>The main study design was prospective and observational. We used baseline data f ...[more]

PMID: 26078787

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Project description:RationalePatients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS).MethodsBalb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined.ResultsMice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A.ConclusionsVD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Dataset Information

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.

Publications

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.

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