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Published in: Diabetology & Metabolic Syndrome 1/2015

Open Access 01-12-2015 | Research

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

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

Published in: Diabetology & Metabolic Syndrome | Issue 1/2015

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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
Literature
1.
go back to reference Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015;74:115–24.PubMedCrossRef Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015;74:115–24.PubMedCrossRef
2.
go back to reference Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes. 2008;57:2619–25.PubMedCentralPubMedCrossRef Forouhi NG, Luan J, Cooper A, Boucher BJ, Wareham NJ. Baseline serum 25-hydroxy vitamin d is predictive of future glycemic status and insulin resistance: the Medical Research Council Ely Prospective Study 1990-2000. Diabetes. 2008;57:2619–25.PubMedCentralPubMedCrossRef
3.
go back to reference Knekt P, Laaksonen M, Mattila C, Harkanen T, Marniemi J, Heliovaara M, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19:666–71.PubMedCrossRef Knekt P, Laaksonen M, Mattila C, Harkanen T, Marniemi J, Heliovaara M, et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology. 2008;19:666–71.PubMedCrossRef
4.
go back to reference Afzal S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem. 2013;59:381–91.PubMedCrossRef Afzal S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of type 2 diabetes: a prospective cohort study and metaanalysis. Clin Chem. 2013;59:381–91.PubMedCrossRef
5.
go back to reference Schottker B, Herder C, Rothenbacher D, Perna L, Muller H, Brenner H. Serum 25-hydroxyvitamin D levels and incident diabetes mellitus type 2: a competing risk analysis in a large population-based cohort of older adults. Eur J Epidemiol. 2013;28:267–75.PubMedCrossRef Schottker B, Herder C, Rothenbacher D, Perna L, Muller H, Brenner H. Serum 25-hydroxyvitamin D levels and incident diabetes mellitus type 2: a competing risk analysis in a large population-based cohort of older adults. Eur J Epidemiol. 2013;28:267–75.PubMedCrossRef
6.
go back to reference Saliba W, Barnett O, Rennert HS, Rennert G. The risk of all-cause mortality is inversely related to serum 25(OH)D levels. J Clin Endocrinol Metab. 2012;97:2792–8.PubMedCrossRef Saliba W, Barnett O, Rennert HS, Rennert G. The risk of all-cause mortality is inversely related to serum 25(OH)D levels. J Clin Endocrinol Metab. 2012;97:2792–8.PubMedCrossRef
7.
go back to reference Kramer H, Sempos C, Cao G, Luke A, Shoham D, Cooper R, et al. Mortality rates across 25-hydroxyvitamin D (25[OH]D) levels among adults with and without estimated glomerular filtration rate <60 ml/min/1.73 m2: the third national health and nutrition examination survey. PLoS One. 2012;7:e47458.PubMedCentralPubMedCrossRef Kramer H, Sempos C, Cao G, Luke A, Shoham D, Cooper R, et al. Mortality rates across 25-hydroxyvitamin D (25[OH]D) levels among adults with and without estimated glomerular filtration rate <60 ml/min/1.73 m2: the third national health and nutrition examination survey. PLoS One. 2012;7:e47458.PubMedCentralPubMedCrossRef
8.
go back to reference Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int. 2008;74:170–9.PubMedCrossRef Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int. 2008;74:170–9.PubMedCrossRef
9.
go back to reference Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint Bone Spine. 2010;77:552–7.PubMedCrossRef Guillot X, Semerano L, Saidenberg-Kermanac'h N, Falgarone G, Boissier MC. Vitamin D and inflammation. Joint Bone Spine. 2010;77:552–7.PubMedCrossRef
10.
go back to reference Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Houshiarrad A, Kalayi A, et al. Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes Metab Res Rev. 2012;28:424–30.PubMedCrossRef Shab-Bidar S, Neyestani TR, Djazayery A, Eshraghian MR, Houshiarrad A, Kalayi A, et al. Improvement of vitamin D status resulted in amelioration of biomarkers of systemic inflammation in the subjects with type 2 diabetes. Diabetes Metab Res Rev. 2012;28:424–30.PubMedCrossRef
11.
go back to reference Durup D, Jorgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab. 2012;97:2644–52.PubMedCrossRef Durup D, Jorgensen HL, Christensen J, Schwarz P, Heegaard AM, Lind B. A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab. 2012;97:2644–52.PubMedCrossRef
12.
go back to reference Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, Yetley EA, Looker AC, Schleicher RL, et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab. 2013;98:3001–9.PubMedCentralPubMedCrossRef Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, Yetley EA, Looker AC, Schleicher RL, et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the U.S. nationally representative NHANES. J Clin Endocrinol Metab. 2013;98:3001–9.PubMedCentralPubMedCrossRef
13.
go back to reference Hagstrom E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundstrom J, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119:2765–71.PubMedCrossRef Hagstrom E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundstrom J, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009;119:2765–71.PubMedCrossRef
14.
go back to reference Natoli JL, Boer R, Nathanson BH, Miller RM, Chiroli S, Goodman WG, et al. Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis. BMC Nephrol. 2013;14:88.PubMedCentralPubMedCrossRef Natoli JL, Boer R, Nathanson BH, Miller RM, Chiroli S, Goodman WG, et al. Is there an association between elevated or low serum levels of phosphorus, parathyroid hormone, and calcium and mortality in patients with end stage renal disease? A meta-analysis. BMC Nephrol. 2013;14:88.PubMedCentralPubMedCrossRef
15.
go back to reference Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care. 2010;33:2238–43.PubMedCentralPubMedCrossRef Joergensen C, Gall MA, Schmedes A, Tarnow L, Parving HH, Rossing P. Vitamin D levels and mortality in type 2 diabetes. Diabetes Care. 2010;33:2238–43.PubMedCentralPubMedCrossRef
16.
go back to reference Joergensen C, Hovind P, Schmedes A, Parving HH, Rossing P. Vitamin D levels, microvascular complications, and mortality in type 1 diabetes. Diabetes Care. 2011;34:1081–5.PubMedCentralPubMedCrossRef Joergensen C, Hovind P, Schmedes A, Parving HH, Rossing P. Vitamin D levels, microvascular complications, and mortality in type 1 diabetes. Diabetes Care. 2011;34:1081–5.PubMedCentralPubMedCrossRef
17.
go back to reference Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002;106:2085–90.PubMedCrossRef Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002;106:2085–90.PubMedCrossRef
18.
go back to reference Djaberi R, Beishuizen ED, Pereira AM, Rabelink TJ, Smit JW, Tamsma JT, et al. Non-invasive cardiac imaging techniques and vascular tools for the assessment of cardiovascular disease in type 2 diabetes mellitus. Diabetologia. 2008;51:1581–93.PubMedCentralPubMedCrossRef Djaberi R, Beishuizen ED, Pereira AM, Rabelink TJ, Smit JW, Tamsma JT, et al. Non-invasive cardiac imaging techniques and vascular tools for the assessment of cardiovascular disease in type 2 diabetes mellitus. Diabetologia. 2008;51:1581–93.PubMedCentralPubMedCrossRef
19.
go back to reference Jennersjo P, Ludvigsson J, Lanne T, Nystrom FH, Ernerudh J, Ostgren CJ. Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes. Diabet Med. 2012;29:1119–25.PubMedCrossRef Jennersjo P, Ludvigsson J, Lanne T, Nystrom FH, Ernerudh J, Ostgren CJ. Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes. Diabet Med. 2012;29:1119–25.PubMedCrossRef
20.
go back to reference Wijkman M, Lanne T, Engvall J, Lindstrom T, Ostgren CJ, Nystrom FH. Masked nocturnal hypertension–a novel marker of risk in type 2 diabetes. Diabetologia. 2009;52:1258–64.PubMedCrossRef Wijkman M, Lanne T, Engvall J, Lindstrom T, Ostgren CJ, Nystrom FH. Masked nocturnal hypertension–a novel marker of risk in type 2 diabetes. Diabetologia. 2009;52:1258–64.PubMedCrossRef
21.
go back to reference Spangeus A, Wijkman M, Lindstrom T, Engvall JE, Ostgren CJ, Nystrom FH, et al. Toe brachial index in middle aged patients with diabetes mellitus type 2: not just a peripheral issue. Diabetes Res Clin Pract. 2013;100:195–202.PubMedCrossRef Spangeus A, Wijkman M, Lindstrom T, Engvall JE, Ostgren CJ, Nystrom FH, et al. Toe brachial index in middle aged patients with diabetes mellitus type 2: not just a peripheral issue. Diabetes Res Clin Pract. 2013;100:195–202.PubMedCrossRef
22.
go back to reference Sjoblom P, Nystrom FH, Lanne T, Engvall J, Ostgren CJ. Microalbuminuria, but not reduced eGFR, is associated with cardiovascular subclinical organ damage in type 2 diabetes. Diabetes Metab. 2014;40:49–55.PubMedCrossRef Sjoblom P, Nystrom FH, Lanne T, Engvall J, Ostgren CJ. Microalbuminuria, but not reduced eGFR, is associated with cardiovascular subclinical organ damage in type 2 diabetes. Diabetes Metab. 2014;40:49–55.PubMedCrossRef
23.
go back to reference Hallan S, Asberg A, Lindberg M, Johnsen H. Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. Am J Kidney Dis. 2004;44:84–93.PubMedCrossRef Hallan S, Asberg A, Lindberg M, Johnsen H. Validation of the Modification of Diet in Renal Disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay. Am J Kidney Dis. 2004;44:84–93.PubMedCrossRef
25.
go back to reference Wu SH, Ho SC, Zhong L. Effects of vitamin D supplementation on blood pressure. South Med J. 2010;103:729–37.PubMedCrossRef Wu SH, Ho SC, Zhong L. Effects of vitamin D supplementation on blood pressure. South Med J. 2010;103:729–37.PubMedCrossRef
26.
go back to reference Forman JP, Scott JB, Ng K, Drake BF, Suarez EG, Hayden DL, et al. Effect of vitamin D supplementation on blood pressure in blacks. Hypertension. 2013;61:779–85.PubMedCentralPubMedCrossRef Forman JP, Scott JB, Ng K, Drake BF, Suarez EG, Hayden DL, et al. Effect of vitamin D supplementation on blood pressure in blacks. Hypertension. 2013;61:779–85.PubMedCentralPubMedCrossRef
27.
go back to reference Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, Binkley N, Stein JH. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. 2012;7:e36617.PubMedCentralPubMedCrossRef Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, Binkley N, Stein JH. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. 2012;7:e36617.PubMedCentralPubMedCrossRef
28.
go back to reference Wood AD, Secombes KR, Thies F, Aucott L, Black AJ, Mavroeidi A, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab. 2012;97:3557–68.PubMedCrossRef Wood AD, Secombes KR, Thies F, Aucott L, Black AJ, Mavroeidi A, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab. 2012;97:3557–68.PubMedCrossRef
29.
go back to reference Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. The Lancet Diabetes & Endocrinology 2014;doi:10.1016/S2213-8587(13)70212-2 Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. The Lancet Diabetes & Endocrinology 2014;doi:10.1016/S2213-8587(13)70212-2
30.
go back to reference Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study. Eur J Endocrinol. 2012;167:553–60.PubMedCrossRef Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, et al. Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study. Eur J Endocrinol. 2012;167:553–60.PubMedCrossRef
31.
go back to reference Brock KE, Huang WY, Fraser DR, Ke L, Tseng M, Mason RS, et al. Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Br J Nutr. 2011;106:339–44.PubMedCentralPubMedCrossRef Brock KE, Huang WY, Fraser DR, Ke L, Tseng M, Mason RS, et al. Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Br J Nutr. 2011;106:339–44.PubMedCentralPubMedCrossRef
32.
go back to reference Lee JI, Oh SJ, Ha WC, Kwon HS, Sohn TS, Son HS, et al. Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes. Diabetes Res Clin Pract. 2012;95:42–7.PubMedCrossRef Lee JI, Oh SJ, Ha WC, Kwon HS, Sohn TS, Son HS, et al. Serum 25-hydroxyvitamin D concentration and arterial stiffness among type 2 diabetes. Diabetes Res Clin Pract. 2012;95:42–7.PubMedCrossRef
34.
go back to reference Kaseda R, Hosojima M, Sato H, Saito A. Role of megalin and cubilin in the metabolism of vitamin D(3). Ther Apher Dial. 2011;15 Suppl 1:14–7.PubMedCrossRef Kaseda R, Hosojima M, Sato H, Saito A. Role of megalin and cubilin in the metabolism of vitamin D(3). Ther Apher Dial. 2011;15 Suppl 1:14–7.PubMedCrossRef
35.
go back to reference Hilpert J, Wogensen L, Thykjaer T, Wellner M, Schlichting U, Orntoft TF, et al. Expression profiling confirms the role of endocytic receptor megalin in renal vitamin D3 metabolism. Kidney Int. 2002;62:1672–81.PubMedCrossRef Hilpert J, Wogensen L, Thykjaer T, Wellner M, Schlichting U, Orntoft TF, et al. Expression profiling confirms the role of endocytic receptor megalin in renal vitamin D3 metabolism. Kidney Int. 2002;62:1672–81.PubMedCrossRef
36.
go back to reference Yavuz B, Ertugrul DT, Cil H, Ata N, Akin KO, Yalcin AA, et al. Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther. 2009;23:295–9.PubMedCrossRef Yavuz B, Ertugrul DT, Cil H, Ata N, Akin KO, Yalcin AA, et al. Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther. 2009;23:295–9.PubMedCrossRef
Metadata
Title
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
Authors
Pär Jennersjö
Hans Guldbrand
Stefan Björne
Toste Länne
Mats Fredrikson
Torbjörn Lindström
Magnus Wijkman
Carl Johan Östgren
Fredrik H. Nystrom
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2015
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-015-0049-9

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