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A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, West County Primary Health Care.ORCID iD: 0000-0002-2432-3846
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
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2015 (English)In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, no 53Article in journal (Refereed) Published
Abstract [en]

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 D-3 (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 greater than 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.

Place, publisher, year, edition, pages
BioMed Central , 2015. Vol. 7, no 53
Keyword [en]
Arteriosclerosis; Calcium; Mortality; Parathyroid hormone; Type 2 diabetes; Vitamin D
National Category
Endocrinology and Diabetes
URN: urn:nbn:se:liu:diva-120044DOI: 10.1186/s13098-015-0049-9ISI: 000356219100001PubMedID: 26078787OAI: diva2:840012

Funding Agencies|Medical Research Council of Southeast Sweden; Futurum; King Gustaf V and Queen Victoria Freemason Foundation; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; County Council of Ostergotland; Linkoping University, Department of Medical and Health Sciences

Available from: 2015-07-06 Created: 2015-07-06 Last updated: 2016-04-11
In thesis
1. Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D
Open this publication in new window or tab >>Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]


Type 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes.


Data from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of  sagittal abdominal diameter.


Paper 1:

Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure.

Paper 2:

The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV.

Paper 3:

At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up.

Paper 4:

Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses.


Ambulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 55 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1507
National Category
Family Medicine Cardiac and Cardiovascular Systems Endocrinology and Diabetes Geriatrics Public Health, Global Health, Social Medicine and Epidemiology
urn:nbn:se:liu:diva-125911 (URN)10.3384/diss.diva-125911 (DOI)978-91-7685-848-6 (Print) (ISBN)
Public defence
2016-04-08, Belladonna, ingång 78, Campus US, Linköping, 09:00 (English)
Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2016-03-08Bibliographically approved

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Division of Community MedicineFaculty of Medicine and Health SciencesWest County Primary Health CareDepartment of Medical and Health SciencesDivision of Cardiovascular MedicineDepartment of Thoracic and Vascular SurgeryCenter for Medical Image Science and Visualization (CMIV)Division of Neuro and Inflammation ScienceDepartment of EndocrinologyDepartment of Internal Medicine in Norrköping"Primary Health Care in Motala"
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