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Association between serum 25(OH)D-3 and cardiovascular morbidity and mortality in people with Type 2 diabetes: a community-based cohort study
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-2797-764X
University of Auckland, New Zealand.
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.ORCID iD: 0000-0002-9095-403X
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 Endocrinology.ORCID iD: 0000-0002-1680-1000
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2017 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 3, p. 372-379Article in journal (Refereed) Published
Abstract [en]

Aim We aimed to explore the association between vitamin D and cardiovascular morbidity and mortality in people with Type 2 diabetes recruited from a community-based study because there is limited and inconsistent research of this group. Methods A prospective community-based cohort study among people aged 55-66 years with Type 2 diabetes as part of The Cardiovascular Risk in Type 2 Diabetes -A Prospective Study in Primary Care (CARDIPP). We analysed serum 25-hydroxyvitamin D-3 [25(OH)D-3] at baseline. Cox regression analyses were used to calculate hazard ratios (HR) for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D-3. Results We examined 698 people with a mean follow-up of 7.3 years. Serum 25(OH)D-3 was inversely associated with the risk of cardiovascular morbidity and mortality: HR 0.98 [95% confidence interval (CI) 0.96 to 0.99, P = 0.001]. Compared with the fourth quartile (Q4) [25(OH)D-3 amp;gt; 61.8 nmol/l], HR (with 95% CI) was 3.46 (1.60 to 7.47) in Q1 [25(OH)D-3 amp;lt; 35.5 nmol/l] (P = 0.002); 2.26 (1.01 to 5.06) in Q2 [25(OH)D-3 35.5-47.5 nmol/l] (P = 0.047); and 1.62 (0.70 to 3.76) in Q3 [25(OH)D-3 47.5-61.8 nmol/l] (P = 0.26) when adjusting for age, sex and season. The results remained significant after adjusting also for cardiovascular risk factors, physiological variables including parathyroid hormone and previous cardiovascular disease (P = 0.027). Conclusions Low 25(OH)D-3 is associated with an increased risk of cardiovascular morbidity and mortality in people with Type 2 diabetes independent of parathyroid hormone. Vitamin D could be considered as a prognostic factor. Future studies are needed to explore whether vitamin D deficiency is a modifiable risk factor in Type 2 diabetes.

Place, publisher, year, edition, pages
WILEY , 2017. Vol. 34, no 3, p. 372-379
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:liu:diva-136630DOI: 10.1111/dme.13290ISI: 000397404200009PubMedID: 27862247OAI: oai:DiVA.org:liu-136630DiVA, id: diva2:1089855
Note

Funding Agencies|Medical Research Council of Southeast Sweden; Futurum; King Gustaf V and Queen Victoria Freemason Foundation; Department of Medical and Health Sciences at Linkoping University; County Council of Ostergotland; Swedish Society of Medicine; National Research School in General Practice

Available from: 2017-04-21 Created: 2017-04-21 Last updated: 2021-10-04
In thesis
1. Aspects of Vitamin D Deficiency in Elderly People in Nursing Homes and in Patients with Type 2 Diabetes: with Emphasis on Mortality, Cardiovascular Morbidity and Mental Health
Open this publication in new window or tab >>Aspects of Vitamin D Deficiency in Elderly People in Nursing Homes and in Patients with Type 2 Diabetes: with Emphasis on Mortality, Cardiovascular Morbidity and Mental Health
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Institutionalised elderly people living in northern latitudes may be at elevated risk for vitamin D deficiency. They are recommended to take oral vitamin D supplements, but the main source of vitamin D is sunlight. Previous studies have shown an association between low levels of vitamin D and several diseases, but important knowledge about vitamin D in elderly people in nursing homes and in patients with type 2 diabetes is lacking. The aims of this thesis were to study aspects of vitamin D deficiency in these two populations and to explore whether low vitamin D levels were associated with mortality, cardiovascular morbidity and mental health. Also, we aimed to examine whether an intervention with encouragement to spend time outdoors during summer could increase vitamin D levels in the elderly in nursing homes.

Methods

The present thesis is based on four papers. Papers I and IV are confined to nursing home residents >65 years. Paper I is based on data from SHADES (The Study of Health and Drugs in the Elderly). Paper IV is based on the study Sunlight and Vitamin D in Older People in Nursing Homes. Papers II and III are based on data from CARDIPP (Cardiovascular Risk Factors in Patients with Diabetes—a Prospective Study in Primary Care), with patients with type 2 diabetes aged 55-66 years. Papers I-III were prospective observational cohort studies and Paper IV was a cluster randomised intervention trial.

In Paper I, serum 25-hydroxyvitamin D3 (25(OH)D3) was analysed on three occasions. The vital status of the subjects was ascertained and hazard ratios (HRs) for mortality according to baseline 25(OH)D3 quartiles (Q) were calculated.

In Paper II, serum 25(OH)D3 was analysed at baseline. HRs for the first myocardial infarction, stroke or cardiovascular mortality according to 25(OH)D3 were calculated.

In Paper III, serum 25(OH)D3 was analysed at baseline. The SF-36 questionnaires measuring vitality and mental health were administered at baseline and after four years.

In Paper IV, the intervention group was encouraged to go outside for 20-30 minutes every day for two months during the summer of 2018. Before and after the summer, serum 25(OH)D was analysed and SF-36 questionnaires measuring vitality and mental health were administered.

Results

In Paper I, 80% of the participants had 25(OH)D3 < 50 nmol/l. Vitamin D deficiency was associated with an increased mortality risk. Compared with Q4 (25(OH)D3 >48 nmol/l), the HR (with a 95% confidence interval (CI)) for mortality was 2.02 (1.31-3.12) in Q1 (25(OH)D3 <29 nmol/l) (p<0.05), 2.03 (1.32-3.14) in Q2 (25(OH)D3 30-37 nmol/l) (p<0.05) and 1.6 (1.03-2.48) in Q3 (25(OH)D3 38-47 nmol/l) (p<0.05).

In Paper II, serum 25(OH)D3 was inversely associated with the risk of cardiovascular morbidity and mortality. The HR per nmol/l was 0.98 (95% CI: 0.96-0.99) (p=0.001), when adjusted for age, sex and season.

In Paper III, serum 25(OH)D3 was inversely associated with poor mental health at baseline. The odds ratio (OR) for 10 nmol/l increase in 25(OH)D3 was 0.90 (95% CI: 0.83-0.96) (p=0.003), but not at follow-up (p>0.05). Serum 25(OH)D3 was not associated with vitality at baseline (p>0.05), nor at follow-up after adjustments.

In Paper IV, the 25(OH)D levels increased significantly in the intervention group during the summer: from a median (interquartile range (IQR)) of serum 25(OH)D of 42.5 (23.0) nmol/l to 53.5 (33.0) nmol/l (p=0.011). The 25(OH)D levels increased in the control group as well, but the increase was not significant. The intervention group reported better mental health after the summer compared to before the summer (p=0.015), unlike the control group.

Conclusions

Low vitamin D levels were associated with increased mortality in elderly people in nursing homes, and with cardiovascular morbidity/ mortality and poor mental health in patients with type 2 diabetes. From our studies, we cannot draw conclusions about causality. The results indicate that the vitamin D levels give prognostic information. Active encouragement to spend time outdoors during summer improved the vitamin D levels and mental health in elderly people in nursing homes, and such activity could be considered as a complement to oral vitamin D supplementation in the summer.

Abstract [sv]

D-vitamin bildas i huden när vi utsätts för solljus och i mindre mängder så kan vi även få D-vitamin via mat såsom fet fisk och berikade mejeriprodukter. På våra breddgrader i Sverige så tillverkar inte huden D-vitamin under vinterhalvåret (mellan oktober och mars), vilket medför att nivåerna av D-vitamin i kroppen sjunker. Äldre personer på särskilt boende löper särskilt stor risk för D-vitaminbrist och alla äldre rekommenderas att ta ett dagligt tillskott med D-vitamin. Tidigare studier har visat ett samband mellan låga D-vitaminnivåer och en rad olika sjukdomar, men det finns fortfarande kunskapsluckor bl. a. gällande äldre personer som bor på särskilt boende och patienter med typ 2-diabetes.

Syftet med denna avhandling var att studera olika aspekter på D-vitaminbrist hos dessa två grupper och att undersöka om D-vitaminnivåerna var kopplade till risken för död, hjärtkärlsjukdom och nedsatt mental hälsa. Vi ville också undersöka om man genom att aktivt uppmuntra äldre personer på särskilt boende att vara utomhus sommartid kunde öka deras D-vitaminnivåer.

I SHADES-studien (delarbete 1) visades att det fanns ett samband mellan D-vitaminbrist och en ökad risk för tidigare död hos äldre (>65 år) på särskilt boende i södra Sverige (Eslöv, Jönköping och Linköping). Risken att dö var dubbelt så stor hos de två fjärdedelar av studiedeltagarna som hade lägst och näst lägst D-vitaminvärden jämfört med den fjärdedel som hade högst värden. D-vitaminbrist var mycket vanligt, då 80% av studiedeltagarna hade för lågt D-vitaminvärde.

I CARDIPP-studien visades att det fanns ett samband mellan låga D-vitaminnivåer och risken för hjärtkärlsjukdom (hjärtinfarkt och stroke) och död pga hjärtkärlsjukdom hos medelålders (55-66 år) patienter med typ 2- diabetes (delarbete 2).

I CARDIPP-studien sågs även ett samband mellan låga D-vitaminnivåer och nedsatt mental hälsa utifrån svar på en enkät som heter SF-36 (delarbete 3). Patienterna fick svara på samma enkät 4 år senare, men det sågs inget samband mellan D-vitaminvärdet när de gick in i studien och den mentala hälsan vid uppföljningen. Ett annat område som enkäten undersökte var vitalitet, men något tydligt samband mellan D-vitaminnivåerna och patienternas vitalitet kunde inte visas.

I studien Solljus och D-vitamin hos äldre på särskilt boende (delarbete 4) visades att den grupp av de äldre på särskilt boende som blev aktivt uppmuntrade till att vara utomhus 20-30 minuter mitt på dagen varje dag under 2 månader sommaren 2018 fick ökade D-vitaminnivåer och bättre mental hälsa enligt enkäten SF-36, medan vi inte såg lika tydlig skillnad i D-vitaminnivå eller mental hälsa hos den grupp som inte fick denna uppmuntran.

Sammanfattningsvis så fann vi ett samband mellan låga D-vitaminnivåer och ökad risk för tidigare död hos äldre på särskilt boende samt mellan låga D-vitaminnivåer och hjärtkärlsjukdom och nedsatt mental hälsa hos patienter med typ 2-diabetes. Detta behöver dock inte betyda att det är de låga D-vitaminnivåerna som är den bakomliggande orsaken, men dessa studier antyder att D-vitaminvärdet ändå kan ge information om prognosen. Eftersom aktivt uppmuntrande till att spendera tid utomhus på sommaren ledde till ökade D-vitaminnivåer och förbättrad mental hälsa hos äldre på särskilt boende, så kan man överväga detta som ett komplement till D-vitamintabletter hos de äldre på sommaren.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2020. p. 74
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1748
Keywords
vitamin D, nursing homes, older people, type 2 diabetes, mortality, cardiovascular morbidity, mental health, vitality
National Category
General Practice
Identifiers
urn:nbn:se:liu:diva-170197 (URN)10.3384/diss.diva-170197 (DOI)9789179298029 (ISBN)
Public defence
2020-11-06, Belladonna, Campus US, Entrance 78, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2020-10-06 Created: 2020-10-02 Last updated: 2021-10-04Bibliographically approved

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Samefors, MariaÖstgren, Carl Johan

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