DIABETICMedicine DOI: 10.1111/dme.12834
Research: Epidemiology Vitamin D status and health-related quality of life in patients with Type 2 diabetes Y. H. M. Krul-Poel1,*, S. Westra1,*, H. J. J. van Wijland2, F. Stam1, P. Lips3, F. Pouwer4 and S. Simsek1,3 1 Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, 2Department of General Practice, DIAZON, Alkmaar, 3Department of Internal Medicine/ Endocrinology, VU University Medical Centre, Amsterdam and 4Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands
Accepted 4 June 2014
Abstract Aims To test whether vitamin D status was associated with health-related quality of life in people with Type 2 diabetes mellitus. Methods Demographic and clinical characteristics, including health-related quality of life scores, were obtained from 241 adult patients with Type 2 diabetes managed with oral hypoglycaemic agents. Health-related quality of life was assessed using the Short-Form 36 Health Survey. Multiple logistic regression analysis was used to investigate the association between vitamin D status and health-related quality of life, with adjustment for confounders.
The mean age of the patients included in the study was 67 8 years. Their mean HbA1c concentration was 52 8 mmol/mol (6.9 0.7%) and their mean serum 25-hydroxyvitamin D concentration was 59 23 nmol/l. Vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/l) was present in 38% of patients. No significant associations were found between vitamin D status and health-related quality of life.
Results
Conclusions Vitamin D status was not associated with health-related quality of life in patients with Type 2 diabetes. This could be explained by the relatively high serum 25-hydroxyvitamin D concentration, good glycaemic control and relatively good health-related quality of life of all patients. A prospective study among patients with vitamin D deficiency and poor glycaemic control would be interesting for future research.
Diabet. Med. 33, 300–306 (2016)
Introduction Diabetes mellitus is a chronic disease, affecting ~382 million people worldwide in 2013 [1]. Patients with Type 2 diabetes mellitus are at increased risk of developing micro- and macrovascular complications and cardiovascular disease, which subsequently compromises health-related quality of life (HRQoL) [2,3]. Previous research has shown that patients with Type 2 diabetes had a poorer (health-related) quality of life, a higher prevalence of generalized anxiety disorder and elevated symptoms of anxiety compared with the general population [2–5]. In addition, depression is common in patients with Type 2 diabetes, with a prevalence up to 24% in women and 13% in men. Depression in diabetes is associated with a considerably lower quality of life, higher HbA1c levels, increased risk of developing diabetes-specific
Correspondence to: S. Simsek. E-mail: [email protected] *These authors contributed equally to this work.
300
micro- and macrovascular complications, an increased mortality risk and higher healthcare costs [6–10]. Much research has been conducted examining the factors that contribute to a decreased quality of life in patients with Type 2 diabetes [2,3]. A potential factor could be low vitamin D status, which is highly prevalent in patients with Type 2 diabetes, and has been linked to quality of life in several other populations, with conflicting results [11–16]. Vitamin D is a secosteroid that is obtained from dietary sources, either food or supplements, and exposure to sunlight. It needs to be hydroxylated twice to become biologically active. In addition to its known action in calcium and bone homeostasis, vitamin D deficiency has recently been linked to numerous non-skeletal conditions, including Type 2 diabetes. This is the result of the discovery that most tissues and cells, including the brain, immune system and pancreatic b cells, contain the vitamin D receptor and the enzyme 1-a hydroxylase to convert serum 25hydroxyvitamin D [25(OH)D] to its biologically active form,
ª 2015 The Authors. Diabetic Medicine ª 2015 Diabetes UK
Research article
What’s new? In observational studies vitamin D deficiency is associated with poor glycaemic control. Poor glycaemic control is associated with a reduced health-related quality of life. No association between vitamin D status and healthrelated quality of life was found in patients with wellcontrolled Type 2 diabetes. which allows intracrine and paracrine functions [17]. Vitamin D deficiency is a growing worldwide problem. In a cross-sectional study from a population-based cohort among 538 white Dutch patients with Type 2 diabetes aged 60–87 years, the prevalence of serum 25(OH) D < 50 nmol/l was 34% in the summer and up to 51% during winter [11]. Low serum 25(OH)D has been linked to quality of life in several observational studies including study populations other than Type 2 diabetes, e.g. patients with osteoporosis, Crohn’s disease, end-stage renal disease (new on dialysis) and patients with chronic pain [11–15]. The mechanism by which vitamin D status may affect quality of life in patients with Type 2 diabetes is not known. Hypothetically, vitamin D may indirectly improve quality of life by influencing glycaemic control, which has been correlated to vitamin D status in many observational studies [18]. A recent meta-analysis performed by George et al. [19] found a small, non-significant, effect on glycaemic control (i.e. fasting glucose and insulin resistance) after vitamin D supplementation in patients with Type 2 diabetes or impaired glucose tolerance compared with control subjects. In addition, vitamin D might influence systemic inflammation, which is linked to insulin resistance in Type 2 diabetes, by modulating immune responses and oxidative stress [20]. Moreover, vitamin D may have cardioprotective and antidepressant effects that could help to maintain a good HRQoL [21,22]. The aim of the present study was to investigate whether vitamin D status was associated with HRQoL in patients with stable Type 2 diabetes managed with oral hypoglycaemic therapy.
Patients and methods Study design and patients
We conducted a cross-sectional study among 241 patients with Type 2 diabetes derived from five general practices in and around Alkmaar, the Netherlands at a latitude of 52. The patients were included between July 2012 and April 2013 in a randomized placebo-controlled trial (the SUNNY trial), in which the effect on glycaemic control of 50 000 IU vitamin D3 once a month for 6 months, compared with ª 2015 The Authors. Diabetic Medicine ª 2015 Diabetes UK
DIABETICMedicine
placebo, was examined in patients with Type 2 diabetes. The trial was approved by the Medical Ethics Committee of North Holland, the Netherlands. The trial protocol is described in greater detail elsewhere [23]. In brief, adult patients (age ≥ 18 years) with Type 2 diabetes treated with lifestyle advice, metformin or sulphonylurea derivatives, alone or in combination, were invited to participate in the study. Serum HbA1c levels had to be stable and ≤64 mmol/ mol (8.0%) for the last 3 months, without recent changes in hypoglycaemic agents. The main exclusion criteria were: impaired renal function (estimated GFR < 30 ml/min calculated from serum creatinine using the Modification of Diet in Renal Disease, MDRD, formula); any granuloma-forming disorder; hypercalcaemia (serum calcium > 2.65 nmol/l) for any reason; serum 25(OH)D < 15 nmol/l or > 150 nmol/l; urolithiasis; psychiatric treatment for schizophrenia; organic mental disorder or bipolar disorder currently or in the past; insufficient knowledge of the Dutch language; substance abuse (other than nicotine); or no signed informed consent. The patients were allowed to take vitamin D supplements at a maximum dose of 400 IU a day before inclusion.
Study variables
The following data were collected: age, gender, ethnicity, marital status, education level, employment status, diabetes duration, diabetes-specific complications, medication use and diabetic therapy, comorbidities, smoking status, alcohol use, dietary fish and dairy intake, physical activity, sun exposure and season of blood collection. Also standard anthropometric data (height, weight) and venous blood collection were obtained from each patient. Serum 25(OH)D was measured on an iSYS automated immunoanalyser (IDS GmbH, Frankfurt, Germany). The total 25(OH) D assay detects 25(OH)D2 and 25(OH)D3, both with a specificity of 100%. The quality of the test is controlled by applying Westgard quality control rules on three different quality control samples.
Health-related quality of life
We used the Dutch-language version of the Short-Form 36 Health Survey (SF-36) to assess HRQoL at baseline. The SF36 consists of 36 questions and set response choices on an ordinal scale. There are eight domains and two summary measures: physical functioning, role limitations attributable to physical problems, bodily pain, general health perceptions (together presenting the physical component summary), and mental health, vitality, social functioning and role limitations attributable to emotional problems (together presenting the mental component summary measure) [24]. For each domain, the HRQoL scores are converted to a scale of 0 to 100, with higher scores indicating a better HRQoL. The SF36 has adequate internal consistency (Cronbach’s a from 0.65 to 0.94, diabetes-specific from 0.76 to 0.93) and test-
301
DIABETICMedicine
Vitamin D status and quality of life in Type 2 diabetes Y. H. M. Kruk-Poel et al.
retest reliability (r = 0.63–0.81) [25,26]. In 1994, Aaronson et al. [27] translated and validated the Dutch language version of the SF-36 (Cronbach’s a from 0.66 to 0.93, mean 0.84).
Statistical analyses
For the purpose of the present cross-sectional study patients were stratified into two groups according to their vitamin D status: 1) serum 25(OH)D < 50 nmol/l, which was defined as vitamin D deficiency, and 2) serum 25(OH)D ≥ 50 nmol/l, which indicated a sufficient vitamin D status. Patient demographic and clinical characteristics were compared using a Pearson’s chi-squared test for categorical variables and an independent sample t-test or Mann–Whitney test for continuous variables, depending on normality. Multiple logistic regression analyses were performed to explore the association between vitamin D status [serum 25(OH) D < 50 nmol/l and > 50 nmol/l] and each HRQoL domain. All analyses were adjusted for age, gender, season of measurement, pre-existing cardiovascular disease and BMI, based on earlier literature and in case of a regression correlation coefficient difference > 10%. Subgroup analyses regarding glycaemic control [HbA1c ≥ 53 mmol/mol (≥ 7.0%)] and poor level of HRQoL for each domain (using national Dutch means stratified by gender and found by Aaronson et al. [27] to distinguish reduced HRQoL), were performed using the same method as the primary analysis. Subgroup analyses regarding patients with a lower HRQoL, however, were solely adjusted for season of measurement and BMI because of the small number of patients included in the analysis, which resulted in insufficient power to correct for all confounders. All analyses were also performed stratified by gender because of differences in HRQoL between men and women. All data were analysed using the SPSS statistical software package (IBM version 20.0; SPSS Inc., Chicago, IL, USA). Data are presented as numbers (%), median [interquartile range (IQR)] or means SD. A P value of < 0.05 was considered to indicate statistical significance.
Results A total of 300 patients were recruited to the SUNNY trial, of whom 275 attended the first visit and were randomized. Of these 275 patients, 241 (88%) returned the SF-36 questionnaire that they received at the first visit. The mean patient age was 67 8 years and 65% were men. The median (IQR) diabetes duration was 6 (3–8) years with a mean HbA1c of 52 8 mmol/mol (6.9 0.7%). Overall mean serum 25 (OH)D was 59 23 nmol/l. The prevalence of vitamin D deficiency, serum 25(OH)D < 50 nmol/l, was 38% and 150 patients (68%) had a serum 25(OH)D ≥ 50 nmol/l. The demographic and clinical characteristics and HRQoL scores of all patients, stratified by serum 25(OH)D < 50 nmol/l and >50 nmol/l, are shown in Table 1. Patients with vitamin D
302
deficiency were more likely to be women, more often had dark-coloured skin, had a higher incidence of smoking, were less physically active, had less sun exposure, had a higher BMI, and were more often single compared with the group with a serum 25(OH)D ≥ 50 nmol/l (all P < 0.05). No differences were observed in the eight HRQoL domains, nor in the physical or mental component summary, between the groups. HRQoL scores were higher in men than in women, particularly the domains physical functioning, bodily pain, social functioning, mental health, vitality and general health perceptions (data not shown). Concerning the main outcome, the association between HRQoL and serum 25(OH)D in patients with Type 2 diabetes, no significant associations were observed after correction for the following confounders: age, gender, season of measurement, pre-existent cardiovascular disease and BMI (Table 2). In addition, no effect was seen in the summary components. A significant association was observed between physical functioning and serum 25(OH)D ≥ 50 nmol/l (odds ratio 1.01, 95% CI 1.00–1.03; P = 0.04), but this no longer remained significant after adjustment for confounders. Prespecified subgroup analysis in patients with lower glycaemic control [HbA1c ≥ 53 mmol/mol, (≥ 7.0%), n = 71] showed a small association between serum 25(OH) D ≥ 50 nmol/l and role limitations attributable to emotional problems before and after adjustment for confounders (odds ratio 1.02, 95% CI 1.00–1.04; P = 0.02, data not shown). The results did not differ significantly when including only patients with a relatively poor HRQoL for one of the SF-36 domains.
Discussion In the present cross-sectional study in Dutch patients with Type 2 diabetes managed with oral hypoglycaemic therapy, no association between serum 25(OH)D and HRQoL was observed. The question of whether vitamin D status and HRQoL are associated has not been studied before in patients with Type 2 diabetes; however, studies examining the association between vitamin D status and HRQoL in other populations are available. In a large population-based cohort study in 15 954 post-menopausal women, a small difference in mental HRQoL was seen between women with a low (< 400 IU/day) and high vitamin D3 intake (≥ 800 IU/ day); however, this result was attenuated after controlling for the confounders: age; energy intake; BMI; education; smoking; living arrangement;antidepressant usage; comorbidity history; and physical activity [16]. In contrast to the results of the present study, a recent population-based observational study among Dutch patients aged > 70 years, found a significantly lower score on the physical component of HRQoL in patients with a severe vitamin D-deficient status [serum 25(OH)D < 25 nmol/l]; however, physical performance, depressive symptoms and the number of chronic diseases explained this association largely [28].
ª 2015 The Authors. Diabetic Medicine ª 2015 Diabetes UK
Research article
DIABETICMedicine
Table 1 Demographic, clinical characteristics and health-related quality of life of all patients, stratified by vitamin D level Serum 25(OH)D
Demographic characteristics Male, n (%)* Mean SD age, years Median (IQR) diabetes duration, years White skin colour, n (%)* Antidiabetic treatment, n (%) Lifestyle adjustments Metformin Sulphonylurea derivatives Metformin and sulphonylurea derivatives Microvascular complications† ≥1, n (%) Cardiovascular disease, n (%) Single, n (%)* Education level, n (%) Low Middle High Employment status, n (%) Paid employment Unemployed or incapacitated Retired Current smoker, n (%)* Alcohol use >2 units/day, n (%) Physical activity, n (%)* 5 h/week Sun exposure, n (%)* 10 h/week Season of blood collection, n (%) Spring Summer Autumn Winter Clinical characteristics, mean sd BMI, kg/m²* HbA1c, mmol/mol HbA1c, % Estimated GFR, ml/min Serum 25(OH)D, nmol/l* Serum parathyroid hormone, pmol/l Health-related quality of life, median (IQR) score Physical component summary Physical functioning Role limitations physical Bodily pain General health perceptions Mental component summary Mental health Role limitations emotional Vitality Social functioning
All patients n = 241
Research: Epidemiology Vitamin D status and health-related quality of life in patients with Type 2 diabetes Y. H. M. Krul-Poel1,*, S. Westra1,*, H. J. J. van Wijland2, F. Stam1, P. Lips3, F. Pouwer4 and S. Simsek1,3 1 Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, 2Department of General Practice, DIAZON, Alkmaar, 3Department of Internal Medicine/ Endocrinology, VU University Medical Centre, Amsterdam and 4Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands
Accepted 4 June 2014
Abstract Aims To test whether vitamin D status was associated with health-related quality of life in people with Type 2 diabetes mellitus. Methods Demographic and clinical characteristics, including health-related quality of life scores, were obtained from 241 adult patients with Type 2 diabetes managed with oral hypoglycaemic agents. Health-related quality of life was assessed using the Short-Form 36 Health Survey. Multiple logistic regression analysis was used to investigate the association between vitamin D status and health-related quality of life, with adjustment for confounders.
The mean age of the patients included in the study was 67 8 years. Their mean HbA1c concentration was 52 8 mmol/mol (6.9 0.7%) and their mean serum 25-hydroxyvitamin D concentration was 59 23 nmol/l. Vitamin D deficiency (serum 25-hydroxyvitamin D < 50 nmol/l) was present in 38% of patients. No significant associations were found between vitamin D status and health-related quality of life.
Results
Conclusions Vitamin D status was not associated with health-related quality of life in patients with Type 2 diabetes. This could be explained by the relatively high serum 25-hydroxyvitamin D concentration, good glycaemic control and relatively good health-related quality of life of all patients. A prospective study among patients with vitamin D deficiency and poor glycaemic control would be interesting for future research.
Diabet. Med. 33, 300–306 (2016)
Introduction Diabetes mellitus is a chronic disease, affecting ~382 million people worldwide in 2013 [1]. Patients with Type 2 diabetes mellitus are at increased risk of developing micro- and macrovascular complications and cardiovascular disease, which subsequently compromises health-related quality of life (HRQoL) [2,3]. Previous research has shown that patients with Type 2 diabetes had a poorer (health-related) quality of life, a higher prevalence of generalized anxiety disorder and elevated symptoms of anxiety compared with the general population [2–5]. In addition, depression is common in patients with Type 2 diabetes, with a prevalence up to 24% in women and 13% in men. Depression in diabetes is associated with a considerably lower quality of life, higher HbA1c levels, increased risk of developing diabetes-specific
Correspondence to: S. Simsek. E-mail: [email protected] *These authors contributed equally to this work.
300
micro- and macrovascular complications, an increased mortality risk and higher healthcare costs [6–10]. Much research has been conducted examining the factors that contribute to a decreased quality of life in patients with Type 2 diabetes [2,3]. A potential factor could be low vitamin D status, which is highly prevalent in patients with Type 2 diabetes, and has been linked to quality of life in several other populations, with conflicting results [11–16]. Vitamin D is a secosteroid that is obtained from dietary sources, either food or supplements, and exposure to sunlight. It needs to be hydroxylated twice to become biologically active. In addition to its known action in calcium and bone homeostasis, vitamin D deficiency has recently been linked to numerous non-skeletal conditions, including Type 2 diabetes. This is the result of the discovery that most tissues and cells, including the brain, immune system and pancreatic b cells, contain the vitamin D receptor and the enzyme 1-a hydroxylase to convert serum 25hydroxyvitamin D [25(OH)D] to its biologically active form,
ª 2015 The Authors. Diabetic Medicine ª 2015 Diabetes UK
Research article
What’s new? In observational studies vitamin D deficiency is associated with poor glycaemic control. Poor glycaemic control is associated with a reduced health-related quality of life. No association between vitamin D status and healthrelated quality of life was found in patients with wellcontrolled Type 2 diabetes. which allows intracrine and paracrine functions [17]. Vitamin D deficiency is a growing worldwide problem. In a cross-sectional study from a population-based cohort among 538 white Dutch patients with Type 2 diabetes aged 60–87 years, the prevalence of serum 25(OH) D < 50 nmol/l was 34% in the summer and up to 51% during winter [11]. Low serum 25(OH)D has been linked to quality of life in several observational studies including study populations other than Type 2 diabetes, e.g. patients with osteoporosis, Crohn’s disease, end-stage renal disease (new on dialysis) and patients with chronic pain [11–15]. The mechanism by which vitamin D status may affect quality of life in patients with Type 2 diabetes is not known. Hypothetically, vitamin D may indirectly improve quality of life by influencing glycaemic control, which has been correlated to vitamin D status in many observational studies [18]. A recent meta-analysis performed by George et al. [19] found a small, non-significant, effect on glycaemic control (i.e. fasting glucose and insulin resistance) after vitamin D supplementation in patients with Type 2 diabetes or impaired glucose tolerance compared with control subjects. In addition, vitamin D might influence systemic inflammation, which is linked to insulin resistance in Type 2 diabetes, by modulating immune responses and oxidative stress [20]. Moreover, vitamin D may have cardioprotective and antidepressant effects that could help to maintain a good HRQoL [21,22]. The aim of the present study was to investigate whether vitamin D status was associated with HRQoL in patients with stable Type 2 diabetes managed with oral hypoglycaemic therapy.
Patients and methods Study design and patients
We conducted a cross-sectional study among 241 patients with Type 2 diabetes derived from five general practices in and around Alkmaar, the Netherlands at a latitude of 52. The patients were included between July 2012 and April 2013 in a randomized placebo-controlled trial (the SUNNY trial), in which the effect on glycaemic control of 50 000 IU vitamin D3 once a month for 6 months, compared with ª 2015 The Authors. Diabetic Medicine ª 2015 Diabetes UK
DIABETICMedicine
placebo, was examined in patients with Type 2 diabetes. The trial was approved by the Medical Ethics Committee of North Holland, the Netherlands. The trial protocol is described in greater detail elsewhere [23]. In brief, adult patients (age ≥ 18 years) with Type 2 diabetes treated with lifestyle advice, metformin or sulphonylurea derivatives, alone or in combination, were invited to participate in the study. Serum HbA1c levels had to be stable and ≤64 mmol/ mol (8.0%) for the last 3 months, without recent changes in hypoglycaemic agents. The main exclusion criteria were: impaired renal function (estimated GFR < 30 ml/min calculated from serum creatinine using the Modification of Diet in Renal Disease, MDRD, formula); any granuloma-forming disorder; hypercalcaemia (serum calcium > 2.65 nmol/l) for any reason; serum 25(OH)D < 15 nmol/l or > 150 nmol/l; urolithiasis; psychiatric treatment for schizophrenia; organic mental disorder or bipolar disorder currently or in the past; insufficient knowledge of the Dutch language; substance abuse (other than nicotine); or no signed informed consent. The patients were allowed to take vitamin D supplements at a maximum dose of 400 IU a day before inclusion.
Study variables
The following data were collected: age, gender, ethnicity, marital status, education level, employment status, diabetes duration, diabetes-specific complications, medication use and diabetic therapy, comorbidities, smoking status, alcohol use, dietary fish and dairy intake, physical activity, sun exposure and season of blood collection. Also standard anthropometric data (height, weight) and venous blood collection were obtained from each patient. Serum 25(OH)D was measured on an iSYS automated immunoanalyser (IDS GmbH, Frankfurt, Germany). The total 25(OH) D assay detects 25(OH)D2 and 25(OH)D3, both with a specificity of 100%. The quality of the test is controlled by applying Westgard quality control rules on three different quality control samples.
Health-related quality of life
We used the Dutch-language version of the Short-Form 36 Health Survey (SF-36) to assess HRQoL at baseline. The SF36 consists of 36 questions and set response choices on an ordinal scale. There are eight domains and two summary measures: physical functioning, role limitations attributable to physical problems, bodily pain, general health perceptions (together presenting the physical component summary), and mental health, vitality, social functioning and role limitations attributable to emotional problems (together presenting the mental component summary measure) [24]. For each domain, the HRQoL scores are converted to a scale of 0 to 100, with higher scores indicating a better HRQoL. The SF36 has adequate internal consistency (Cronbach’s a from 0.65 to 0.94, diabetes-specific from 0.76 to 0.93) and test-
301
DIABETICMedicine
Vitamin D status and quality of life in Type 2 diabetes Y. H. M. Kruk-Poel et al.
retest reliability (r = 0.63–0.81) [25,26]. In 1994, Aaronson et al. [27] translated and validated the Dutch language version of the SF-36 (Cronbach’s a from 0.66 to 0.93, mean 0.84).
Statistical analyses
For the purpose of the present cross-sectional study patients were stratified into two groups according to their vitamin D status: 1) serum 25(OH)D < 50 nmol/l, which was defined as vitamin D deficiency, and 2) serum 25(OH)D ≥ 50 nmol/l, which indicated a sufficient vitamin D status. Patient demographic and clinical characteristics were compared using a Pearson’s chi-squared test for categorical variables and an independent sample t-test or Mann–Whitney test for continuous variables, depending on normality. Multiple logistic regression analyses were performed to explore the association between vitamin D status [serum 25(OH) D < 50 nmol/l and > 50 nmol/l] and each HRQoL domain. All analyses were adjusted for age, gender, season of measurement, pre-existing cardiovascular disease and BMI, based on earlier literature and in case of a regression correlation coefficient difference > 10%. Subgroup analyses regarding glycaemic control [HbA1c ≥ 53 mmol/mol (≥ 7.0%)] and poor level of HRQoL for each domain (using national Dutch means stratified by gender and found by Aaronson et al. [27] to distinguish reduced HRQoL), were performed using the same method as the primary analysis. Subgroup analyses regarding patients with a lower HRQoL, however, were solely adjusted for season of measurement and BMI because of the small number of patients included in the analysis, which resulted in insufficient power to correct for all confounders. All analyses were also performed stratified by gender because of differences in HRQoL between men and women. All data were analysed using the SPSS statistical software package (IBM version 20.0; SPSS Inc., Chicago, IL, USA). Data are presented as numbers (%), median [interquartile range (IQR)] or means SD. A P value of < 0.05 was considered to indicate statistical significance.
Results A total of 300 patients were recruited to the SUNNY trial, of whom 275 attended the first visit and were randomized. Of these 275 patients, 241 (88%) returned the SF-36 questionnaire that they received at the first visit. The mean patient age was 67 8 years and 65% were men. The median (IQR) diabetes duration was 6 (3–8) years with a mean HbA1c of 52 8 mmol/mol (6.9 0.7%). Overall mean serum 25 (OH)D was 59 23 nmol/l. The prevalence of vitamin D deficiency, serum 25(OH)D < 50 nmol/l, was 38% and 150 patients (68%) had a serum 25(OH)D ≥ 50 nmol/l. The demographic and clinical characteristics and HRQoL scores of all patients, stratified by serum 25(OH)D < 50 nmol/l and >50 nmol/l, are shown in Table 1. Patients with vitamin D
302
deficiency were more likely to be women, more often had dark-coloured skin, had a higher incidence of smoking, were less physically active, had less sun exposure, had a higher BMI, and were more often single compared with the group with a serum 25(OH)D ≥ 50 nmol/l (all P < 0.05). No differences were observed in the eight HRQoL domains, nor in the physical or mental component summary, between the groups. HRQoL scores were higher in men than in women, particularly the domains physical functioning, bodily pain, social functioning, mental health, vitality and general health perceptions (data not shown). Concerning the main outcome, the association between HRQoL and serum 25(OH)D in patients with Type 2 diabetes, no significant associations were observed after correction for the following confounders: age, gender, season of measurement, pre-existent cardiovascular disease and BMI (Table 2). In addition, no effect was seen in the summary components. A significant association was observed between physical functioning and serum 25(OH)D ≥ 50 nmol/l (odds ratio 1.01, 95% CI 1.00–1.03; P = 0.04), but this no longer remained significant after adjustment for confounders. Prespecified subgroup analysis in patients with lower glycaemic control [HbA1c ≥ 53 mmol/mol, (≥ 7.0%), n = 71] showed a small association between serum 25(OH) D ≥ 50 nmol/l and role limitations attributable to emotional problems before and after adjustment for confounders (odds ratio 1.02, 95% CI 1.00–1.04; P = 0.02, data not shown). The results did not differ significantly when including only patients with a relatively poor HRQoL for one of the SF-36 domains.
Discussion In the present cross-sectional study in Dutch patients with Type 2 diabetes managed with oral hypoglycaemic therapy, no association between serum 25(OH)D and HRQoL was observed. The question of whether vitamin D status and HRQoL are associated has not been studied before in patients with Type 2 diabetes; however, studies examining the association between vitamin D status and HRQoL in other populations are available. In a large population-based cohort study in 15 954 post-menopausal women, a small difference in mental HRQoL was seen between women with a low (< 400 IU/day) and high vitamin D3 intake (≥ 800 IU/ day); however, this result was attenuated after controlling for the confounders: age; energy intake; BMI; education; smoking; living arrangement;antidepressant usage; comorbidity history; and physical activity [16]. In contrast to the results of the present study, a recent population-based observational study among Dutch patients aged > 70 years, found a significantly lower score on the physical component of HRQoL in patients with a severe vitamin D-deficient status [serum 25(OH)D < 25 nmol/l]; however, physical performance, depressive symptoms and the number of chronic diseases explained this association largely [28].
ª 2015 The Authors. Diabetic Medicine ª 2015 Diabetes UK
Research article
DIABETICMedicine
Table 1 Demographic, clinical characteristics and health-related quality of life of all patients, stratified by vitamin D level Serum 25(OH)D
Demographic characteristics Male, n (%)* Mean SD age, years Median (IQR) diabetes duration, years White skin colour, n (%)* Antidiabetic treatment, n (%) Lifestyle adjustments Metformin Sulphonylurea derivatives Metformin and sulphonylurea derivatives Microvascular complications† ≥1, n (%) Cardiovascular disease, n (%) Single, n (%)* Education level, n (%) Low Middle High Employment status, n (%) Paid employment Unemployed or incapacitated Retired Current smoker, n (%)* Alcohol use >2 units/day, n (%) Physical activity, n (%)* 5 h/week Sun exposure, n (%)* 10 h/week Season of blood collection, n (%) Spring Summer Autumn Winter Clinical characteristics, mean sd BMI, kg/m²* HbA1c, mmol/mol HbA1c, % Estimated GFR, ml/min Serum 25(OH)D, nmol/l* Serum parathyroid hormone, pmol/l Health-related quality of life, median (IQR) score Physical component summary Physical functioning Role limitations physical Bodily pain General health perceptions Mental component summary Mental health Role limitations emotional Vitality Social functioning
All patients n = 241
