Assessment of the Role of Serum
25-Hydroxy Vitamin D Level on Coronary
Heart Disease Risk With Stratification
Among Patients With Type 2 Diabetes
Mellitus
Abdu¨lbari Bener, PhD
1,2,3, Abdulla O. A. A. Al-Hamaq, PhD
4,
Susu M. Zughaier, PhD
5, Mustafa O
¨ ztu¨rk, MD
3, and Abdu¨lkadir O
¨ mer, MD
3Abstract
We investigated the role of vitamin D on glycemic regulation and cardiac complications in patients with type 2 diabetes mellitus (T2DM). A total of 1139 patients (49.3% males vs 50.7% females) were included. Information on sociodemographic lifestyle, family history, blood pressure (BP), and coronary heart disease (CHD) complications was collected. Significant differences were found between males and females regarding age-groups (P¼ .002), body mass index (BMI; P ¼ .008), physical activity (P ¼ .010), sheesha smoking (P¼ .016), cigarette smoking (P ¼ .002), hypertension (P ¼ .050), metabolic syndrome (P ¼ .026), and CHD (P¼ .020). There were significant differences between vitamin D deficiency, insufficiency, and sufficiency in relation to age-group (P¼ .002), income (P ¼ .002), waist circumference (P ¼ .002), hip circumference (P ¼ .028), waist–hip ratio (P ¼ .002), and BMI (P¼ .002). Further, mean values of hemoglobin, magnesium, creatinine, hemoglobin A1c(HbA1c), total cholesterol, uric acid, and diastolic BP were significantly higher among patients with vitamin D deficiency compared with those with insufficiency and suf-ficiency. Multiple logistic regression analysis revealed that 25-hydroxy vitamin D, 25(OH)D, HbA1c, waist circumference, uric acid, duration of T2DM, total cholesterol, systolic and diastolic BP, and BMI were strong predictor risk factors for CHD among patients with T2DM. The present study supports that 25(OH)D may have a direct effect on CHD and on its risk factors.
Keywords
epidemiology, diabetes, complications, coronary heart disease, vitamin D
Introduction
Type 2 diabetes mellitus (T2DM) is a major worldwide health problem1 that also affects the economic status of countries regardless of their socioeconomic status or geographic loca-tion.2 Moreover, T2DM increases the risk of coronary heart disease (CHD) and kidney disease. The mortality rate for CHD and its adverse effects are increasing despite developments in the prevention and management of CHD.1,2 There is an increased risk for CHD among diabetic patients.3-5It follows that risk prediction is of interest. Therefore, new risk factors were added to conventional models used to calculate CHD risk.6 In this context, a number of studies have found that 25-hydroxy vitamin D, 25(OH)D, deficiency is common and associated with increased CHD.7-10Deficiency of 25(OH)D is prevalent in 41% of American adults,11while nearly 75% of patients with myocardial infarction had 25(OH)D deficiency also in America or elsewhere.12
Epidemiological studies have demonstrated that vitamin D deficiency contributes to increased risk for obesity and T2DM.9,13,14 Vitamin D deficiency in obese patients is
associated with T2DM and metabolic syndrome (MetS).13-14 Vitamin D deficiency can contribute to various conditions, such as hypertension, coronary artery disease, stroke, and atherosclerosis.15Some studies consider evidence as adequate
1Department of Biostatistics and Medical Informatics, Cerrahpas¸a Faculty
of Medicine, Istanbul University, Istanbul, Turkey
2Department of Evidence for Population Health Unit, School of Epidemiology
and Health Sciences, The University of Manchester, United Kingdom
3Department of Endocrinology, International School of Medicine, Istanbul
Medipol University, Regenerative and Medicine Research Centre, Istanbul, Turkey
4Qatar Diabetic Associations and Qatar Foundation, Doha, Qatar
5Department of Basic Medical Sciences, College of Medicine, QU Health,
Qatar University, Doha, Qatar Corresponding Author:
Abdu¨lbari Bener, Department of Biostatistics and Medical Informatics, Cerrahpas¸a Faculty of Medicine, Istanbul University Cerrahpasa and Istanbul Medipol University, International School of Medicine, 34098 Cerrahpasa, Istanbul, Turkey.
Emails: abdulbari.bener@istanbul.edu.tr; abener99@yahoo.com Angiology
2021, Vol. 72(1) 86-92 ªThe Author(s) 2020 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/0003319720951411 journals.sagepub.com/home/ang
to establish low vitamin D levels as a cardiovascular disease (CVD) risk factor.16,17Furthermore, several studies have inves-tigated the association between vitamin D deficiency, MetS, obesity, insulin resistance, dyslipidemia, hypertension, and the risk of CVDs and/or T2DM.18,19An Australian study examined the role of vitamin D deficiency in increasing the risk of devel-oping T2DM.20Moreover, another study showed that the level of 25(OH)D was higher in healthy controls compared with patients with T2DM.21
Vitamin D insufficiency is common in diabetic patients and is associated with CHD. A limited number of studies evaluated vitamin D status in patients with CHD and T2DM. Vitamin D status is assessed by measuring circulating 25(OH)D levels; <12 ng/mL indicates deficiency and <20 ng/mL represents insufficiency.5,9-10
The present study investigated the role of vitamin D in glycemic regulation and cardiac complications in patients with T2DM. We also assessed the role of gender on sociodemo-graphic characteristics and lifestyle habits.
Participants, Methods, and Modeling
This study is based on a prospective cohort. It was conducted between February 2015 and December 2018 at the Medipol University Hospitals and Primary Health Care centers in Istan-bul among Turkish citizens aged >35 years. The patients were followed up for 3 years. Patients were screened every 6 months for MetS, neuropathy, nephropathy, and retinopathy. The study was approved by Institutional Review Board of the Medipol International School of Medicine, Istanbul Medipol University (IRB# 604.01.01-E.3193 and IRB# 10840098-604.01.01-E.8421).
Sampling Procedure
The prevalence of impaired fasting glucose in Turkey is 17% to 20%,1,5and the sample size was determined by assuming 0.1% level of significance and 2% error of estimation. The minimum sample size was calculated as 1500 participants, and 1139 (75.9%) gave consent and were enrolled. Due to limitation in time, finance, technical staff availability, and resources to com-plete medical records for patients’ data extraction, 361 patients were lost for follow up from the total 1500 patients. Therefore, 75.9% of patient recruitment was completed. Inclusion criteria were being a diabetic patient for3 years. The endocrinologist screened (eg, electrocardiogram, magnetic resonance imaging, and computed tomography) patients according to needs.
Laboratory Measurements
Blood samples were collected at the morning of the catheter-ization procedure and after overnight fasting. A venous blood sample was obtained from patients after 10 hours of fasting. Blood glucose was measured using a ROCHE COBAS 6000 auto-analyzer, Roche Diagnostics.
The definition of diabetes by World Health Organization (WHO) expert group was used.2 Patients with a history of T2DM and usage of oral antidiabetic drugs for treatment. The inclusion criteria of this study included: (1) older than 20 years, (2) fasting plasma glucose (FPG)7.0 mmol/L and/or 2-hour postprandial plasma glucose or casual plasma glucose 11.1 mmol/L, (3) antidiabetic medication treatment for 3 years, and (4) written informed consent.
National Cholesterol Education Program—
Third Adult Treatment Panel
According to the Third Adult Treatment Panel criteria, a parti-cipant has MetS if3 of the following criteria are presnt1,18
: (1) FPG100 mg/dL (5.6 mmol/L), (2) blood pressure 130/ 85 mm Hg, (3) triglycerides 150 mg/dL (1.7 mmol/L), (4) high-density lipoprotein cholesterol (HDL-C): men <40 mg/dL (1.03 mmol/L) and women <50 mg/dL (1.29 mmol/L, and (5) men with waist circumference >102 cm and women with waist circumference >88 cm.18
Serum samples were stored at70C until analysis. Serum 25(OH)D levels were detected using competitive radioimmu-noassay (RIA; DiaSorin), which is considered as the best approach to measure this vitamin D metabolite.13 The RIA procedure used to measure 25(OH)D levels was used following manufacturer instructions (DiaSorin).13The basis is a selective immunoextraction of 25(OH)D from serum or plasma with a specific monoclonal antibody bound to a solid support, and this antibody is directed toward the H-hydroxylated A ring of 25(OH)D. The DiaSorin tests have been utilized in the vast majority of large-clinical studies worldwide to define “normal” circulating 25(OH)D levels in a variety of disease states.13This test still remains today the only RIA-based assay that provides a “total” 25(OH)D value. According to the serum levels of vitamin D, patients were categorized into the following 3 sub-groups: (1) deficiency, 25(OH)D <20 ng/mL; (2) insufficiency, 25(OH)D 20 to 29 ng/mL; and (3) sufficiency, >30 ng/mL.6,13
Other Measurements
The WHO criteria were used to categorize obesity and over-weight.2Participants were obese if body mass index (BMI) was 30 kg/m2and overweight if BMI was >25 kg/m2.
The definition of hypertension by the WHO International Society of Hypertension Writing Group22 was adopted with standardized criteria as systolic blood pressure (SBP) 140 mm Hg or diastolic blood pressure (DBP) 90 mm Hg or antihypertensive drug usage. Patients who were walking or cycling for more than 30 minutes/d were considered as physi-cally active.
Statistical Analysis
The Statistical Package for Social Sciences (IBM SPSS Statis-tics for Windows, Version 25.0, IBM Corp) was used. Student t tests determined the significance of the difference between 2
means of a continuous variable. The differences in proportions of categorical variables between 2 or more groups were tested by a Chi-square test. One-way analysis of variance was per-formed to compare several group means and to determine the presence of significant differences between group means. Mul-tiple stepwise logistic regression analysis was used to assess the relationship between dependent and independent variables and adjusted for potential confounders and orders the importance of risk factors (determinant) for CHD among patients with T2DM. All hypotheses were examined using 2-tailed tests and P < .05 was used as the significance level.
Results
The results obtained from the preliminary analysis of data show that the median length of patients follow-up was 7 years (mean and standard deviation: 7.2 + 3.6 years). A total of 361 patients did not participate or were lost for follow-up were excluded from the database and statistical analysis.
Table 1 shows the comparison of sociodemographic char-acteristic between males and females. There were significant differences between males and females regarding age (P¼ .002), BMI (P ¼ .008), physical activity (P ¼ .010), sheesha smoking (P¼ .016), cigarette smoking (P ¼ .002), family history of hypertension (P¼ .050), MetS (P ¼ .026), and CHD (P ¼ .02), respectively.
Table 2 presents sociodemographic characteristics and life-style habits according to vitamin D levels. Statistically signif-icant differences were found between 3 groups of vitamin D deficiency, insufficiency, and sufficiency regarding age (P¼ .004), household income (P ¼ .002), waist circumference (cm; P¼ .002), hip circumference (cm; P ¼ .028), waist–hip ratio (P¼ .002), and BMI (kg/m2
; P¼ .002), respectively. Table 3 shows the comparison of clinical and biochemical parameters according to the 25(OH)D (ng/mL) levels. Mean values of the biochemical parameters serum creatinine, fasting blood glucose, hemoglobin A1c(HbA1c), total cholesterol, uric acid, and DBP were significantly higher among the patients with vitamin D deficiency compared with those with insuffi-ciency and suffiinsuffi-ciency.
Table 4 shows the comparison of clinical and biochemical parameter baseline values among patients having T2DM with CHD and without CHD. Mean values of the biochemical para-meters BMI vitamin D, fasting blood glucose, HbA1c, total cholesterol, low-density lipoprotein cholesterol, uric acid, SBP, and DBP were significantly higher among the patients having T2DM with CHD compared with those without CHD.
Multiple logistic regression analysis was used to predict potential confounding risk factors for CHD among patients with T2DM (Table 5). The analysis revealed that 25(OH)D (ng/mL; odds ratio [OR] ¼ 4.40; 95% CI: 2.28-8.30, P < .001), HbA1c(OR¼ 3.36; 95% CI: 2.14-5.17, P < .001), waist circumference (cm; OR¼ 3.22; 95% CI: 2.46-4.78, P < .001), uric acid (mmol/L; OR¼2.88; 95% CI: 2.31-5.05, P ¼ .003), duration of diabetes mellitus in years (OR¼ 2.59; 95% CI: 2.14-3.48, P¼ .007), total cholesterol (mmol/L; OR ¼ 2.45;
95% CI: 1.89-3.26, P¼ .012), systolic blood pressure (mm Hg; OR ¼ 1.99; 95% CI: 1.31-3.07, P ¼ .029), DBP (mm Hg; OR ¼ 1.86; 95% CI: 1.52-2.73, P ¼ .036), and BMI (kg/m2
; OR¼ 1.67; 95% CI: 1.38-1.94, P ¼ .042) were strong predictors and significant risk factors for CHD among patients with T2DM.
Discussion
Vitamin D deficiency is common worldwide.11-12The associ-ation of low vitamin D status with numerous chronic diseases such as T2DM, CVD, cancer, and autoimmune diseases is established.23 Several studies have reported that serum Table 1. Sociodemographic Characteristics and Lifestyle Habits
by Gender Among Patients With T2DM.a
Variables Gender Males¼ 561 n (%) Females¼ 578 n (%) P value significance Age groups (in years):
<40 101 (18) 156 (27) .002 40-49 147 (26.2) 149 (25.9) 50-59 187 (33.3) 128 (22.1) >60 and above 126 (22.5) 45 (25.1) Marital status Single 54 (9.6) 51 (8.8) .513 Married 455 (81.1) 483 (83.6) Divorced/widow 52 (9.3) 44 (7.6)
Body mass index, kg/m2
Normal (<25) 123 (21.9) 174 (30.1) .008 Overweight (29-30) 288 (51.4) 250 (43.3) Obese (>30) 150 (26.7) 154 (26.6) Physical activity, 30 minutes/d Yes 121 (21.6) 166 (28.7) .010 No 440 (78.4) 412 (71.3) Household income: Low 177 (21.6) 223 (38.6) .082 Medium 187 (33.3) 179 (31.0) High 197 (35.1) 176 (30.4) Sheesha smoking: Never 64 (19.4) 69 (12.8) .016 Current smoker 266 (80.6) 472 (87.2) Cigarette smoking: Never 442 (78.8) 504 (87.2) .002 Current smoker 69 (12.3) 50 (8.7) Past smoker 44 (7.9) 24 (4.2) Family history of hypertension Yes 131 (23.4) 104 (18.0) .050 No 430 (76.6) 474 (82) Metabolic syndrome Yes 161 (28.7) 129 (22.3) .026 No 400 (71.3) 449 (77.7)
Coronary heart disease
Yes 128 (22.8) 78 (13.5) .002
No 433 (77.2) 500 (86.5)
Abbreviation: T2DM, type 2 diabetes mellitus.
a
25(OH)D levels were lower in patients with T2DM compared with healthy individuals.6,8,11The authors found that the level of HbA1cis higher in patients with T2DM who have vitamin D deficiency. This observation is consistent with other studies reporting that vitamin D deficiency is widely common in patients with T2DM.6,8,11
Type 2 diabetes mellitus is a major risk for CHD24which is the leading cause of death among these patients. Type 2 dia-betes mellitus has many complications where hyperglycemia contributes to complications.25The Diabetes Control and Com-plication Trial determined that hyperglycemia increases the development of diabetic macrovascular complications in patients with type 1 diabetes.26Glycemic control plays an key role to decrease the risk of all diabetes complications and mor-tality and morbidity because of CVD in patients with type 1
diabetes.26 Moreover, there was a relationship between high prevalence of vitamin D deficiency and prevalent CVD in patients with T2DM.9
Glycaemia and insulin sensitivity are impacted by vitamin D status in diabetic patients as well as healthy people. A direct association was found between vitamin D deficiency and high insulin resistance, as vitamin D has an effect on insulin sensi-tivity and b-cell function.27Vitamin D deficiency is associated with an increase in cardiovascular risks and mortality among patients with T2DM.9,28 A study investigated the correlation between vitamin D deficiency and CVD in healthy individuals and patients with T2DM; they observed that severe vitamin D deficiency is associated with increased cardiovascular mortal-ity.29In our study, we observed that fasting blood glucose and HbA1care higher in diabetic patients with vitamin D deficiency Table 2. Sociodemographic Characteristics and Lifestyle Habits According to Vitamin D Levels.a
Variables Deficiency 25(OH)D <20 ng/mL n¼ 495 Insufficiency 25(OH)D 20-29 ng/mL n¼ 349 Sufficiency 25(OH)D > 30 ng/mL n¼ 295 n (%) n (%) n (%) Pb
Age groups, in years
<40 117 (23.6) 88 (25.7) 52 (17.6) 40-49 146 (28.7) 87 (24.9) 67 (22.7) .004 50-59 143 (28.9) 90 (25.8) 82 (27.8) >60 and above 93 (18.6) 84 (24.1) 94 (31.9) Gender Male 242 (48.9) 171 (49) 148 (50.2) .935 Female 253 (51.1) 178 (51) 147 (49.8)
Body mass index, kg/m2
Normal (<25) 131 (26.5) 88 (25.5) 77 (26.1)
Overweight (29-30) 228 (46.1) 171 (49) 139 (47.1) .945
Obese (>30) 136 (27.5) 89 (25.5) 79 (26.8)
Physical activity 30 minutes/d
Yes 130 (26.3) 83 (23.8) 63 (21.4) .289 No 365 (73.6) 266 (76.2) 232 (78.6) Household income Low 162 (32.7) 109 (31.2) 129 (43.7) Medium 156 (31.5) 115 (33.0) 95 (32.2) .002 High 177 (35.8) 125 (35.8) 71 (24.1) Smoking status Never smoker 418 (84.4) 280 (80.2) 239 (81.0) Past smoker 50 (10.1) 44 (12.6) 40 (13.6) .420 Current smoker 27 (5.5) 25 (7.2) 16 (5.4) Smoking sheesha Yes 76 (15.4) 58 (16.6) 53 (18.0) No 419 (84.6) 291 (83.4) 242 (82.0) .627 Sleep quality Good 121 (24.4) 74 (21.2) 58 (19.7) Average 125 (50.3) 80 (22.9) 88 (29.8) .320 Poor 249 (39.0) 195 (55.9) 149 (50.5) Waist circumference (cm) 89.0 + 10.2 89.0 + 10.6 85.0 + 11.7 .002 Hip circumference, cm 102.6 + 10.3 100.7 + 9.5 98.7 + 9.4 .028 Waist–hip ratio 0.9 + 0.1 0.9 + 0.01 0.8 + 0.1 .002
Body mass index, kg/m2 31.9 + 7.1 28.4 + 5.4 27.4 + 5.9 .002
Abbreviations: T2DM, type 2 diabetes mellitus; 25(OH)D, 25-hydroxy vitamin D.
an¼ 1139.
when compared with those without vitamin D deficiency. Our finding is in agreement with other studies.21,30,31 Similarly, high HbA1c, high uric acid, and low HDL-C levels are common
among patients with vitamin D deficiency.32Vitamin D has an effect on CHD directly and indirectly.33Furthermore, vitamin D levels <21 ng/mL is associated with an increased risk of Table 3. Clinical Biochemistry Parameters Value and Vitamin D Levels Among Patients With T2DM.a
Parameters Deficiency 25(OH)D <20 ng/mL, n¼ 495 Mean + SD Insufficiency 25(OH)D 20-29 g/mL, n¼ 349 Mean + SD Sufficiency 25(OH)D >30 ng/mL, n¼ 295
Mean + SD P valuebsignificance
Hemoglobin, g/dL 11.15 + 2.41 12.48 + 2.65 12.96 + 2.72 .046
Magnesium, mmol/L 0.73 + 0.09 0.81 + 0.10 0.89 + 0.08 .002
Potassium, mmol/L 5.08 + 0.63 4.50 + 0.39 4.53 + 0.40 .548
Calcium, mmol/L 1.89 + 0.38 2.09 + 0.38 2.25 + 0.26 .076
Phosphorous, mmol/L 1.29 + 0.30 1.42 + 0.30 1.56 + 0.26 .090
Serum creatinine, mmol/L 75.8 + 29.6 72.9 + 26.6 67.6 + 18.8 .002
Fasting blood glucose, mmol/L 8.4 + 1.1 7.5 + 1.3 7.4 + 0.9 .006
HbA1c 7.7 + 1.11 7.5 + 0.88 7.2 + 0.8 .002
Total cholesterol, mmol/L 2.5 + 0.6 2.3 + 0.6 2.3 + 0.5 .006
HDL-C, mmol/L 1.1 + 0.2 1.1 + 0.2 1.2 + 0.2 .072
LDL-C, mmol/L 2.8 + 0.7 2.9 + 0.7 2.8 + 0.7 .064
Albumin, g/L 38.2 + 8.4 38.9 + 8.1 36.8 + 9.3 .228
Bilirubin, mmol/L 8.4 + 3.6 8.5 + 3.5 8.2 + 3.4 .733
Triglycerides, mmol/L 1.6 + 0.4 1.4 + 0.3 1.4 + 0.8 .092
Uric acid, mmol/L 313 + 102 277 + 87 281 + 74 .002
Systolic blood pressure, mm Hg 140.6 + 12.4 139.8 + 12.1 141.4 + 12.0 .098
Diastolic blood pressure, mm Hg 86.3 + 5.9 84.4 + 6.3 83.8 + 6.2 .002
Abbreviations: HbA1c, hemoglobin A1c; LDL, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; SD, standard deviation; T2DM,
type 2 diabetes mellitus; 25(OH)D, 25-hydroxy vitamin D.
an¼ 1139.
bComparison between 3 vitamin D levels among T2DM.
Table 4. Clinical Biochemistry Parameters Value With and Without CHD Among Patients With T2DM.a
Parameters
Patients with CHD, n¼ 206 Mean + SD
Patients without CHD, n¼ 933
Mean + SD P value significance
Age in years 54.8 + 9.8 54.0 + 9.7 .325
Body mass index, kg/m2 30.5 + 4.5 27.7 + 4.0 .002
25(OH) vitamin D, ng/mL 18.6 + 10.0 22.8 + 11.1 .002
Diabetes duration in years 10.4 + 3.6 8.0 + 4.1 .002
Hemoglobin, g/dL 11.4 + 2.6 13.0 + 2.9 .050
Magnesium, mmol/L 0.78 + 0.10 0.81 + 0.12 .482
Potassium, mmol/L 5.2 + 0.6 4.7 + 0.4 .040
Calcium, mmol/L 1.77 + 0.36 2.06 + 0.35 .078
Phosphorous, mmol/L 1.38 + 0.32 2.12 + 0.30 .004
Serum creatinine, mmol/L 77 + 33 73 + 29 .100
Fasting blood glucose, mmol/L 8.3 + 1.3 7.4 + 1.2 .002
HbA1c, % 7.8 + 0.9 7.4 + 0.9 .002
Total cholesterol, mmol/L 2.5 + 0.6 2.4 + 0.6 .040
HDL-C, mmol/L 1.1 + 0.2 1.2 + 0.2 .002
LDL-C, mmol/L 2.1 + 0.9 1.9 + 0.8 .010
Albumin, g/liter 38.7 + 9.4 37.5 + 8.3 .444
Bilirubin, mmol/L 8.4 + 3.7 8.3 + 3.4 .991
Triglycerides, mmol/L 1.6 + 0.5 1.5 + 0.4 .428
Uric acid, mmol/L 294 + 84 278 + 78 .018
Systolic blood pressure, mm Hg 140.4 + 12.0 135.7 + 7.7 .002
Diastolic blood pressure, mm Hg 86.2 + 5.7 84.8 + 6.3 .002
Abbreviations: CHD, coronary heart disease; HbA1c, hemoglobin A1c; LDL, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol;
SD, standard deviation; T2DM, type 2 diabetes mellitus; 25(OH)D, 25-hydroxy vitamin D.
hypertension, T2DM, obesity, and triglycerides that contribute to increased cardiovascular mortality.6,15-17Overall, vitamin D deficiency has been found to contribute to various cardiac con-ditions, such as hypertension, CHD, stroke, and atherosclero-sis.15,34 In addition, several studies considered evidence as adequate to establish low vitamin D levels as a CVD risk fac-tor.16-17,35Further, due to its immune modulator activity vita-min D exerts extraskeletal functions. Sufficient levels of vitamin D are anti-inflammatory and the hormonally active 1a-25-dihyroxyvitamin D was shown to downregulate inflam-matory cytokines such as interleukin (IL) 6 and Il-1b gene expression.36 Vitamin D also downregulates serum hepcidin level, the master iron regulating hormone.36In our study, we found significant difference in hemoglobin level between patients having T2DM with CHD and those without, suggest-ing anemia of chronic disease that is induced by inflammation. This observation warrant further investigation since hepcidin is directly regulated by vitamin D as it contains a vitamin D response element binding site on its promoter.36Those previ-ous reports6,15-17,32-34lend support to our current study.
Limitations
The design of current study is an observational cohort, which does not allow us to derive any cause-effect relation, therefore, it is not possible to predict the complications but only suggest that the best suitable indicators of CHD risk. Secondly, follow-up was short. Thirdly, patient recruitment was at 75.9% rather than 100% as 361 patients were lost for follow-up.
Conclusions
Our findings confirm that 25(OH)D has potential direct and indirect associations with CHD by links with risk factors such as hypertension, high level HbA1c, waist circumference, BMI, T2DM duration, and uric acid. Therefore, increasing 25(OH)D levels in patients with T2DM may improve CHD-related outcomes.
Authors’ Note
AB, AO¨ , and MO¨ contributed to conception and design; organized study; collected data; performed statistical analysis; wrote the first draft of the article; contributed to the interpretation of the data and writing; revised critically and approved final version of the manu-script. AOAA contributed to the funding, conception, design, inter-pretation of the data and writing the manuscript, revised critically, and approved final version of manuscript. SMZ contributed to the concep-tion, design, interpretation of the data, and writing the manuscript; revised critically and approved final version of the manuscript. The study received no cash financial support. The Qatar Foundation pro-vided 20% of reagents and consumable materials used in this study. Written and verbal informed consent was obtained.
Acknowledgments
This work was partially supported by the Qatar Diabetes Association, Qatar Foundation. The authors would like to thank the Istanbul Medipol University for their support and ethical approval (Research Protocol and IRB# 604.01.01-E.3193 and IRB# 10840098-604.01.01-E.8421).
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-ship, and/or publication of this article.
ORCID iD
Abdu¨lbari Bener https://orcid.org/0000-0002-7902-5803
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Table 5. Multivariate Stepwise Logistic Regression Analysis for
Pre-dictors of Risk Factors Related to the CHD Among Patients With T2DM.a Independent variables Odds ratio (95% CI) P value significance 25(OH)D, ng/mL 4.40 (2.28-8.30) <.001 HbA1c 3.36 (2.14-5.17) <.001 Waist circumference, cm 3.22 (2.46-4.78) <.001
Uric acid, mmol/L 2.88 (2.31-5.05) .003
Duration of DM in years 2.59 (2.14-3.48) .007
Total cholesterol, mmol/L 2.45 (1.89-3.26) .012
Systolic blood pressure, mm Hg 1.99 (1.31-3.07) .029
Diastolic blood pressure, mm Hg 1.86 (1.52-2.73)) .036
Body mass index, kg/m2 1.67 (1.38-1.94) .042
Abbreviations: CHD, coronary heart disease; DM, diabetes mellitus; T2DM, type 2 diabetes mellitus; 25(OH)D, 25-hydroxy vitamin D.
a
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