|Year : 2019 | Volume
| Issue : 4 | Page : 253-257
Association of Vitamin D levels with blood pressure changes and mean arterial pressure in prediabetics
K Goel1, R Rajput2, Simmi Kharb1
1 Department of Biochemistry, Medicine, Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India
2 Department of Biochemistry, Endocrinology, Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India
|Date of Submission||17-Jun-2019|
|Date of Acceptance||09-Sep-2019|
|Date of Web Publication||03-Dec-2019|
Dr. Simmi Kharb
#1396, Sector-1, Rohtak, Haryana
Source of Support: None, Conflict of Interest: None
Background: Hypertension, which is associated with cardiovascular disease, is emerging as a risk factor for prediabetes and diabetes. A few studies have taken into account of the impact of Vitamin D on blood pressure (BP) in individuals who have hypertension. It is still not clear whether serum Vitamin D concentration plays an important role in causing hypertension or not. Methods: The present study was planned to study the correlation of Vitamin D with BP and changes in mean arterial in prediabetics. This case–control study was conducted in Department of Biochemistry in collaboration with Department of Endocrinology, PGIMS, Rohtak. Forty consecutive diagnosed cases of prediabetes and forty age- and sex-matched healthy normoglycemic controls were enrolled. Routine biochemistry investigations were done as per standard methods. Serum 25-hydroxy vitamin D was analyzed by radioimmunoassay. SPSS version 23 was used, and results were expressed as mean ± standard deviation. Results: Systolic as well as diastolic BP (DBP) and mean arterial BP were higher in prediabetes cases as compared to controls. Vitamin D levels showed a negative correlation with systolic BP, DBP, and mean arterial pressure (MAP) in both prediabetes cases as well as in controls. Conclusions: The findings of the present study suggest that BP changes and MAP might be causative factor in the pathogenesis of prediabetes.
Keywords: Hypertension, insulin resistance, metabolic syndrome, prediabetes
|How to cite this article:|
Goel K, Rajput R, Kharb S. Association of Vitamin D levels with blood pressure changes and mean arterial pressure in prediabetics. Biomed Biotechnol Res J 2019;3:253-7
|How to cite this URL:|
Goel K, Rajput R, Kharb S. Association of Vitamin D levels with blood pressure changes and mean arterial pressure in prediabetics. Biomed Biotechnol Res J [serial online] 2019 [cited 2019 Dec 9];3:253-7. Available from: http://www.bmbtrj.org/text.asp?2019/3/4/253/272191
| Introduction|| |
Prediabetes is an intermediate stage between normal glucose levels and the clinical entity of type 2 diabetes (T2D), which includes both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).
Worldwide, epidemiological trends demonstrate an increase in the prevalence of prediabetes in general population. Prevalence rate of prediabetes in the general population in the UK has been reported to be increased from 11.6% to 35.3% from 2003 to 2011. An increase in prediabetes prevalence has also been observed in China where prediabetes has risen to 15.5% in general population. In US, the prevalence of prediabetes has increased from 9% to 23%. According to Indian Council of Medical Research report, prevalence of diabetes in India is about 62.4 million and of prediabetes is about 77.2 million. According to WHO report, diabetes caused 1.5 million deaths in 2012. It has been reported that 5%–10% of individuals with prediabetes develop diabetes annually with up to 70% eventually developing diabetes.
Hypertension is associated with cardiovascular disease (CVD) and one of the emerging risk factor for prediabetes and diabetes. Several cross-sectional studies have shown an increased prevalence of coronary heart disease in individuals with prediabetes, but this relationship may be confounded by the common risk factors present between CVDs and prediabetes. Several studies have reported hypertension as one of the risk factors for the development of prediabetes and diabetes.,,,
Mean arterial pressure (MAP) and pulse pressure are important predictive parameters for cardiovascular risk both in diabetics and non-diabetic population. MAP is considered as a better indicator of perfusion to vital organs than systolic blood pressure (SBP). In the advance study, a trial among T2D patients, MAP was correlated with major CVD events: with a 13% increase in risk per 13 mmHg increase in MAP.
Endothelial dysfunction due to impairment of nitric oxide (NO) is an important risk factor for both hypertension and CVD, and it represents a major link between the conditions. NO is a potent endothelium-derived vasorelaxant substance which plays a major role in regulating blood pressure (BP). Mice with disruption of the gene for endothelial NO synthase have elevated BP levels compared with control animals, suggesting a genetic component to the link between impaired NO bioactivity and hypertension. Furthermore, production of NO is stimulated by insulin through Akt pathway. Insulin induces NO-dependent vasodilation in skeletal muscle and coronary vasculature. Insulin resistance contributes to endothelial dysfunction in prediabetes due to disturbances of NO generation.
Vitamin D has positive effects on insulin secretion and sensitivity and on inflammation. Vitamin D deficiency may have negative effects on glucose intolerance, insulin secretion, and T2D, either directly via Vitamin D receptor (VDR) activation or indirectly via calcemic hormones and also via inflammation. Studies have reported the presence of VDRs in endothelial cells and effect of Vitamin D supplement in improving endothelial functions even in diabetic patients. Several studies have reported decreased expression of endothelial NO synthase due to absence of Vitamin D activities., It is still not clear whether serum Vitamin D concentration plays an important role in causing hypertension or not. Because of the opposing consequences of different reviews on the role of Vitamin D in preventing hypertension development or its treatment, it appears that Vitamin D levels in the body modulate the BP indirectly.
Hence, the present study was planned to study the correlation of Vitamin D with BP and changes in mean arterial in prediabetics.
| Methods|| |
The present study was carried out in Department of Biochemistry in collaboration with Department of Endocrinology and Medicine (Unit IV), Pt. B. D. Sharma, PGIMS, Rohtak in forty consecutive diagnosed cases of prediabetes and forty age- and sex-matched healthy normoglycemic controls.
Individuals were selected as per American Diabetes Association criteria. Individuals with IFG of 100–125 mg/dL and/or IGT of 140–199 mg/dL and/or HbA1c between 5.7%–6.4% were included as prediabetic cases. Informed consent was obtained from all the individuals. There were no ethical issues, and the study was approved by the ethical board of the institute on December 18, 2017.
Pregnant women, women who were breastfeeding, critically ill patients, patients with diabetes, tuberculosis, renal/hepatic impairment, malabsorption syndrome, CVD, hypoglycemia, history of cancer, underweight, individuals taking drugs known to alter glucose tolerance, taking Vitamin D supplementation for last 1 year, steroids, oral contraceptive pills, beta blockers, phenytoin, and diuretics or fasting serum triglycerides >400 mg/dL (in both the groups) were excluded from the study.
Four milliliters venous blood was collected aseptically from antecubital vein in red-capped vacutainer and serum was separated by centrifugation. Routine biochemistry investigations were done as per standard methods. Serum 25-hydroxy Vitamin D (25[OH]D) was analyzed by radioimmunoassay (RIA).
SBP and diastolic BP (DBP) were measured twice with a mercury sphygmomanometer from the nondominant arm of patients in a sitting position after 5 min of rest, and average value was calculated. MAP (in mmHg) was calculated as:
MAP = (SBP + [2 × DBP])/3
IBM SPSS Statistics for Windows, Version 25.0. (Armonk, NY: IBM Corp.) was used for statistical analysis. Results were expressed as mean ± standard deviation and unpaired t-test and Pearson's correlation test was applied.
| Results|| |
The study was carried out in 40 diagnosed cases of prediabetes and 40 healthy normoglycemic controls.
Majority of prediabetic cases (35%, n = 14) were in the age group of 40–49 years followed by 11 (27.5%) each in the age groups of 20–29 years and 50–59 years and 4 (10%) in age group of 30–39 years. Fifteen (37.5%) controls were in the age group of 20–29 years followed by 12 (30%) in the age group of 50–59, 7 (17.5%) in the age group of 40–49 years, and 6 (15%) in the age group of 30–39 years. Age distribution of both the groups was comparable (P > 0.05 [0.39]).
Seventeen (42.5%) prediabetic cases were females and 23 (57.5%) were males. Whereas, 18 (45%) controls were females and 22 (55%) were males. No statistically significant difference was observed in gender distribution of both the groups (χ2 = 0.051; P > 0.05 [0.82]).
The mean hemoglobin level was 12.69 ± 1.80 g/dL in prediabetes cases and 13.06 ± 2.6 g/dL in controls, but no statistically significant difference was observed (P< 0.05 [0.45]). The mean serum 25(OH) Vitamin D levels were 24.51 ± 7.48 ng/mL in prediabetes cases and 31.19 ± 9.12 ng/mL in controls, and a statistically significant relation was present between both the groups (P< 0.001 [0.00059]).
Systolic as well as DBP were higher in prediabetes cases as compared to controls, and this difference was statistically significant (P< 0.05[0.0023], P < 0.001[2.45 × 10−6] respectively), [Table 1].
|Table 1: Blood pressure and mean arterial pressure (mean arterial pressure) in both the groups (mean±standard deviation, mmHg) (n=40)|
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MAP was higher in prediabetes cases as compared to controls, and this difference was statistically highly significant (P< 0.001[6.52 × 10 − 6]), [Table 1].
Vitamin D levels showed a negative correlation with SBP, DBP, and MAP in both prediabetes cases as well as in controls, and the difference was statistically insignificant in both groups [Table 2] and [Figure 1], [Figure 2].
|Table 2: Correlation of Vitamin D with systolic and diastolic blood pressure and mean arterial pressure (n=40)|
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|Figure 1: Correlation between serum 25(OH) Vitamin D, systolic blood pressure, and diastolic blood pressure in prediabetes cases|
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|Figure 2: Correlation between serum 25(OH) Vitamin D and mean arterial pressure in prediabetes cases|
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| Discussion|| |
Hypertension, which is associated with CVD, is emerging as a risk factor for prediabetes and diabetes. A cross-sectional study from China showed that hypertensive individuals with diabetic risk had a greater risk of CVD than normoglycemic individuals.
Muthunarayanan et al. reported that the prevalence of diabetes was higher in respondents with DBP of more than 90 mmHg than in respondents with DBP of <90 mmHg. The prevalence of prediabetes and diabetes was higher among respondents with SBP of more than 140 mmHg as compared to respondents with SBP of <140 mmHg, and the difference was found statistically significant (P = 0.003). Other studies have also reported that prediabetes and diabetes were significantly associated with hypertension, and it was one of the risk factors for the development of prediabetes and diabetes.,,
In present study, both SBP as well as DBP were higher in prediabetes cases as compared to controls, and this difference was statistically significant (P< 0.05 [0.0023], P < 0.001 [2.45 × 10−6] respectively), [Table 1], and results are in agreement with previous studies.,,,
About 25% of people with type 1 diabetes and 80% of people with T2D have high BP. Various pathophysiological mechanisms explaining the association between BP and T2D have been proposed by many workers. High BP induces microvascular dysfunction, which may contribute to the pathophysiology of diabetes development. Endothelial dysfunction is related to both insulin resistance and hypertension, and biomarkers of endothelial dysfunction are independent predictors of T2D. In addition, inflammatory markers, especially C-reactive protein are related to both incident T2D and increased BP levels.
Hyperglycemia due to insulin deficiency plays a role in the pathogenesis of hypertension in type 1 diabetes mellitus. Intensive insulin therapy can control blood glucose concentrations which may delay the onset and slows the progression of clinically important retinopathy, including vision-threatening lesions, nephropathy, and neuropathy, by a range of 35 to more than 70%%. However, it is also possible that the modestly greater quantities of insulin (3 or more insulin injections daily) were used to control hyperglycemia, and the weight gain often associated with intensive insulin therapy may adversely affect BP.
Hypertension is an important contributor to both the microvascular and the macrovascular complications of diabetes. Generally, diabetics without renal disease has normal BP, whereas patients with diabetic nephropathy have hypertension which suggests a possible role of high BP in the progression of diabetic nephropathy and other vascular lesions.
MAP reflects both peripheral resistance and cardiac output. In a study among T2D patients, MAP was correlated with major CVD events with 13% increase in risk per 13 mmHg increase in MAP. Data regarding individual in prediabetes and diabetes are scanty.
In the present study, MAP was higher in prediabetes cases as compared to controls, and this difference was statistically highly significant (P< 0.001[6.52 × 10−6]), [Table 1]. A few studies have taken into account of the impact of Vitamin D on BP in individuals who have hypertension. A study by Jorde et al. in 2010 exhibited a connection between low serum Vitamin D levels and hypertension.
Vitamin D supplementation may have a role in regulation of BP. Sugden et al. found that a single dose supplement of 100,000 U of ergocalciferol (Vitamin D2) significantly improved flow-mediated vasodilation of the brachial artery by 2.3% and decreased SBP by 14 mmHg compared with placebo. Furthermore, endothelial cells were reported to contain VDRs, and Vitamin D supplement improved endothelial functions. An animal study found that absence of Vitamin D activities caused reduced expression of endothelial NO synthase resulting in increased arterial stiffness. In several studies, a single high dose of active Vitamin D (100,000 IU) showed improvement in SBP among T2D patients, but the highest single dose of vitamin D3 (300,000 IU) did not reduce BP in the patients with T2D., However, a study reported that combination of vitamin D3 plus calcium supplementation had an effect on SBP and DBP in 100 patients with T2D. However, in the present study, no supplementation with Vitamin D was done in both the groups.
To test whether 25(OH)D levels are significantly associated with BP and hypertension risk, Vimaleswaran et al. conducted a study using different variants of genes that affect 25(OH)D synthesis or substrate availability (Vitamin D 25-hydroxylase and 7-dehydrocholesterol reductase). They found that each 10% increment in genetically instrumented 25(OH)D concentration was associated with a decrease in SBP and DBP, and an 8.1% reduced odds of hypertension. The findings of a study conducted later further confirmed that increased 25(OH)D concentrations might decrease the risk of hypertension.
Metabolic syndrome is a cluster of conditions that occur together and increase the risk of heart disease, stroke, and diabetes. Insulin resistance plays a direct causative role in the pathogenesis of T2D and has been associated with other features of metabolic syndrome. Vitamin D deficiency seems to play a role in the development of some of these risk factors. Many studies have demonstrated an inverse relationship between serum 25(OH)D and diabetes, metabolic syndrome, insulin resistance, and beta cell function.
Vitamin D3 deficiency may play a role in the pathogenesis of hypertension as Vitamin D3 inhibits renin and endothelin synthesis and the proliferation of smooth muscle cells. Furthermore, deficiency of Vitamin D3 has a role in causation of metabolic syndrome and diabetes due to development of insulin resistance. Few studies suggest a significant relationship between serum 25(OH)D levels and the incidence of metabolic syndrome, whereas others found no relation.
| Conclusion|| |
The findings of the present study suggest that BP changes and MAP might be causative factor in the pathogenesis of prediabetes. Furthermore, their correlation with Vitamin D suggests that Vitamin D supplementation might have a role in improving insulin resistance and reducing the risk of prediabetes.
Financial support and sponsorship
The author is grateful to Bill and Melinda Gates Foundation, through Grant No. #OPP52155 for funding the current study.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]