Low Vitamin D Serum Level Is Associated with HDL-C Dyslipidemia and Increased Serum Thrombomodulin Levels of Insulin-Resistant Individuals

Fatemeh Saheb Sharif-Askari; Narjes Saheb Sharif-Askari; Rabih Halwani; Salah Abusnana; Rifat Hamoudi; Nabil Sulaiman

doi:10.2147/DMSO.S245742

Low Vitamin D Serum Level Is Associated with HDL-C Dyslipidemia and Increased Serum Thrombomodulin Levels of Insulin-Resistant Individuals

Diabetes Metab Syndr Obes. 2020 May 12:13:1599-1607. doi: 10.2147/DMSO.S245742. eCollection 2020.

Authors

Fatemeh Saheb Sharif-Askari¹, Narjes Saheb Sharif-Askari¹, Rabih Halwani^{1

2}, Salah Abusnana^{2

3}, Rifat Hamoudi^{1

2}, Nabil Sulaiman^{1

4

5}

Affiliations

¹ Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
² Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
³ Department of Diabetes and Endocrinology, University Hospital Sharjah, Sharjah, United Arab Emirates.
⁴ Department of Family and Community Medicine, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁵ Department of Epidemiology, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Abstract

Background: Insulin-resistant individuals are known to have dyslipidemia and are predicted to be at high risk of cardiovascular events. Vitamin D deficiency was shown to be associated with dyslipidemia; however, the type of dyslipidemia associated with vitamin D deficiency in insulin-resistant individuals is not determined. Furthermore, there is evidence linking insulin resistance with low-grade inflammation suggesting levels of pro-inflammatory cytokines to be increased in insulin-resistant states.

Objective: This study was performed to evaluate the impact of vitamin D deficiency, defined as serum level of 25(OH)D below 20 ng/mL, on lipid profile and inflammatory markers such as interleukin (IL-6) and IL-8, as well as soluble thrombomodulin (TM) in the serum of insulin-resistant individuals.

Methods: A total of 4114 individuals had simultaneous serum 25(OH)D, insulin, and lipid panel testing during 2013 as part of the United Arab Emirates National Diabetes and Lifestyle (UAEDIAB) study. Multivariate logistic regression analysis was used to assess the association between serum level of 25(OH)D and lipid profile in insulin-sensitive versus -resistant individuals. The lipid panel was stratified into high total cholesterol (TC: >6.2 mmol/L), high low-density lipoprotein-cholesterol (LDL-C: >2.59 mmol/L), high triglycerides (TG: >2.3 mmol/L), and low high-density lipoprotein-cholesterol (HDL-C: <1.55 mmol/L) dyslipidemia. Furthermore, the immunomodulatory and vasculoprotective effects of 25(OH)D were assessed by measuring the levels of IL-6, IL-8, and soluble TM in serum using ELISA.

Results: More than half of the 4114 individuals were insulin resistant (n=2760, 67%) and around one-fifth of them were vitamin D-deficient (n=796, 19%). After adjusting for age, gender, body mass index, smoking, ethnicity, and educational level, the only dyslipidemia associated with vitamin D-deficient-insulin-resistant individuals (OR 2.09 [95]; P=0.009) was lower HDL-C. Furthermore, deficient 25(OH)D individuals with low HDL-C levels had higher circulatory IL-6 and IL-8 levels, and higher serum soluble TM compared to individuals with sufficient 25(OH)D and normal lipid profiles (median, IL-6 pg/mL 0.82 vs 1.71, P=0.001; median, IL-8 pg/mL 51.31 vs 145.6, P=0.003; and median, soluble TM ng/mL 5.19 vs 7.38, P<0.0001; in sufficient vs deficient groups, respectively).

Conclusion: The results of our study showed that in insulin-resistant individuals, vitamin D deficiency status is associated with HDL-C dyslipidemia and higher serum inflammatory and endothelial damage markers.

Keywords: 25(OH)D; HDL-C dyslipidemia; IL-6; IL-8; UAEDIAB; insulin-resistant; lipid panels; thrombomodulin; vitamin D-deficient.

Grants and funding

N.S. is funded by Al-Jalila Foundation (Grant Code: AJF150326), Diabetes and Metabolic Syndrome Research Group (University of Sharjah code 150306), and National Diabetes and Lifestyle Survey (MOH Code 120301).