Correlation of TNF-α and IL-6 expression with vitamin D levels in insulin-resistant type 2 diabetes mellitus patients: exploring the role of vitamin D in inflammation and disease pathogenesis
Muhammad Razi Ul Islam Hashmi, Sarah Sadiq, Shoaib Naiyar Hashmi, Rumsha Zubair, Huma Shafique, Tayyaba Afsar, Dara Aldisi, Suhail Razak
Abstract
BACKGROUND: Chronic low-grade inflammation is often seen in individuals with insulin resistance, characterised by increased levels of pro-inflammatory cytokines, such as TNF-α (tumour necrosis factor-alpha) and IL-6 (interleukin-6). Insulin resistance (IR) and vitamin D deficiency are increasingly recognised as interconnected metabolic issues. Research indicated that low vitamin D levels may impair insulin sensitivity, while insulin resistance can worsen vitamin D deficiency, creating a vicious cycle. This study aims to explore the relationship between TNF-α and IL-6 expression levels and vitamin D levels in insulin-resistant patients with type 2 diabetes mellitus (DM), and compare them with non-diabetic controls to better understand the role of vitamin D in inflammation, disease development, and progression. METHODS: From a total of 150 participants, 30 were healthy individuals (the control group), and 120 were patients with type II diabetes. The current case-control study compared TNF-α, IL-6 expression levels, and serum vitamin D levels between insulin-resistant patients and non-diabetic controls. RESULTS: The demographic and clinical variables were statistically significant. The case-to-control ratio was 4:1. Higher levels of TNF-α and IL-6 were found in DM patients compared to non-diabetic controls. Insulin-resistant patients exhibited higher IL-6 levels (5.47 ± 0.30 pg/ml) than healthy participants (2.64 ± 0.83 pg/ml), with p-value < 0.001. Vitamin D levels were significantly lower in DM patients (22.33 ± 11.43 ng/ml) compared to healthy subjects (34.12 ± 2.08 ng/ml), with p-value < 0.001. TNF-α levels were also significantly higher in DM patients (7.99 ± 0.35 pg/ml) (p-value < 0.001) than in the healthy group (4.24 ± 0.27 pg/ml). Using qPCR and measuring disease severity, the relationship between cytokine gene expression and insulin resistance was assessed. The positive associations between TNF-α, IL-6, vitamin D deficiency, poor glycaemic control, and other disease conditions reflect a fundamental pathophysiological mechanism in insulin resistance in DM patients. This ultimately leads to increased inflammation and tissue damage, worsening the complications of diabetes.