In this study, the higher levels of systemic inflammation, hypertension, significant dyslipidaemia, and poor glucose control observed in patients with T2DM are reflective of the complex and interconnected pathophysiological mechanisms underlying the disease and its associated cardiovascular risks. Chronic low-grade inflammation, characterized by increased levels of inflammatory cytokines, is a hallmark of T2DM and plays a key role in endothelial dysfunction, atherogenesis, and insulin resistance.(18) Inflammation promotes the activation of the renin-angiotensin-aldosterone system (RAAS), leading to vasoconstriction and increased blood pressure.(19, 20) This explains the significant association between elevated hs-CRP levels and hypertension among T2DM patients as observed in the study. Also, insulin resistance (IR), a core defect in T2DM, disrupts normal lipid metabolism, leading to an overproduction of very low-density lipoprotein (VLDL) and sd-LDL particles, which are more atherogenic.(21) This dyslipidaemia is exacerbated by poor glucose control leading to an increase in free fatty acid flux from adipose tissue to the liver, further promoting the production of VLDL which contributes to the development of atherosclerosis and perpetuates a vicious cycle.(22) Previous and recent studies have shown that elevated hs-CRP levels are strongly associated with an increased risk of CVD, independent of traditional risk factors such as dyslipidaemia, and that tight glycaemic control reduces cardiovascular events in T2DM patients.(23–25)
This study aimed to explore the association between systemic inflammation (elevated hs-CRP) and dyslipidaemia in Nigerian patients with T2DM, and the lack of an association observed may be due to the intricate and multifactorial nature of dyslipidaemia in diabetes. Dyslipidaemia is primarily driven by insulin resistance, with inflammation playing a potentially secondary role.(26) Other factors unique to the Nigerian population such as genetics and diet might also influence lipid levels in T2DM, diluting the impact of inflammation on lipid metabolism. Additionally, hs-CRP might reflect increased CVD risk through pathways unrelated to dyslipidaemia, such as endothelial dysfunction and plaque instability. This finding diverges from some previous studies, which have reported a significant association between elevated hs-CRP levels and dyslipidaemia in T2DM patients while agreeing with a few others where no association was found.(5, 27, 28) The variability in findings across different populations suggests that the relationship between inflammation and dyslipidaemia may be modulated by other factors, and the influence of systemic inflammation on CVD risk may occur through mechanisms beyond just lipid abnormalities.
The lack of association between elevated systemic inflammation (hs-CRP) and dyslipidaemia in this study and previous similar studies may suggest that relying solely on lipid profiles for CVD risk prediction could be insufficient in this population. Hs-CRP, as an independent marker of systemic inflammation, might capture cardiovascular risk through pathways unrelated to lipid metabolism, such as endothelial dysfunction and arterial stiffness, which are also significant contributors to atherosclerosis and CVD. Therefore, integrating hs-CRP into CVD risk prediction models could enhance the identification of high-risk individuals who may not present with overt dyslipidaemia but are still at elevated risk due to underlying inflammation. This emphasizes the need for more comprehensive risk assessment tools in Nigerian T2DM patients, incorporating both traditional lipid-based measures and novel biomarkers like hs-CRP. Also, by including genetics and environmental influences unique to Nigeria, such a population-specific approach could improve early detection and targeted intervention strategies, ultimately reducing the burden of CVD in the study population.
The subgroup analysis among T2DM patients revealed a significant positive correlation between elevated hs-CRP levels and BMI, with patients in the elevated hs-CRP group also showing higher SBP, a characteristic phenotype of hypertension in T2DM, and a greater likelihood of using antihypertensive medications. This finding aligns with the established pathophysiological link between obesity, inflammation, and cardiovascular risk, as adipose tissue in obese individuals secretes pro-inflammatory cytokines such as interleukin-6, which stimulates hepatic production of C-reactive protein (CRP), thereby promoting systemic inflammation and endothelial dysfunction.(29–31) Elevated SBP further exacerbates cardiovascular risk by increasing arterial stiffness and promoting atherogenesis.(32) These results are consistent with other studies that highlight the strong association between obesity, inflammation, and hypertension in T2DM populations.(29, 33) However, unlike certain Caucasian populations where dyslipidaemia has been closely associated with systemic inflammation, this study found no such correlation between hs-CRP and lipid parameters.(5, 34) This discrepancy may be attributed to variations in genetic predispositions, differences in access to healthcare, and distinct lifestyle factors across populations.
There are some limitations to the index study. The cross-sectional design limits the ability to draw causal inferences between elevated hs-CRP levels and cardiovascular risk factors in T2DM patients, suggesting the need for longitudinal studies to assess these associations over time. Additionally, being a hospital-based study, the findings may not fully represent the broader Nigerian T2DM population, limiting their generalizability. As such, future research should include larger, more diverse samples from multiple healthcare centres across different regions for a more comprehensive understanding. Lastly, although we excluded patients with conditions known to influence hs-CRP levels, residual confounding from unmeasured factors, such as diet, stress, and genetic predisposition, cannot be ruled out. Incorporating these variables into future studies would provide a clearer picture of the complex relationship between inflammation, dyslipidaemia, and cardiovascular risk in T2DM patients.