In this study, the relationship between inflammatory markers and their interactions and IR was analyzed. The results indicated that SII increases the risk of IR, as measured by HOMA-IR, and that PLR reduces the risk of IR. Meanwhile, PLR and SII are better predictors than the other inflammatory response markers.
While the pathophysiological mechanism of the development of T2DM is complex, many epidemiological studies have emphasized the association between chronic low-grade inflammation and DM. High leukocyte counts and decreased insulin sensitivity were previously associated with T2DM patients. One of the probable reasons of glucose intolerance is thought to be insulin resistance, which when combined with other metabolic disorders increases the risk of coronary artery disease.[22] Previous research found that individuals with diabetes, prodrome diabetes, and metabolic syndrome had higher-than-normal leukocyte counts.[23] The NLR is a dynamic metric that would seem to have superior predictive value when compared to total WBC/leukocyte count.[24, 25] Additionally, the NLR shows how the immune system's two complementary but opposing components are balanced. Lymphocytes are the immune system's regulatory or protective components of inflammation, while neutrophils operate as the first line of defense's active nonspecific inflammatory mediators.[26] Interestingly, the NLR is positively correlated not only with the presence of metabolic syndrome but also with its severity.[27] While Lehto, S. et al. showed that the NLR is connected with the severity of glucose intolerance and IR, Imtiaz et al. discovered that systemic inflammation evaluated by the NLR was strongly associated with common chronic illnesses including diabetes and hypertension. As the level of inflammatory markers rises along with the progression of glucose intolerance, the inflammatory process may start as early as the impaired glucose tolerance stage. [23]
In the present study, high levels of NLR increased the risk of IR among the participants. However, in the adjusted model, this risk disappeared, which is not in line with previous studies, meaning the effect of NLR on IR requires further research. It's interesting to note that recent research supports the idea that NLR can potentially be used as a prognostic indicator to forecast microvascular complications in diabetes.[22]Ulu et al. recently demonstrated that as a fast and trustworthy predictor, NLR can not only predict the retinopathy of diabetes but also its severity.[28] Patients with diabetes will have more leukocytes, which will increase the production of ROS. This will raise vascular endothelial permeability and encourage leukocyte adhesion, which will alter endothelial function. [28] Endothelium-derived nitric oxide deficiency is considered to be the main defect connecting IR and endothelial dysfunction.[29] Hyperglycemia has different effects on white blood cells. While enhanced lymphocyte apoptosis was reported in diabetic rats and patients,[30] enhanced oxidative DNA damage in the peripheral blood lymphocytes was confirmed in patients with T2DM.[31] It has also been demonstrated that in diabetic mice, hyperglycemia decreases the neutrophil apoptosis, impairing neutrophil clearance and prolonging inflammation.[32] Excessive inflammation could be one mechanism by which elevated neutrophil levels mediate IR. Increased neutrophil activation and increased neutrophil protease release in T2DM patients suggest that the increase in NLR is the cause of the increase in proinflammatory levels.[33]
Like NLR, MLR is also a marker that is easy to obtain and is used as an inflammatory marker in many studies, such as determining the disease activity of patients with ulcerative colitis, evaluating the disease severity of axial spondylitis, and it is possible to predict the relapse of gastrointestinal stromal tumors using the preoperative MLR level. Yue et al. found that the MLR was confirmed to be a risk factor for the development of diabetic retinopathy, while it can also be used as a predictor and effective marker of diabetes nephropathy.[34] However, the present study found no relationship between MLR and IR.
When it comes to predicting chronic liver infections, the PLR has been found to be more accurate than the NLR. According to the former study, the PLR decreases in the prediabetic and early diabetic period, then increases in the further stages of diabetes.[35] The PLR is really thought to be a potential inflammation indicator in oncologic, cardiac, and chronic kidney illness. [36] Furthermore, much like the NLR, the PLR can serve as a cheap predictor of diabetic microvascular complications.[37] Elsewhere, Mineoka et al. reported that the PLR can serve as a useful marker for the assessment of high-risk diabetic foot and foot ulcers in patients with T2DM.[38] In the present study, a high level of PLR was found to be a protective factor of IR, with this protective effect continuing to exist after adjusting the model, which is inconsistent with previous studies. Therefore, the role of PLR in the IR among diabetes patients remains inconclusive.
The SII, a brand-new comprehensive inflammatory biomarker, is based on platelet, lymphocyte, and neutrophil counts. This indicator is currently thought to properly reflect the inflammatory state and was originally used to assess the prognosis of patients with solid tumors and coronary heart disease. [39] Here, it was found that SII may be a risk factor for IR and may serve as an effective predictor.
The innovation of this study lies in the proposal that PLR may be a protective factor of IR and that SII is a potential predictor of IR. In addition, this study was the first to explore the relationship between the interaction of inflammation indicators and IR. It was concluded that PLR has a multiplicative interaction with ELR, MLR, and SII, which could reduce the risk of IR and indicates that the PLR may be a potential protective factor.
The study involved a number of limitations. First, this study used a cross-sectional design, which is not ideal for investigating causal relationships. Future studies that employ a prospective design may provide more conclusive proof of the role of these indicators in diseases. Second, it is possible that the relationship between elevated inflammatory markers may have been confounded by certain unmeasured covariates. Despite the limitations, it was concluded that individuals with prevalent chronic conditions are significantly more likely to have a higher level of systemic inflammation.