This study sought to determine the relationship between hematologic inflammatory biomarkers and Hb A1c among Type 2 DM patients, with a view to using them for monitoring glycemic control in communities of low socioeconomic status, where Hb A1c testing may not be available and affordable. We did not find a significant correlation between these markers and HbA1c.
In contrast, similar studies, which assessed the relationship between NLR and Hb A1c found some correlation. A study by Mazhar Hussain et al. on the use of NLR as a well assessment tool of glycemic control, found a positive correlation between NLR and Hb A1c in diabetic patients. [12] Also, a study by Sefil et al. on the relationship between NLR and blood glucose regulation in diabetic patients in Turkey also found a positive association between NLR and HbA1c. [19] These two studies unlike our study excluded patients on antiplatelet and lipid-lowering medications. Studies have reported anti-inflammatory properties of antiplatelet agents such as aspirin; and glucose lowering agents like metformin apart from their primary pharmacologic actions.[20, 21] Aspirin reduces inflammation by lowering CRP, a byproduct of interleukin-6 (IL-6), which is an inflammatory mediator. [22] Metformin, a first-line glucose-lowering agent, used by over 90% of the patients in our study, reduces inflammation by inhibiting the signaling of NF-κB, a pro-inflammatory transcription factor in vascular tissues and hepatocytes, the expression of IL-6, IL-1ß, thereby, ultimately reducing NLR. [23, 24] The anti-inflammatory effects of the medications used, might have been responsible for the lack of association between NLR and HbA1c in our study. This may also explain why there was no significant difference in the white cell count parameters between patients with optimal and sub-optimal glycemic control. We included patients on these medications, in order to assess the usefulness of these markers in predicting glycemic control in day-to-day clinical practice. Most of the Type 2 diabetic patients in Nigeria and other African countries are on statins, antiplatelets and metformin.[25]
We did not find a correlation between PLR and Hb A1c. Subclinical inflammation expressed as elevated interleukin-1, IL-6, and TNF-alpha levels stimulate increased production of thrombopoietin, leading to increased platelet production. [26] Elevated PLR has been reported in patients with diabetes.[9, 27] The use of aspirin, an antiplatelet by our patients is likely responsible for the lack of correlation Few studies have investigated the relationship of glycemic control with PLR. Atak et al. studied PLR as a novel inflammatory marker in 63 patients with Type 2 DM and found a positive correlation with Hb A1c.[28] They excluded patients on aspirin, which is known to have anti-inflammatory and antiplatelet properties, which may lower PLR.
Similar to our findings with NLR and PLR, our study found no correlation between MPV and Hb A1c. A few studies also found no relationship between MPV and Hb A1c.[29, 30, 31] In contrast, a retrospective study by Giuseppe Lippi et al, involving over 4000 patients, which examined the relationship between MPV and HbA1c reported a positive correlation between Hb A1c and MPV [32] Ozder et al., in Turkey, studied MPV in patients with Type 2 DM and impaired fasting plasma glucose and found a positive correlation between MPV and Hb A1c. They excluded patients on antiplatelets in that study.[33] Besides the larger sample size of their studies, the exclusion of patients on routine medications for diabetes - glucose lowering medications, aspirin, and statins – may explain their findings. Mean platelet volume represents the average size of platelets. Platelets with high MPV are larger, younger, and more reactive and occur in chronic inflammatory states. [14, 34] In diabetes, hyperglycemia creates a chronic inflammatory milieu, which increases oxidative stress and can lead to endothelial dysfunction. [35, 36] These factors increase platelet reactivity, leading to thrombopoiesis and higher MPV in diabetic patients. [29, 37] In a retrospective study by Basir Sivri et al., they investigated the effects of statins on MPV and found that statins lower MPV irrespective of lipid levels.[38] Statins reduce MPV through inhibiting the action of CD 36 – a glycoprotein, which promotes platelet activation and thrombosis when bound to oxidized low density lipoprotein.[39] A prospective study by Ilhan Dolasik et al. among newly diagnosed patients with Type 2DM looked at the effect of Metformin on MPV and found a significant reduction in MPV from initiation of Metformin to six months following treatment but no correlation with Hb A1c.[40] Metformin reduces leukocyte oxidative stress on the vascular endothelium, which in effect reduces platelet activation, platelet hyperreactivity and consequently mean platelet volume.[41]
Our study certainly had limitations. Given the study's cross-sectional design, the information obtained was only at a given time. It, therefore, does not provide information on the long-term effect of glycemic control of these markers. A large multi-center, prospective study involving a larger population of Type 2 DM patients, including newly diagnosed and treatment naïve patients, will be valuable in understanding the effect of hyperglycemia on these biomarkers.