The neutrophil count is superior to the neutrophil/lymphocyte ratio as a biomarker of inflammation in nascent metabolic syndrome

Metabolic syndrome (MetS) is a common global disorder that appears to be increasing in prevalence. In a series of studies, we have documented that it is a pro-inflammatory state driven by dysregulation of adipose tissue and phagocytes.^1–4 In previous studies, we have excluded diabetes with a fasting plasma glucose and HBAIC in the non-diabetic range, atherosclerotic cardiovascular disease (ASCVD), smoking and macroinflammation (by documenting a high sensitivity CRP <10 mg/L and a leukocyte count in the reference range); we have used the term ‘nascent metabolic syndrome’ for patients who fulfil these criteria. The increased inflammatory burden is manifest by increased cellular markers such as increased macrophage and mast cell infiltration in adipose tissue and increased toll-like receptor 2 and 4 expression and signalling in monocytes.^1–4 Furthermore, we showed dysregulation of adipokines such as increase in leptin, retinol-binding protein-4, chemerin and decreased adiponectin and omentin-1 and increase in circulation cytokines and chemokines such as interleukin-1,-6,-8, monocyte chemotactic protein-1, high sensitivity C-reactive protein (hsCRP), etc. The pro-inflammatory burden in nascent MetS is underscored by increased neutrophil counts in these patients, adjusted for age, body mass index and gender. ⁵

In some studies, the neutrophil/lymphocyte ratio (NLR) has been found to be a valid biomarker of increased inflammation of MetS, and correlates with the severity of MetS.^6–8 We examined the NLR in our well-defined cohort of patients with nascent MetS where diabetes, ASCVD, smoking and macroinflammation have been excluded. In this group, the NLR was not significantly different between MetS and controls: 2.2 ± 0.7 versus 1.94 ± 0.7 k/mm³ (P = 0.1). Moreover, using the Jonckeere-Terpsta test for trend, neutrophil counts increased with increase severity of MetS (P = 0.002); however, the NLR did not increase with increasing severity of MetS (P = 0.21). Neutrophil counts correlated significantly with plasma glucose (r = 0.26, P = 0.01), triglycerides (r = 0.33, P = 0.001), HDL-cholesterol (r = −0.26, P = 0.01), hsCRP (r = 0.36, P = 0.0003) and insulin resistance, assessed by homeostasis model assessment (HOMA-IR) (r = 0.30, P = 0.004). However, the non-significant increase in NLR correlated only with hsCRP (r = 0.26, P = 0.01) and HOMA-IR (r = 0.28, P = 0.005). Hence, in patients with nascent MetS, we have not confirmed the published findings. This may reflect the inclusion in the published studies of patients with diabetes, smoking, chronic obstructive pulmonary disease, all of which can alter the NLR and could explain the different findings. In conclusion, while the NLR appears to be a robust cost-effective marker of inflammation in MetS, our findings suggest that in carefully selected patients with nascent MetS, it is not as good as hsCRP. Furthermore, the absolute neutrophil count appears to be superior to the NLR in this group.