Diabetes mellitus (DM) is a major health concern globally, with a significant prevalence in China. Obesity, particularly central adiposity (measured by WHR), is a key risk factor for type 2 diabetes (T2DM). The precise mechanisms underlying this association remain unclear, but inflammation is suspected to play a role. Increased adiposity, especially central adiposity, is thought to stimulate systemic inflammation via the production of inflammatory cytokines by adipocytes. Peripheral WBCs, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils, serve as indicators of low-grade inflammation, which is implicated in the pathogenesis of T2DM. While some studies have examined the link between anthropometric measurements and inflammatory markers, research focusing on circulating WBC types as inflammation indicators is less common. This study aimed to investigate the relationship between central adiposity and glycemic status, exploring the potential mediating role of total and distinct WBC counts in this association using a cross-sectional design.

Existing literature strongly supports a link between obesity, particularly central adiposity (as indicated by WHR), and increased risk of T2DM. Studies consistently show that WHR is a more sensitive predictor of diabetes than BMI. The role of inflammation in the pathogenesis of T2DM is also well-established. Obesity is associated with increased production of pro-inflammatory cytokines, leading to low-grade systemic inflammation. Elevated total WBC counts have been linked to a higher risk of glucose metabolism disorders, but the specific roles of different WBC subtypes in this context require further investigation. While previous research has examined the effects of anthropometric measurements on inflammatory markers, studies specifically examining the mediating role of different WBC types in the obesity-diabetes relationship are limited.

This cross-sectional study utilized baseline data from the Fuqing cohort study (July 2020-June 2021), encompassing 6,613 participants aged 35-75. Central adiposity was defined using WHR, with cut-off points based on WHO guidelines. Peripheral WBC counts (total and differential) were measured using a fully automated blood cell analyzer. Glycemic status was categorized into normoglycemia, prediabetes, and diabetes using WHO criteria. Covariates included demographics, lifestyle factors, and the presence of hypertension and hyperlipidemia. Logistic regression analysis assessed the associations between WHR and WBC counts with glycemic status. Spearman's rank correlation analysis examined the relationship between WHR and WBC counts. Simple and multiple mediation analyses (using CMAverse R package and bias-corrected CIs from 10000 bootstrapping samples) explored the mediating effects of WBC counts (total and differential) on the association between WHR and diabetes. A sensitivity analysis was conducted excluding participants who used antibiotics or had abnormal WBC counts (<2.5% or >97.5% of the distribution).

The study revealed a significant positive association between WHR and the risk of prediabetes (OR = 1.53; 95% CI, 1.35 to 1.74) and diabetes (OR = 2.89; 95% CI, 2.45 to 3.40). Elevated peripheral WBC counts were associated with both central adiposity and worsening glycemic status. Simple mediation analyses showed significant indirect effects of central adiposity on prediabetes risk through total WBC count (9.92% mediated), neutrophil count (6.98%), lymphocyte count (6.07%), and monocyte count (3.84%). For diabetes, significant mediation was observed for total WBC count (11.79%), neutrophil count (11.51%), lymphocyte count (6.29%), monocyte count (4.78%), and basophil count (1.76%). The parallel multiple mediation model, including all five WBC types simultaneously, showed a significant indirect effect (OR = 1.09; 95% CI, 1.06 to 1.14) for diabetes, with 12.77% of the total effect mediated. Sensitivity analysis supported these findings.

This study provides robust evidence for the association between central adiposity and increased diabetes risk in a Chinese adult population, confirming previous research. Importantly, the mediation analyses highlight the role of circulating WBC counts in this relationship. The findings suggest that the inflammatory process, as reflected by WBC levels, may be a key mechanism through which central adiposity increases the risk of prediabetes and diabetes. The significant mediation effects observed for various WBC subtypes underscore the complexity of this relationship and the potential for targeting specific inflammatory pathways in future interventions. The study’s results align with the growing body of evidence implicating low-grade inflammation in the development of obesity-related insulin resistance.

This study confirms the strong association between central adiposity and increased diabetes risk. The significant mediating role of circulating WBC counts, both total and differential, suggests that inflammation plays a key role in this association. Future research should explore the longitudinal relationships between these factors and investigate potential therapeutic interventions targeting specific inflammatory pathways to mitigate the risk of diabetes in individuals with central adiposity. Further research could also explore the interaction of genetic predisposition and lifestyle factors on the studied relationship.

The cross-sectional design limits the ability to determine causal relationships between central adiposity, WBC counts, and glycemic status. The lack of detailed information on drug use (e.g., steroids, NSAIDs, antibiotics) and other comorbidities that could influence WBC counts represents a limitation. While the study adjusted for several covariates, the possibility of residual confounding cannot be completely excluded. Finally, other mediating factors beyond WBC counts may contribute to the association between central adiposity and diabetes.