Abstract
ObjectiveBiological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.Research Design and MethodsStudies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.ResultsThe combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10−18). Substantial heterogeneity was present (I2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10−4), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10−13), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10−5). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.ConclusionsA raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.
Highlights
We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 was attenuated to 1.82 after further accounting for smoking, type 2 diabetes (T2D) family history, physical activity, education, BMI and waist circumference
Chronic inflammation, characterized by the increased production of cytokines and acute-phase reactants and activation of inflammatory signalling networks [1,2,3,4,5], may be involved in the pathogenesis of type 2 diabetes (T2D).Various markers of inflammation have been shown to predict the future diabetes risk, including Interleukin-6 (IL-6) and C-reactive protein (CRP) [1,5].Obesity, a strong risk factor for T2D is associated with inflammation as fat tissue releases inflammatory cytokines[6,7]
Evidence from epidemiological studies suggests an association between total peripheral white blood cell (WBC) or leukocyte count, a non-specific marker of inflammation, and diabetes risk[9,10]
Summary
Chronic inflammation, characterized by the increased production of cytokines and acute-phase reactants and activation of inflammatory signalling networks [1,2,3,4,5], may be involved in the pathogenesis of type 2 diabetes (T2D).Various markers of inflammation have been shown to predict the future diabetes risk, including Interleukin-6 (IL-6) and C-reactive protein (CRP) [1,5].Obesity, a strong risk factor for T2D is associated with inflammation as fat tissue releases inflammatory cytokines[6,7]. Inflammation on its own can affect insulin signalling [3], indirectly increasing the risk of T2D, without the presence of obesity. Evidence from epidemiological studies suggests an association between total peripheral white blood cell (WBC) or leukocyte count, a non-specific marker of inflammation, and diabetes risk[9,10]. Little is known about the association of each of the subfractions with T2D
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