Aims/hypothesis Light cell count has been shown to predict incident type 2 diabetes but differential white cell count has received scant attention. 138 (15.9%) incident cases of diabetes. Demographically adjusted ORs for incident diabetes comparing the top and bottom tertiles of white cell (1.80 [95% CI 1.10 2.92 neutrophil (1.67 [1.04 2.71 and lymphocyte counts (2.30 [1.41 3.76 were statistically significant. No association was exhibited for monocyte count (1.18 [0.73 1.9 or neutrophil:lymphocyte ratio (0.89 [0.55 1.45 White cell and neutrophil associations were no longer significant after further adjusting for family history of diabetes fasting glucose and smoking but the OR comparing the top and bottom tertiles of lymphocyte count remained significant (1.92 [1.12 3.29 This last relationship was MK 3207 HCl better explained by SI rather than C-reactive protein. Conclusions/interpretation A lymphocyte association with incident diabetes which was the strongest association among the major white cell types was partially explained by insulin sensitivity rather than subclinical inflammation. Keywords: Clinical science Epidemiology Human Insulin sensitivity and resistance Pathogenic mechanisms Prediction and prevention of type 2 diabetes Introduction Low-grade inflammation is usually a key component in the pathophysiology of type 2 diabetes  particularly in the development of obesity-related insulin resistance . Obesity increases the quantity of macrophages in adipose tissue and upregulates the production of inflammatory factors . In patients with type 2 diabetes treatment with an IL-1 receptor antagonist and salsalate (a non-acetylated form of salicylate) has been shown to improve glycaemic control and/or beta cell secretory function [4 5 Increased diabetic risk  and insulin resistance  have been explained in patients with chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. Treatment of these conditions with anti-TNF-α blockers ameliorates disease activity inflammatory mediators and insulin resistance [8 9 MK 3207 HCl White cell count a marker of subclinical inflammation is directly associated with insulin resistance [10-13] and inversely with insulin secretion . White cell count has been shown to predict both worsening insulin sensitivity  and incident type 2 diabetes [10 14 although there is usually controversy on its usefulness in risk prediction [19-21]. Data on the ability to predict type 2 diabetes by major white cell types are scant [10 15 16 A significant association has been reported for both neutrophil and lymphocyte counts but not for monocyte count [15 16 However the incidence of diabetes was predicted by white cell count but not by any major white cell type in a relatively small study among Pima Indians . Distinct metabolic characteristics may account (at least partially) for the relationship between white cell subfractions and diabetic risk. Neutrophil count has been shown to correlate with high-sensitivity C-reactive protein (hsCRP) concentration better than any other major white cell type in nondiabetic individuals . Lymphocytes are expanded in obese Prkwnk1 adipose tissue  and regulate macrophage production of inflammatory mediators . Raised levels of neutrophils lymphocytes and the neutrophil:lymphocyte ratio have been linked to the metabolic syndrome [23 24 However whether major white cell types are associated with the future development of type 2 diabetes beyond the effect of insulin sensitivity and subclinical inflammation is not known . The aims of this study were twofold: (1) to examine the risk of developing diabetes associated with total and differential white cell counts and neutrophil:lymphocyte ratio; and (2) to assess the effects of glucose tolerance insulin sensitivity insulin secretion and low-grade inflammation on white cell associations. We analysed these issues in 866 participants who were non-diabetic at baseline . Incident diabetes was ascertained after a 5.2 12 months follow-up using the 2003 ADA diagnostic criteria. The insulin sensitivity index (SI) and acute insulin response (Air flow) were directly measured using the frequently sampled IVGTT (FSIVGTT). Methods Study sample The Insulin Resistance Atherosclerosis Study (IRAS) is usually a multicentre observational epidemiologic study of the associations between insulin resistance cardiovascular disease and the known risk factors for insulin resistance in different ethnic groups and varying states of glucose tolerance. The design MK 3207 HCl and methods of this study have previously been explained in detail . Briefly the MK 3207 HCl study was.