White blood cell subtypes, insulin resistance and β‐cell dysfunction in high‐risk individuals – the PROMISE cohort

Abstract

Higher white blood cell count (WBC) is associated with incident type 2 diabetes; however, little is known about the potential relationship of WBC subtypes with metabolic abnormalities underlying diabetes. Cross-sectional analysis. Six hundred and fifty-six nondiabetic participants in the Prospective Metabolism and Islet Cell Evaluation cohort. Granulocytes (basophils, neutrophils and eosinophils), lymphocytes and monocytes were measured in fasting blood samples. Neutrophil lymphocyte ratio (NLR) is the ratio of neutrophil to lymphocyte. Insulin resistance was measured by insulin sensitivity index (ISOGTT) and homeostasis model assessment of insulin resistance (HOMA-IR). Beta-cell dysfunction was measured by insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and Insulin Secretion Sensitivity Index-2 (ISSI-2). All WBC subtypes were inversely associated with ISOGTT [β = -0·12 (-0·15, -0·083) for granulocytes, β = -0·23 (-0·31, -0·15) for lymphocytes, β = -0·67 (-1·00, -0·34) for monocytes] and positively associated with HOMA-IR [β = 0·11 (0·074, 0·15) for granulocytes, β = 0·22 (0·14, 0·30) for lymphocytes, β = 0·64 (0·33, 0·97) for monocytes]. Granulocytes and lymphocytes were inversely associated with IGI/IR [β = -0·10 (-0·15, -0·047), β = -0·23 (-0·35, -0·11), respectively] and ISSI-2 [β = -0·048 (-0·074, -0·022), β = -0·14 (-0·19, -0·089), respectively]. BMI attenuated the associations of monocytes with IGI/IR and ISSI-2, and those of NLR with ISOGTT and HOMA-IR. NLR was not associated with IGI/IR and ISSI-2. All WBC subtypes were independently associated with insulin resistance, whereas granulocytes and lymphocytes, but not monocytes, were associated with β-cell dysfunction. NLR was not associated with β-cell dysfunction, and its association with insulin resistance was confounded by obesity.