Differential White Cell Count and Incident Type 2 Diabetes: the Insulin Resistance Atherosclerosis Study

Aims/hypothesis: White cell count has been shown to predict incident type 2 diabetes, but differential white cell count has received scant attention. We examined the risk of developing diabetes associated with differential white cell count and neutrophil:lymphocyte ratio and the effect of insulin sensitivity and subclinical inflammation on white cell associations.

Methods: Incident diabetes was ascertained in 866 participants aged 40-69 years in the Insulin Resistance Atherosclerosis Study after a 5 year follow-up period. The insulin sensitivity index (SI) was measured by the frequently sampled IVGTT.

Results: C-reactive protein was directly and independently associated with neutrophil (p < 0.001) and monocyte counts (p < 0.01) and neutrophil:lymphocyte ratio (p < 0.001), whereas SI was inversely and independently related to lymphocyte count (p < 0.05). There were 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 demonstrated for monocyte count (1.18 [0.73, 1.90]) 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 (1.96 [1.13, 3.37]). This last relationship was 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.