title: High white blood cell count is associated with a worsening of insulin sensitivity and predicts the development of type 2 diabetes.
abstract: Chronic low-grade inflammation may be involved in the pathogenesis of insulin resistance and type 2 diabetes. We examined whether a high white blood cell count (WBC), a marker of inflammation, predicts a worsening of insulin action, insulin secretory function, and the development of type 2 diabetes in Pima Indians. We measured WBC in 352 nondiabetic Pima Indians (215 men and 137 women, aged 27 +/- 6 years [means +/- SD], body fat 32 +/- 8%, WBC 8,107 +/- 2,022 cells/mm(3)) who were characterized for body composition (by hydrodensitometry or dual-energy X-ray absorptiometry), glucose tolerance (by 75-g oral glucose tolerance test), insulin action (M; by hyperinsulinemic clamp), and acute insulin secretory response (AIR; by 25-g intravenous glucose challenge). Among 272 subjects who were normal glucose tolerant (NGT) at baseline, 54 developed diabetes over an average follow-up of 5.5 +/- 4.4 years. Among those who remained nondiabetic, 81 subjects had follow-up measurements of M and AIR. Cross-sectionally, WBC was related to percent body fat (r = 0.32, P < 0.0001) and M (r = -0.24, P < 0.0001), but not to AIR (r = 0.06, P = 0.4). In a multivariate analysis, when adjusted for age and sex, both percent body fat (P < 0.0001) and M (P = 0.03) were independently associated with WBC. A high WBC value predicted diabetes (relative hazard 90th vs. 10th percentiles [95%CI] of 2.7 [1.3-5.4], P = 0.007) when adjusted for age and sex. The predictive effect of WBC persisted after additional adjustment for established predictors of diabetes, i.e., percent body fat, M, and AIR (relative hazard 2.6 [1.1-6.2], P = 0.03). After adjustment for follow-up duration, a high WBC at baseline was associated with a subsequent worsening of M (P = 0.003), but not a worsening of AIR. A high WBC predicts a worsening of insulin action and the development of type 2 diabetes in Pima Indians. These findings are consistent with the hypothesis that a chronic activation of the immune system may play a role in the pathogenesis of type 2 diabetes.
authors.affiliation: Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA. bvozarov@mail.nih.gov
authors.forename: Barbora
authors.initials: B
authors.lastname: Vozarova
authors.forename: Christian
authors.initials: C
authors.lastname: Weyer
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lindsay
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
authors.forename: Clifton
authors.initials: C
authors.lastname: Bogardus
authors.forename: P Antonio
authors.initials: PA
authors.lastname: Tataranni
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D005544:Forecasting; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies