High White Blood Cell Count Is Associated With a Worsening of Insulin Sensitivity and Predicts the Development of Type 2 Diabetes

  1. Barbora Vozarova,
  2. Christian Weyer,
  3. Robert S. Lindsay,
  4. Richard E. Pratley,
  5. Clifton Bogardus and
  6. P. Antonio Tataranni
  1. From the Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona

    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/mm3) 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.

    Footnotes

    • Address correspondence to Barbora Vozarova, Clinical Diabetes and Nutrition Section, National Institutes of Health, 4212 N. 16th Street. Rm. 5-41, Phoenix, AZ 85016. E-mail: bvozarov{at}mail.nih.gov.

      Received for publication 16 May 2001 and accepted in revised form 30 October 2001.

      AIR, acute insulin secretory response; EMBS, estimated metabolic body size; IL-6, interleukin-6; M, insulin-stimulated glucose disposal; M-low, M during low-dose insulin infusion; M-high, M during high-dose insulin infusion; NGT, normal glucose tolerant; OGTT, oral glucose tolerance test; PAI-1, plasminogen activator inhibitor; WBC, white blood cell count.

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