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Differential white cell count and incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study.

ABSTRACT: 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.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.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.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.

SUBMITTER: Lorenzo C

PROVIDER: S-EPMC3969879 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Differential white cell count and incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study.

Lorenzo Carlos C Hanley Anthony J AJ Haffner Steven M SM

Diabetologia 20131019 1

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>Incident diabetes was ascertained in 866 participants aged 40-69 years in the Insulin Resistance Atherosclerosi ...[more]

PMID: 24141640

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Project description:BackgroundThe contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).MethodsWe evaluated 424 407 adults aged 37-73?years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.ResultsThere were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HRQ4 = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers (n cases / n?=?244 / 19?464, HRQ4 = 2.15, 95% CI = 1.46 to 3.16), former smokers (n cases / n?=?280 / 69?198, HRQ4 = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (ncases / n?=?108 / 111?294, HRQ4 = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (ncase s / n?=?329 / 22?934, HRQ4 = 2.95, 95% CI = 2.04 to 4.26) and former smokers (nc ases / n?=?358/71?616, HRQ4 = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.ConclusionsElevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.

Project description:OBJECTIVE:This study evaluates insulin sensitivity, pancreatic beta-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA(1c) to insulin sensitivity and BCF. RESEARCH DESIGN AND METHODS:The subjects were 14 adolescents with type 2 diabetes and 20 obese control subjects of comparable age, BMI, body composition, and puberty. Insulin sensitivity was evaluated with a 3-h hyperinsulinemic (80 mU . m(-2) . min(-1)) euglycemic clamp. First-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a 2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was determined with the use of [6,6-(2)H(2)]glucose. RESULTS:Fasting glucose rate of appearance was higher in type 2 diabetic patients than in obese control subjects (16.5 +/- 1.1 vs. 12.3 +/- 0.5 micromol . kg(-1) . min(-1); P = 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 +/- 0.1 vs. 2.0 +/- 0.2 micromol . kg(-1) . min(-1) per pmol/l; P = 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 +/- 24.6 vs. 220.2 +/- 18.0 pmol/l; P = 0.007), and FPIS and SPIS were lower (FPIS: 357.6 +/- 42.0 vs. 1,365.0 +/- 111.0 pmol/l; SPIS: 652.2 +/- 88.8 vs. 1,376.4 +/- 88.8 pmol/l; P < 0.001 for both). The glucose disposition index (GDI = insulin sensitivity x FPIS) was approximately 86% lower in type 2 diabetic patients than in obese control subjects. HbA(1c) correlated with FPIS (r = -0.61, P = 0.025) with no relationship to insulin sensitivity. CONCLUSIONS:Despite the impairment in both insulin sensitivity and BCF in youth with type 2 diabetes, the magnitude of the derangement is greater in BCF than insulin sensitivity when compared with that in obese control subjects. The inverse relationship between BCF and HbA(1c) may either reflect the impact of deteriorating BCF on glycemic control or be a manifestation of a glucotoxic phenomenon on BCF. Future studies in youth type 2 diabetes should target the natural course of beta-cell failure and means of retarding and/or preventing it.

Dataset Information

Differential white cell count and incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study.

Publications

Differential white cell count and incident type 2 diabetes: the Insulin Resistance Atherosclerosis Study.

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