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Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.

ABSTRACT: High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes.Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45-73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22-1.53) for total leukocytes, 1.33 (1.19-1.49) for neutrophils and 1.29 (1.15-1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes.Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the R262W polymorphism suggests that the associations may not be causal, although limitations in statistical power and balancing pleiotropic effects cannot be excluded.

SUBMITTER: Borne Y

PROVIDER: S-EPMC4758613 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.

Borné Yan Y Smith J Gustav JG Nilsson Peter M PM Melander Olle O Hedblad Bo B Engström Gunnar G

PloS one 20160218 2

<h4>Objective</h4>High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes.<h4>Methods and results</h4>Leukocyte count and its subtype ...[more]

PMID: 26891449

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Project description:BackgroundTotal leukocyte and differential Leukocyte counts are prognostic indictors in patients with coronary artery disease (CAD). However, there is no data available regarding their prognostic utility in very old patients with acute myocardial infarction (AMI). The aim of this study is to investigate the potential role of different leukocyte parameters in predicting the mortality among very old patients with AMI.MethodsA total of 523 patients aged over 80 years with AMI were consecutively enrolled into this study. Leukocyte and its subtypes were obtained at admission in each patient. The primary study endpoint was cardiovascular mortality. Patients were followed up for an average of 2.2 years and 153 patients died. The associations of leukocyte parameters with mortality were assessed using Cox regression analyses. The concordance index was calculated to test the model efficiency.ResultsIn multivariable regression analysis, neutrophils-plus-monocytes-to-lymphocytes ratio (NMLR) and neutrophils-to-lymphocytes ratio (NLR) were two most significant predictors of mortality among all the leukocyte parameters (HR = 3.21, 95% CI 1.75-5.35; HR = 2.79, 95% CI 1.59-4.88, respectively, all p < 0.001, adjusted for age, male gender, body mass index, family history of CAD, smoking, hypertension, diabetes mellitus, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, high sensitivity C-reactive protein, creatinine, left ventricular ejection fraction, troponin I, use of statin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and percutaneous coronary intervention). Furthermore, adding NMLR and NLR into the Cox model increased the C-statistic by 0.038 and 0.037 respectively, which were more significant than that of other leukocyte parameters. Besides, addition of NMLR and NLR to the Canada Acute Coronary Syndrome Risk Score model also increased the C-statistic by 0.079 and 0.077 respectively.ConclusionOur data firstly indicated that most leukocyte subtypes were independent markers for the mortality in very old patients with AMI, while NMLR and NLR appeared to be more effective.

Project description:RationaleThe evidence regarding the potential health benefits of nut consumption among individuals with type 2 diabetes mellitus is limited.ObjectiveTo examine intake of total and specific types of nuts, including tree nuts and peanuts, in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease and stroke, and all-cause and cause-specific mortality among individuals with diabetes mellitus.Methods and resultsThis prospective analysis included 16 217 men and women with diabetes mellitus at baseline or diagnosed during follow-up (Nurses' Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2014). Nut consumption was assessed using a validated food frequency questionnaire and updated every 2 to 4 years. During 223 682 and 254 923 person-years of follow-up, there were 3336 incident CVD cases and 5682 deaths, respectively. Higher total nut consumption was associated with a lower risk of CVD incidence and mortality. The multivariate-adjusted hazard ratios (95% CIs) for participants who consumed 5 or more servings of total nuts per week (1 serving=28 g), compared with those who consumed <1 serving per month, were 0.83 (0.71-0.98; P trend=0.01) for total CVD incidence, 0.80 (0.67-0.96; P trend=0.005) for coronary heart disease incidence, 0.66 (0.52-0.84; P trend <0.001) for CVD mortality, and 0.69 (0.61-0.77; P trend <0.001) for all-cause mortality. Total nut consumption was not significantly associated with risk of stroke incidence or cancer mortality. For specific types of nuts, higher tree nut consumption was associated with lower risk of total CVD, coronary heart disease incidence, and mortality because of CVD, cancer, and all causes, whereas peanut consumption was associated with lower all-cause mortality only (all P trend <0.001). In addition, compared with participants who did not change the consumption of total nuts from pre- to post-diabetes mellitus diagnosis, participants who increased consumption of total nuts after diabetes mellitus diagnosis had an 11% lower risk of CVD, a 15% lower coronary heart disease risk, a 25% lower CVD mortality, and a 27% lower all-cause mortality. The associations persisted in subgroup analyses stratified by sex/cohort, body mass index at diabetes mellitus diagnosis, smoking status, diabetes mellitus duration, nut consumption before diabetes mellitus diagnosis, or diet quality.ConclusionsHigher consumption of nuts, especially tree nuts, is associated with lower CVD incidence and mortality among participants with diabetes mellitus. These data provide novel evidence that supports the recommendation of incorporating nuts into healthy dietary patterns for the prevention of CVD complications and premature deaths among individuals with diabetes mellitus.

Dataset Information

Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.

Publications

Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study.

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