ObjectiveRisk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population.MethodsParticipants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008–2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥126 mg/dl, random plasma glucose ≥200 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort.ResultsThe area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703–0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883–0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715–0.753) and 0.882 (0.868–0.895), respectively. Participants with a non-invasive score of ≥15 and invasive score of ≥19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years.ConclusionsThe simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c.

AimsTo examine the association of smoking status, smoking intensity, and smoking cessation with the risk of type 2 diabetes (T2D) using a large database.MethodsThe present study included 53,930 Japanese employees, aged 15 to 83 years, who received health check-up and did not have diabetes at baseline. Diabetes was defined as fasting plasma glucose ≥126 mg/dl, random plasma glucose ≥200 mg/dl, HbA1c ≥6.5% (≥48 mmol/mol), or receiving medication for diabetes. Cox proportional-hazards regression models were used to investigate the association between smoking and the risk of diabetes.ResultsDuring 3.9 years of median follow-up, 2,441 (4.5%) individuals developed T2D. The multivariable-adjusted hazard ratios (95% CI) for diabetes were 1 (reference), 1.16 (1.04 to 1.30) and 1.34 (1.22 to 1.48) for never smokers, former smokers, and current smokers, respectively. Diabetes risk increased with increasing numbers of cigarette consumption among current smokers (P for trend <0.001). Although the relative risk of diabetes was greater among subjects with lower BMIs (< 23 kg/m2), attributable risk was greater in subjects with higher BMIs (≥ 23 kg/m2). Compared with individuals who had never smoked, former smokers who quit less than 5 years, 5 to 9 years, and 10 years or more exhibited hazards ratios for diabetes of 1.36 (1.14 to 1.62), 1.23 (1.01 to 1.51), and 1.02 (0.85 to 1.23), respectively.ConclusionsResults suggest that cigarette smoking is associated with an increased risk of T2D, which may decrease to the level of a never smoker after 10 years of smoking cessation.

Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47phox؊/؊ mouse model of CGD, we evaluated the residual antibacterial activity of XO. Clearance of Burkholderia cepacia, a major pathogen in CGD, was reduced in p47 phox؊/؊ mice compared to that in wild-type mice and was further inhibited in p47 phox؊/؊ mice by pretreatment with the specific XO inhibitor allopurinol. Hepatic B. cepacia burden was similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47 phox؊/؊ mice. Clearance and killing of intravenous Escherichia coli was intact in p47 phox؊/؊ mice and was unaffected by pretreatment with allopurinol. In CGD, XO may contribute to host defense against a subset of reactive oxidant-sensitive pathogens.Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase complex in which phagocytes are defective in generating superoxide anion and the downstream reactive oxidant products, hydrogen peroxide, hypohalous acid, and hydroxyl radical (2,10,30,37,38). As a result of the defect in this key host defense pathway, CGD patients suffer from recurrent life-threatening infections caused by catalase-positive bacteria and fungi (1,27,31,33,35).NADPH oxidase is localized on the membranes of secondary granules in neutrophils and can be displayed on the phagocytic vacuoles and plasma membranes of myeloid cells (neutrophils, monocytes, and eosinophils). In response to phagocytosis and the chemoattractants interleukin 8, leukotriene B 4 , C5a, and platelet-activating factor, as well as nonphysiologic stimuli such as phorbol myristate acetate or the calcium ionophore A23817, a rapid and dramatic increase in oxygen consumption, termed the "respiratory burst," whereby molecular oxygen is reduced to superoxide, occurs.Xanthine oxidase (XO) is a ubiquitous enzyme involved in purine catabolism that, when activated from its constitutively expressed precursor, xanthine dehydrogenase, generates superoxide anion under certain circumstances. Moreover, in the presence of Fe 3ϩ , XO can generate a highly potent oxidant that behaves like the hydroxyl anion, via a Fenton reduction (13,20). The role of XO in host defense has been supported by in vitro studies using isolated macrophages and Kupffer cells (28, 36) and by exacerbations of experimental infections in which animals received XO inhibitors (39, 40). However, the relative role of XO in superoxide generation has been difficult to determine because the NADPH oxidase system usually generates much more superoxide from phagocytes.We hypothesized that in the absence of a functional NADPH oxidase, the role of XO in host defense against certain pathogens might be revealed. We have generated a knockout mouse model...

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