Takahide Okumura

Circulating TNF receptor 2 is associated with the development of chronic kidney disease in non-obese Japanese patients with type 2 diabetes

AIMS Chronic low-grade inflammation and/or obesity are suggested to induce chronic kidney disease (CKD) in patients with type 2 diabetes. This cross-sectional study was performed to investigate the relationship between inflammatory biomarkers and CKD in non-obese patients with type 2 diabetes. METHODS 106 non-obese Japanese patients with type 2 diabetes were recruited for the measurement of GFR, TNF, HMW adiponectin, leptin, hsCRP and some variables including urinary albumin. BMI, serum creatinine, and urinary albumin levels were 22.2 ± 0.2 kg/m(2) (17.1-24.9 kg/m(2)), 0.76 ± 0.02 mg/dl (0.39-1.38 mg/dl), 40.4 ± 4.3mg/gCr (1.6-195.0mg/gCr), respectively. They were stratified into two groups based on the value of eGFR: low eGFR (eGFR<60 ml/min/1.73 m(2)) and normal eGFR (eGFR>60 ml/min/1.73 m(2)). Logistic regression analysis was used for statistical analysis. RESULTS Whereas univariate logistic regression analysis showed that gender, diabetes duration, triglyceride, HDL cholesterol, uric acid, urinary albumin, and soluble TNF receptors (sTNF-R1, sTNF-R2) are associated with the development of stage 3 CKD, multivariate logistic regression analysis revealed that sTNF-R2 (Odds ratio 1.003, 95% confidence interval 1.000 to 1.005, P=0.030) showed significant associations with the development of stage 3 CKD. CONCLUSIONS Circulating TNF receptor 2 is an independent risk factor for CKD in non-obese Japanese patients with type 2 diabetes.

Smoking, white blood cell counts, and TNF system activity in Japanese male subjects with normal glucose tolerance

BackgroundCigarette smokers have increased white blood cell (WBC) counts and the activation of tumor necrosis factor (TNF). The effect of smoking on WBC counts and TNF system activity, however, has not been separately investigated yet.Subjects and MethodsOne hundred and forty-two Japanese male subjects with normal glucose tolerance were recruited. They were stratified into two groups based on the questionnaire for smoking: one with current smokers (n = 48) and the other with current non-smokers (n = 94). Whereas no significant differences were observed in age, BMI, high molecular weight (HMW) adiponectin, and TNF-α between the two groups, current smokers had significantly higher soluble TNF receptor 1 (sTNF-R1) (1203 ± 30 vs. 1116 ± 21 pg/ml, p = 0.010) and increased WBC counts (7165 ± 242 vs. 5590 ± 163/μl, p < 0.001) and lower HDL cholesterol (55 ± 2 vs. 60 ± 1 mg/dl, p = 0.031) as compared to current non-smokers. Next, we classified 48 current smokers into two subpopulations: one with heavy smoking (Brinkman index ≥ 600) and the other with light smoking (Brinkman index < 600).ResultsWhereas no significant difference was observed in age, BMI, HMW adiponectin, WBC counts and TNF-α, sTNF-R1 and sTNF-R2 were significantly higher in heavy smoking group (1307 ± 44 vs. 1099 ± 30 pg/ml, p < 0.001; 2166 ± 86 vs. 827 ± 62 pg/ml, p = 0.005) than in light smoking group, whose sTNF-R1 and sTNF-R2 were similar to non-smokers (sTNF-R1: 1116 ± 15 pg/ml, p = 0.718, sTNF-R2; 1901 ± 32 pg/ml, p = 0.437). In contrast, WBC counts were significantly increased in heavy (7500 ± 324/μl, p < 0.001) or light (6829 ± 352/μl, p = 0.001) smoking group as compared to non-smokers (5590 ± 178/μl). There was no significant difference in WBC counts between heavy and light smoking group (p = 0.158).ConclusionWe can hypothesize that light smoking is associated with an increase in WBC counts, while heavy smoking is responsible for TNF activation in Japanese male subjects with normal glucose tolerance.