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OBJECTIVE: It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed. RESEARCH DESIGN AND METHODS: The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin. RESULTS: During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT. CONCLUSIONS: GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes.Research Design and Methods: Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG >or=126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves.Results: During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001).Conclusions: The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.Research Design and Methods: The study participants were nondiabetic Japanese men (n = 8,570) aged 40-55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was >or=126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.Results: During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44-2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.Conclusions: Lower serum creatinine increased the risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

The biotransformation following oral administration of dimethylarsinic acid (DMA), an organoarsenical herbicide and the main metabolite of inorganic arsenic in mammals, was studied in rats. Male F344/DuCrj rats were administered a single dose of DMA (50 mg/kg) orally. Urine was collected at 0, 2, 4, 8, 10, 24, and 48 h after administration byforced urination. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry (IC-ICP-MS). The proportions of urinary elimination of DMA, trimethylarsine oxide (TMAO), methylarsonic acid (MMA), an unidentified arsenic metabolite, and arsenite were determined at various timepoints after administration. Unmetabolized DMA was the most common form excreted during the first 4 h. Thereafter, a gradual decrease in the proportion of DMA was observed, while progressive increases in those of TMAO, theunidentified metabolite, and arsenite occurred. The proportion of TMAO excreted amounted to over 50% of all arsenic in urine between 6 and 24 h. The proportion of the unidentified metabolite and arsenite were each approximately 10% at 10 and 24 h after administration. The findings indicate that DMA administered to rats was initially excreted as unchanged DMA, and later as the methylated metabolite, TMAO. Arsenite, a demethylated metabolite of DMA, also was excreted later than elimination of DMA and TMAO. The hypothesis of demethylation by intestinal microorganisms can be supported by comparing the metabolites following oral and intraperitoneal administration. The unidentified metabolite was readily decomposed by HCl but was left unchanged by NaOH; these findings suggest that it was present in a complexed form in urine. [ABSTRACT FROM AUTHOR]

The toxic effects of arsenic compounds on cell division were studied, using Chinese hamster V79 cells. Seven arsenic compounds were tested. Inorganic arsenic compounds (arsenite and arsenate), which have been found in drinking water, inhibited cell growth at very low concentrations. Monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsine oxide (TMAO), which are methylated metabolites of inorganic arsenics, were less cytotoxic than the inorganic arsenics themselves. The cytotoxicity of the three methylated metabolites decreased as the number of methyl groups increased. Arsenobetaine (AsBe) and arsenocholine (AsC), which have been found in some marine products,did not show any cytotoxicity. Three methylated metabolites; MMA, DMA and TMAO induced mitotic arrest. Tetraploidy production was observed in cells exposed to DMA or TMAO. Arsenite, arsenate, AsBe and AsC did not induce mitotic arrest or tetraploids. These results suggest that MMA, DMA and TMAO exert some effect on cell division in metaphase and may thereby give some clue as to the carcinogenic mechanism of arsenic. [ABSTRACT FROM AUTHOR]