Oxidative stress is considered to be an important factor in producing lethal hepatocyte injury associated with nonalcoholic fatty liver disease (NAFLD). Glucose fluctuation, more pronounced in patients with diabetes, has been recognized as an even stronger oxidative stress inducer than the sustained hyperglycemia. Here, we investigated the role of glucose variability in the development of the NAFLD based on hepatocyte apoptosis and possible mechanisms. To achieve this goal we studied C57BL/6J mice that were maintained on a high fat diet (HFD) and injected with glucose (3 g/kg) twice daily to induce intermittent high glucose (IHG). We also studied hepatic L02 cells incubated with palmitic acid (PA) to induce steatosis. The following experimental groups were compared: normal glucose (NG), sustained high glucose (SHG) and IHG with or without PA. We found that, although hepatic enzyme levels and liver lipid deposition were comparable between HFD mice injected with glucose or saline, the glucose injected mice displayed marked hepatocyte apoptosis and inflammation, accompanied by increased lipid peroxide in liver. In vitro, in the presence of PA, IHG increased L02 cell apoptosis and oxidative stress and produced pronounced mitochondrial dysfunction relative to the NG and SHG groups. Furthermore, treatment with the mitochondrial permeability transition (MPT) inhibitor, cyclosporin A (1.5 mmol/l), prevented mitochondrial dysfunction, oxidative stress and hepatocyte apoptosis. Our data suggests that IHG under lipotoxicity might contribute to the development of NAFLD by increasing oxidative stress and hepatocyte apoptosis via MPT and its related mitochondrial dysfunction.

The incidence of diabetes is increasing globally. We investigated the relationship between diabetes prevalence and patient socioeconomic status across multiple countries. We searched PubMed to identify population-based surveys reporting diabetes prevalence between 1990 and May 2016. Search results were filtered, and Human Development Index (HDI) values from the United Nations Development Programme were used to assess socioeconomic status for a given nation. Our analysis included 45 national surveys from 32 countries. Diabetes prevalence was positively correlated with national HDI (r = 0.421 P = 0.041) in developing countries, and negatively correlated with HDI (r = −0.442 P = 0.045) in developed countries. Diabetes prevalence trends were the same in women and men, although men were associated with increased diabetes risk in developed countries (r = 0.459 P = 0.048). Thus, diabetes prevalence rises with increasing HDI in developing countries, and this is reversed in developed countries. Ours is the first study to investigate the relationship between diabetes and socioeconomic status at global level using HDI values. These results will aid in evaluating global diabetes prevalence and risk with respect to patient socioeconomic status, and will be useful in the development of policies that help reduce disease incidence.

Abstract. Various noninvasive algorithms have been developed for predicting the presence of nonalcoholic fatty liver disease (NAFLD). The evaluation of the indexes' diagnostic performance has been reported in Europe and Asia over the past decade; however, external validation of them in China is rare. This study was aimed to evaluate various indexes for NAFLD in western China. It was a retrospective cross-sectional study, using data from a large-scale health check-up project at Sichuan provincial hospital. Receiver operating characteristic (ROC) curves of eight indexes, including the fatty liver index (FLI), the hepatic steatosis index, lipid accumulation product and etc., were developed to predict ultrasonographic NAFLD. There were 13,122 subjects in this study (2,692 NAFLD patients and 10,430 non-NAFLD participants). The area under ROC curve of FLI for predicting NAFLD was 0.880 (95% confidence interval, 0.874-0.886), which was significantly higher than other seven indexes. Accuracy, sensitivity and specificity of FLI for NAFLD were good (cut-off value = 30, 0.782, 0.832, 0.770 and cut-off value = 60, 0.838, 0.443, 0.940, respectively). Furthermore, FLI also presented advantages in expenditure and accessibility, compared with other indexes. It supports FLI as an easily accessible index for physicians and a reliable predictor for NAFLD screening in western China.