Objective: The aim of this study was to examine an impact of body mass index (BMI) and weight change on the risk of diabetes according to metabolic health status. Methods: Cohort study of 34,999 Korean men and women 30-59 years of age free of diabetes at baseline were followed-up annually or biennially for an average of 5.1 years. Being metabolically healthy was defined as not having any metabolic syndrome component. Results: During 176,878.6 person-years of follow-up, 889 participants developed diabetes (incidence rate 5.0 per 1000 person-years). Compared to metabolically healthy normal-weight individuals, the adjusted hazard ratios for diabetes in metabolically unhealthy obese and in metabolically healthy obese were 13.7 (95% confidence interval [CI] 9.8-19.0) and 2.7 (95% CI: 1.7-4.3), respectively. The aHR (95% CI) for incident diabetes for weight changes of <20.9, 0.5 to 2.0, and !2.1 kg compared to a weight change of 20.9 to 0.4 kg (reference) were 0.80 (0.66-0.97), 0.99 (0.82-1.20), and 1.24 (1.02-1.49), respectively (P-trend<0.001). Conclusions:In this large cohort of young and middle age Koreans, metabolic health status, obesity, and weight change were all independently associated with increased incidence of diabetes over 5 years of follow-up.
PurposeRecent studies have revealed that branched-chain amino acids (BCAA) reduce the development of hepatocellular carcinoma (HCC) in patients with obesity and hepatitis C virus infection by improving insulin resistance (IR). The aim of this study was to examine the anti-cancer and anti-fibrotic effects of BCAA on the development of diethylnitrosamine (DEN)-induced HCC and liver cirrhosis in a rat model.MethodsMale SD rats received weekly intraperitoneal injections of DEN (50 mg/kg of body weight) for 16 weeks to induce HCC. They were fed a diet containing 3% casein, 3% or 6% BCAA for 13 weeks beginning 6 weeks after DEN administration. DEN was used to induce HCC through stepwise development from cirrhosis to HCC. The effect of BCAA was evaluated in tumor tissues by histopathologic analyses, reverse transcription-polymerase chain reaction, and Western blotting.ResultsThe mean area and number of dysplastic nodules (DNs) and tumors in the casein group tended to be larger than those in the BCAA group 16 weeks after DEN administration. The mean fibrotic area in the BCAA group was smaller than that in the casein group. The BCAA group showed decreased mRNA levels for markers of fibrosis, angiogenesis, and apoptosis inhibition. Compared with the casein group, the BCAA group had lower levels of α-smooth muscle actin, vascular endothelial growth factor, p-β-catenin, p-p38 mitogen-activated protein kinase, proliferating cell nuclear antigen, and caspase-3 protein expression, as well as a higher level of cleaved caspase-3 protein expression.ConclusionsBCAA supplementation of the diet ameliorated liver fibrosis and HCC development in a DEN-induced rat model of HCC with liver cirrhosis, but not in the IR model. These results provide a rationale for anti-fibrosis and chemoprevention using BCAA treatment for HCC with liver cirrhosis, as well as decreasing the ammonia level.
Background: Insulin resistance and progressive pancreatic beta cell dysfunction have been identified as the two fundamental features in the type 2 diabetes. Homeostasis model assessment (HOMA), based on plasma levels of fasting glucose and insulin, has been widely validated and applied for quantifying insulin resistance and secretion. This study was performed to assess the predictive value of HOMA indices for future diabetes risk. Methods: In 14,976 Korean men, in which medical check-up was performed both in 2002 and 2006 in a university hospital health promotion center in Seoul, Korea, prospective assessment for diabetes risk was assessed. At baseline, anthropometric measurements were done and fasting glucose, insulin, lipid profiles were measured. HOMA-insulin resistance (HOMA-IR) and beta cell function (HOMA β-cell) were calculated from fasting glucose and insulin levels. Results: After 4 years, 286 subjects (1.9%) were newly diagnosed as diabetes mellitus. These patients (mean age 40.3 years) were age-matched with 632 control subjects (mean age 39.8 years) and diabetes risk was assessed with HOMA indices. Among the parameters, body mass index, fasting glucose and HOMA β-cell were the significant determinants for future diabetes risk. When the subjects were divided into two groups according to the baseline median values of HOMA-IR and HOMA β-cell, and assessed jointly, those with the low HOMA β-cell and high HOMA-IR showed the highest risk for future diabetes (RR 39.065, 95% CI 11.736~130.035, P < 0.01). The subjects with low baseline HOMA β-cell showed higher RR for diabetes than those with high baseline HOMA-IR (4.413 vs. 3.379, P = 0.018, P = 0.051). Conclusion:High HOMA-IR and low HOMA β-cell were associated with the highest risk for future diabetes in this prospective study of Korean male subjects. These data suggest the value of HOMA indices for diabetes risk in epidemiologic studies in Asian subjects.
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