Weight change and the incidence of heart failure in the Korean population: data from the National Health Insurance Health checkup 2005-2015.

AIMS: Heart failure (HF) is associated with obesity, but the relationship between weight change and HF is inconsistent. We examined the relationship between weight change and the incidence of HF in the Korean population. DESIGN: Retrospective cohort study design. METHODS AND RESULTS: A total of 11 210 394 subjects (6 198 542 men and 5 011 852 women) >20 years of age were enrolled in this study. Weight change over 4 years divided into seven categories from weight loss ≥15% to weight gain ≥15%. The hazard ratios (HRs) and 95% confidence intervals for the incidence of HF were analysed. The HR of HF showed a slightly reverse J-shaped curve by increasing weight change in total and >15% weight loss shows the highest HR (HR 1.647) followed by -15 to -10% weight loss (HR = 1.444). When using normal body mass index with stable weight group as a reference, HR of HF decreased as weight increased in underweight subjects and weight gain ≥15% in obesity Stage II showed the highest HR (HR = 2.97). Sustained weight for 4 years in the underweight and obesity Stages I and II increased the incidence of HF (HR = 1.402, 1.092, and 1.566, respectively). CONCLUSION: Both weight loss and weight gain increased HR for HF. Sustained weight in the obesity or underweight categories increased the incidence of HF.

Effects of DA-9801 on the inflammation and apoptosis induced by angiotensin II in human dermal microvascular endothelial cells.

DA-9801, a plant-based drug used for the treatment of diabetic neuropathy, is known to improve angiotensin II (Ang II)-induced vascular endothelial cell dysfunction. However, the underlying mechanism is not fully understood. We aimed to determine whether the protective effect of DA-9801 against Ang II-induced endothelial cell dysfunction was mediated via inhibition of endothelial cell inflammation and apoptosis. Ang II-induced oxidative stress was attenuated by pretreatment of human dermal microvascular endothelial cells (HDMECs) with DA-9801. This prevented the Ang II-induced upregulation of NAD(P)H oxidase (the NOX4 and p22phox subunits) and reactive oxygen species. Further, pretreatment of HDMECs with DA-9801 ameliorated Ang II-mediated nuclear factor kappa B activity via prevention of the upregulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. It also decreased the Ang II-stimulated increase in inducible nitric oxide synthase (NOS) and decreased endothelial NOS protein expression. DA-9801 decreased Ang II-induced upregulation of intercellular adhesion molecule 1, vascular adhesion molecule, and E-selectin in HDMECs. Moreover, TUNEL and annexin V-FITC fluorescence staining for apoptosis and the activities of caspases 9, 7, and 3 decreased in HDMECs pretreated with DA-9801, indicating that the drug enhanced anti-apoptotic pathways. Thus, DA-9801 modulated Ang II-induced endothelial cell dysfunction via inflammatory and apoptotic pathways.

Alpha-lipoic acid preserves skeletal muscle mass in type 2 diabetic OLETF rats.

BACKGROUND: Increased oxidative stress and impaired antioxidant defense are important mechanisms in the pathogenesis of diabetic myopathy. Alpha-lipoic acid (ALA) has been indicated as a weight-loss treatment in rodents and humans, but studies are limited. In the present study, we aimed to determine the influence of ALA, a potent biological antioxidant, on metabolic and growth processes in diabetic rat skeletal muscle. METHODS: Male 25-week-old type 2 diabetic rats (OLETF) were randomly divided into two groups, a control group (OLETF-C) and an ALA-treated group (OLETF-ALA) supplemented with 100 mg/kg ALA for 8 weeks. Age-matched, healthy, nondiabetic LETO (LETO-C) rats were used as controls. RESULTS: At 32 weeks of age, body weight was decreased by 6.8%, and the areas under the curve of IP-GTT, fasting glucose, and insulin were less in OLETF-ALA rats compared with OLETF-C rats. ALA significantly preserved muscle mass and enhanced muscle fiber cross-sectional area and fiber frequency percentage in the skeletal muscle of OLETF rats. Although the activation of myoD, myogenin, and myostatin in gastrocnemius muscle was significantly inhibited in OLETF-ALA rats relative to OLETF-C rats, there were no differences in the expression levels of muscle atrogin-1 and MuRF1 between the two groups. ALA treatment significantly increased the levels of phosphorylated 5'-AMPK, SIRT1, and PGC-1α, as well as the levels of phosphorylated AKT, mTOR, and p70S6 kinase in OLETF-ALA rats compared with OLETF-C rats. In contrast, the levels of phosphorylated p38 MAPK, IRS-1, and FOXO1 were decreased in OLETF-ALA rats compared with OLETF-C rats. CONCLUSIONS: ALA treatment preserved mass in the gastrocnemius muscles of OLETF rats. ALA significantly upregulated the AMPK/SIRT1/PGC-1α and AKT/mTOR/p70S6K signaling pathways in OLETF rat skeletal muscle. Therefore, ALA may be a potential therapeutic intervention for skeletal muscle loss in animal models of insulin resistance.