A persistent intake of excess calories increases plasma levels of free fatty acids, particularly the saturated form that has been shown to exert toxic effects on pancreatic beta cells by inducing dysfunction and apoptosis (i.e., lipotoxicity). An insufficient supply of insulin due to beta cell failure is a major factor in the onset and progression of type 2 diabetes; therefore, it is crucial to understand the cellular mechanisms of lipotoxicity to prevent beta cell failure. Many studies on the effects of lipotoxicity have demonstrated the various factors responsible for beta cell impairment, but the mechanisms of dysfunction and apoptosis resulting from lipotoxicity have not been fully described. This review discusses lipotoxicity-induced alterations of cellular mechanisms, and assesses drugs such as incretin mimetics, thiazolidinedione, and clusterin. Understanding the molecular mechanisms of lipotoxicity-induced beta cell failure is useful in guiding the development of new therapeutic targets for diabetes treatment.
Citations
Citations to this article as recorded by
ВПЛИВ ПОЛІВІТАМІННОГО КОМПЛЕКСУ НА СТАН ПІДШЛУНКОВОЇ ЗАЛОЗИ ХОМ’ЯКІВ ЗА УМОВ ЕКСПЕРИМЕНТАЛЬНОГО МЕТАБОЛІЧНОГО СИНДРОМУ Н. Ю. Духніч, К. О. Калько, О. Я. Міщенко Medical and Clinical Chemistry.2023; (3): 72. CrossRef
Antiplatelet therapy is important for reducing systemic and local thrombotic events in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Antiplatelet treatment regimens, along with dual antiplatelet therapy consisting of aspirin and a P2Y12 inhibitor for patients receiving PCI, have frequently changed over the years. With improvements in the understanding of the prognostic relevance of bleeding events in patients with PCI, as well as the safety and efficacy of drug-eluting stents, several randomized controlled trials (RCTs) have been conducted on antiplatelet treatment strategies associated with a more favorable balance between ischemic and bleeding risks. Several key RCTs for appropriate antiplatelet therapy in patients receiving PCI for ACS have been reported, and practical guidelines have been updated. This manuscript presents the results of major RCTs on de-escalation strategies of dual antiplatelet treatment in patients receiving PCI for ACS.
Obesity is a risk factor for heart failure and cardiovascular disease. Of particular note, over 80% of patients with heart failure with a preserved ejection fraction (HFpEF) are overweight or obese. In this study, we aimed to review the association between obesity and HFpEF. Obese patients with HFpEF exhibit a distinct phenotype. In addition to impaired left ventricular (LV) diastolic function and high filling pressures, obese patients with HFpEF possess other factors that cause elevated LV filling pressure, such as a greater dependence on plasma volume expansion, aggravated pericardial restraint, and increased ventricular interaction. Obesity can contribute to HFpEF through hemodynamic, neurohormonal, inflammatory, and mechanical mechanisms. An increased amount of body fat can induce plasma volume expansion, resulting in chamber remodeling, pericardial restraint, and ultimately elevations in LV filling pressure. Obesity can mediate the activation of sympathetic nervous system signaling and the renin-angiotensin-aldosterone system. These unique pathophysiological characteristics of individuals with both obesity and HFpEF suggest that obesity with HFpEF can be considered a specific phenotype. Future research is expected to clarify effective treatment modalities for obesity-related HFpEF.
Background Exercise and estrogen play key roles in preventing diabetes and obesity. Women’s risk of diabetes could increase due to the loss of the protective effect of estrogen after menopause. Therefore, we investigated the relationship of the intensity and frequency of exercise with diabetes risk in Korean women.
Methods Hazard ratios (HRs) for the development of diabetes were analyzed in 926,807 premenopausal and 1,188,346 postmenopausal women without diabetes over the age of 40 who underwent the Korean National Health Examination in 2009 and were followed up until 2018. The number of days of physical activity according to exercise intensity and metabolic equivalent of task-minutes per week (MET-min/wk) were calculated.
Results In total, 38,096 premenopausal (4.1%) and 120,605 postmenopausal (10.2%) women were newly diagnosed with diabetes. Regardless of menopausal history, the risk of diabetes was significantly lower in groups with higher MET-min/wk than in sedentary participants (0 MET-min/wk, reference), although this effect disappeared in postmenopausal women with the highest level of MET-min/wk (MET-min/wk ≥1,500) after adjusting for all variables (HR, 1.0; 95% confidence interval, 0.97–1.02). Participants who exercised for more than 1 day per week had a significantly lower risk of diabetes, regardless of the intensity. However, this benefit was lost in women with near-daily exercise (≥6 days/wk).
Conclusions Exercise was effective in preventing diabetes in both premenopausal and postmenopausal women. A moderate amount of exercise should be actively encouraged to lower the risk of diabetes in women, especially after menopause, while simultaneously considering the insignificant benefits of excessive exercise.
Background Liraglutide, a drug used for the management of obesity, has many known side effects. In this study, we developed a predictive model for the occurrence of liraglutide-related side effects using data from electronic medical records (EMRs).
Methods This study included 237 patients from Seoul St. Mary's Hospital and Eunpyeong St. Mary's Hospital who were prescribed liraglutide. An endocrinologist obtained medical data through an EMR chart review. Model performance was evaluated using the mean of the area under the receiver operating characteristic curve (AUROC) with a 95% confidence interval (CI).
Results A predictive model was developed for patients who were prescribed liraglutide. However, 37.1% to 75.5% of many variables were missing, and the AUROC of the developed predictive model was 0.630 (95% CI, 0.551–0.708). Patients who had previously taken antiobesity medication had significantly fewer side effects than those without previous antiobesity medication use (20.7% vs. 41.4%, P<0.003). The risk of side effect occurrence was significantly higher in patients with diabetes than in patients without diabetes by 2.389 times (odds ratio, 2.389; 95% CI, 1.115–5.174).
Conclusions This study did not successfully develop a predictive model for liraglutide-related side effects, primarily due to issues related to missing data. When prescribing antiobesity drugs, detailed records and basic blood tests are expected to be essential. Further large-scale studies on liraglutide-related side effects are needed after obtaining high-quality data.
Citations
Citations to this article as recorded by
The effects and side effects of liraglutide as a treatment for obesity Jeonghoon Ha, Jin Yu, Joonyub Lee, Hun-Sung Kim Cardiovascular Prevention and Pharmacotherapy.2022; 4(4): 142. CrossRef