Efficacy and Safety of High-Dose Atorvastatin in Moderate-to-High Cardiovascular Risk Postmenopausal Korean Women with Dyslipidemia.

OBJECTIVE: Postmenopausal women show a more atherogenic lipid profile and elevated cardiovascular risk compared to premenopausal women. The aim of this study was to investigate the efficacy and safety of high-dose atorvastatin on the improvement of the blood lipid profile of postmenopausal women in Korea. METHODS: This study is a prospective, open-label, single-arm clinical trial that was conducted in 3 teaching hospitals. Postmenopausal women with a moderate-to-high cardiovascular risk, according to guidelines from the Korean Society of Lipid & Atherosclerosis, were enrolled. Participants were administered 20 mg of atorvastatin daily for the first 8 weeks, and if the targeted low-density lipoprotein cholesterol (LDL-C) level was not achieved, the dose was increased to 40 mg for the second 8 weeks. The primary endpoint was percentage change of LDL-C from baseline after 16 weeks of drug administration. RESULTS: Forty-four women were enrolled, 28 of whom (75.6%) had diabetes mellitus. By the end of treatment period (16 weeks) all patients had achieved LDL-C target levels, with 33 (94.2%) of the participants achieving it after only 8 weeks of administration. After 16 weeks, LDL-C decreased by 45.8±16.7% (p<0.001) from the baseline, and total cholesterol (33.2±10.9%; p<0.001), triglyceride (24.2±37.5%; p=0.001), and apolipoprotein B (34.9±15.6%; p<0.001) also significantly decreased. Blood glucose and liver enzyme levels slightly increased, but none of the participants developed serious adverse events that would cause them to prematurely withdraw from the clinical trial. CONCLUSION: 20 and 40 mg atorvastatin was effective and safe for treating dyslipidemia in postmenopausal Korean women with moderate-to-high cardiovascular risk.

Fasting and Postprandial Hyperglycemia: Their Predictors and Contributions to Overall Hyperglycemia in Korean Patients with Type 2 Diabetes.

BACKGROUND: This study aimed to identify factors that affect fasting hyperglycemia (FHG) and postprandial hyperglycemia (PPG) and their contributions to overall hyperglycemia in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: This was a retrospective study conducted on 194 Korean T2DM patients with 7-point self-monitoring blood glucose (SMBG) profiles plotted in 4 days in 3 consecutive months. We calculated the areas corresponding to FHG and PPG (area under the curve [AUC]FHG and AUCPPG) and contributions (%) in the graph of the 7-point SMBG data. The levels of glycated hemoglobin (HbA1c) were categorized by tertiles, and the contributions of FHG and PPG were compared. RESULTS: The relative contribution of FHG increased (44.7%±5.6%, 58.0%±4.4%, 66.5%±2.8%; PANOVA=0.002, PTREND <0.001), while that of PPG decreased (55.3%±5.5%, 42.0%±4.4%, 33.5%±2.8%; PANOVA=0.002, PTREND <0.001) with the elevated HbA1c. Multivariate analysis showed that HbA1c (ß=0.615, P<0.001), waist circumference (ß=0.216, P=0.042), and triglyceride (ß=0.121, P=0.048) had a significant association with AUCFHG. Only HbA1c (ß=0.231, P=0.002) and age (ß=0.196, P=0.009) was significantly associated with AUCPPG. CONCLUSION: The data suggested that in Korean T2DM patients, FHG predominantly contributed to overall hyperglycemia at higher HbA1c levels, whereas it contributed to PPG at lower HbA1c levels. It is recommended that certain factors, namely age, degree of glycemic control, obesity, or triglyceride levels, should be considered when prescribing medications for T2DM patients.

Clinical Evidence and Mechanisms of High-Protein Diet-Induced Weight Loss.

Several clinical trials have found that consuming more protein than the recommended dietary allowance not only reduces body weight (BW), but also enhances body composition by decreasing fat mass while preserving fat-free mass (FFM) in both low-calorie and standard-calorie diets. Fairly long-term clinical trials of 6-12 months reported that a high-protein diet (HPD) provides weight-loss effects and can prevent weight regain after weight loss. HPD has not been reported to have adverse effects on health in terms of bone density or renal function in healthy adults. Among gut-derived hormones, glucagon-like peptide-1, cholecystokinin, and peptide tyrosine-tyrosine reduce appetite, while ghrelin enhances appetite. HPD increases these anorexigenic hormone levels while decreasing orexigenic hormone levels, resulting in increased satiety signaling and, eventually, reduced food intake. Additionally, elevated diet-induced thermogenesis (DIT), increased blood amino acid concentration, increased hepatic gluconeogenesis, and increased ketogenesis caused by higher dietary protein contribute to increased satiety. The mechanism by which HPD increases energy expenditure involves two aspects: first, proteins have a markedly higher DIT than carbohydrates and fats. Second, protein intake prevents a decrease in FFM, which helps maintain resting energy expenditure despite weight loss. In conclusion, HPD is an effective and safe tool for weight reduction that can prevent obesity and obesity-related diseases. However, long-term clinical trials spanning more than 12 months should be conducted to further substantiate HPD effects.

System χc- overexpression prevents 2-deoxy-d-ribose-induced ß-cell damage.

Pancreatic ß-cells are vulnerable to oxidative stress, which promotes ß-cell failure in type 2 diabetes. System χc- is a sodium-independent, cystine/glutamate antiporter that mediates the exchange of extracellular l-cystine and intracellular l-glutamate. The import of l-cystine through this transporter is the rate-limiting step in the glutathione (GSH) biosynthesis pathway that plays a significant role in antioxidative defense. Previously, we reported that 2-deoxy-d-ribose (dRib) induces oxidative damage through GSH depletion in pancreatic ß-cells. In the current study, we elucidated the mechanism underlying the oxidative stress-induced ß-cell damage. We measured the intracellular l-[14C]cystine uptake, GSH content, reactive oxygen species (ROS) levels, cytotoxicity, and apoptosis in rat insulinoma cell line, RINm5F. Treatment of dRib decreased the intracellular l-[14C]cystine uptake and GSH content and increased the intracellular ROS levels, cytotoxicity, and apoptosis in a time- and dose-dependent manner. Conversely, 2-mercaptoethanol (2-ME), a cystine uptake enhancer, recovered the dRib-induced decrease in l-[14C]cystine uptake, GSH content, and cell viability in a Na+-independent manner. In the case of isolated islets, dRib dose-dependently decreased the intracellular l-[14C]cystine uptake and cell viability; however, dRib-induced cytotoxicity was completely recovered by adding N-acetyl cysteine (NAC). To confirm that system χc- mediates the oxidative stress-induced ß-cell damage, we overexpressed xCT (the substrate-specific subunit of system χc-) using a lentiviral vector in RINm5F cells. Overexpression of xCT fully recovered the dRib-induced decrease in l-[14C]cystine uptake and GSH content and prevented the dRib-induced increase in ROS levels, cytotoxicity, and apoptosis. The overexpression of xCT showed a protective effect against dRib-induced oxidative damage in RINm5F cells. Our study showed that dRib depletes intracellular GSH content through inhibition of cystine transport via system χc- in ß-cells.

Increased pulse wave velocity and augmentation index after isometric handgrip exercise in patients with coronary artery disease.

BACKGROUND: Arterial stiffness of patients with coronary artery disease (CAD), which is expected to be increased due to a generalized atherosclerotic process of human body, may be more evident after the acute increase of blood pressure (BP) or peripheral vascular resistance. Isometric handgrip exercise is a simple and easily applicable method to achieve this goal. We investigated the changes of hemodynamic parameters and arterial stiffness indexes after handgrip exercise in patients with CAD. METHODS: Forty-two subjects, who underwent coronary angiography (CAG), were enrolled. After CAG, baseline arterial waveforms were traced at the aortic root and external iliac artery using right coronary catheters. Arterial waveforms were recorded at 1, 2, and 3 min in the aortic root and at 3 min in the external iliac artery after isometric handgrip exercise at 30% ~ 40% of the maximal handgrip power. Augmentation pressure (AP) and augmentation index (AIx) were measured at aortic pressure waveforms. Pulse wave velocity (PWV) was calculated using the ECG-gated time difference of the upstroke of arterial waveforms and the distance between the aortic root and the external iliac artery. RESULTS: Thirty patients had CAD (CAD group), and others showed no significant coronary stenosis (non-CAD group). Baseline hemodynamic parameters including AIx and PWV were not different between both groups. After isometric handgrip exercise, central systolic blood pressure (BP), central diastolic BP, central pulse pressure, peripheral systolic BP, and peripheral pulse pressure were increased in all patients. AIx inclined significantly from 1 min after exercise only in patients with CAD (before 17.7% ± 9.7% vs. 3 min after exercise 22.3% ± 10.7%, p < 0.001). PWV also increased significantly after exercise only in patients with CAD (before 10.03 ± 1.99 m/s vs. 3 min after 11.09 ± 2.45 m/s, p < 0.001). CONCLUSIONS: Arterial stiffness indexes at rest were not different between patients with and without CAD. After isometric handgrip exercise, increased arterial stiffness became evident only in patients with CAD.

A case of hepatic cyst-induced inferior vena cava thrombosis.

A 92-year-old woman visited the hospital with edema of both lower extremities. Computed tomography revealed her inferior vena cava (IVC) was compressed by a massive hepatic cyst. A massive IVC thrombosis and pulmonary thromboembolism (PTE) were also observed. Medical treatment rather than radiologic intervention was preferred because of the patient's advanced age and poor performance status. IVC thrombosis and PTE disappeared after 6 months of anticoagulation therapy. To the best of our knowledge, this is the first study in the English literature to report IVC thrombosis caused by congenital hepatic cysts that was treated without vascular intervention.