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 (β=0.615, P<0.001), waist circumference (β=0.216, P=0.042), and triglyceride (β=0.121, P=0.048) had a significant association with AUCFHG. Only HbA1c (β=0.231, P=0.002) and age (β=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.

Factors Related to Blood Intact Incretin Levels in Patients with Type 2 Diabetes Mellitus

BACKGROUND: We performed this study to identify factors related to intact incretin levels in patients with type 2 diabetes mellitus (T2DM). METHODS: We cross-sectionally analyzed 336 patients with T2DM. Intact glucagon-like peptide 1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 minutes after ingestion of a standard mixed meal. The differences between 30 and 0 minute iGLP-1 and iGIP levels were indicated as ΔiGLP-1 and ΔiGIP. RESULTS: In simple correlation analyses, fasting iGLP-1 was positively correlated with glucose, C-peptide, creatinine, and triglyceride levels, and negatively correlated with estimated glomerular filtration rate. ΔiGLP-1 was positively correlated only with ΔC-peptide levels. Fasting iGIP showed positive correlations with glycosylated hemoglobin (HbA1c) and fasting glucose levels, and negative correlations with ΔC-peptide levels. ΔiGIP was negatively correlated with diabetes duration and HbA1c levels, and positively correlated with Δglucose and ΔC-peptide levels. In multivariate analyses adjusting for age, sex, and covariates, fasting iGLP-1 levels were significantly related to fasting glucose levels, ΔiGLP-1 levels were positively related to ΔC-peptide levels, fasting iGIP levels were related to fasting C-peptide levels, and ΔiGIP levels were positively related to ΔC-peptide and Δglucose levels. CONCLUSION: Taken together, intact incretin levels are primarily related to C-peptide and glucose levels. This result suggests that glycemia and insulin secretion are the main factors associated with intact incretin levels in T2DM patients.

Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors

BACKGROUND: The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). METHODS: We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations. RESULTS: GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (beta=0.209, P=0.009) and MAG (beta=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk. CONCLUSION: GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.

Apolipoprotein B Is Related to Metabolic Syndrome Independently of Low Density Lipoprotein Cholesterol in Patients with Type 2 Diabetes

BACKGROUND: Increased low density lipoprotein cholesterol (LDL-C) level and the presence of metabolic syndrome (MetS) are important risk factors for cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Recent studies demonstrated apolipoprotein B (apoB), a protein mainly located in LDL-C, was an independent predictor of the development of CVD especially in patients with T2DM. The aim of this study was to investigate the relationship between apoB and MetS in T2DM patients. METHODS: We analyzed 912 patients with T2DM. Fasting blood samples were taken for glycated hemoglobin, high-sensitivity C-reactive protein, total cholesterol, triglyceride (TG), high density lipoprotein cholesterol, LDL-C, and apoB. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria. We performed a hierarchical regression analysis with apoB as the dependent variable. Age, sex, the number of components of MetS and LDL-C were entered at model 1, the use of lipid-lowering medications at model 2, and the individual components of MetS were added at model 3. RESULTS: Seventy percent of total subjects had MetS. ApoB level was higher in subjects with than those without MetS (104.5+/-53.3 mg/dL vs. 87.7+/-33.7 mg/dL, P<0.01) even after adjusting for LDL-C. ApoB and LDL-C were positively correlated to the number of MetS components. The hierarchical regression analysis showed that the increasing number of MetS components was associated with higher level of apoB at step 1 and step 2 (beta=0.120, P<0.001 and beta=0.110, P<0.001, respectively). At step 3, TG (beta=0.116, P<0.001) and systolic blood pressure (beta=0.099, P<0.05) were found to significantly contribute to apoB. CONCLUSION: In patients with T2DM, apoB is significantly related to MetS independently of LDL-C level. Of the components of MetS, TG, and systolic blood pressure appeared to be determinants of apoB.