Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

The Effect of Metformin Treatment on CRBP-I Level and Cancer Development in the Liver of HBx Transgenic Mice.

Retinoids regulate not only various cell functions including proliferation and differentiation but also glucose and lipid metabolism. After we observed a marked up-regulation of cellular retinol-binding protein-I (CRBP-I) in the liver of hepatitis B virus x antigen (HBx)-transgenic (HBx Tg) mice which are prone to hepatocellular carcinoma (HCC) and fatty liver, we aimed to evaluate retinoid pathway, including genes for the retinoid physiology, CRBP-I protein expression, and retinoid levels, in the liver of HBx Tg mice. We also assessed the effect of chronic metformin treatment on HCC development in the mice. Many genes involved in hepatic retinoid physiology, including CRBP-I, were altered and the tissue levels of retinol and all-trans retinoic acid (ATRA) were elevated in the liver of HBx Tg mice compared to those of wild type (WT) control mice. CRBP-I protein expression in liver, but not in white adipose tissue, of HBx Tg mice was significantly elevated compared to WT control mice while CRBP-I protein expressions in the liver and WAT of high-fat fed obese and db/db mice were comparable to WT control mice. Chronic treatment of HBx Tg mice with metformin did not affect the incidence of HCC, but slightly increased hepatic CRBP-I level. In conclusion, hepatic CRBP-I level was markedly up-regulated in HCC-prone HBx Tg mice and neither hepatic CRBP-I nor the development of HCC was suppressed by metformin treatment.

Low-dose glucocorticoid can lead to hypokalemic paralysis.

Glucocorticoids are widely used in clinical practice, and a rare adverse effect of glucocorticoid administration is hypokalemic paralysis. Recently, we experienced two cases of hypokalemic paralysis after low-dose glucocorticoid administration for urticaria in healthy men. Excluding possible endocrinologic disorders, we concluded that hypokalemic paralysis could be attributed to glucocorticoid administration in our patients. Only few cases of hypokalemic paralysis induced by relatively high glucocorticoid dose are reported. In our cases, we suggest that a very low dose of glucocorticoid injection results in hypokalemic paralysis, even in healthy individuals. Clinicians should be aware that a very low dose of glucocorticoid can cause hypokalemic paralysis. Furthermore, when evaluating patient complaints of muscle weakness with hypokalemia, history of glucocorticoid administration should be thoroughly reviewed.

Association between Bone Mineral Density and Albuminuria: Cross-Sectional Analysis of Data from the 2011 Korea National Health and Nutrition Examination Survey V-2.

BACKGROUND: Albuminuria is known to be independently associated with progression of renal and cardiovascular disease. However, little is known regarding the exact relationship between albuminuria and bone mineral density (BMD). The aim of this population-based study conducted in Korea was to identify the association between albuminuria and BMD. METHODS: We performed a cross-sectional analysis of data from the Korea National Health and Nutrition Examination Survey (KNHANES V-2) 2011. BMD was measured for total hip (TH), femur neck (FN), and lumbar spine (LS). Analysis of covariance was used to compare BMD levels between the groups at the TH, FN, and LS sites, after adjusting for age. Separate analyses were performed according to sex; women were divided into two groups according to menopausal status and each group was subdivided into three according to urine albumin-to-creatinine ratio (level 1, <30 mg/g; level 2, 30 to 299 mg/g; level 3, ≥300 mg/g). RESULTS: Data on a total of 1,831 adults (857 men and 974 women) were analyzed. In postmenopausal women, after adjusting for age, BMD of TH tended to decrease as levels of albuminuria increased (0.767±0.117, 0.757±0.129, 0.752±0.118, respectively; P=0.040). However, there was no significant difference in BMD according to albuminuria level in premenopausal women and men. CONCLUSION: Level of albuminuria was closely related with BMD of TH in postmenopausal women, after adjusting for age, but there was no significant relationship between albuminuria and BMD in premenopausal women and men.

Efficacy and tolerability of acarbose in Asian patients with type 2 diabetes inadequately controlled with diet and sulfonylureas.

The objective of this study was to investigate the efficacy, tolerability, and safety of acarbose in the improvement of glycemic control in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas. A 24-week, double-blind, placebo-controlled multicenter group comparison study was conducted. Patients were randomized to receive acarbose titrated up to 100-mg tid (n=36) or matching placebo (n=33). Concomitant sulfonylurea treatment remained unchanged throughout the study. The primary efficacy parameter was the change in HbA(1c) from baseline to double-blind endpoint. Secondary efficacy variables consisted of the change from baseline to endpoint in blood glucose (fasting and 1-h postprandial), serum insulin (fasting and 1-h postprandial), and urinary glucose. In the intention-to-treat (ITT) analysis, acarbose treatment was associated with significantly greater reductions in glycated hemoglobin (HbA(1c)) (-0.91% vs. placebo 0.13%, P=.0018) and 1-h postprandial blood glucose levels (-2.84 mmol/l vs. placebo -0.28 mmol/l, P=.002) compared to placebo. There were no significant differences between the treatment groups regarding changes in fasting blood glucose, fasting or 1-h postprandial serum insulin, urinary glucose, or body weight. Adverse events occurred with similar frequency in both treatment arms except for drug-related gastrointestinal side-effects associated with acarbose (acarbose 48.5% and placebo 12.5%). This study has shown that the use of acarbose in Asian patients with type 2 diabetes inadequately controlled by diet and sulfonylureas is efficacious in improving metabolic control and that acarbose is safe and well tolerated.

Hypoglycemia at admission in patients with acute myocardial infarction predicts a higher 30-day mortality in patients with poorly controlled type 2 diabetes than in well-controlled patients.

OBJECTIVE: We aimed to evaluate the association between hypoglycemia at admission and 30-day mortality in patients with acute myocardial infarction (AMI) and to determine whether these associations differed according to diabetes-control status in AMI patients with diabetes. RESEARCH DESIGN AND METHODS: We analyzed the prognostic significance of hypoglycemia and hyperglycemia in 34,943 AMI patients with or without type 2 diabetes from two AMI registries: the Korea Acute Myocardial Infarction Registry (KAMIR) and the Korea Working Group on Myocardial Infarction (KorMI). RESULTS: The patients were divided into five groups according to serum-glucose levels at admission: <3.9 mmol/L (<70 mg/dL); 3.9-7.72 mmol/L (70-139 mg/dL); 7.78-11.06 mmol/L (140-199 mg/dL); 11.11-14.39 mmol/L (200-259 mg/dL); and ≥14.44 mmol/L (≥260 mg/dL). The 30-day mortality rates in the lowest and highest glucose groups were higher than those in other groups; the lowest glucose group had the highest mortality for patients with type 2 diabetes, after adjusting for multiple factors. We also extracted and compared four subgroups from the patients with type 2 diabetes, based on hemoglobin A1c and serum-glucose levels at admission: group A, <6.5% (48 mmol/mol) and <3.9 mmol/L; group B, <6.5% (48 mmol/mol) and ≥11.11 mmol/L; group C, ≥8% (64 mmol/mol) and <3.9 mmol/L; and group D, ≥8% (64 mmol/mol) and ≥11.11 mmol/L. Group C had the highest 30-day mortality rate among the groups. CONCLUSIONS: These data suggest that hypoglycemia at admission affects clinical outcomes differently in AMI patients with type 2 diabetes depending on the diabetes-control status.

The effects of L-thyroxine treatment on QT dispersion in primary hypothyroidism.

Hypothyroidism has various cardiovascular manifestation and exhibits electrocardiographic change. The QT dispersion on surface ECG reflects regional variations in myocardial repolarization. The effect of L-thyroxine treatment on ECG parameters, such as QT dispersion, in patients with primary hypothyroidism were investigated. This study involved 18 patients (3 men, 15 women, ages: 48+/-18 yr) with primary hypothyroidism. All patients were checked with a standard 12-lead ECG before and after L-thyroxine treatment. Various ECG parameters were then measured twice. The mean L-thyroxine treatment duration was 22+/-2.7 months. The mean thyroid-stimulating hormone levels of patients before and after therapy were 40.2+/-29.8 microU/mL, 3.6+/-4.6 microU/mL (p<0.001) and free-T4 levels were 0.44+/-0.38 ng/dL, 1.51+/-0.39 ng/dL (p<0.001). After L-thyroxine treatment, QT interval (395+/-42 vs. 380+/-24 msec, p<0.05), QTc interval (434+/-32 vs. 417+/-23 msec, p<0.05), QT dispersion (45+/-23 vs. 30+/-13 msec, p=0.008), QTc dispersion (49+/-23 vs. 32+/-14 msec, p=0.005) significantly decreased. There were no significant changes in the PR and RR intervals, as well as the QRS duration. Our findings suggest that the thyroid hormone affects ventricular inhomogenicity, and that L-thyroxine replacement therapy may reduce malignant ventricular arrhythmia and sudden cardiac death in primary hypothyroidism.