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Determine whether the twice daily (BID) regimen is superior to the once daily (QD) regimen for managing glycemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD.A double-blinded, randomized, multicenter study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5%HbA1c 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring (CGM) was used to measure the mean amplitude of glycemic excursion (MAGE) and postprandial time in range (TIR) before and after DPP-4 inhibitor treatment to compare glycemic variability.The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (p0.05); -30.4 ± 25.6 mg/dL (p0.001) in the anagliptin group versus -9.5 ± 38.0 mg/dL (p=0.215) in the sitagliptin group. The TIR after dinner increased by 33.0 ± 22.0% (p0.001) in the anagliptin group and by 14.6 ± 28.2% (p=0.014) in the sitagliptin group, with a statistically significant difference (p=0.009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG).The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycemic variability, as indicated by MAGE and TIR but equivalent to the QD regimen in terms of HbA1c and FPG. This article is protected by copyright. All rights reserved.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p

SummaryObjective Nonalcoholic fatty liver disease (NAFLD) is a well-known contributor for the development of cardiovascular disease (CVD). We examined the influence of NAFLD and metabolic syndrome (MetS) on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), brachial–ankle pulse wave velocity (baPWV) and ankle–brachial pressure index (ABI), after adjusting for cardiometabolic risk factors. Design A cross-sectional study. Patients and measurements The association between NAFLD, MetS and markers of subclinical atherosclerosis was assessed in 955 participants without CVD using multiple logistic regression analysis after adjusting for multiple cardiometabolic risk variables. Results After adjusting for age and sex, CIMT and baPWV were found to be significantly correlated with multiple cardiometabolic risk variables, whereas ABI was only associated with obesity parameters. The prevalence of NAFLD differed significantly according to the presence of subclinical atherosclerosis as defined by both CIMT and baPWV (P = 0·004 and P = 0·007, respectively). After adjusting for potential confounding factors, NAFLD or MetS was not associated with subclinical atherosclerosis as defined by CIMT and baPWV. However, individuals with both NAFLD and MetS had a significantly higher risk of subclinical atherosclerosis as defined by CIMT (OR = 2·06, 95% CI = 1·13–3·74) or baPWV (OR = 2·64, 95% CI = 1·46–4·76) compared to normal subjects, even after adjusting for potential confounders. Conclusions The results show that NAFLD and MetS have a synergistic impact on the subclinical atherosclerosis, which suggests that individuals with both NAFLD and MetS should be strongly advised to engage in CVD prevention strategies.

Aims/Introduction To assess the current status of glycemic control in patients with type 2 diabetes treated with a combination of metformin and sulfonylurea for >3 months, as measured by glycosylated hemoglobin (HbA1c). Materials and Methods Data on patient demographics, diabetic complications, HbA1c, fasting plasma glucose (FPG) and type of treatment were collected in this multicenter, cross-sectional, non-interventional study. Results From April 2008 to February 2009, 5,628 patients were recruited from 299 centers in Korea. Patients characteristics (mean ± SD) were as follows: age 58.4 ± 10.8 years, duration of diabetes 6.1 ± 4.7 years, body mass index 24.7 ± 2.9 kg/m2, HbA1c 7.77 ± 1.22%, FBG 147.4 ± 46.5 mmol/L and FPG 164.0 ± 54.3 mmol/L. The most common diabetic complication was neuropathy (22.5%), followed by retinopathy (18.3%) and microalbuminuria (16.1%). Just 1,524 (27.1%) patients achieved HbA1c ≤7%. A higher number of patients (32.6%) treated by endocrinologists achieved HbA1c ≤7% than those treated by internists (24.4%) and primary care physicians (23.2%). In multivariate analyses, diabetic retinopathy (odds ratio 0.455, 95% confidence interval 0.341–0.606), nephropathy (odds ratio 0.639, 95% confidence interval 0.43–0.949), diabetes for ≥5 years (odds ratio 0.493, 95% confidence interval 0.4–0.606) and older age added by 1 year (odds ratio 1.019, 95% confidence interval 1.01–1.029) was significantly associated with achieving target HbA1c. In addition, treatment by endocrinologists rather than internists significantly increased chances of achieving target HbA1c (odds ratio 1.417, 95% confidence interval 1.146–1.751). Conclusions The majority of patients with type 2 diabetes in Korea had inadequate glycemic control, despite receiving a combination of metformin and sulfonylurea.

Free fatty acid-induced lipotoxicity via increased endoplasmic reticulum (ER) stress and hepatocyte apoptosis is a key pathological mechanism of non-alcoholic steatohepatitis. A role of hypoxia-inducible factor 1α (HIF-1α) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF-1α can reduce palmitic acid-induced lipotoxicity and ER stress. In HepG2 cells treated with 500 µM palmitic acid, HIF-1α expression increased transiently, the decline was associated with increased cleaved caspase-3 expression. Overexpression and knockdown of HIF-1α decreased and exacerbated, respectively, palmitic acid-induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF-1α binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF-1α expression. It also suggests that upregulation of HIF-1α can be a possible strategy to reduce lipotoxicity in non-alcoholic fatty liver disease. J. Cell. Biochem. 115: 1147–1158, 2014. © 2014 Wiley Periodicals, Inc.

Objective The purpose of this study was to investigate the impact of body mass index (BMI) and the presence of metabolic syndrome (MetS) on all-cause and cardiovascular mortality in elderly Korean men and women, and especially to compare metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) subjects. Patients and methods A total of 2317 elderly people (over 60 years of age) were studied using follow-up data from the South-West Seoul (SWS) Study, a prospective cohort study. Mortality from all causes and cardiovascular disease (CVD) were evaluated according to the combination of the presence or absence of MetS and Asian-specific body mass index (BMI) criteria (BMI

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2-HS-glycoprotein gene (AHSG) and its protein, fetuin-A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA-dependent manner. In HepG2 cells treated with 300 μmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 μmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA-overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid-induced ER stress markers, CHOP, Bip, ATF-6, XBP-1, ATF-4, and PERK. In addition, in the high-fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one-third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p-AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.

Objective Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the serum in several insulin-resistant states. We investigated the relationship between non-alcoholic fatty liver disease (NAFLD) and serum RBP4 in nondiabetic adults. Methods One hundred and fifty-nine nondiabetic, non-alcoholic subjects (95 males and 64 females) participated in this study. Division of subjects into a NAFLD group (n = 73; 45 males and 28 females) or a normal group (n = 86; 50 males and 36 females) was based on the presence of fatty liver disease determined by sonography. Results Serum RBP4 levels in the NAFLD group were significantly higher than those in the normal group (62·8 ± 16·0 mg/l vs. 51·7 ± 14·6 mg/l, P < 0·0001). Multiple logistic regression analysis revealed that the RBP4 level was an independent factor associated with NAFLD (P = 0·0042). In addition, serum RBP4 levels were positively correlated with serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (GGT) levels. The significant association between serum RBP4 and GGT levels remained even after adjusting for age, gender, body mass index, the homeostasis model of assessment (HOMA) value and the presence of NAFLD (r = 0·3097, P = 0·0002). Conclusion Serum RBP4 levels are significantly associated with NAFLD and liver enzymes.

Summary Objective We examined the association between serum osteoprotegerin (OPG) levels, systemic inflammation and arterial stiffness in normal and diabetic patients. Patients and measurements The study subjects comprised 49 newly diagnosed diabetic patients and 72 age- and sex-matched normal glucose controls. Anthropometric parameters, blood pressure, fasting blood glucose (FBG), lipid profiles, serum OPG, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and brachial-ankle pulse wave velocity (baPWV) were measured. Results Serum OPG levels (6·1 ± 1·4 vs. 5·4 ± 1·3 pmol/l, P = 0·011) and baPWV (1562 ± 354 vs. 1399 ± 257 cm/s, P = 0·004) were significantly higher in the diabetic group than in the normal glucose group. Serum OPG levels in normal and diabetic patients correlated significantly with systolic blood pressure (r = 0·20, P = 0·035), FBG (r = 0·30, P = 0·002), right baPWV (r = 0·22, P = 0·021), left baPWV (r = 0·26, P = 0·006), homeostasis model assessment insulin resistance (HOMA-IR) (r = 0·19, P = 0·045), IL-6 (r = 0·32, P = 0·001) and hsCRP (r = 0·21, P = 0·027) after adjusting for age and sex. Multiple regression analysis showed that serum OPG level was significantly associated with age, FBG, IL-6, systolic blood pressure, triglyceride and hsCRP (R2 = 0·299). Conclusions In summary, serum OPG and baPWV levels are elevated in diabetic patients and serum OPG levels are significantly associated with inflammation and arterial stiffness.

Aims To examine the relationship between the components of the metabolic syndrome and to explore whether insulin resistance unifies the clustering of components of the metabolic syndrome among urban elderly Koreans using exploratory factor analysis. Methods We included 1314 non-diabetic subjects over the age of 60 years, selected from a cross-sectional study, which was conducted in 1999 in Seoul, Korea. Factor analysis was carried out using the principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. Results We found four major factors of cardiovascular disease risk variables in our study subjects. Impaired glucose tolerance, dyslipidaemia, hypertension and obesity aggregated as the major domain. Obesity and dyslipidaemia variables were closely related and loaded on the same factor. However, hypertension was not linked closely with other factors of the metabolic syndrome. Conclusions Insulin resistance is not the only contributor to the metabolic syndrome among urban elderly Koreans. Although the components of the metabolic syndrome were closely related, the finding of more than one factor suggests that more than one pathophysiological mechanism underlies full expression of the metabolic syndrome among elderly Koreans.