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The article focuses on the study that compares the effect of rosuvastatin and colestimide on adipokines and markers of oxidative stress and diabetic nephropathy in type 2 diabetic patients with hyperlipidemia. It states that 40 patients with the disease were recruited and assigned randomly to the two groups. Their blood and urine were assessed at the beginning of the study and after 12 weeks. The study found out that rosuvastatin and colestimide exert different beneficial effects.

Objective: We investigated the correlation between acute-phase reactants, ie, high-sensitivity C-reactive protein (hsCRP) or fibrinogen and diabetic complications. Methods: In 73 patients with type 2 diabetes, we investigated associations between both markers and carotid artery intimal medial complex thickness (IMT), heart rate variability, or urinary albumin excretion (UAE). Results: Log hsCRP and fibrinogen correlated significantly with each other (r = 0.3701, P = 0.0013). Fibrinogen correlated negatively with the coefficient of variation of RR intervals (CV(RR)) and positively with log UAE (r = -0.2433, P = 0.0381; r = 0.4815, P < 0.0001), while log hsCRP did not. Furthermore both log hsCRP and fibrinogen did not correlate with IMT. Conclusion: We concluded that despite their close correlation, fibrinogen compared with hsCRP might be closely associated with diabetic microangiopathy and that both markers might not correlate with IMT as a marker of macroangiopathy. [ABSTRACT FROM AUTHOR]

Retinal binding protein (RBP)-4 is a newly identified adipocytokine that can cause insulin resistance. The main purpose of the current study was to investigate the relationship between RBP4 and various markers related to insulin resistance, including triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), blood pressure (BP), endothelial function, oxidative stress, inflammation, and diabetic complications in patients with type 2 diabetes. The effect of pioglitazone (a thiazolidinedione) on RBP4 was also examined. Circulating RBP4 levels were measured in 101 hospitalized patients with type 2 diabetes and in 22 non-hospitalized control subjects. Endothelial function and oxidative stress were evaluated using flow-mediated vasodilatation (FMD) and urinary 8-iso-prostaglandin-F2α, respectively. Pioglitazone was administered for 12 weeks at a dose of 30 mg/day in a further 22 patient with type 2 diabetes in outpatient department. There was a significant elevation of RBP4 levels in diabetic patients compared with healthy subjects. RBP4 showed significant positive correlations with TG, systolic BP and log urinary albumin excretion (UAE), and significant negative correlations with HDL-C and FMD. By stepwise regression analysis log UAE, TG and gender showed a significant association with RBP4. There was a significant elevation of RBP4 in patients with proliferative-diabetic retinopathy compared with non-diabetic retinopathy and simple-diabetic retinopathy patients. Pioglitazone therapy for 12 weeks did not significantly affect the RBP4 concentration. In conclusion, this current study indicates the possibility that circulating RBP4 levels are associated with variables related to insulin resistance and diabetic complications. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the relationship between vascular endothelial function and diabetic microangiopathy (nephropathy, retinopathy, and neuropathy) in patients with type 2 diabetes. Furthermore, the association between endothelial function and macroangiopathy evaluated by intimal-medial complex thickness (IMT) was also investigated. Endothelial function was evaluated by measurement of flow-mediated dilatation (FMD) of the brachial artery. Diabetic nephropathy and neuropathy were assessed by urinary albumin excretion (UAE) and motor or sensory nerve conduction velocity (MCV, SCV), respectively, and retinopathy was evaluated by an ophthalmologist using the Davis classification. FMD was measured in 102 patients with type 2 diabetes and in 20 control subjects, and showed a tendency to be lower in the diabetic patients. A significant decrease was obtained in FMD in patients with proliferative diabetic retinopathy (PDR), compared with those in patients with no diabetic retinopathy (NDR). FMD showed significant positive correlations with MCV and SCV, and significant negative correlations with log UAE, systolic blood pressure (SBP) and diabetic duration, but no correlation was obtained between FMD and IMT. By stepwise regression analysis, MCV alone showed a significant association with FMD. In conclusion, the current study suggests that in patients with type 2 diabetes FMD is closely associated with all types of microangiopathy, with neuropathy being most strongly associated with FMD; however, FMD is not associated with macroangiopathy evaluated by IMT. [ABSTRACT FROM AUTHOR]

Obejective. To investigate short-term effects of pioglitazone or voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) and on plasma fibrinolysis indicators, in type 2 diabetic patients with a second failure of treatment with sulfonylureas. Methods. Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI)-1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors. Results. At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with type 2 diabetes (r=0.367, P=0.0423). Both groups showed similar improvements in glycemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, while showing no significant changes in patients treated with voglibose. The HMW/total adiponectin ratio increased significantly after treatment with pioglitazone (P=0.0004). Changes in HbA1c showed significant negative correlations with changes in serum HMW adiponectin in patients treated with pioglitazone (r=-0.694, P=0.0034). Plasma PAI-1 tended to decrease after pioglitazone treatment (P=0.0908), while plasma TAFI did not change. Conclusion. Increased serum HMW adiponectin may contribute to the improvement in glycemic control after pioglitazone treatment. Plasma PAI-1 decreased somewhat after treatment with pioglitazone, while plasma TAFI was unchanged by either drug. [ABSTRACT FROM AUTHOR]

Canagliflozin has a robust inhibitory effect on sodium glucose transporter (SGLT)-2 and a mild inhibitory effect on SGLT1. The main purpose of this study was to investigate the effect of canagliflozin on circulating active glucagon-like peptide 1 (GLP-1) levels in patients with type 2 diabetes. Patients were randomly divided into a control group (n =15) and a canagliflozin-treated group (n =15). After hospitalization, the canagliflozin-treated group took 100 mg/day canagliflozin for the entire study, and after 3 days both groups took 20 mg/day teneligliptin for an additional 3 days. In a meal test, canagliflozin significantly decreased the area under curve (AUC) (0-120 min) for plasma glucose (PG) after 3 days when compared with that at baseline, and addition of teneligliptin to the canagliflozin-treated group further decreased it. A significant decrease in the AUC (0-120 min) for serum insulin by canagliflozin was obtained, but the addition of teneligliptin elevated the AUC, and thus abolished the significant difference from baseline. A significant increase in the AUC (0-120 min) of plasma active GLP-1 by canagliflozin-treatment compared with that at baseline was observed, and the addition of teneligliptin resulted in a further increase. However, canagliflozin-treatment did not change the AUC (0-120 min) of plasma active glucose-dependent insulinotropic peptide (GIP). In conclusions, canagliflozin-administration before meals decreased PG and serum insulin, and increased plasma active GLP-1 levels in patients with type 2 diabetes. Canagliflozin did not greatly influence plasma active GIP levels.

Background: Betatrophin is a hormone mainly secreted by the liver that influences lipid metabolisms. The main purposes of this study were to investigate the effect of canagliflozin (a sodium glucose transporter 2 inhibitor) on circulating betatrophin levels, and to investigate the correlation of various markers associated with glucose and lipid metabolisms with betatrophin in patients with poorly controlled type 2 diabetes., Methods: Patients were randomly divided into a control group (n = 15) and a canagliflozin-treated group (n = 15). After hospitalization, the canagliflozin-treated group took 100 mg/day of canagliflozin for 3 days. Blood tests were performed at baseline and after 3 days of treatment., Results: Canagliflozin treatment for 3 days did not significantly change fasting and postprandial serum betatrophin levels. On the other hand, betatrophin levels had a significant positive correlation with hemoglobin A1c, fasting plasma glucose, and high-density lipoprotein cholesterol levels at baseline., Conclusions: The current study suggests that short-term treatment by canagliflozin does not influence circulating betatrophin levels, and that betatrophin is positively associated with markers of glycemic control and high-density lipoprotein cholesterol in patients with poorly controlled type 2 diabetes., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The goal of the current study was to investigate the long-term effects (after 3 years or more) of alogliptin on glycemic control in Japanese patients with type 2 diabetes., Methods: We retrospectively studied the effect of alogliptin on glycemic control in the patients with type 2 diabetes who had participated in our previous 3-month study and who continued to take alogliptin for at least 36 months., Results: The mean duration of alogliptin treatment was 42.8 ± 2.2 months. In all 39 patients, a significant reduction in hemoglobin A1c (HbA1c) levels was noted between the baseline and final visit: 7.8±0.6% to 7.2±1.0% (P = 0.0001). A significant reduction in HbA1c levels was found in a subgroup of patients who did not change their anti-diabetic drugs or did decrease the dose of their sulfonylureas (SUs) or did change to a lower strength repaglinide (n = 32): 7.7±0.6% to 7.2±1.0% (P = 0.0005). A significant decrease in low-density lipoprotein cholesterol (LDL-C) levels was observed in all of the patients that had LDL-C levels determined (P = 0.0406) (n = 37), and in a subgroup of patients who had not taken either statins, fibrates, or pioglitazone, or who had taken one or more of these drugs but the doses were not changed during the observation period (P = 0.0250) (n = 27)., Conclusion: The current study found that alogliptin performed well for glycemic control when evaluated by HbA1c levels in a long-term observation period exceeding 3 years in Japanese patients with type 2 diabetes. Alogliptin may also decrease circulating LDL-C levels with long-term use.

Objective: The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance., Research Design and Methods: The study included 30 patients with type 2 diabetes hospitalized for glycemic control and 10 control subjects., Results: SerpinB1 levels were significantly higher in patients with type 2 diabetes, compared with that in heathy control subjects (10.01±3.59 vs 5.69±1.64 ng/mL, p<0.0001). Serum SerpinB1 levels had a significant negative correlation with low-density lipoprotein cholesterol (LDL-C) (p=0.0123). Serum SerpinB1 levels had a significant positive association or trend toward a positive association with age and with hemoglobin A1c (HbA1c), and significant negative association with LDL-C levels in some multiple regression analysis models. Patients treated with statins had a tendency toward higher serum SerpinB1 levels, compared with those patients not treated with statins. During a 3-day observation period both with and without canagliflozin treatment, the serum SerpinB1 levels did not change., Conclusions: Serum SerpinB1 levels are elevated in patients with type 2 diabetes compared with that in healthy subjects and are negatively correlated with serum LDL-C., Competing Interests: Conflicts of Interest: None declared.

The main purpose of the current study was to investigate the effect of a combination of alogliptin [a dipeptydil peptidase (DPP)-4 inhibitor] and lansoprazole [a proton pump inhibitor (PPI)] compared with alogliptin mono-therapy on glycemic control in patients with type 2 diabetes. This study was a multicenter randomized open-label study. One hundred type 2 diabetic patients were randomly assigned to either the alogliptin with lansoprazole group or the alogliptin mono-therapy group. After 3 months of treatment, the changes in hemoglobin (Hb)A1c, fasting plasma glucose (FPG), serum gastrin, homeostasis model assessment (HOMA)-β, and HOMA-insulin resistance (IR) were evaluated. A significant decrease in HbA1c and FPG, and a significant increase in HOMA-β were observed in both groups (all with P <0.0001). However, there were no significant differences in changes in HbA1c, FPG, or HOMA-β before and after therapy between the combination and alogliptin mono-therapy group (P =0.2945, P =0.1901, P =0.3042, respectively). There was a significant elevation of serum gastrin in the combination group compared with the alogliptin mono-therapy group (P =0.0004). This study showed that, although combination therapy with alogliptin and lansoprazole more effectively elevated serum gastrin levels compared with alogliptin mono-therapy, the effect of the combination therapy on glycemic control was equal to that of alogliptin mono-therapy during a 3-month study period.

Objective: To examine involvement of oxidative stress in the pathogenesis and vascular complications of diabetes., Methods: This cross sectional study was conducted at the Joint Laboratory Office (JLO), Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan from April 2010 to December 2011. Fasting glucose, glycosylated hemoglobin (HbA1c), serum lipids, urinary albumin excretion (UAE), ankle brachial index and pulse wave velocity were measured in 51 patients with type 2 diabetes and 20 healthy controls. The fundus oculi and Achilles` tendon reflex were also examined in the patients. Oxidative stress was measured by a reactive oxygen metabolites (ROM) test and antioxidant potency was evaluated by a biological antioxidant potential (BAP) test in the Free Radical Analytical System (FRAS)-4. Superoxide dismutase (SOD) activity was assayed using electron spin resonance (ESR)., Results: Diabetic patients tended to have increased ROM compared with healthy subjects, and ROM showed a marked increase with progression of diabetic retinopathy. A significant reduction of BAP was found in patients who were smokers, and BAP was significantly negatively correlated with UAE (p=0.029). Serum SOD activity significantly decreased with progression of diabetic retinopathy (p=0.017)., Conclusion: The FRAS-4 measurements showed that increased oxidative stress and decreased antioxidative potency are linked to deteriorated blood glucose control, heavy smoking, and progression of retinopathy and nephropathy in patients with type 2 diabetes.