Correlation between mean platelet volume and blood glucose levels after oral glucose loading in normoglycemic and prediabetic Japanese subjects

Aims/Introduction

Mean platelet volume (MPV) reflects platelet activity, and high MPV is associated with thrombogenic activation and increased cardiovascular disease risk. Although a positive correlation between MPV and fasting plasma glucose (FPG) levels has been reported, the correlation between MPV and postprandial glucose levels remains unclear. The purpose of the present study was to evaluate the correlation between MPV and postprandial glucose levels in prediabetic and normoglycemic participants.

Materials and Methods

We evaluated 1,080 Japanese participants who underwent the 75‐g oral glucose tolerance test (OGTT). Based on these results, the participants were divided into three groups: normal glucose tolerance group (NGT; n = 582), impaired fasting glucose group (IFG; n = 205) and impaired glucose tolerance group (IGT; n = 252). The relationship between MPV, FPG, and postchallenge glucose levels after 1 h (1 h‐PG) and 2 h (2 h‐PG) were analyzed.

Results

Bivariate correlation analyses showed a significant positive correlation between MPV and both FPG and 1 h‐PG levels in the NGT group, as well as between MPV and 2 h‐PG, total cholesterol, and low‐density lipoprotein cholesterol in the IGT group. In contrast, no significant correlation was observed between MPV and postchallenge glucose levels in the IFG group. Multiple correlation analyses showed that FPG levels significantly correlated with MPV in the NGT and IGT groups. In addition, 1 h‐PG and 2 h‐PG levels correlated with MPV in the NTG and IGT groups, respectively.

Conclusions

These results suggest a possible mechanism by which subjects with postprandial hyperglycemia might be at increased cardiovascular risk.     

Prevalence of retinopathy and its risk factors in a Japanese population

Aims/Introduction

To determine the prevalence and risk factors of retinopathy and validity of the current diagnostic cut‐offs for diabetes by using data of health check‐up examinees.

Materials and Methods

The study comprises 1,864 Japanese who participated in the general health check‐up program and did not have a previous history of cardiovascular disease. Non‐mydriatic 45° digital fundus photographs were taken twice annually. Multivariate logistic regression model was used to identify risk factors for retinopathy in participants without previously diagnosed diabetes.

Results

The overall prevalence of retinopathy in participants with and without previously diagnosed diabetes were 23.3% (28/120) and 4.2% (74/1,744), respectively. Univariate logistic regression analysis identified age, systolic blood pressure (SBP), fasting plasma glucose (FPG) and hemoglobin A1c (HbA_1c) as risk factors for retinopathy. Multivariate logistic regression analysis showed that FPG or both HbA_1c and SBP were significant, positive and independent risk factors for retinopathy. The prevalence of retinopathy increased with deterioration of glucose categories (P < 0.001 for FPG or HbA_1c). However, a statistically significant increased risk of retinopathy remained only in participants with FPG ≥ 7.0 mmol/L or HbA1c ≥ 6.5% compared with those with the lowest quartile of glucose in the participants without previously diagnosed diabetes after adjusting for age and SBP.

Conclusions

The prevalence of retinopathy was 4.2%, and FPG or both HbA_1c and SBP were positive and independent risk factors for retinopathy in health check‐up examinees without previously diagnosed diabetes. The FPG 7.0 mmol/L or HbA_1c 6.5% seems to be appropriate to diagnose diabetes in view of its association with retinopathy.     

Usefulness of a novel system for measuring glucose area under the curve while screening for glucose intolerance in outpatients

Aims/Introduction

To realize the effectiveness of a novel system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET), outpatients undergoing oral glucose tolerance tests (OGTT) were investigated for the efficacy of screening for glucose intolerance using this system.

Materials and Methods

Fifty outpatients scheduled to undergo a 75‐g OGTT for medical reasons were recruited to the study. An area of skin on the forearm was pretreated with microneedle arrays before the application of hydrogels for interstitial fluid extraction. Plasma glucose (PG) levels were measured every 30 min for 2 h to calculate reference (actual) AUC. The AUC was predicted by MIET on the basis of glucose extracted by the hydrogel using sodium ion levels as the internal standard.

Results

Good correlation between MIET‐predicted and reference AUCs obtained using PG levels was confirmed for a wide AUC range. By introducing a threshold level for AUC to separate glucose intolerance with peak glucose ≥180 mg/dL from normal glucose tolerance, the system was demonstrated to provide better screening accuracy compared with conventional methods that use HbA1c and fasting PG levels. The results of a questionnaire‐based survey administered to the subjects suggested that this system was readily accepted by the majority as a painless monitoring method.

Conclusions

The findings suggest that our glucose AUC measurement system using MIET would be useful for screening of glucose intolerance. In the future, this system may prove to be a useful aid as a screen for glucose intolerance before performing an OGTT for diagnosis.     

Effect of periodontal treatment on glycemic control of patients with diabetes: A systematic review and meta‐analysis

Aims/Introduction

The aim of the present study was to investigate whether non‐surgical periodontal treatment reduces glycated hemoglobin (HbA_1c) and fasting plasma glucose (FPG) levels in diabetic patients.

Materials and Methods

An electronic search was carried out on MEDLINE (through PubMed interface), EMBASE and the Cochrane Central Register of Controlled Trials. Randomized controlled trials with a minimum of 3 months follow up were included. The risk of bias was assessed for each study. A meta‐analysis was carried out to evaluate the effect of non‐surgical periodontal treatment on HbA_1c and FPG levels. The effect of the adjunctive use of antimicrobials was also assessed.

Results

A total of 15 studies were included. A reduction of −0.38% (95% confidence interval [CI] −0.23 to −0.53) after 3–4 months (P < 0.001) and of −0.31% (95% CI 0.11 to −0.74) after 6 months (P = 0.15) of follow‐up was found for HbA_1c, favoring the treatment group. Similarly, in treated patients, a significantly greater decrease in FPG was observed in respect to control participants. Such difference amounted to −9.01 mg/dL (95% CI −2.24 to −15.78) after 3–4 months (P = 0.009) and −13.62 mg/dL (95% CI 0.45 to −27.69) after 6 months (P = 0.06) from treatment, respectively. In participants treated with adjunctive antimicrobials, a non‐significant increase of HbA_1c was observed 3 months after treatment, whereas FPG decreased by 0.27 mg/dL (95% CI 39.56 to −40.11; P = 0.99).

Conclusions

The meta‐analysis showed that non‐surgical periodontal treatment improves metabolic control in patients with both periodontitis and diabetes.     

Correlations of serum visfatin and metabolisms of glucose and lipid in women with gestational diabetes mellitus

Aims/Introduction

Visfatin is a newly discovered adipocytokine hormone, which exerts an insulin‐like effect by binding to the insulin receptor‐1. However, the role of visfatin in human gestational diabetes mellitus (GDM) remains controversial. The purpose of the present study was to investigate the correlation between serum visfatin and metabolism of glucose and lipid in GDM.

Materials and Methods

This was a prospective study. A total of 38 GDM patients and 35 age‐ and body mass index‐matched controls were studied between January 2012 and October 2013. Fasting serum levels of visfatin, fasting plasma glucose, hemoglobin A1c and lipid profile were measured. Two‐tailed t‐tests and Pearson''s correlation coefficient were used to analyze the data.

Results

Perinatal visfatin levels were negatively correlated with fasting plasma glucose, insulin resistance index and triglycerides in controls (r = −0.47, −0.51, −0.57, respectively; P < 0.05), and positively correlated with high‐density lipoprotein cholesterol (r = 0.32, P < 0.05). A positive correlation with visfatin level only appeared in weight gain and body mass index in women with GDM (r = 0.36, 0.45, respectively; P < 0.05).

Conclusions

Visfatin appears to be involved in glucose and lipid metabolism regulation and insulin resistance, suggesting a role in GDM pathogenesis.     

Pharmacokinetics,pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus

Introduction

To evaluate the pharmacodynamics, pharmacokinetics, safety and tolerability of empagliflozin in Japanese patients with type 2 diabetes mellitus.

Materials and methods

In this 4‐week, multiple dose, randomized, parallel‐group, double‐blind, placebo‐controlled trial, patients (n = 100) were randomized to receive 1, 5, 10 or 25 mg of empagliflozin, or placebo once daily. Key end‐points were urinary glucose excretion (UGE), fasting plasma glucose (FPG) and eight‐point glucose profile.

Results

Data are presented for 1, 5, 10, 25 mg of empagliflozin and placebo groups, respectively. Adjusted mean changes from baseline to day 27 in UGE were 40.8, 77.1, 80.9, 93.0 and −2.1 g (P < 0.0001 for all empagliflozin groups vs placebo). Adjusted mean changes from baseline to day 28 in FPG were −1.56, −1.96, −2.31, −2.37 and −0.86 mmol/L (P < 0.01 for all empagliflozin groups vs placebo). Adjusted mean changes from baseline to day 27 in eight‐point glucose profile were −1.96, −2.21, −2.42, −2.54 and −0.97 mmol/L (P < 0.01 for all empagliflozin groups vs placebo). Empagliflozin reached peak plasma concentration 1.5–2 h after dosing. Mean steady state terminal elimination half‐lives ranged from 13.2 to 18.0 h. Of 100 patients, 25 experienced an adverse event, occurring more frequently for empagliflozin (29.1%) than placebo (9.5%); frequency was not dose related.

Conclusions

In Japanese patients with type 2 diabetes mellitus, empagliflozin at doses up to 25 mg once daily for 4 weeks was well tolerated and resulted in significant improvements in glycemic control compared with placebo. This trial was registered with ClinicalTrials.gov (no. NCT00885118).     

Efficacy and safety of sitagliptin in Japanese patients with type 2 diabetes switched from glinides

Aims/Introduction

The efficacy and safety of sitagliptin, a dipeptidyl peptidase (DPP)‐4 inhibitor, were compared with those of glinides in Japanese patients with type 2 diabetes.

Materials and Methods

The participants were 82 patients with type 2 diabetes (glycated hemoglobin [HbA1c] ≥6.0% and <10%) under treatment with glinides for glucose control. The participants were randomly assigned to a group (n = 44) receiving continuous treatment with glinides and a group (n = 38) switched to sitagliptin. Patients were followed for 12 weeks to evaluate glucose control. A meal tolerance test was carried out in weeks 0 and 12 to examine the pancreatic secretory response to postprandial hyperglycemia.

Results

The changes in HbA1c from week 0 to week 12 were −0.25 and −0.05% in the sitagliptin and glinide groups, respectively, with a significant improvement with sitagliptin. The differences in fasting plasma glucose (FPG), glycoalbumin and 1,5‐anhydroglucitol between the two groups were 14.2 mg/dL, 0.7% and 1.7 μg/mL, respectively, showing significant improvements with sitagliptin. In the meal tolerance test, glucose at 0 min was lower in the sitagliptin group; however, there were no differences in glucose elevation at 30 and 60 min compared with 0 min. Plasma insulin and glucagon secretion at week 12 were significantly lower than at baseline in the sitagliptin group. Adverse events including hypoglycemia did not differ between the groups.

Conclusions

FPG decreased and glucose control improved in patients who switched from glinides to sitagliptin. Sitagliptin decreased secretion of insulin and glucagon in a meal tolerance test compared with glinides, whereas the agents showed similar inhibition of postprandial hyperglycemia. This trial was registered with UMIN (UMIN‐CTR no. 000003479).     

Postprandial C‐peptide to glucose ratio as a predictor of β‐cell function and its usefulness for staged management of type 2 diabetes

Aims/Introduction

Type 2 diabetes is characterized by progressive deterioration of β‐cell function. Recently, it was suggested that the C‐peptide‐to‐glucose ratio after oral glucose ingestion is a better predictor of β‐cell mass than that during fasting. We investigated whether postprandial C‐peptide‐to‐glucose ratio (PCGR) reflects β‐cell function, and its clinical application for management of type 2 diabetes.

Materials and Methods

We carried out a two‐step retrospective study of 919 Korean participants with type 2 diabetes. In the first step, we evaluated the correlation of PCGR level with various markers for β‐cell function in newly diagnosed and drug‐naïve patients after a mixed meal test. In the second step, participants with well‐controlled diabetes (glycated hemoglobin <7%) were divided into four groups according to treatment modality (group I: insulin, group II: sulfonylurea and/or dipeptityl peptidase IV inhibitor, group III: metformin and/or thiazolidinedione and group IV: diet and exercise group).

Results

In the first step, PCGR was significantly correlated with various insulin secretory indices. Furthermore, PCGR showed better correlation with glycemic indices than homeostatic model assessment of β‐cell function (HOMA‐β). In the second step, the PCGR value significantly increased according to the following order: group I, II, III, and IV after adjusting for age, sex, body mass index and duration of diabetes. The cut‐off values of PCGR for separating each group were 1.457, 2.870 and 3.790, respectively (P < 0.001).

Conclusions

We suggest that PCGR might be a useful marker for β‐cell function and an ancillary parameter in the choice of antidiabetic medication in type 2 diabetes.     

Expression profiling analysis: Uncoupling protein 2 deficiency improves hepatic glucose,lipid profiles and insulin sensitivity in high‐fat diet‐fed mice by modulating expression of genes in peroxisome proliferator‐activated receptor signaling pathway

Aims/Introduction

Uncoupling protein 2 (UCP2), which was an important mitochondrial inner membrane protein associated with glucose and lipid metabolism, widely expresses in all kinds of tissues including hepatocytes. The present study aimed to explore the impact of UCP2 deficiency on glucose and lipid metabolism, insulin sensitivity and its effect on the liver‐associated signaling pathway by expression profiling analysis.

Materials and Methods

Four‐week‐old male UCP2−/− mice and UCP2+/+ mice were randomly assigned to four groups: UCP2−/− on a high‐fat diet, UCP2−/− on a normal chow diet, UCP2+/+ on a high‐fat diet and UCP2+/+ on a normal chow diet. The differentially expressed genes in the four groups on the 16th week were identified by Affymetrix gene array.

Results

The results of intraperitoneal glucose tolerance test and insulin tolerance showed that blood glucose and β‐cell function were improved in the UCP2−/− group on high‐fat diet. Enhanced insulin sensitivity was observed in the UCP2−/− group. The differentially expressed genes were mapped to 23 pathways (P < 0.05). We concentrated on the ‘peroxisome proliferator‐activated receptor (PPAR) signaling pathway’ (P = 3.19 × 10⁻¹¹), because it is closely associated with the regulation of glucose and lipid profiles. In the PPAR signaling pathway, seven genes (PPARγ, Dbi, Acsl3, Lpl, Me1, Scd1, Fads2) in the UCP2−/− mice were significantly upregulated.

Conclusions

The present study used gene arrays to show that activity of the PPAR signaling pathway involved in the improvement of glucose and lipid metabolism in the liver of UCP2‐deficient mice on a long‐term high‐fat diet. The upregulation of genes in the PPAR signaling pathway could explain our finding that UCP2 deficiency ameliorated insulin sensitivity. The manipulation of UCP2 protein expression could represent a new strategy for the prevention and treatment of diabetes.     

Admission hyperglycemia predicts poorer short‐ and long‐term outcomes after primary percutaneous coronary intervention for ST‐elevation myocardial infarction

Aims/Introduction

Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST‐elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Materials and Methods

The 959 consecutive STEMI patients undergoing primary PCI were divided into five groups based on admission glucose levels of <100, 100–139, 140–189, 190–249 and ≥250 mg/dL. Their short‐ and long‐term outcomes were compared.

Results

Higher admission glucose levels were associated with significantly higher in‐hospital morbidity and mortality, the overall mortality rate at follow up, and the incidence of reinfarction or heart failure requiring admission or leading to mortality at follow up. The odds ratios (95% confidence interval) for in‐hospital morbidity, in‐hospital mortality, mortality at follow up and re‐infarction or heart failure or mortality at follow up of patients with admission glucose levels ≥190 mg/dL, compared with those with admission glucose levels <190 mg/dL, were 2.12 (1.3–3.4, P = 0.001), 2.74 (1.4–5.5, P = 0.004), 2.52 (1.2–5.1, P = 0.01) and 1.70 (1.03–2.8, P = 0.04), respectively. Previously non‐diabetic patients with admission glucose levels ≥250 mg/dL had significantly higher in‐hospital morbidity or mortality (44 vs 70%, P = 0.03). Known diabetic patients had higher rates of reinfarction, heart failure or mortality at follow up in the 100–139 mg/dL (8 vs 27%, P = 0.04) and 140–189 mg/dL (11 vs 26%, P = 0.02) groups.

Conclusions

Admission hyperglycemia, especially at glucose levels ≥190 mg/dL, is a predictor of poor prognosis in STEMI patients undergoing primary PCI.     

Usefulness of the insulin tolerance test in patients with type 2 diabetes receiving insulin therapy

Aims/Introduction

To establish the validity of the plasma glucose disappearance rate (KITT), derived from an insulin‐tolerance test (ITT), for evaluating the insulin sensitivity of patients with type 2 diabetes after insulin therapy.

Materials and Methods

In the first arm of the study, 19 patients with poorly controlled diabetes were treated with insulin and underwent an ITT and a euglycemic clamp test (clamp‐IR). The relationship between the insulin resistance index, as assessed by both the clamp‐IR and KITT tests, was examined. In the second arm of the study, the relationships between KITT values and various clinical parameters were investigated in 135 patients with poorly controlled diabetes, after achieving glycemic control with insulin.

Results

In study 1, a close correlation between KITT and the average glucose infusion rate during the last 30 min of the standard clamp‐IR test (M‐value) was noted (P < 0.001). In study 2, body mass index (P = 0.0011), waist circumference (P = 0.0004), visceral fat area (P = 0.0011) and the log‐transformed homeostasis model assessment of insulin resistance value (P = 0.0003) were negatively correlated with the log‐transformed KITT. High‐density lipoprotein cholesterol (P = 0.0183), low‐density lipoprotein cholesterol (P = 0.0121) and adiponectin (P = 0.0384) levels were positively correlated with the log‐transformed KITT.

Conclusions

The ITT is a valid and useful test for evaluating the insulin sensitivity of patients with diabetes, even after treatment with insulin.     

Dipeptidyl peptidase‐4 inhibitors are effective in Japanese type 2 diabetic patients with sustained endogenous insulin‐secreting capacity,a higher body mass index and insulin resistance

Aims/Introduction

Recently, dipeptidyl peptidase‐4 (DPP‐4) inhibitors have become available in Japan. It has not yet been clarified what clinical parameters could discriminate DPP‐4 inhibitor‐effective patients from DPP‐4 inhibitor‐ineffective patients.

Materials and Methods

We reviewed 33 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control. All of the patients were treated with medical nutrition therapy plus insulin therapy to improve fasting plasma glucose (FPG) and postprandial glucose below 150 and 200 mg/dL, respectively. After insulin secretion and insulin resistance were evaluated, insulin was replaced by DPP‐4 inhibitors. The efficacy of DPP‐4 inhibitors was determined according to whether glycemic control was maintained at the target levels.

Results

Dipeptidyl peptidase‐4 inhibitors were effective in 16 of 33 patients. DPP‐4 inhibitor‐effective patients were younger than DPP‐4 inhibitor‐ineffective patients. Body mass index (BMI) was significantly higher in DPP‐4 inhibitor‐effective patients. Endogeneous insulin‐secreting capacity, including insulinogenic index (II), fasting plasma C‐peptide (F‐CPR) and C‐peptide index (CPI), was more sustained in DPP‐4 inhibitor‐effective patients than DPP‐4 inhibitor‐ineffective patients. Insulin resistance evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR) was significantly higher in DPP‐4 inhibitor‐effective patients than DPP‐4 inhibitor‐ineffective patients. In receiver operating characteristic analyses, the cut‐off values for predicting the efficacy of DPP‐4 inhibitors were 0.07 for II, 1.5 ng/mL for F‐CPR, 1.0 for CPI, 23.0 kg/m² for BMI, 1.3 for HOMA‐IR and 67.5 years for age.

Conclusions

Dipeptidyl peptidase‐4 inhibitors were effective in Japanese type 2 diabetic patients with sustained endogenous insulin‐secreting capacity, a higher BMI and insulin resistance.     

Postprandial serum C‐peptide value is the optimal index to identify patients with non‐obese type 2 diabetes who require multiple daily insulin injection: Analysis of C‐peptide values before and after short‐term intensive insulin therapy

Aims/Introduction

Type 2 diabetes is a progressive disease characterized by a yearly decline in insulin secretion; however, no definitive evidence exists showing the relationship between decreased insulin secretion and the need for insulin treatment. To determine the optimal insulin secretory index for identifying patients with non‐obese type 2 diabetes who require multiple daily insulin injection (MDI), we evaluated various serum C‐peptide immunoreactivity (CPR) values.

Materials and Methods

We near‐normalized blood glucose with intensive insulin therapy (IIT) over a 2‐week period in 291 patients with non‐obese type 2 diabetes, based on our treatment protocol. After improving hyperglycemia, we challenged with oral hypoglycemic agent (OHA), and according to the responsiveness to OHA, patients were classified into three therapy groups: OHA alone (n = 103), basal insulin plus OHA (basal insulin‐supported oral therapy [BOT]; n = 56) and MDI (n = 132). Glucagon‐loading CPR increment (ΔCPR), fasting CPR (FCPR), CPR 2 h after breakfast (CPR2h), the ratio of FCPR to FPG (CPI), CPI 2 h after breakfast (CPI2h) and secretory unit of islets in transplantation (SUIT) were submitted for the analyses. Receiver operating characteristic (ROC) and multiple logistic analyses for these CPR indices were carried out.

Results

Many CPR values were significantly lower in the MDI group compared with the OHA alone or BOT groups. ROC and multiple logistic analyses disclosed that post‐prandial CPR indices (CPR2h and CPI2h) were the most reliable CPR markers to identify patients requiring MDI.

Conclusions

Postprandial CPR level after breakfast is the most useful index for identifying patients with non‐obese type 2 diabetes who require MDI therapy.     

Efficacy of α‐glucosidase inhibitors combined with dipeptidyl‐peptidase‐4 inhibitor (alogliptin) for glucose fluctuation in patients with type 2 diabetes mellitus by continuous glucose monitoring

Aims/Introduction

The combination therapy of dipeptidyl‐peptidase (DPP)‐4 inhibitor and α‐glucosidase inhibitors (α‐GIs) is highly effective in suppressing postprandial hyperglycemia. The aim of the present study was to compare the effects of voglibose and miglitol on glucose fluctuation, when used in combination with DPP‐4 inhibitor by using continuous glucose monitoring (CGM).

Materials and Methods

In a randomized cross‐over study, 16 patients with type 2 diabetes who presented with postprandial hyperglycemia despite alogliptin (25 mg) were treated with voglibose (0.9 mg) or miglitol (150 mg). We measured standard deviation (SD); mean amplitude of glycemic excursions (MAGE), and mean, minimum and maximum glucose measured by CGM during three phases (alogliptin monotherapy, dual therapy of alogliptin and voglibose, and dual therapy of alogliptin and miglitol). The primary outcome measure was SD between α‐GIs.

Results

SD was significantly improved by the addition of either voglibose (18.9 ± 10.1) or miglitol (19.6 ± 8.2) to alogliptin monotherapy (36.2 ± 8.7). MAGE improved significantly with the addition of either voglibose (57.5 ± 26.1, P < 0.01) or miglitol (64.6 ± 26.2, P < 0.01) to alogliptin monotherapy (101.5 ± 21.5). There was no significant difference in glucose fluctuation between α‐GIs. There were no differences between two groups in mean (132.6 ± 21.4 and 138.7 ± 25.4) and maximum (184.3 ± 48.7 and 191.9 ± 38.3). The minimum glucose under alogliptin plus voglibose (94.9 ± 20.2) was significantly lower than that under alogliptin and miglitol (105.3 ± 21.0).

Conclusions

Glucose fluctuation was improved by the addition of voglibose or miglitol to alogliptin. Glucose fluctuations and postprandial hyperglycemia were similar between α‐GIs. This trial was registered with the University Hospital Medical Information Network (no. UMIN R000010028).     

Replication study for the association of rs391300 in SRR and rs17584499 in PTPRD with susceptibility to type 2 diabetes in a Japanese population

Aims/Introduction

Genetic risk variants for type 2 diabetes; rs391300‐G in SRR and rs17584499‐T in PTPRD, have been identified by a genome‐wide association study using Han Chinese individuals living in Taiwan. In an attempt to know the effects of these two variants in conferring susceptibility to type 2 diabetes in the Japanese, we carried out a replication study for the association of the two single nucleotide polymorphisms (SNPs) with type 2 diabetes in a Japanese population.

Materials and Methods

We genotyped 11,530 Japanese individuals (8,552 type 2 diabetes patients and 2,978 controls) for rs391300 and rs17584499, and analyzed the association of these two SNPs with type 2 diabetes by logistic regression analysis.

Results

Neither of the variants was associated with susceptibility to type 2 diabetes in the Japanese population (rs391300‐G: odds ratio [OR] = 0.97; 95% confidence interval [CI] 0.91–1.04; P = 0.44; rs17584499‐T: OR = 1.04; 95% CI 0.96–1.14; P = 0.34). Adjustment or stratified analysis for age, sex and body mass index (BMI) did not affect the association of these variants with the disease. We did not observe a significant association of the SNPs with any metabolic traits, BMI, fasting plasma glucose, homeostasis model assessment of β‐cell function (HOMA‐β) and HOMA of insulin resistance (HOMA‐IR) (P > 0.05).

Conclusions

Neither rs391300 nor rs17584499 had a significant effect on conferring susceptibility to type 2 diabetes in the Japanese population.     

Changes of blood glucose and gastrointestinal hormones 4 months after Roux‐en‐Y gastric bypass surgery in Chinese obese type 2 diabetes patients with lower body mass index

Aims/Introduction

The goal of this study was to evaluate the effect of Roux‐en‐Y gastric bypass (RYGB) on hyperglycemia and gastrointestinal hormones in Chinese obese type 2 diabetic patients with body mass index (BMI) between 28 and 35 kg/m².

Materials and Methods

A total of eight obese type 2 diabetes patients with BMI 28–35 kg/m² who underwent RYGB and 10 obese normal glucose tolerance (NGT) patients with no surgery were identified. BMI and blood glucose on baseline, and 2–4 months postoperative, changes of glucagon‐like peptide‐1 (GLP‐1), glucose‐dependent insulinotropic polypeptide (GIP), peptide YY (PYY), and oxyntomodulin (OXM) were recorded. Efficacy of RYGB was defined by the percentage of excess weight loss (%EWL) and amelioration of type 2 diabetes.

Results

The %EWL was 53.00 ± 26.25% in 2 month and 63.65 ± 33.71% in 4 month. Glycated hemoglobin changed from 7.2 ± 1.0% preoperative to 6.2 ± 0.9% in 2 month and 6.3 ± 1.2% in 4 month postoperative. The improvement rate of type 2 diabetes 4 months after RYGB was 83.3%. After surgery, area under the curve (AUC) GLP‐1 120 increased with no significance. AUC PYY 120 changed from 10.37 ± 5.45 pmol/L/min preoperative to 22.19 ± 10.61 pmol/L/min in 2 month and 22.04 ± 7.73 pmol/L/min in 4 month postoperative. Postoperative AUC OXM 120 was also higher than that of the preoperative level. AUC GIP 120 decreased from 13.06 ± 8.45 pg/mL/min preoperative to 8.71 ± 3.28 pg/ml/min in 2 month and 6.88 ± 2.33 pg/mL/min in 4 month postoperative.

Conclusions

Roux‐en‐Y gastric bypass has a beneficial effect on weight loss and glucose metabolism in obese type 2 diabetes patients with lower BMI. Postoperative concentrations of GLP‐1, PYY and OXM increased, whereas GIP decreased.     

Combination therapy with an angiotensin‐converting‐enzyme inhibitor and an angiotensin II receptor antagonist ameliorates microinflammation and oxidative stress in patients with diabetic nephropathy

Aims/Introduction

Recent studies have pointed to the effectiveness of combination therapy with an angiotensin‐converting‐enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) for diabetic nephropathy. However, some controversy over this combination treatment remains and the mechanisms underlying its renoprotective effects have not been fully clarified. Therefore, we compared the renoprotective effects of imidapril (ACEI) and losartan (ARB) combination therapy with losartan monotherapy in patients with diabetic nephropathy. We also compared the anti‐inflammatory and anti‐oxidative stress effects of these two treatments.

Materials and Methods

A total of 32 Japanese patients with type 2 diabetes and nephropathy were enrolled. Patients were randomized to either 100 mg/day losartan (n = 16) or 50 mg/day losartan plus 5 mg/day imidapril (n = 16). We evaluated clinical parameters, serum concentrations of high‐sensitivity C‐reactive protein (hs‐CRP), soluble intercellular adhesion molecule‐1 (sICAM‐1), interleukin‐18 (IL‐18) and monocyte chemotactic protein‐1 (MCP‐1), and the urinary concentrations of IL‐18, MCP‐1 and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) at 24 and 48 weeks after starting treatment.

Results

Blood pressure was not significantly different between the two groups. The serum levels of hs‐CRP, sICAM‐1 and IL‐18, as well as urinary excretion of albumin, IL‐18 and 8‐OHdG decreased significantly in the combination therapy group at 48 weeks. The percent decreases in serum IL‐18 concentrations and urinary IL‐18 and 8‐OHdG were significantly greater in the combination therapy group than in the monotherapy group.

Conclusions

Combination therapy with an ACEI and an ARB could be beneficial for treating diabetic nephropathy through its anti‐inflammatory and anti‐oxidative stress effects.     

Efficacy and safety of exenatide once‐weekly vs exenatide twice‐daily in Asian patients with type 2 diabetes mellitus

Aims/Introduction

To compare safety and efficacy of the extended‐release formulation exenatide once weekly (EQW) vs exenatide twice daily (EBID) for 26 weeks in type 2 diabetes patients from China, India, Japan, South Korea and Taiwan.

Materials and Methods

A randomized, comparator‐controlled, open‐label study included 681 patients with type 2 diabetes inadequately controlled (hemoglobin A1c [HbA_1c] ≥7 and ≤11%) with oral antihyperglycemic medications (OAMs). Patients added 2 mg EQW or 10 μg EBID to current OAMs. Safety was re‐evaluated 10 weeks after last treatment.

Results

EQW was superior to EBID on HbA_1c measures at week 26 (Least‐squares mean treatment difference: −0.31% [95% confidence interval −0.49, −0.14%]). More EQW‐treated patients achieved target HbA_1c ≤7.0% (P = 0.003), ≤6.5% (P < 0.001), or ≤6.0% (P = 0.003). Fasting serum glucose reductions were greater among EQW‐treated patients (P < 0.001). Blood glucose profiles improved in both treatment groups (P < 0.001). Weight loss occurred with both treatments, but was greater with EBID. Adverse events (≥10%, either group) were nausea, injection‐site induration, dyslipidemia and vomiting. Injection‐site induration was more frequent with EQW, whereas nausea, vomiting and hypoglycemia were less frequent. One episode each of major hypoglycemia (EBID) and pancreatitis (EQW) were reported.

Conclusion

In this population, EQW and EBID showed efficacious glucose and weight control; safety and tolerability were consistent with observations in non‐Asian patients. This trial was registered with ClinicalTrials.gov (no. NCT00917267).     

Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52‐week,open‐label study

Introduction

To examine the long‐term efficacy and safety of duloxetine in the treatment of Japanese patients with diabetic neuropathic pain, we carried out a 52‐week, randomized, open‐label extension of a 12‐week, double‐blind, placebo‐controlled study.

Materials and Methods

Japanese adults with diabetic neuropathic pain who completed the double‐blind study were eligible for this long‐term study, carried out at 71 sites in Japan (March 2008 to March 2010). Participants (n = 258) were re‐randomized (1:1) to 40 mg/day or 60 mg/day duloxetine. Pain (Brief Pain Inventory severity and interference), quality of life (Patient''s Global Impression of Improvement), and safety (primary outcome; adverse events, vital signs, metabolic measures) were measured.

Results

Significant (P < 0.0001) and sustained improvements (change ± standard deviation; n = 257) were observed in Brief Pain Inventory severity (average pain score −2.1 ± 1.7). Improvements were also seen in Brief Pain Inventory interference (mean of subscores −0.96 ± 1.52) and Patient''s Global Impression of Improvement (−0.9 ± 1.1) scores; these scores decreased significantly (P < 0.0001) during the long‐term study. Frequently reported adverse events included somnolence (13.6%), constipation (13.2%) and nausea (10.5%). Increases were observed in plasma glucose, glycosylated hemoglobin and total cholesterol levels, and in bodyweight and heart rate; however, none of these were clinically meaningful. Overall, there were no clinically significant safety concerns.

Conclusions

This is the first publication of a long‐term study carried out in Asia with an entirely Japanese patient population to suggest that long‐term duloxetine therapy for diabetic neuropathic pain is effective and has an acceptable safety profile.     

Interactive effects of an isocaloric high‐protein diet and resistance exercise on body composition,ghrelin, and metabolic and hormonal parameters in untrained young men: A randomized clinical trial

Aims/Introduction

The interactive effects of resistance training and dietary protein on hormonal responses in adults are not clear and remain controversial. We tested the effect of an isocaloric high‐protein diet on body composition, ghrelin, and metabolic and hormonal parameters during a 12‐week resistance training program in untrained healthy young men.

Material and Methods

We randomized 18 healthy young men to a standard diet (ST group) or an isocaloric high protein diet (HP group). Both groups participated in a 12‐week resistance exercise program. We measured body composition, lipid profile, homeostatic model assessment of insulin resistance (HOMA‐IR) indices, total ghrelin, and exercise‐related hormones at baseline and 12 weeks.

Results

In the HP group, lean body mass (LBM), total ghrelin, growth hormone, testosterone and cortisol levels showed an increase, whereas body fat percentage and HOMA‐IR showed a decrease at 12 weeks, compared with baseline (P ≤ 0.05). In the ST group, no changes in these parameters were observed during the 12‐week period. During the 12‐week period, significant differences in the pattern of change of LBM (P = 0.032), total ghrelin (P = 0.037), HOMA‐IR (P = 0.040) and high‐density lipoprotein cholesterol (P = 0.011) over time were observed between the groups.

Conclusions

The findings of the present study suggest that an isocaloric high‐protein diet can ameliorate body composition, metabolic profiles and energy metabolism during a 12‐week scheduled resistance training program in untrained healthy young men. This trial was registered with ClinicalTrials.gov (no. NCT01714700).