Diabetes mellitus,but not small dense low‐density lipoprotein,is predictive of cardiovascular disease: A Korean community‐based prospective cohort study

Aims/Introduction

Small dense low‐density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular diseases (CVD).

Materials and Methods

We carried out a prospective nested case–control study in the Korean Health and Genome Study. Participants were men and women aged 40–69 years who developed CVD (n = 313), and were matched by age and sex to controls who remained free of CVD (n = 313) during the 8‐years follow‐up period (from 2001 to 2009). LDL subfractions were analyzed in frozen samples collected from the 626 participants using polyacrylamide tube gel electrophoresis.

Results

Patients with CVD had a significantly higher glycated hemoglobin level compared with the controls (5.72 vs 5.56). The proportion of patients with diabetes mellitus (DM) was higher in those who developed CVD during follow up (8.0% vs 1.9%). The frequency of CVD according to each tertile of LDL particle size and the number of metabolic syndrome components did not differ significantly. In the multivariate analysis, DM (odds ratio 4.244, 95% confidence interval 1.693–10.640, P = 0.002) was the only independent predictive factor of CVD. LDL particle size was not associated with the risk for future CVD.

Conclusions

Small dense LDL might not be a significant predictor of CVD in this Korean community‐based prospective cohort study.     

Obesity as an effect modifier of the association between leptin and diabetic kidney disease

Aims/Introduction

Obesity has been shown to be a modifier of the association between leptin levels and cardiovascular events. We examined whether obesity modifies the association between serum leptin levels and the progression of diabetic kidney disease.

Materials and Methods

This was an observational longitudinal study on patients with type 2 diabetes. We enrolled 410 and 348 patients in the eGFR and ACR cohorts, respectively. Patients were classified into three groups by sex‐specific tertile of leptin levels. Obesity was defined as body mass index ≥25 kg/m². Outcomes were the rate of change in estimated glomerular filtration rate (eGFR) and progression to a more advanced stage of albuminuria.

Results

In the eGFR cohort, the mean eGFR change during the median follow‐up period of 4.7 years was −1.4 mL/min/1.73 m²/year. An interaction between leptin levels (low, medium or high) and obesity (present or absent) on the change in eGFR was detected (P interaction = 0.003). In the lean group, adjusted eGFR decline in patients with low leptin was steeper than that in patients with medium leptin (2.1 and 0.8 mL/min/1.73 m²/year, P = 0.023). In the obese group, patients with high leptin had a steeper adjusted eGFR decline than those with medium leptin (1.7 and 0.6 mL/min/1.73 m²/year, P = 0.044). In the ACR cohort, 29 patients showed progression of albuminuria during the median follow‐up period of 3.9 years. There was no interaction between leptin levels and obesity on the outcome (P interaction = 0.094).

Conclusions

Obesity might modify the effects of leptin on kidney function decline in patients with type 2 diabetes.     

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.     

Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus

Introduction

The aim of the present study was to determine the effect of sitagliptin on microalbuminuria in patients with type 2 diabetes mellitus.

Materials and Methods

A total of 85 patients with type 2 diabetes mellitus (age >20 years, <80 years, hemoglobin A1c [HbA1c] <8.4%) were randomized to patients taking sitagliptin 50 mg or other oral glucose‐lowering agents. The following parameters were evaluated at 0, 3 and 6 months after the treatment: bodyweight, blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglycerides, estimated glomerular filtration rate and urinary albumin excretion. The primary outcome was changes in urinary albumin excretion at 6 months.

Results

Significant and comparable falls in HbA1c and fasting plasma glucose were found in both groups. However, sitagliptin significantly reduced urinary albumin excretion within 6 months, especially in patients with high urinary albumin at baseline. A total of 27 patients with normoalbuminuria showed a reduction in urinary albumin excretion, suggesting that sitagliptin prevents the development of albuminuria. A total of 15 patients with albuminuria showed a reduction in urinary albumin excretion, suggesting the beneficial effect of sitagliptin in the early stage of diabetic nephropathy. There was a significant correlation between improvement of proteinuria and that of diastolic blood pressure.

Conclusions

The results suggested that sitagliptin improved albuminuria, in addition to improving glucose. The mechanism of the reduction of albuminuria by sitagliptin could be a direct effect, as well as an increase in active glucagon‐like peptide‐1, independently affecting blood pressure, bodyweight and glucose metabolism. This trial was registered with the University Hospital Medical Information Network (UMIN no. #000010871).     

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.     

Combined effects of physiologically relevant disturbed wall shear stress and glycated albumin on endothelial cell functions associated with inflammation,thrombosis and cytoskeletal dynamics

Aims/Introduction

Diabetes mellitus is a major risk factor in the development of cardiovascular diseases (CVDs). The presence of advanced glycation end‐products (AGEs) promotes CVDs by upregulating endothelial cell (EC) inflammatory and thrombotic responses, in a similar manner as disturbed shear stress. However, the combined effect of disturbed shear stress and AGEs on EC function has yet to be determined. Our goal was to evaluate these effects on EC responses.

Materials and Methods

ECs were incubated with AGEs for 5 days. ECs were then subjected to physiological or pathological shear stress. Cell metabolic activity, surface expression of intercellular adhesion molecule‐1, thrombomodulin, connexin‐43 and caveolin‐1, and cytoskeleton organization were quantified.

Results

The results show that irreversibly glycated albumin and pathological shear stress increased EC metabolic activity, and upregulated and downregulated the EC surface expression of intercellular adhesion molecule‐1 and thrombomodulin, respectively. Expression of connexin‐43, caveolin‐1 and cytoskeletal organization was independent of shear stress; however, the presence of irreversibly glycated AGEs markedly increased connexin‐43, and decreased caveolin‐1 expression and actin cytoskeletal connectivity.

Conclusions

Our data suggest that irreversibly glycated albumin and disturbed shear stress could promote CVD pathogenesis by enhancing EC inflammatory and thrombotic responses, and through the deterioration of the cytoskeletal organization.     

Secretory units of islets in transplantation index is a useful predictor of insulin requirement in Japanese type 2 diabetic patients

Aims/Introduction

The objective of the present study was to clarify the validity of β‐cell function‐related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients.

Materials and Methods

In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross‐sectional study examining the relationship between the homeostasis model assessment of β‐cell function (HOMA‐β) and C‐peptide‐based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several β ‐cell function‐related indices using a receiver operating characteristic (ROC) curve analysis.

Results

The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA‐β, followed by the fasting serum C‐peptide immunoreactivity index (CPI); the fasting serum C‐peptide immunoreactivity itself (F‐CPR) had the least correlation. The CPI, HOMA‐β and SUIT were significantly lower in the insulin‐requiring group than in the non‐insulin‐requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F‐CPR, CPI, SUIT, and HOMA‐β, respectively. The cut‐off values of SUIT, CPI, and HOMA‐β for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively.

Conclusions

The present study shows that SUIT is the best predictor of insulin requirement among these β‐cell function‐related markers.     

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.     

Changes in oral antidiabetic prescriptions and improved glycemic control during the years 2002–2011 in Japan (JDDM32)

Aims/Introduction

Six kinds of oral antidiabetic drugs (OADs), including the new dipeptidyl peptidase 4 (DPP‐4) inhibitors, are available. The present study aimed to define trends within the prescribing patterns of OADs, as well as changes in glycemic control in Japan over a 10‐year period from 2002 to 2011.

Materials and Methods

We carried out a cross‐sectional study using data of type 2 diabetes mellitus patients from 24 clinics for 2002, 2005, 2008 and 2011. OAD use was analyzed combined with clinical data.

Results

Sulfonylureas (SUs) were the most commonly used OAD, but their use for monotherapy markedly decreased over the study period. Biguanides (BGs) were the second most commonly used OAD, and their prescribing rate increased both for mono‐ and combination therapy. DPP‐4 inhibitors (DPP‐4I), released in 2009, were the third most commonly prescribed OAD in 2011 both for mono‐ and combination therapy. Among combination therapies, two OADs were mostly prescribed, but the use of three OADs and four OADs in 2011 was two‐ and 14.8‐fold those in 2002. These trends were accompanied by an improvement in average glycated hemoglobin from 7.5 ± 1.2% in 2002 to 7.1 ± 0.9% in 2011.

Conclusions

The OAD prescribing trend has moved away from monotherapy with SUs and toward combination therapies to achieve better glycemic control. Increased use of BGs and DPP‐4I was predominant in 2011. These trends were accompanied by an improvement of the glycated hemoglobin level.     

Circulating cell‐free mitochondrial deoxyribonucleic acid is increased in coronary heart disease patients with diabetes mellitus

Aims/Introduction

Circulating cell‐free mitochondrial deoxyribonucleic acid (ccf‐mtDNA) is presumably derived from injured tissues or cells in the body and has been suggested to be potential biomarker in several diseases. The present study explored whether mtDNA could be used as a biomarker to evaluate disease in coronary heart disease (CHD) patients with or without diabetes mellitus (DM).

Materials and Methods

A total of 50 CHD patients with type 2 diabetes, 50 CHD patients without type 2 diabetes, and 50 age‐ and sex‐matched patients without CHD and DM (non‐CHD‐DM) were recruited. Ccf‐mtDNA levels were assessed by measuring the nicotinamide adenine dinucleotide dehydrogenase 1 gene using quantitative real‐time polymerase chain reaction. Receiver operating characteristic curve analysis of plasma mtDNA in CHD with or without DM was also determined. Multivariate logistic regression analyses were carried out to determine the correlation between the mtDNA levels and traditional CHD risk factors.

Results

The plasma ccf‐mtDNA levels were significantly elevated in CHD patients with DM compared with those without and non‐CHD‐DM. The area under the receiver operating characteristic curves of mtDNA in CHD patients with DM vs non‐CHD‐DM was 0.907%. Correlation analyses of the mtDNA levels and traditional CHD risk factors showed that the mtDNA levels were significantly correlated with fasting blood glucose in CHD patients with DM.

Conclusions

Ccf‐mtDNA levels can be used as a biomarker in CHD patients with DM.     

Association of chemokine ligand 5/chemokine receptor 5 gene promoter polymorphisms with diabetic microvascular complications: A meta‐analysis

Aims/Introduction

Chemokine ligand 5 (CCL5) is a member of the CC‐chemokine family expressed in various organs. It contributes to the migration of monocytes/macrophages into injured vascular walls by binding with its receptor chemokine receptor 5 (CCR5). Many studies have accessed the association between CCL5/CCR5 gene promoter polymorphisms and diabetic microvascular complications (DMI). However, the results are conflicting and inconclusive. The aim of the present study was to evaluate the association more precisely.

Materials and Methods

Trials were retrieved through PubMed, Embase, Medline, China National Knowledge Infrastructure, Web of Science and Cochrane database without restrictions on language. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association with DMI.

Results

Data were obtained from 11 case–control studies that included 2,737 DMI patients and 2,435 diabetic control subjects. In the overall analysis, the CCL5‐403 G/A and CCL5‐28 C/G gene polymorphisms were not significantly associated with the risk of DMI. However, CCR5‐59029 G/A was an independent risk factor of DMI in a dominant model (OR 1.77, 95% CI 1.06–2.97). Subgroup analysis showed that the risk of the CCR5 59029A‐positive genotype was significant in Asians (OR 2.08, 95% CI 1.68–2.57). In addition, the CCR5 59029A‐positive genotype was associated with increased risk of albuminuria.

Conclusions

There were no associations of CCL5 gene promoter polymorphism with the risk of DMI. However, the 59029A polymorphism in CCR5 might affect individual susceptibility for DMI.     

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 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.     

Anthropometric indicators of obesity for identifying cardiometabolic risk factors in a rural Bangladeshi population

Aims/Introduction

The aim of the present study was to evaluate the predictive ability of body mass index (BMI), waist circumference (WC), waist‐to‐hip ratio (WHR), waist‐to‐height ratio (WHtR) and body fat percentages (BF%) for the presence of cardiometabolic risk factors, namely type 2 diabetes (DM), hypertension (HTN), dyslipidemia and metabolic syndrome (MS).

Materials and Methods

A total of 2293 subjects aged ≥20 years from rural Bangladesh were randomly selected in a population‐based, cross‐sectional survey. The association of anthropometric indicators with cardiometabolic risk conditions was assessed by using receiver operating characteristic curve analysis and adjusted odds ratios (ORs) for DM, HTN, dyslipidemia and MS.

Results

Area under the curve cut‐off values showed that the association of WHR, BF% and WC was higher than that for other indices for DM, HTN and MS, respectively, for both sexes, and WHtR for men and WHR for women for dyslipidemia. The ORs were highest for WHR for DM and WC for MS for both sexes, and WHtR for men and WC for women for HTN and dyslipidemia, respectively. The optimal cut‐off values for obesity for the present study in men and women showed BMIs of 22 and 22.8 kg/m², WHRs of 0.93 and 0.87, WHtRs of 0.52 and 0.54, BF% of 21.4 and 32.4%, and WCs of 82 and 81 cm, except for MS, which were 90 for men and 80 for women.

Conclusions

Compared with BMI, measures of central obesity, particularly WHR, WC, WHtR and BF%, showed a better association with obesity‐related cardiometabolic risk factors for both sexes.     

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).     

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.     

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.     

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.     

Association of glycated albumin with the presence of carotid plaque in patients with type 2 diabetes

Aims/Introduction

Postprandial hyperglycemia is a potent risk factor for cardiovascular disease. Serum glycated albumin (GA) has been reported to reflect postprandial blood glucose fluctuations. In the present study, we assessed the possible correlation of GA with the presence of carotid plaque to evaluate the potential clinical usefulness of GA for predicting atherosclerotic cardiovascular complications in patients with type 2 diabetes.

Materials and Methods

Patients with type 2 diabetes (n = 236) admitted to Nippon Medical School Hospital (Tokyo, Japan) for glycemic control (aged 19–86 years, 81 females and 155 males) were examined. Clinical measurements were taken on admission. The presence of carotid plaque was assessed by ultrasonography.

Results

In patients with carotid plaque (n = 154), GA (P = 0.023) was higher than those without carotid plaque (n = 82). In contrast, neither fasting plasma glucose (P = 0.48) nor glycated hemoglobin (P = 0.41) was significantly different between the groups. The results of logistic regression analysis showed that GA (age‐ and sex‐adjusted odds ratio [95% confidence interval], 1.05 [1.01–1.09]; P = 0.017) and glycated hemoglobin (1.17 [1.01–1.37]; P = 0.036) were significantly associated with the presence of carotid plaque.

Conclusions

The positive correlation of serum GA with the presence of carotid plaque in type 2 diabetes suggests that GA will serve as a useful clinical marker for predicting diabetic cardiovascular complications.