Jun-Sing Wang

Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring

Previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin (

Genome-wide association study in a Chinese population with diabetic retinopathy

\hbox{HbA}_{{\rm 1c}}

Performance of HbA1c and Fasting Plasma Glucose in Screening for Diabetes in Patients Undergoing Coronary Angiography

) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring.

Coronary severity score and C-reactive protein predict major adverse cardiovascular events in patients with stable coronary artery disease (from the Taichung CAD study)

Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults. To identify genetic contributions in DR, we studied 2071 type 2 diabetics. We first conducted a genome-wide association study of 1007 individuals, comparing 570 subjects with ≥8 years duration without DR (controls) with 437 PDR (cases) in the Chinese discovery cohort. Cases and controls were similar for HbA1c, diabetes duration and body mass index. Association analysis with imputed data identified three novel loci: TBC1D4-COMMD6-UCHL3 (rs9565164, P = 1.3 × 10(-7)), LRP2-BBS5 (rs1399634, P = 2.0 × 10(-6)) and ARL4C-SH3BP4 (rs2380261, P = 2.1 × 10(-6)). Analysis of an independent cohort of 585 Hispanics diabetics with or without DR though did not confirm these signals. These genes are still of particular interest because they are involved in insulin regulation, inflammation, lipid signaling and apoptosis pathways, all of which are possibly involved with DR. Our finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.

Trajectories of fasting plasma glucose variability and mortality in type 2 diabetes

OBJECTIVE The performance of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) was compared in screening for diabetes by an oral glucose tolerance test (OGTT) in patients undergoing coronary angiography (CAG). RESEARCH DESIGN AND METHODS Patients without known diabetes admitted for CAG were eligible. OGTT and HbA1c were assessed 2–4 weeks after hospital discharge. The performance of HbA1c and FPG was evaluated by using receiver operating characteristic (ROC) analysis. RESULTS Diabetes was diagnosed in 83 of 400 patients (20.8%). The area under the ROC curve was higher for FPG than for HbA1c (0.81 vs. 0.73, P = 0.032). We proposed a screening algorithm and validated it in another 170 patients. Overall, this algorithm reduced the number of OGTTs by 71.4% (sensitivity 74.4%, specificity 100%). CONCLUSIONS FPG performed better than HbA1c in screening for diabetes in patients undergoing CAG. A screening algorithm might help to reduce the number of OGTTs.

Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes

BACKGROUND Whether angiographic coronary severity really predicts future major adverse cardiovascular events (MACEs) in patients with coronary artery disease (CAD) is uncertain. Few studies have compared the efficacy of SYNTAX, Gensini and Jeopardy scores in predicting MACE in stable CAD. METHODS We collected data of MACE, including all-cause mortality, all strokes, new myocardial infarction and unplanned repeat revascularization, in subjects with stable CAD from our catheterization databank. Coronary severity was graded with SYNTAX, Gensini and Jeopardy scoring systems. RESULTS During a median follow-up period of 42months, 39 out of the 181 subjects developed at least 1 MACE. Those with MACE had a significantly higher baseline high sensitivity C-reactive protein (hs-CRP) (p=0.025). Multivariate analysis showed that coronary severity score, hs-CRP and diabetes mellitus were significant predictors for MACE. Kaplan-Meier estimates showed a significant difference in MACE-free rates between SYNTAX binary scores (≥15 vs. <15, p=0.043), Gensini binary scores (≥36 vs. <36, p=0.048) and Jeopardy binary scores (≥4 vs. <4, p=0.001). CONCLUSION Coronary severity score, hs-CRP and diabetes mellitus independently predicted MACE in patients with stable CAD. The Jeopardy score is simple to calculate and as effective for predicting MACE in stable CAD as the complex SYNTAX score.

Hemoglobin glycation index as a useful predictor of therapeutic responses to dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes

AIM To investigate the effect of changes in fasting plasma glucose (FPG) variability, as assessed by 2-year trajectories of FPG variability, on mortality risk in patients with type 2 diabetes (T2D). METHODS From 2009 to 2012, outpatients with T2D, aged>18 years, were enrolled from a medical centre. FPG was measured every 3 months for 2 years in 3569 people. For each of the eight 3-month intervals, FPG variability and means were calculated, with variability defined as the coefficient of variation of FPG. Also, trajectories of FPG variability and means were determined separately, using group-based trajectory analysis with latent class growth models. These models were fitted using the SAS Proc Traj procedure. The primary outcome was all-cause mortality, which was followed-up to the end of 2014. RESULTS Five distinct trajectories of FPG variability (low, increasing, fluctuating, decreasing and high) and means (well controlled, stable control, worsening control, improving control and poor control) were established. The five trajectories of mean FPG were all associated with the same mortality risk. In contrast, in comparison to the low FPG variability trajectory, the fluctuating, decreasing and high variability trajectories all had significantly higher risks of mortality, with respective hazards ratios of 2.63 (95% CI: 1.40-4.93; P=0.003), 2.78 (95% CI: 1.33-5.80; P=0.007) and 4.44 (95% CI: 1.78-11.06; P=0.001) after multivariable adjustment. CONCLUSION Changes in FPG variability were independently associated with increased mortality risk in patients with T2D.

The synergistic effect of vascular cell adhesion molecule-1 and coronary artery disease on brain-derived neurotrophic factor.

AIM The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). METHODS Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM. RESULTS A total of 50 patients (mean age 53.5 ± 8.2 years, male 48%, mean baseline HbA1c 8.4 ± 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 ± 13.8 to 18.8 ± 35.8 min/day, p=0.041), but not with acarbose (from 2.9 ± 10.9 to 14.7 ± 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (β coefficient 0.345, p=0.036) or acarbose (β coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). CONCLUSIONS Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.

Glycemic excursions were positively associated with HbA1c reduction from baseline after treatment with acarbose in patients with type 2 diabetes on metformin monotherapy.

Introduction A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. Methods This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level. The subjects were divided into two groups based on HGI (HGI = observed HbA1c - estimated HbA1c). Mixed model repeated measures were used to compare the treatment efficacy after 1 year in patients with a low (HGI<0, n = 199) and high HGI (HGI≧0, n = 269). Results There were no significant group differences in mean changes of FPG after 1 year (-12.8 and -13.4 mg/dL in the low and high HGI groups, respectively). However, the patients with a high HGI had a significantly greater reduction in HbA1c from baseline compared to those with a low HGI (-1.9 versus -0.3% [-20.8 versus -3.3 mmol/mol]). Improvements in glycemic control were statistically significantly associated with the tested DPP-4 inhibitors in the high HGI group (-2.4, -1.4, -1.2 and -2.2% [-26.2, -15.3, -13.1 and -24.0 mmol/mol] for vildagliptin, linagliptin, saxagliptin and sitagliptin, respectively) but not in the low HGI group. Conclusions The HGI index derived from FPG and HbA1c may be able to identify who will have a better response to DPP-4 inhibitors.

Physical activity and albuminuria were associated with painful diabetic polyneuropathy in type 2 diabetes in an ethnic Chinese population

BACKGROUND Brain-derived neurotrophic factor (BDNF) is important for neural protection and energy homeostasis. In this study, we examined the effects of vascular cell adhesion molecule-1 (VCAM-1) and coronary artery disease (CAD) on BDNF. METHODS Subjects who had undergone diagnostic angiography for angina were recruited, and a total of 240 subjects (144 with CAD and 96 without CAD) were enrolled. Serum BDNF was determined at 0, 30, and 120min during an oral glucose tolerance test (OGTT) to calculate the area under the curve (AUC) for BDNF. Serum VCAM-1 was determined at fasting. RESULTS Significantly lower AUC of BDNF (42.8±10.7 vs. 47.4±11.7ng-h/ml, P=0.002) and higher serum VCAM-1 (583±383 vs. 482±171ng/ml, P=0.017) were noted in subjects with CAD compared to those without CAD. High VCAM-1 level was an independent predictor of low AUC of BDNF in subjects with and without CAD (95%CI between -0.011 and -0.002, P=0.008; -0.033 and -0.002, P=0.029, respectively). Serum BDNF was lowest in the CAD subjects with high VCAM-1 levels at all time points during OGTT. CONCLUSION Our results showed that CAD was associated with low serum BDNF in response to OGTT, and VCAM-1 had a synergistic effect with CAD on the BDNF.