Diabetes self-management education on the sustainability of metabolic control in type 2 diabetes patients: Diabetes share care program in Taiwan.

BACKGROUND: Diabetes self-management education (DSME) improves glycemic and metabolic control. However, the frequency, duration and sustainability of DSME for improving metabolic control have not been well studied. METHODS: The Diabetes Share Care Program (DSCP) stage 1 provided DSME every 3 months. If participants entering DSCP stage 1 ≥ 2 years and HbA1c < 7%, they can be transferred to stage 2 (DSME frequency: once a year). Three-to-one matching between DSCP stage 1 and stage 2 groups based on the propensity score method to match the two groups in terms of HbA1c and diabetes duration. We identified 311 people living with type 2 diabetes in DSCP stage 1 and 86 in stage 2 and evaluated their metabolic control and healthy behaviors annually for 5 years. RESULTS: In the first year, HbA1c in the DSCP stage 2 group was significantly lower than that in the stage 1 group. In the first and the fifth years, the percentage of patients achieving HbA1c < 7% was significantly higher in the DSCP stage 2 group than the stage 1 group. There was no significant difference in other metabolic parameters between the two groups during the 5-year follow-up. Self-monitoring of blood glucose (SMBG) frequency was associated with a reduced HbA1c after 5 years (95% CI: -0.0665 to -0.0004). CONCLUSION: We demonstrated sustainable effects of at least 2-year DSME on achieving better glycemic control for at least 1 year. SMBG contributed to improved glycemic control. The results may be applied to the reimbursement strategy in diabetes education.

A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes.

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.

Hemoglobin glycation index predicts renal function deterioration in patients with type 2 diabetes and a low risk of chronic kidney disease.

AIMS: Hemoglobin glycation index (HGI) is used to describe the difference between estimated and measured glycated hemoglobin (HbA1c). We aimed to study whether HGI can predict renal function deterioration in patients with type 2 diabetes and a low risk of chronic kidney disease (CKD). METHODS: This retrospective cohort study enrolled 780 patients with type 2 diabetes and a low CKD risk according to the criteria of kidney disease: improving global outcomes. Participants were divided into two subgroups according to the baseline HGI calculated by fasting blood glucose and HbA1c. Multivariate Cox proportional hazard models were used to evaluate the hazard ratios of the study endpoints. Longitudinal data was analyzed using generalized estimating equation (GEE). RESULTS: The participants were followed for a median of 7.3 years. A high HGI predicted rapid renal function decline without or with a resultant eGFR < 60 ml/min/1.73 m2, but not onset of macroalbuminuria. The longitudinal GEE model demonstrated a negative association between HGI and the predicted eGFR changes in both the 1-year and 3-year intervals. CONCLUSIONS: HGI independently predicted renal function deterioration in patients with type 2 diabetes and a low CKD risk. Further investigations are warranted to elucidate its potential clinical impact.

Visit-to-visit variability in albuminuria predicts renal function deterioration in patients with type 2 diabetes.

AIMS/INTRODUCTION: We aimed to study the predictive ability of visit-to-visit variability in albuminuria for changes in renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: The cohort study was carried out in a single medical center. In the model development cohort of 1008 subjects, we developed the albuminuria variability score (AVS) to evaluate the visit-to-visit variability in albuminuria, which was the percentage of the number of changes in the urine albumin : creatinine ratio ≥3.39 mg/mmol among all visit-to-visit urine albumin : creatinine ratio differences within an individual. Multivariate logistic regression was applied to predict the influence of AVS levels on the occurrence of study end-points. In another independent validation cohort of 310 participants, survival analysis was carried out to evaluate the ability of AVS in predicting the study end-point. RESULTS: In the model development cohort, a higher AVS was associated with higher adjusted odds of having a declined or rapidly declined estimated glomerular filtration rate (eGFR) trajectory (1.84, 95% confidence interval 1.23-2.76 and 5.70, 95% confidence interval 2.28-14.25, respectively), a resultant eGFR <60 mL/min/1.73 m2 (2.61, 95% confidence interval 1.63-4.16) and a >40% decline in eGFR from baseline (6.44, 95% confidence interval 2.15-19.26). In the validation cohort, a higher AVS independently predicted a 5-year decrease of >40% in eGFR to <60 mL/min/1.73 m2 (adjusted hazard ratio 3.33, 95% confidence interval 1.10-10.05). Integrated discrimination index and concordance statistics showed that AVS significantly improved the predictive ability of the models. CONCLUSIONS: Visit-to-visit variability in albuminuria can independently predict long-term renal function deterioration in patients with type 2 diabetes mellitus. Further investigations are warranted to elucidate the potential clinical applications.

Application of deep learning image assessment software VeriSee™ for diabetic retinopathy screening.

PURPOSE: To develop a deep learning image assessment software VeriSee™ and to validate its accuracy in grading the severity of diabetic retinopathy (DR). METHODS: Diabetic patients who underwent single-field, nonmydriatic, 45-degree color retinal fundus photography at National Taiwan University Hospital between July 2007 and June 2017 were retrospectively recruited. A total of 7524 judgeable color fundus images were collected and were graded for the severity of DR by ophthalmologists. Among these pictures, 5649 along with another 31,612 color fundus images from the EyePACS dataset were used for model training of VeriSee™. The other 1875 images were used for validation and were graded for the severity of DR by VeriSee™, ophthalmologists, and internal physicians. Area under the receiver operating characteristic curve (AUC) for VeriSee™, and the sensitivities and specificities for VeriSee™, ophthalmologists, and internal physicians in diagnosing DR were calculated. RESULTS: The AUCs for VeriSee™ in diagnosing any DR, referable DR and proliferative diabetic retinopathy (PDR) were 0.955, 0.955 and 0.984, respectively. VeriSee™ had better sensitivities in diagnosing any DR and PDR (92.2% and 90.9%, respectively) than internal physicians (64.3% and 20.6%, respectively) (P < 0.001 for both). VeriSee™ also had better sensitivities in diagnosing any DR and referable DR (92.2% and 89.2%, respectively) than ophthalmologists (86.9% and 71.1%, respectively) (P < 0.001 for both), while ophthalmologists had better specificities. CONCLUSION: VeriSee™ had good sensitivity and specificity in grading the severity of DR from color fundus images. It may offer clinical assistance to non-ophthalmologists in DR screening with nonmydriatic retinal fundus photography.

Commentary on the effects of receptor activator of nuclear factor-B ligand inhibition on bone mass and muscle strength.

The pathophysiology of osteoporosis and sarcopenia.

Trends in prevalence and incidence of diabetes mellitus from 2005 to 2014 in Taiwan.

BACKGROUND/PURPOSE: Diabetes mellitus (DM) and DM-related complications place a high socioeconomic burden on individuals and society. Updating nationwide information periodically is thus pivotal to preventing DM and improving its management in Taiwan. METHODS: We used the National Health Insurance Research Database; disease diagnosis codes were assigned according to the International Classification of Diseases, 9th Revision, Clinical Modification. DM was defined as ≥3 outpatient visits or 1 hospitalization within a year. We excluded individuals with gestational DM, those with missing data, and those aged >100 years. Type 1 DM (T1DM) was defined based on information from the catastrophic illness registry. RESULTS: From 2005 to 2014, total population with DM increased by 66% and age-standardized prevalence in patients aged 20-79 years increased by 41%. The DM prevalence was generally higher in men; however, the prevalence was higher in women aged ≥65 years. The prevalence of DM was approximately 50% in those aged >80 years. DM incidence increased by 19%; the increase was most obvious in patients aged 20-39 years (p < 0.001). The standardized incidence of T1DM slightly decreased by 11% (p = 0.118) and standardized prevalence of T1DM increased from 0.04% to 0.05%. Number of T1DM accounted for 0.51-0.59% of the entire diabetic population during the observation period. CONCLUSION: DM prevalence is continually increasing, but the incidence only marginally increased from 2005 to 2014. Moreover, DM is a major problem in elderly people. The higher incidence of DM in men is consistent with the pandemic of overweight and obesity in men in Taiwan.

Diabetes related fatigue sarcopenia, frailty.

The rationale of diabetes related fatigue syndrome and interventions.

A Systematic Review and Meta-Analysis of the Effect of Lifestyle Modification on Metabolic Control in Overweight Children.

Childhood obesity is associated with type 2 diabetes mellitus. We aimed to determine the effects of lifestyle modification programs on fasting plasma glucose (FPG) levels in overweight children. We queried six relevant electronic databases and manually searched for studies published before December 2016. Overweight/obese children who underwent a lifestyle modification for more than 6 months were included. A total of 3923 children from eight randomized controlled trials (RCTs) were included. Compared with the control group, the lifestyle modification group had significantly lower FPG levels by 1.3 mg/dL. The mean differences were significantly decreased for both secondary outcomes; BMI z-score decreased by 0.16 units and insulin levels decreased by 2.4 mU/L. The metaregression showed that the follow-up duration was associated with FPG levels and BMI and insulin levels and half year is a suitable follow-up duration for this population. This study showed that lifestyle modification programs may be effective in reducing the FPG levels of overweight/obese children. Further high-quality RCTs with longer follow-up periods are needed to evaluate the long-term effect of this complementary approach for diabetes mellitus prevention on overweight/obese children.

Integrative traditional Chinese medicine therapy reduces the risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Life-long insulin is the standard treatment for type 1 diabetes mellitus (T1DM). The role of traditional Chinese medicine (TCM) in T1DM is still not clear. The aim of this study is to explore the prescription pattern of TCM and its impact on the risk of diabetic ketoacidosis (DKA) in patients with T1DM. MATERIALS AND METHODS: We retrieved samples from the registry for catastrophic illness patients from the National Health Insurance Research Database (NHIRD). Based on a frequency (1:4) matched case-control design, patients with T1DM in 2000-2011 were designated as cases (TCM users) and controls (non-TCM users). TCM treatment for patients with T1DM was analyzed. The incidence of DKA and the annual costs of emergency visits and hospitalizations were evaluated for all causes. RESULTS: Overall, 416 subjects were TCM users, whereas a total of 1608 matched subjects were classified as non-TCM users. The most common Chinese herbal formula and single herb is Liu-wei-di-huang-wan (Six-ingredient pill of Rehmannia) and Huang-qi (Radix Astragali; Astragalus membranaceus (Fisch.) Bunge, Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao), respectively. Compared with non-TCM users, we found a 33% reduction in DKA incidence for all TCM users (aHR 0.67, 95% CI 0.56-0.81, p <0.000) and a 40% reduction for users receiving TCM treatment for more than 180 days (aHR 0.58, 95% CI 0.41-0.82, p <0.01). There were no significant differences between TCM users and non-users in the frequency and medical costs of emergency visits and hospitalizations. CONCLUSIONS: Integrative TCM use may reduce the risk of DKA in patients with T1DM. Our results suggest that TCM may have a substantial positive impact on the management of TIDM.

Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes.

BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects. METHODS: In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay. RESULTS: Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12-2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871-0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively. CONCLUSIONS: In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects.

Early Myocardial Repolarization Heterogeneity Is Detected by Magnetocardiography in Diabetic Patients with Cardiovascular Risk Factors.

Multi-channel magnetocardiography (MCG) is a sensitive technique to map spatial ventricular repolarization with high resolution and reproducibility. Spatial ventricular repolarization heterogeneity measured by MCG has been shown to accurately detect and localize myocardial ischemia. Here, we explored whether these measurements correlated with cardiovascular risk factors in patients with type 2 diabetes. Two hundreds and seventy-seven type 2 diabetic patients without known coronary artery disease (CAD) and arrhythmia were recruited consecutively from the outpatient clinic of National Taiwan University Hospital. The spatially distributed QTc contour maps were constructed with 64-channel MCG using the superconducting quantum interference device (SQUID) system. Indices of myocardial repolarization heterogeneity including the smoothness index of QTc (SI-QTc) and QTc dispersion were derived and analyzed for association with conventional cardiovascular risk factors. SI-QTc correlated strongly with the QTc dispersion (r = 0.70, p <0.0001). SI-QTc was significantly higher in patients with presence of metabolic syndrome in comparison to those without metabolic syndrome (8.56 vs. 7.96 ms, p = 0.02). In univariate correlation analyses, QTc dispersion was associated with smoking status (average 79.90, 83.83, 86.51, and 86.00 ms for never smokers, ex-smokers, current smokers reporting less than 10 cigarettes daily, and current smoker reporting more than 10 cigarettes daily, respectively, p = 0.03), body weight (r = 0.15, p = 0.01), and hemoglobin A1c (r = 0.12, p = 0.04). In stepwise multivariate regression analyses, QTc dispersion was associated with smoking (p = 0.02), body weight (p = 0.04), total cholesterol levels (p = 0.05), and possibly estimated glomerular filtration rate (p = 0.07). In summary, spatial heterogeneity of myocardial repolarization measured by MCG is positively associated cardiovascular risk factors including adiposity, smoking, and total cholesterol levels.

Genetic Variations in the Kir6.2 Subunit (KCNJ11) of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan.

To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4) and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0) from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044). After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047). K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading.

Serum vascular adhesion protein-1 level predicts risk of incident cancers in subjects with type II diabetes.

BACKGROUND: Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects. METHODS: From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m(2). The subjects were followed until first occurrence of cancer or until December 31, 2011. RESULTS: During a mean follow-up of 11.3 years, 71 subjects developed incident cancers. The HRs for incident cancers in subjects with highest tertile of serum VAP-1 and in subjects with CKD were 2.95 [95% confidence interval (CI), 1.31-6.63; P = 0.009] and 2.29 (95% CI, 1.18-4.44; P = 0.015), respectively, after multivariate adjustment. There was an interaction between serum VAP-1 and CKD on the risk of incident cancers (P = 0.01 for log-transformed VAP-1 × CKD). The relationship among serum VAP-1, CKD, and incident cancers was similar if death was considered in the competing risk models or if subjects with shorter follow-up period were excluded. CONCLUSIONS: Higher serum VAP-1 and CKD can independently predict future development of cancers in type II diabetic subjects. IMPACT: Physicians should be aware of the early signs of cancer in diabetic individuals with elevated VAP-1 or renal dysfunction. More aggressive treatment strategies might be considered.

Validation of type 2 diabetes risk variants identified by genome-wide association studies in Han Chinese population: a replication study and meta-analysis.

BACKGROUND: Several genome-wide association studies (GWAS) involving European populations have successfully identified risk genetic variants associated with type 2 diabetes mellitus (T2DM). However, the effects conferred by these variants in Han Chinese population have not yet been fully elucidated. METHODS: We analyzed the effects of 24 risk genetic variants with reported associations from European GWAS in 3,040 Han Chinese subjects in Taiwan (including 1,520 T2DM cases and 1,520 controls). The discriminative power of the prediction models with and without genotype scores was compared. We further meta-analyzed the association of these variants with T2DM by pooling all candidate-gene association studies conducted in Han Chinese. RESULTS: Five risk variants in IGF2BP2 (rs4402960, rs1470579), CDKAL1 (rs10946398), SLC30A8 (rs13266634), and HHEX (rs1111875) genes were nominally associated with T2DM in our samples. The odds ratio was 2.22 (95% confidence interval, 1.81-2.73, P<0.0001) for subjects with the highest genetic score quartile (score>34) as compared with subjects with the lowest quartile (score<29). The incoporation of genotype score into the predictive model increased the C-statistics from 0.627 to 0.657 (P<0.0001). These estimates are very close to those observed in European populations. Gene-environment interaction analysis showed a significant interaction between rs13266634 in SLC30A8 gene and age on T2DM risk (P<0.0001). Further meta-analysis pooling 20 studies in Han Chinese confirmed the association of 10 genetic variants in IGF2BP2, CDKAL1, JAZF1, SCL30A8, HHEX, TCF7L2, EXT2, and FTO genes with T2DM. The effect sizes conferred by these risk variants in Han Chinese were similar to those observed in Europeans but the allele frequencies differ substantially between two populations. CONCLUSION: We confirmed the association of 10 variants identified by European GWAS with T2DM in Han Chinese population. The incorporation of genotype scores into the prediction model led to a small but significant improvement in T2DM prediction.