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.

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.

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.

Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries.

BACKGROUND: Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. METHODS AND RESULTS: The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. CONCLUSIONS: Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Plasma YKL-40 predicts 10-year cardiovascular and all-cause mortality in individuals with type 2 diabetes.

OBJECTIVE: Elevated YKL-40 concentrations have been observed in both coronary heart disease (CHD) and diabetes. Thus, YKL-40 may play a role in pathogenesis of CHD in patients with diabetes. We evaluated whether plasma YKL-40 concentration can predict all-cause and cardiovascular mortality in individuals with type 2 diabetes. DESIGN: This is a prospective, observational study. PATIENTS: A total of 628 subjects with type 2 diabetes were recruited between July 1996 and June 2003. MEASUREMENTS: Plasma YKL-40 concentrations were measured via enzyme-linked immunosorbent assay (ELISA). The cohort was followed up until 31 December 2008, when vital status and causes of death were obtained. Survival analysis and concordance statistics were performed. All-cause and cardiovascular mortalities were documented. RESULTS: There were 153 (24·36%) mortalities, including 48 participants (7·64%) who died from cardiovascular diseases (CVDs). Participants with higher plasma YKL-40 (defined with a level above the median of 87·5 µg/l) had an increased risk of mortality. After adjusting for confounding variables, the hazard ratios (HR) for all-cause and cardiovascular mortality in participants with higher plasma YKL-40 were 1·97 (95% CI, 1·31-2·95, P < 0·01) and 2·45 (95% CI, 1·11-5·37, P < 0·05). The results remained similar after adjustment for age. Concordance statistics revealed that plasma YKL-40 concentration significantly increases the predictive power for both all-cause and cardiovascular mortality in different models. CONCLUSIONS: Plasma YKL-40 concentration is an independent predictor of 10-year all-cause and cardiovascular mortality in subjects with type 2 diabetes. Further investigations on the role of YKL-40 in the pathogenesis of CVD are required to elucidate the underlying mechanisms.

Evaluating self-management behaviors of diabetic patients in a telehealthcare program: longitudinal study over 18 months.

BACKGROUND: Self-management is an important skill for patients with diabetes, and it involves frequent monitoring of glucose levels and behavior modification. Techniques to enhance the behavior changes of diabetic patients have been developed, such as diabetes self-management education and telehealthcare. Although the patients are engaged in self-management activities, barriers to behavior changes remain and additional work is necessary to address the impact of electronic media and telehealthcare on patient self-care behaviors. OBJECTIVE: The aims of this study were to (1) explore the behaviors of diabetic patients interacting with online applications, (2) determine the impact of a telehealthcare program among 7 self-care behaviors of the patients, and (3) determine the changes in glycosylated hemoglobin (HbA1c) levels. METHODS: A telehealthcare program was conducted to assist the patients with 7 self-care activities. The telehealthcare program lasted for 18 months and included the use of a third-generation mobile telecommunications glucometer, an online diabetes self-management system, and a teleconsultant service. We analyzed the data of 59 patients who participated in the telehealthcare program and 103 who did not. The behavioral assessments and the HbA1c data were collected and statistically analyzed to determine whether the telehealthcare services had an impact on the patients. We divided the 18-month period into 3 6-month intervals and analyzed the parameters of patients assisted by the telehealthcare service at different time points. We also compared the results of those who were assisted by the telehealthcare service with those who were not. RESULTS: There was a significant difference in monitoring blood glucose between the beginning and the end of the patient participation (P=.046) and between the overall period and the end of patient participation (P<.001). Five behaviors were significantly different between the intervention and control patients: being active (P<.001), healthy eating (P<.001), taking medication (P<.001), healthy coping (P=.02), and problem solving (P<.001). Monitoring of blood glucose was significantly different (P=.02) during the 6-12 month stage of patient participation between the intervention and control patients. A significant difference between the beginning and the 6-12 month stage of patient participation was observed for the mean value of HbA1c level (P=.02), and the differences between the overall HbA1c variability and the variability of each 6-month interval was also significant. CONCLUSIONS: Telehealthcare had a positive effect on diabetic patients. This study had enhanced blood glucose monitoring, and the patients in the program showed improvements in glycemic control. The self-care behaviors affect patient outcomes, and the changes of behavior require time to show the effects.

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.

Incidence and prevalence rates of diabetes mellitus in Taiwan: analysis of the 2000-2009 Nationwide Health Insurance database.

BACKGROUND/PURPOSE: Formerly, Taiwan's diabetic population has been estimated by surveys conducted at irregular intervals and using different sampling methods. To obtain nationwide data on the incidence and prevalence of diabetes mellitus (DM) in Taiwan, we performed an analysis of the 2000-2009 claim data from the National Health Insurance (NHI) database. METHODS: One-third of the claims in the NHI database from 2000 to 2009 were randomly sampled. DM was defined by three or more outpatient visits with diagnostic codes (ICD-9-CM: 250 or A code: A181) within 1 year or by one inpatient discharge diagnosis of DM. Confirmation of type 1 diabetes mellitus was based on the issue of a catastrophic illness certificate with the same diagnostic codes. Age and/or gender distribution for DM were determined. RESULTS: In accordance with the global trend for DM, with a near constant standardized incidence rate, there was a more than 70% increase in the total diabetic population, or a 35% increase in the standardized prevalence rate, in Taiwan from 2000 to 2009. The incidence of diabetes was higher in men, especially in the 20-59-year-old age group, and the total number of men with diabetes exceeded the number of women with diabetes in 2005. However, the prevalence and incidence rates in women over the age of 60 years were higher than those in men. Type 1 DM was present in less than 1% of the diabetic population in Taiwan. CONCLUSION: The incidence of diabetes, including type 1, remained stable over this 10-year period in Taiwan. However, the incidence rate in men aged 20-59 years was higher than that in age-matched women. With our nationwide database, subgroup analysis of DM incidence can be performed to refine our health policies for the prevention, screening, and treatment of diabetes mellitus.

National trends in anti-diabetic treatment in Taiwan, 2000-2009.

BACKGROUND/PURPOSE: The impact of the introduction of newer anti-diabetic agents on the treatment pattern in the booming diabetic population remains unclear. We examined the patterns and temporal trends of anti-diabetic drug use in Taiwan, with particular emphasis on combination therapy. METHODS: We searched the Taiwan National Health Insurance Database during 2000-2009 to identify outpatient prescriptions of anti-diabetic drugs, including human insulins and insulin analogues, sulfonylureas, glinides, metformin, thiazolidinediones, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors. Glucose-lowering treatments were classified according to pattern (oral agents only, insulins only, and oral agents and insulins combined) and a number of different classes of anti-diabetic drugs. Insulin therapy and combination therapy with two oral anti-diabetic drugs (OAD) were further classified according to individual drug combination patterns. RESULTS: Although metformin remained the mainstay of anti-diabetic treatment, patients receiving combination therapy of oral glucose-lowering agents, either with or without insulin, significantly increased, from approximately 40% in 2000 to 60% in 2009, particularly in relation to the newer agents, including glinides, alpha-glucosidase inhibitors, and long-acting insulin analogues. Use of sulfonylureas and thiazolidinediones decreased substantially. For insulin therapy, the most commonly prescribed drugs were premix insulin analogues and basal insulin analogues, accounting for one-third of total insulin prescriptions in 2009. CONCLUSION: We found an increasing complexity of anti-diabetic therapy during the past decade in Taiwan. Further studies are needed to evaluate whether this treatment pattern will lead to improved clinical outcomes in terms of cost-effectiveness.

Accountability, utilization and providers for diabetes management in Taiwan, 2000-2009: an analysis of the National Health Insurance database.

BACKGROUND/PURPOSE: The prevalence of diabetes has increased worldwide. To obtain nationwide data on accountability and utilization of health resources among diabetes patients in Taiwan, an analysis of the claims data for the National Health Insurance (NHI) from 2000 to 2009 was conducted. METHODS: One-third of the NHI claims database was randomly sampled from 2000 to 2009. Diabetes was defined by three or more outpatient visits with diagnostic codes [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM): 250 or A code: A181] within 1 year, or one inpatient discharge diagnosis. Accountability items and NHI codes of various metabolic parameters and examinations were identified. Medical utilization was measured by the frequency and cost of care associated with ambulatory visits, hospitalizations, and emergency care within each year. RESULTS: The annual check-up frequency for various examinations significantly increased from 2000 to 2009. Both the average outpatient department (OPD) cost per diabetes patient/year and the average inpatient department (IPD) cost per time increased 1.34-fold in the past decade. The average OPD cost per diabetes patient and average IPD cost of each admission for diabetes patients was four times and 1.4 times compare with the general population, respectively. The annual average medical cost of each diabetes patient affected with both micro- and macrovascular complications was four times compared with those without vascular complications. There was an increasing trend for diabetes patients to visit regional hospital for OPD and IPD, whereas visits to the local hospital decreased in the past decade. CONCLUSION: Due to the increased frequency of annual check-ups after various examinations, the quality of diabetes management has improved in the past decade in Taiwan. As diabetes patients affected with both micro- and macrovascular complications incurred costs four times compared with those without complications, it is worth screening high-risk individuals to ensure earlier intervention and thus reduce diabetic complications and healthcare expenditure.

Mortality trends in patients with diabetes in Taiwan: a nationwide survey in 2000-2009.

BACKGROUND/PURPOSE: Medical systems and care for diabetes have changed greatly in Taiwan in recent years. This study investigated mortality trends in patients with diabetes in Taiwan from 2000 to 2009. METHODS: We linked the National Health Insurance (NHI) claims database, which contains data on 99% of the population of Taiwan, to the National Death Registry and Cancer Registry. Patients were classified as having diabetes if they had at least one hospital admission or three or more outpatient visits with a diabetes diagnostic code in each calendar year. Mortality data from the Collaboration Center of Health Information Application were used to estimate age- and sex-specific mortality rates, all-cause mortality, and life expectancy (LE). RESULTS: The mortality of patients with diabetes in Taiwan decreased continuously from 2000 to 2009 for both sexes and all age groups; the mortality rate was generally higher for men than for women (3.92% vs. 3.29% in 2000; 3.64% vs. 3.11% in 2005, and 3.12% vs. 2.71% in 2009, all p < 0.05). Diabetic patients had a shorter LE than the entire population, although this difference decreased over time. The estimated loss of life due to diabetes was 6.1 years in women and 5.3 years in men in 2009, when diabetes was diagnosed at the age of 40. The four major causes of death were diabetes, malignancies, heart diseases, and cerebrovascular diseases. CONCLUSION: The mortality of diabetic patients in Taiwan decreased from 2000 to 2009. Although patients with diabetes had a shorter LE than the entire population, the difference decreased over time.

Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Diabetes is one of the leading causes of dialysis, blindness, and amputation worldwide. However, the prevalence of diabetes-related kidney, eye, and foot diseases has not been investigated in national surveys. METHODS: In this study, we reviewed data sets of the National Health Insurance claims for the years 2000-2009. In 2009, the total population of Taiwan was 23 million. We de-identified the data and then analyzed them on inpatients and outpatients with diabetes mellitus, kidney diseases, eye diseases, peripheral vascular diseases (PVDs), and diabetic foot according to the International Classification of Diseases, 9(th) Revision with Clinical Modification diagnosis codes. RESULTS: The prevalence of diabetic nephropathy increased from 13.32% in 2000 to 15.42% in 2009. The corresponding diabetes dialysis rate increased from 1.5% to 2.46% during the same period (p < 0.001). The prevalence rates of retinopathy and PVD also increased (from 6.17% to 8.91%; p = 0.002 and from 1.87 to 2.47; p < 0.001, respectively). More than 94% of the patients treated for diabetic foot in the hospital had an associated foot infection. The prevalence of in-hospital diabetic foot decreased from 1.68% to 1.02% during the years 2000-2009 (p < 0.001), while the rates of lower extremity amputation as the treatment outcome did not show improvement (mean amputation rate: 28.35%). CONCLUSION: During the years 2000-2009, patients with diabetes in Taiwan had an increased risk for kidney, eye, and PVDs. Multidisciplinary teams need to be set up for the treatment of complications related to diabetic foot, and preventions programs that are specifically designed to target these complications should now be made mandatory.

Prevalence of hypertension and dyslipidemia and their associations with micro- and macrovascular diseases in patients with diabetes in Taiwan: an analysis of nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Cardiovascular complication is the leading cause of mortality in patients with diabetes. Dyslipidemia and hypertension are the major risk factors contributing to cardiovascular disease (CVD). This study was carried out to investigate the prevalence of dyslipidemia and hypertension and their associations with microvascular and macrovascular complications in patients with type 2 diabetes in Taiwan. METHODS: Health-care data and diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files for the years 2000-2009. Based on these data the annual prevalences of dyslipidemia and hypertension were calculated and patients were stratified by age, gender, and diabetic complications. RESULTS: In patients with diabetes, the prevalence of dyslipidemia increased with age, with the highest rate recorded in adults (inclusive of both genders) between 40 and 65 years of age (p for trend <0.001). The prevalence of hypertension also increased with age with the highest rate seen in adults (inclusive of both genders) >65 years of age (p for trend <0.001). The prevalence of stroke and CVD decreased gradually (p for trend 0.025 and <0.001, respectively), while the prevalence of peripheral vascular disease (PVD) increased in patients with diabetes during the study period (p for trend <0.001). The prevalence of dyslipidemia increased in diabetic patients with eye diseases and in men with nephropathies, but decreased in women with nephropathies during the study period. In contrast, the prevalence of dyslipidemia decreased in patients with macrovascular complications, including CVD and cerebrovascular disease (cerebrovascular accident), but increased in those patients with PVD (p for all trends <0.05). In diabetic patients with various macrovascular complications, except PVD, there was a decrease in the prevalence of hypertension in the past 10 years. The prevalence of hypertension increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy. The prevalence of hypertension along with dyslipidemia increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy; however, the rate decreased in all macrovascular complications except in PVD. CONCLUSION: Although progressively increased prevalence of dyslipidemia and hypertension was observed in patients with diabetes in Taiwan, there was a decrease in the prevalence of stroke and CVD in the past 10 years. Among those with macrovascular diseases, except PVD, there was a trend of decreased prevalence of hypertension and dyslipidemia during the study period. In patients with microvascular diseases, prevalence of hypertension and dyslipidemia in patients with eye diseases increased in the past 10 years. More aggressive management of different risk factors is warranted in diabetic patients with various vascular diseases.

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.

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.

Genetic predisposition and nongenetic risk factors of thiazolidinedione-related edema in patients with type 2 diabetes.

OBJECTIVE: This study aimed to analyze the association of thiazolidinedione (TZD)-related edema with genetic and clinical variables and develop a simple points system to predict the risk of developing TZD-related edema. METHODS: Fifty-eight (21.6%) of 268 individuals who received TZD for type 2 diabetes developed peripheral edema. Twenty-eight tag single nucleotide polymorphisms (SNPs) from candidate genes involved in sodium and water reabsorption were genotyped. Cox regression and logistic regression models were used to analyze the associations of different genotypes and weighted genotypic scores with TZD-related edema risk. RESULTS: Individuals with edema were older, predominantly female, and had greater weight gain. The AQP2 rs296766 T allele was associated with TZD-related edema [allelic P=0.0059; odds ratio (OR), 2.89; 95% confidence interval (CI), 1.61-5.17]. The SLC12A rs12904216 G allele had borderline significance (allelic P=0.049), which disappeared after correction for multiple testing. Patients with two SNP-based (AQP2 rs296766 and SLC12A1 rs12904216), who weighted genotypic scores within the top quartile, had a higher risk of developing TZD-related edema (OR, 16.45; 95% CI, 3.05-88.76). Combining the weighted genetic scores of two SNPs or all SNPs with age and sex information significantly improved the predictive power for TZD-related edema. We also developed a simple risk factor-based points system to predict an individual's risk of developing TZD-related edema. CONCLUSION: A clinically applicable prediction model including age, sex, and genetic information from AQP2 rs296766 and/or SLC12A rs12904216 SNPs can be developed to estimate the risk of TZD-related edema in type 2 diabetes patients.

SLC2A10 genetic polymorphism predicts development of peripheral arterial disease in patients with type 2 diabetes. SLC2A10 and PAD in type 2 diabetes.

BACKGROUND: Recent data indicate that loss-of-function mutation in the gene encoding the facilitative glucose transporter GLUT10 (SLC2A10) causes arterial tortuosity syndrome via upregulation of the TGF-ß pathway in the arterial wall, a mechanism possibly causing vascular changes in diabetes. METHODS: We genotyped 10 single nucleotide polymorphisms and one microsatellite spanning 34 kb across the SLC2A10 gene in a prospective cohort of 372 diabetic patients. Their association with the development of peripheral arterial disease (PAD) in type 2 diabetic patients was analyzed. RESULTS: At baseline, several common SNPs of SLC2A10 gene were associated with PAD in type 2 diabetic patients. A common haplotype was associated with higher risk of PAD in type 2 diabetic patients (haplotype frequency: 6.3%, P = 0.03; odds ratio [OR]: 14.5; 95% confidence interval [CI]: 1.3- 160.7) at baseline. Over an average follow-up period of 5.7 years, carriers with the risk-conferring haplotype were more likely to develop PAD (P = 0.007; hazard ratio: 6.78; 95% CI: 1.66- 27.6) than were non-carriers. These associations remained significant after adjustment for other risk factors of PAD. CONCLUSION: Our data demonstrate that genetic polymorphism of the SLC2A10 gene is an independent risk factor for PAD in type 2 diabetes.

Hypothyroidism and the risk of developing open-angle glaucoma: a five-year population-based follow-up study.

OBJECTIVE: To investigate the risk of open-angle glaucoma (OAG) after a diagnosis of hypothyroidism. DESIGN: A retrospective, population-based follow-up study using an administrative database. PARTICIPANTS: The study group comprised 257 hypothyroidism patients. The comparison group included 2056 subjects. METHODS: Data were retrospectively collected from the Taiwan Longitudinal Health Insurance Database. The study cohort comprised patients aged ≥ 60 who received a first diagnosis of hypothyroidism (International Classification of Diseases, Ninth Revision, Clinical Modification code 244.9) from 1997 to 2001 (n = 257). The comparison cohort consisted of randomly selected patients without hypothyroidism who were aged ≥ 60 and had no diagnosis of glaucoma before 2001 (8 for every OAG patient; n = 2056). Each sampled patient was tracked for 5 years from their index visit. Cox proportional hazard regressions were used to compute the 5-year OAG-free survival rate, after adjusting for possible confounding factors. MAIN OUTCOME MEASURES: The risk of developing OAG during the 5-year follow-up period. RESULTS: Open-angle glaucoma developed in 7.4% of patients with hypothyroidism and 3.8% of patients in the comparison cohort during the follow-up period. Hypothyroid patients had a significantly lower 5-year OAG-free survival rate than patients in the comparison cohort. After adjusting for patients' age, gender, monthly income, urbanization level, and comorbid medical disorders, hypothyroidism patients were found to have a 1.78-fold (95% confidence interval [CI], 1.04-3.06) greater risk of developing OAG than the comparison cohort. This association remained significant in untreated hypothyroidism patients (adjusted hazard ratio [HR], 2.37; 95% CI, 1.10-5.09) and became statistically nonsignificant in patients treated with levothyroxine (adjusted HR, 1.73; 95% CI, 0.89-3.38). CONCLUSIONS: Hypothyroid patients had a significantly increased risk of OAG development during the 5-year follow-up period. Levothyroxine seemed to be protective.

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.

Interaction of ADIPOQ genetic polymorphism with blood pressure and plasma cholesterol level on the risk of coronary artery disease.

BACKGROUND: The protective effect of +45T >G polymorphism in the adiponectin gene (ADIPOQ) on coronary artery disease (CAD) has been demonstrated in European populations, so this study investigated the effect of +45T >G polymorphism on the risk of CAD and its interactions with other metabolic risk factors in a Chinese population. METHODS AND RESULTS: The +45T >G polymorphism (rs2241766) of ADIPOQ was genotyped in 600 patients with angiographically diagnosed CAD and in 718 controls. The G allele at the +45T >G polymorphism was associated with a lower risk of CAD (odds ratio (OR), 0.76; 95% confidence interval (CI), 0.64-0.89; P=0.001). The protective effect of the G allele at +45T >G polymorphism was magnified at blood pressure <140/90 mmHg (OR, 0.65; 95%CI, 0.51-0.82; P=0.0004), but disappeared at blood pressure >or=140/90 mmHg (OR, 0.98; 95%CI, 0.76-1.28; P=0.93), indicating an interaction between +45T >G polymorphism and blood pressure on CAD risk (P=0.02 for interaction). A similar interaction was also observed between plasma cholesterol level and the +45T >G polymorphism. CONCLUSIONS: An association of ADIPOQ genetic polymorphism with CAD risk is modified by traditional risk factors, such as blood pressure and plasma cholesterol level.