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Background To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population. Material and methods This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history. Results DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis. Conclusions The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD.

Context There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic β-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of β-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment. Objective This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone. Methods Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. Results A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (−0.36, P = 0.0373) and 450 mg/day (−0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-β score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial. Conclusion Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

Objective: Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc.Method: We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD.Results: After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39-3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97-8.71) and the younger population (HR = 7.09, 95% CI 2.31-21.80).Conclusion: There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.

IntroductionWe investigated health service utilization, including hospitalizations and emergency department visits, for women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan.MethodsData from the Health and Welfare Data Science Center were used to conduct this nationwide population-based study. We identified pregnant women and the date of childbirth according to Birth Certificate Applications from 2007 to 2018. The study population was divided into four groups: known DM, newly diagnosed DM, GDM, and no DM/GDM. To assess quality of healthcare during the gestation period, trends in 30-day readmission rate, number of emergency department visits/hospitalizations per 100 childbirths, and length of hospital stay from 2008 to 2017 were examined.ResultsA total of 1830511 childbirths and 990569 hospitalizations were identified for analyses. Between 2008 and 2017, women with hyperglycemia in pregnancy (known DM, newly diagnosed DM, and GDM) had a higher rate of hospitalization, a longer length of hospital stay, and higher rates of various maternal and fetal outcomes, compared with women with no DM/GDM. Nevertheless, the differences between women with GDM and those with no DM/GDM in the aforementioned outcome measures were modest. Women with GDM had a modest decrease in the 30-day readmission rate (p for trend 0.046) with no significant difference in the number of emergency department visits during the study period.DiscussionOur findings provide evidence of the quality of healthcare for women with GDM between 2008 and 2017 in Taiwan.

Aims/Introduction Diabetic nephropathy (DN) is a complication of diabetes mellitus that is characterized by the gradual loss of kidney function, which results in increased levels of albumin in the urine. The Pro12Ala polymorphism in the peroxisome proliferator‐activated receptor‐γ2 gene has been confirmed to improve insulin sensitivity, but its association with susceptibility to DN in patients with type 2 diabetes remains inconclusive. Materials and Methods To examine whether the Pro12Ala polymorphism leads to the development of DN, a case‐control study was carried out in 554 patients with type 2 diabetes. The genotypes of Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor gamma 2 gene were analyzed by real‐time polymerase chain reaction with TaqMan® probe genotyping assay in all patients. Results The mean age of the study population was 57.7 ± 8.8 years, with average diabetes duration of 12.8 ± 6.9 years. The prevalence of albuminuria was 43.5%. The frequency of genotype Pro12Pro, Pro12Ala and Ala12Ala genotype were 92.6%, 7.0%, 0.4% in our study population, and 90.4%, 8.9% and 0.7% in normal urinary albumin‐to‐creatinine ratio group, respectively. The Ala carriers (Pro12Ala + Ala12Ala) had significantly lower urinary albumin‐to‐creatinine ratio (15.0 vs 20.5 mg/g, P = 0.001) and better renal function (estimated glomerular filtration rate 81.8 [69.8–97.6] vs 78.7 mL/min/1.73 m2 [61.6–96.2]; P = 0.05) compared with those with the genotype Pro12Pro. After adjustment for age, sex and other confounders, the odds ratio of albuminuria for the Ala12 allele was 0.428 (95% confidence interval 0.195–0.940, P = 0.034]). Conclusions Our results suggest that the peroxisome proliferator‐activated receptor gamma 2 Ala12 variant has significant protective effects against albuminuria and DN., The peroxisome proliferator‐activated receptor‐γ2 Ala12 variant has significant protective effects against albuminuria and diabetic nephropathy. These findings suggest that genetic screening can help in the development of personalized therapies for diabetes.

Background: Assessment of renal size is clinically significant for the screening, diagnosis, and follow-up of renal diseases as the basis of clinical decisions. However, the relationship of renal dimension with age, body indices, and the estimated glomerular filtration rate (eGFR) has rarely been reported in the Chinese type 1 diabetes mellitus (T1DM) population. Methods: A total of 220 T1DM patients were retrospectively analyzed from the Chang Gung Research Database in Taiwan. Demographic data, laboratory data, and ultrasonographic images from January 2001 to November 2018 were extracted. Results: Eighty-five participants (38.6%) were male. The mean age was 34.2 years. The median eGFR was 60.0 mL/min/1.73 m2. The mean ultrasonographic left and right renal lengths (LL and RL) with S.D. were 10.9 ± 1.5 cm and 11.0 ± 1.1 cm, respectively. Renal lengths were longer with increasing body height and body weight but shorter with increasing age in patients with T1DM. In trajectory analysis, a linear mixed model revealed no significant trend in the changes in eGFR during the follow-up period. Moreover, renal length did not play a significant role in predicting KDIGO CKD stage 5 in the cohort. Conclusions: Renal length and its comparison to the reference ranges demonstrated very limited advantages in predicting renal function decline in T1DM patients.

Background: Osteoporosis is a cardinal manifestation of Cushing’s syndrome. There is a lack of relevant research on risk factors for osteoporosis among patients with Cushing’s syndrome (CS) in Taiwan. Thus, this study was designed to explore the possible risk factors of osteoporosis. Methods: We gathered patients with a diagnosis of CS between 2001 and 2017 in the Chang Gung Research Database (CGRD). We extracted data including diagnoses and biochemistry from hospital records. The diagnosis of CS was based on ICD-9-CM codes (255.0). Osteoporosis was defined by a T value equal to or less than −2.5 in BMD examination and hypocalcemia was defined as serum calcium concentrations < 8.0 mg/dL. Results: A total of 356 patients with CS who made regular visits to the outpatient department were enrolled in this study. The mean age was 68.6 years, and 74.9% of the patients were female. Of them, 207 patients (58.1%) were diagnosed with osteoporosis. Multivariable logistic regression models indicated that serum calcium level was negatively associated with osteoporosis (OR 0.70, CI 0.54–0.91, p < 0.001) after adjustment for age, sex, and other confounding risk factors. In addition, hypocalcemia was associated with heart failure (HF) (OR 2.14, CI 1.02–4.47, p < 0.05), stroke (OR 2.58, CI 1.21–5.46, p < 0.05) and osteoporosis (OR 3.04, CI 1.24–7.41, p < 0.05) in multivariate analysis. Conclusions: Our study found that lower serum calcium levels were common among patients with CS and osteoporosis. Furthermore, CS patients with HF or stroke had high proportion of hypocalcemia. Therefore, these patients must pay more attention to adequate calcium supplementation and undergo the appropriate osteoporosis drug treatment to reduce the risk of subsequent fracture and disability.

Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN.A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS.Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS.Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN.Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect.

INTRODUCTION The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P

Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life

Objective The aim of this study was to assess the status of bone mass, microarchitecture, and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes mellitus (T2DM). Methods We consecutively enrolled 285 women (aged 60.7 ± 6.9 y) with T2DM who underwent bone mineral density (BMD) and trabecular bone score (TBS) assessment using dual-energy x-ray absorptiometry; T8-S1 lateral spine radiographs; laboratory evaluation; and interviews regarding clinical risk factors based on the fracture risk assessment tool (FRAX). Results Low bone mass and deteriorated bone microarchitecture were observed in 63.2% and 72.6% of women with T2DM, respectively. TBS was correlated with lumbar spine, femoral neck, and total hip BMD. Significant differences in TBS were observed between the normal BMD, osteopenia, and osteoporosis groups. Age, vertebral fracture, and bone-specific alkaline phosphatase significantly differed among groups with different T scores or those classified by TBS categories. Bone-specific alkaline phosphatase was inversely correlated with BMD and TBS but positively with glycated hemoglobin. BMD showed a weaker correlation with vertebral fracture than TBS, TBS and BMD, FRAX, and TBS-adjusted FRAX. Conclusions Low bone mass and deteriorated TBS were noted in approximately two-thirds of T2DM women and was also associated with vertebral fracture. In addition to aging, poor glycemic control may play an important role in bone remodeling, which may be associated with changes in bone strength in T2DM women. Bone strength together with clinical risk factors has the strongest association with fracture, and may potentially be useful to identify women with T2DM at risk.

Aims/Introduction Identifying diabetes‐susceptible genetic variants will help to provide personalized therapy for the management of type 2 diabetes. Previous studies have reported a genetic risk score (GRS), computed by the sum of nuclear DNA (nDNA) risk alleles, that may predict the future requirement for insulin therapy. Although mitochondrial dysfunction has a close association with insulin resistance (IR), there are few studies investigating whether genetic variants of mitochondrial DNA (mtDNA) will affect the clinical characteristics of type 2 diabetes. Materials and Methods Mitochondrial haplogroups were determined using mtDNA whole genome next generation sequencing and 13 single nucleotide polymorphisms (SNPs) in nDNA susceptibility loci of 13 genes in 604 Taiwanese subjects with type 2 diabetes. A GRS of nDNA was computed by summation of the number of risk alleles. The correlation between the mtDNA haplogroup and the clinical characteristics of type 2 diabetes was assessed by logistic regression analysis. The results were compared with the GRS subgroups for the risk of insulin requirement. Results Mitochondrial haplogroups modulate the clinical characteristics of type 2 diabetes, in which patients harboring haplogroup D4, compared with those harboring non‐D4 haplotypes, were less prone to require insulin treatment, after adjusting for age, gender, and diabetes duration. However, there was no association between insulin requirement and GRS calculated from nuclear genetic variants. Conclusions Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement. The results highlight the role of mitochondria in the management of common metabolic diseases., Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement in patients with T2DM.

Introduction: Treatment complexity can impact treatment adherence, which may affect clinical outcomes in people with T2D. This analysis assessed PROs in the SoliMix trial. Methods: SoliMix, an open-label, multicenter study, randomized adults with T2D and HbA1c ≥7.5-≤10 % on BI + OADs to once-daily iGlarLixi or twice-daily premix insulin analog (BiAsp 70/30). Between-treatment differences from baseline to Week 26 (W26) in Treatment-Related Impact Measure for Diabetes (TRIM-D) scores are shown overall and by domain. Global Treatment Effectiveness Evaluation (GTEE) endpoints were analyzed descriptively at W26. Results: As well as providing better glycemic control, iGlarLixi demonstrated greater improvement in each TRIM-D domain vs. BiAsp 70/30 from baseline to W26 (Figure), with the greatest differences seen in diabetes management and treatment burden scores. GTEE scores also showed a greater proportion of participants and physicians who rated complete or marked improvement of diabetes control with iGlarLixi (81% and 83%) vs. BiAsp 70/30 (63% and 65%) at W26. Conclusions: Advancing BI with iGlarLixi resulted in a greater positive impact than with premix 70/30 for people with T2D uncontrolled on BI + OADs, suggesting a potentially lower treatment burden with iGlarLixi. Disclosure W. H. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Inc., Consultant; Self; Abbott Diabetes, ADOCIA, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Novo Nordisk, Onduo LLC., Sanofi US. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. K. H. Whitmire: None. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. J. Chen: None. C. Nicholls: Employee; Self; Sanofi. E. Lew: Employee; Self; Sanofi. A. Alvarez: Employee; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. Funding Sanofi (EudraCT 2017-003370-13)

Past studies have confirmed that glucagon-like peptide 1 (GLP-1) receptor agonists can improve renal outcomes in patients with type 2 diabetes mellitus (DM). This study aimed to evaluate whether dipeptidyl peptidase 4 (DPP-4) inhibitors, which elevate GLP-1 levels, also have similar effects on renal function. In this retrospective study, diabetic patients treated with anti-hyperglycemic agents between 2008 and 2011 were selected. We compared the time to first occurrence of estimated glomerular filtration rate (eGFR) decline ≥30% from the baseline between patients treated with DPP-4 inhibitors and those treated with other anti-hyperglycemic drugs. A total of 2202 patients were enrolled. The incidence of eGFR decline ≥30% from the baseline was 10.08% in the DPP-4 inhibitor group and 16.17% in the non-DPP-4 inhibitor group (p < 0.001). The mean time to event was significantly longer in patients receiving DPP-4 inhibitors (2.84 ± 1.60 vs. 1.96 ± 1.30 years, p < 0.001). Patients who were younger than 65 years old, had better baseline eGFR, did not have preexisting hyperlipidemia, or who were untreated with concomitant statin showed greater reductions in the risk of renal function decline (all p for interaction < 0.05). Conclusively, DPP-4 inhibitors used alone or in combination with other glucose-lowering agents were correlated with lower risks of eGFR decline in patients with type 2 DM.

Objectives Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. Conclusion The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis., Highlights • Bisphosphonates reduced the risk of vertebral fracture in postmenopausal women with osteopenia or osteoporosis but without fracture. • Bisphosphonates increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Limited studies for non-bisphosphonate drugs showed increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Raloxifene decreased the risk of clinical vertebral fractures in postmenopausal women with osteopenia or osteoporosis but without fracture.

Background: Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already suffered from CAN in outpatient clinics.Methods: Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score.Results: The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had a higher CAN score value (PConclusions: Based on our results, a combination of electrophysiologic biomarkers (SDNN and feet ESC) as a test battery can improve the diagnostic accuracy and reinforce the accuracy in estimating CAN severity and can serve as a time-effective screening service in outpatient clinics.

Backgrounds Albuminuria, the earliest clinical manifestation of diabetic kidney disease (DKD), is a major prognostic indicator of renal progression. Obesity itself is associated with the development of DKD and accelerates its progression. Accumulation of peri-renal fat on the kidneys can damage kidney function. Measuring the perirenal fat thickness (PFT) by ultrasound is a non-invasive method to measure ectopic fat deposition on the kidney. In this study, we aim to obtain the association between albuminuria and PFT. Methods Eighty-nine subjects with type 2 diabetes mellitus (T2DM) were enrolled. Albuminuria was defined as a urine albumin-to-creatinine ratio (UACR) ≧30 mg/g. Measurement of the PFT was performed by B-mode ultrasound (Toshiba SSA-680A) and determined from the surface of the abdominal musculature to the surface of kidney. Pearson correlation coefficients were determined to test the significant independent relationship between the PFT and demographic, anthropometric and laboratory parameters. Results Patients were divided into those with (n = 66) and without (n = 23) albuminuria. PFT (odds ratio [OR], 19.3; 95% CI, 2.25–165.00; p = 0.01) was significantly correlated with albuminuria based on multiple logistic regression analysis. Additionally, linear regression confirmed that degree of albuminuria has a positive association with the PFT (r = 0.233; p = 0.03). Conclusions Our study showed that an increased PFT is positively associated with the albuminuria among patients with T2DM. Our findings suggest that measurement of the PFT may represent a helpful tool to assess the risk of developing albuminuria in patients with T2DM.

Background It is thought that adipocytokines contribute to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). We aimed to identify adipocytokines that are associated with the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. Methods The complete cardiovascular autonomic function and biomarkers were assessed for each patient. The severity of CAN was assessed using both the composite autonomic scoring scale (CASS) and the cardiac autonomic reflex tests (CARTs) score. Biomarkers included adipocytokines (leptin, chemerin, adiponectin, and vaspin), oxidative stress (thiols and thiobarbituric acid-reactive substance [TBARS]), endothelial dysfunction (sICAM-1 and sVCAM-1), and insulin resistance (triglyceride/high-density lipoprotein cholesterol [HDL-C] ratio and homeostasis model assessment of insulin resistance [HOMA-IR] index). Results A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. Stepwise logistic regression showed that diabetes duration and leptin level were independently associated with the presence of CAN. Leptin level was positively correlated with body mass index (r = 0.588, P

Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long‐acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra‐long‐acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real‐world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.

Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.

Type 2 diabetes mellitus (T2DM) is significantly associated with osteoarthritis (OA). This study investigated the effects of two resistance exercise approaches on glycated hemoglobin (HbA1c) level and function performance. Enrolled were 70 older patients with both T2DM and knee OA. The dynamic group performed resistance exercises with an elastic resistance band. The isometric group underwent isometric contraction exercises. After the 12-week intervention, a significant within-group improvement (all p &lt, 0.001) was observed for the chair stand test (CST, 10.8%, vs. 7.1%), timed up and go (TUG) test (12.6% vs. 7.6%), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function subscale (62.3% vs. 36.1%), and overall WOMAC (54.5% vs. 34.5%) in the dynamic and isometric group, respectively. In addition, in terms of between-group differences, the dynamic group had significant improvements in CST (p = 0.011), TUG (p &lt, 0.001), WOMAC physical function subscale (p = 0.033), and overall WOMAC (p = 0.036) scores compared with the isometric group. However, no significant change in HbA1c was observed in either group. In conclusion, the dynamic resistance exercise significantly improved muscle strength, dynamic balance, and physical function in this comorbid population, however, there was no notable difference in change in HbA1c among different resistance exercises.

Cardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke).In this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE.The overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio.Besides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting.

BackgroundAlthough greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes.AimTo address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD).DesignThis prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center.MethodWe designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study.ResultsThe patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2.ConclusionWe observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient’s eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.

Fracture Risk Assessment Tool (FRAX)–based intervention threshold (IT) is widely applied for treatment decision-making; however, an IT based on FRAX without the measurement of bone mass density (BMD) has not been validated. The study demonstrated that estimates of fracture risk by FRAX without BMD were higher than those by FRAX with BMD in women with old age. BMD is an integral component for bone strength assessment, but age-specific impacts of BMD on fracture risk assessment and therapeutic decision-making remained unclear. We aimed to investigate whether using BMD measurement changed the interpretation of the FRAX-based fracture probability assessment and treatment decision. The database was provided by the Taiwanese Osteoporosis Association (TOA) which conducted a nationwide survey of BMD. We calculated the 10-year major and hip fracture probabilities using the FRAX for each participant, either with (FRAX + BMD) or without BMD (FRAX − BMD). Age-specific individual intervention thresholds (IITs) were established using the FRAX-based fracture risk, equivalent to a woman with a prior fracture. Participants whose FRAX scores of major fracture were greater than or equal to their IITs were deemed suitable for therapeutic intervention. A total of 14,007 postmenopausal women were enrolled. Compared with FRAX + BMD, FRAX − BMD predicted lower FRAX scores in major and hip fractures in subjects aged 40–60 years; however, FRAX − BMD estimated higher risks for those aged 61–90 years. The therapeutic decision using FRAX − BMD was concordant to that using FRAX + BMD in 90.5% of the subjects, especially in the younger age group (40–70 years). FRAX − BMD identified more treatment candidates (7.7–16.4%) among those aged 71–90 years. The FRAX scores are influenced by age, irrespective of the consideration of BMD. FRAX − BMD is able to identify more subjects for therapeutic intervention in the elderly population. We should reconsider the role of BMD at different ages for therapeutic decision-making.

The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. A total of 16,539 postmenopausal women and men (age ≥ 50 years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ − 2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p

Background/Purpose: Diabetic macrovascular complications contribute to nonignorable causes of morbidity and mortality in patients with diabetes mellitus (DM). In this study, the trends of risk factors and macrovascular complications were examined in patients with DM in Taiwan. Methods: Health care information and International Classification of Diseases, Ninth Revision diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files between 2005 and 2014. Using these data, the number of cases and annual prevalence of diabetic macrovascular complications in individuals with DM were stratified by age and sex. Results: The prevalence of DM with either stroke or cardiovascular disease (CVD) showed a decreasing trend in enrolled patients with DM (p for trend

Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud

Digital, Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6–8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1–5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80–1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p, Ciencias Médicas y de la Salud

Background and purpose Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking. Methods The index mtDNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non-PD controls. Full-length mtDNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria-depleted rho-zero cells and donor mitochondria, were used for a rotenone-induced PD simulation study. Results Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002). Furthermore, a composite mtDNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33–0.78; P = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone. Conclusions Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mtDNA in the risk of PD.

Objective Both diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN. Method All patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively. Results Patients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR_DB. Conclusion Sural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes. Significance The independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity.

In this article the name of the sixth author, E. Michael Lewiecki was rendered incorrectly. The publisher regrets this error and apologizes for the inconvenience caused.

Background Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic inflammation, involving not only the juxta-articular bone erosion, but generalised bone loss[.1 Sex hormone activates RA disease activity and induced bone resorption, but hormone replacement therapy increases bone mass and density. The ambiguous role of sex hormone on bone remodelling is confusing in RA patients. Under the impact of sex hormone, risk factors for osteoporosis might be different at pre- and post-menopausal stage. Objectives To investigate the different clinical risk factors of osteoporosis in pre- and post-menopausal women with RA. Methods A cross-sectional study was performed during 2014 to 2017, enrolling female participants fulfilled 2010 RA criteria[.2 We recorded demographic data, risk factors for osteoporosis and blood test. Osteoporosis is defined if one of hip, distal forearm, and lumbar spine bone mineral density less than −2.5 by T-score for post-menopausal women, or less than −2.0 by Z-sore for pre-menopausal women. Data was analysed by Student’s t test and Chi-square test for continuous and categorical valuables, respectively. Multivariate logistic regression was applied to detect association of osteoporosis and selected variables. Results A total of 451 participants were enrolled in the study, including 89 pre- and 362 post-menopausal women. The prevalence of osteoporosis is 14.6% and 36.7% for pre- and post-menopausal women with RA, respectively. At pre-menopause, low body weight is the only significant risk factors for osteoporosis, while old age, low body height, low body weight, positive anti-cyclic citrullinated peptide antibody (anti-CCP), previous fracture history, elevated white blood cell and platelet count, and lower calcium level are potential risk factors for post-menopausal women developing osteoporosis (table 1). Multivariate stepwise logistic regression analysis (table 2) showed body weight remains the leading risk factors in pre-menopausal women (Odds ratio[OR]=0.84, 95% confidence interval [CI]=0.76~0.94, P-value=0.002), while body weight and previous fracture history are significant risk factors in post-menopausal women(body weight OR=0.91, 95% CI=0.88~0.94, P-value Conclusions Risk factors of osteoporosis are different in pre- and post-menopausal women with RA. For pre-menopausal women, Low body weight is a leading risk factor, while low body weight and previous fracture history are important for post-menopausal women. Without protection of sex hormone, there are Potential roles of anti-CCP and white blood cell participating in osteoporosis pathogenesis and need more survey for confirmation. References [1] Lems WF, Dijkmans BA: Should we look for osteoporosis in patients with rheumatoid arthritis?Ann Rheum Dis1998, 57(6):325–327. [2] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis2010,69(9):1580–1588. Acknowledgements Special thanks to Dr. Tien-Tsai, Cheng for his effort to establish the RA-GIOP database. Disclosure of Interest None declared

Factors predicting success (glycosylated hemoglobin (A1C)7%) with insulin therapy in patients with insulin-requiring type 2 diabetes need to be identified.A retrospective, multi-center, observational study was conducted for outpatients with oral antidiabetic drug (OAD)-treated type 2 diabetes whose A1C levels remained above 7%. Patients were begun on basal insulin between January 2005 and December 2006. Biochemical variables and demographic data were collected before and after 52 weeks of insulin therapy.A total of 565 patients (age, 60.4±11.9 years; A1C levels, 10.11 ±1.81%; duration of diabetes, 11.5±6.8 years) were studied. By study end, 63 patients (11.2%) had achieved the glycemic goal (A1C7%). The glycemic goal attainment rate was only 9.1% in patients with A1C8.8% and who were taking2 OADs at baseline. The highest rate (32.7%) of successful glycemic control was observed in the group of patients with A1C ≤ 8.8% and who used ≤ 2 OADs at baseline.Insulin-naïve diabetic patients with A1C8.8%, especially those who are taking2 OADs, have small chance to achieve good glycemic control with adding only basal insulin therapy.

The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of death in type 2 diabetes are due to ASCVD, including 40% from coronary heart disease (CHD), 15% from heart failure (HF), and 10% from stroke. The association between hyperglycemia and elevated CV risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction did not significantly reduce macrovascular outcomes. It remains unclear whether the absence of demonstrable benefits is attributed to the inclusion of patients with far advanced ASCVD in whom a short treatment period is barely enough for CV protective effects to be shown, or complications associated with the treatment such as hypoglycemia hamper the beneficial effects to manifest, or simply glucose-lowering per se is ineffective. Since the US FDA issued a mandate in December 2008 that every new anti-diabetic agent requires rigorous assessments of its CV safety, there have been more than 200,000 patients enrolled in a number of randomized controlled trials (RCTs), and around half of them have been completed and published. The results of these CV outcome trials are important for clinicians in their clinical practice, and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases. The Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC), aiming to formulate a treatment consensus in type 2 diabetic patients with CVD, have appointed a jointed consensus group for the 2018 Consensus of TSOC/DAROC (Taiwan) on the Pharmacological Management of Patients with Type 2 Diabetes and CV Diseases. The consensus is comprised of 5 major parts: 1) Treatment of diabetes in patients with hypertension, 2) Treatment of diabetes in patients with CHD, 3) Treatment of diabetes in patients with stage 3 chronic kidney disease, 4) Treatment of diabetes in patients with a history of stroke, and 5) Treatment of diabetes in patients with HF. The members of the consensus group comprehensively reviewed all the evidence, mainly RCTs, and also included meta-analyses, cohort studies, and studies using claim data. The treatment targets of HbA1c were provided. The anti-diabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.

The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.

Controlled attenuation parameter (CAP) is a method for measuring steatosis based on FibroScan. Despite observer dependency, ultrasound (US) robustly diagnoses moderate and severe steatosis. Here, we aimed to evaluate the correlation of CAP with US-identified steatosis in real-world clinical practice. Methods: CAP and US were performed for 1554 chronic liver disease (CLD) patients. CAP was performed by two technicians, and US was performed by 30 hepatologists. The performance of the CAP as compared with the US results was assessed using the area under the receiver operating characteristic curve (AUROC). Results: 532 (34.2%) of the patients had hepatitis C virus (HCV) infection, 723 (46.5%) of the patients had hepatitis B virus (HBV) infection, and the rest were patients with metabolic risk factors. CAP values were significantly correlated with the steatosis grades identified by US for all the patients (ρ = 0.497, P

This systematic review aimed to examine the evidence for teriparatide in Asia for osteoporosis with a high fracture risk and for exploratory (unapproved) bone-related indications. MEDLINE (1946+), EMBASE (1966+), and ClinicalTrials.gov (2008+) were searched (16 August 2013); all studies of daily subcutaneous teriparatide 20 μg for bone-related conditions from China, Hong Kong, Japan, Republic of Korea, Philippines, Singapore, and Taiwan were included. Evidence on efficacy/safety was retrieved primarily from randomized controlled trials (10 publications) of postmenopausal women from Japan and China. In these studies, teriparatide was well tolerated; subjects had significantly greater increases in lumbar spine bone mineral density (BMD) from baseline compared with placebo, antiresorptive agents, or elcatonin/calcitonin; bone turnover markers increased from baseline and were sustained at elevated levels during teriparatide treatment. Few studies reported fracture risk, pain, or quality of life; one study showed a lower incidence of new-onset vertebral fracture with teriparatide versus antiresorptive agents. Nonrandomized studies (nine publications, one unpublished trial) conducted mainly in Taiwan, Japan, and the Republic of Korea provided supporting data for efficacy. The exploratory (unapproved) use of teriparatide (17 publications) for fracture healing and osteonecrosis of the jaw was described primarily in case reports. The clinical effectiveness of teriparatide for treatment of postmenopausal women with osteoporosis who are at high risk of fracture in Asia is focused primarily on improvements in BMD and tolerability. Recommended additional studies may include assessment of fracture risk and the effect of teriparatide on pain, quality of life, and mortality in Asia.

Osteoporosis is recognized as a major public health problem worldwide and in Taiwan. However, many patients with osteoporotic fractures do not receive appropriate assessments or treatments. This guideline, proposed by the Taiwanese Osteoporosis Association, is to serve as a quick reference for healthcare providers to improve the assessment of osteoporosis and development of optimal strategies for osteoporotic management in Taiwan. To review and update osteoporosis management, the guideline is constituted with Taiwan-specific osteoporosis epidemiological data, medication protocols, and the 10-year FRAX(®). The guideline is based on evidence-based medicine and public health considerations. Recommendations are not limited to the reimbursement regulations permitted by the National Health Insurance of Taiwan.

Background and aims Controlled attenuation parameter (CAP) is a non-invasive method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease (NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the leading cause of morbidity and mortality in hemodialysis patients. The aim of this study was to investigate the prevalence of NAFLD in hemodialysis patients. Method We prospectively enrolled patients undergoing chronic hemodialysis, as well as patients with normal renal function who served as controls. The control group patients were referred by an endocrinologist to be tested for NAFLD; most of these patients had diabetes, hypertension, or dyslipidemia. We excluded those with excess alcohol intake, use of drugs known to induce HS, chronic viral hepatitis, or CAP failure. CAP ≥ 238 dB/m was used as a cutoff suggesting HS. An increased liver kidney contrast, as defined by ultrasound, was used to make the diagnosis of HS. Results Three hundred and forty-three hemodialysis patients and 252 control group patients were enrolled. Among the hemodialysis patients, 192 (56.0%) had CAP- or ultrasound-identified HS compared with 91 (26.5%) who only had ultrasound-identified HS (P

From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing’s syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing’s disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days,P<0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.

Hypertension is a prevalent condition that is closely associated with chronic complications in patients with diabetes. Fixed-dose combination therapy is currently recommended for the treatment of hypertension due to the advantage of reducing the pill burden. However, the effects of combination therapy may be diverse because of the different components.We examined blood pressure reduction and metabolic alterations after amlodipine/benazepril and valsartan/hydrochlorothiazide treatment in patients with type 2 diabetes mellitus and hypertension and microalbuminuria.This randomized, double-blind, parallel comparison, noninferiority clinical trial included patients with type 2 diabetes mellitus and hypertension and microalbuminuria detected within the past year. After a 2-week, placebo run-in period, patients were assigned to treatment with amlodipine/benazepril or valsartan/hydrochlorothiazide for 16 weeks. The primary end point was mean change in diastolic blood pressure. The prespecified boundary for noninferiority was 3.5 mm Hg of the mean change in diastolic blood pressure between treatments (amlodipine/benazepril minus valsartan/hydrochlorothiazide). If the upper limit of the 95% CI fell within 3.5 mm Hg, amlodipine/benazepril would be considered noninferior to valsartan/hydrochlorothiazide.Of the 226 patients assessed for eligibility, 169 satisfied the inclusion/exclusion criteria and were assigned to a treatment group; 83 patients (54.2% male, mean age of 60.5 [10.0] years) in the amlodipine/benazepril group and 84 patients (64.3% male, mean age of 59.0 [10.6] years) in the valsartan/hydrochlorothiazide group received at least 1 dose of study medication and were included in the intention-to-treat population. In the per-protocol population, amlodipine/benazepril (n = 74) was noninferior to valsartan/hydrochlorothiazide (n = 78) with regard to the mean change in diastolic blood pressure (difference, -0.9 mm Hg; 95% CI, -3.5 to 1.6). The mean change in systolic blood pressure was not significantly different (2.4 mm Hg; 95% CI, -1.2 to 6.0) between study groups (P = 0.195) in the per-protocol population. However, data from the intention-to-treat population suggest that patients in the amlodipine/benazepril group may have better metabolic outcomes than those in the valsartan/hydrochlorothiazide group; specifically, a preservation of the estimated glomerular filtration rate (5.7 mL/min/1.73 m(2) [95% CI, 1.9 to 9.6]; P = 0.004) and improvements in glycosylated hemoglobin (-0.5% [95% CI, -0.7 to -0.2]; P0.001), fasting triglycerides (-0.4 mmol/L [95% CI, -0.7 to -0.2]; P = 0.002), HDL-C (0.07 mmol/L [95% CI, 0.01 to 0.12]; P = 0.022), and uric acid (-57.5 μmol/L [95% CI, -74.8 to -40.3]; P0.001). There were no significant differences in adverse effects between groups, with the exception of more respiratory disorders in the amlodipine/benazepril group than in the valsartan/hydrochlorothiazide group (17 vs 5; P = 0 .006).The study results suggest that amlodipine/benazepril is noninferior to valsartan/hydrochlorothiazide with regard to blood pressure reduction and that this combination exerts beneficial effects on renal function, glucose control, HDL-C, and triglyceride levels compared with valsartan/hydrochlorothiazide. However, respiratory adverse events (particularly coughing) were more frequently reported in the amlodipine/benazepril group. ClinicalTrials.gov identifier: NCT01375322.

Osteoporotic patients with existing fractures are at substantially higher risk of subsequent fractures than those free of fractures. Given the lack of head-to-head comparison trials, indirect comparison of various antiosteoporosis treatments may be an alternative way to develop a preliminary idea. The objective of this study is to conduct a systematic review of antiosteoporosis treatment clinical trials that have investigated on patients with existing fractures. All the results of randomized placebo-controlled trials of the available antiosteoporosis treatments, including bisphosphonates, selective estrogen receptor modulators, calcitonin, strontium ranelate, and agents derived from parathyroid hormone, on patients with existing fractures were summarized. All the antiosteoporotic agents had significant efficacy in increasing lumbar spine bone mineral density and reduction in the occurrence of any new vertebral fractures. All interventions provided gains in quality-adjusted life-years compared with patients without treatment. The results from an indirect comparison must be interpreted with caution due to heterogeneous study design, discrepancies of disease severity at baseline, and differences in analytical methodologies. The devastating complications subsequent to osteoporotic fractures create medical and financial burdens; therefore, treatment of patients with osteoporotic fractures should be positioned in the top priority in the utilization of medical resources.

Bisphosphonates have been used for the treatment of postmenopausal osteoporosis since the early 1990s and studies show that compliant patients experience a lower fracture rate. This cohort study showed that the compliance of Taiwanese patients was poor and the refracture risk was related to compliance with bisphosphonate therapy. Bisphosphonates are potent inhibitors of osteoclast activity, and reduce bone turnover by inhibiting bone resorption. According to Taiwanese reimbursement guidelines, patients with osteoporosis-related fractures are eligible for bisphosphonate treatment. This study aimed to elucidate the relationship of refracture risk with compliance/persistence with bisphosphonate therapy in Taiwan. This was a retrospective, administrative, database analysis measuring the adherence status and impact of poor adherence to bisphosphonate therapy in Taiwan. Study data derived from the National Health Insurance Research Database (NHIRD) were used to assemble a cohort of all osteoporosis patients who initiated bisphosphonate treatment between January 1, 2004, and December 31, 2005. Patients were followed until death, end of registration in NHIRD, or end of study period (December 31, 2006), whichever occurred first. Compliance was calculated as medication possession ratio (MPR; sum of days of supply of osteoporosis medications divided by follow-up duration). The refracture rates for osteoporosis patients were 5.15 %, 7.36 %, and 8.49 % in the first, second, and third year, respectively, and were significantly lower for patients with >80 % compliance than with

Summary Background The aim of this study was to identify the prognostic factors of long-term survival and optimal therapeutic protocol for patients with distant metastasis secondary to differentiated thyroid carcinoma (DTC). Methods A retrospective review of 1665 patients with DTC treated at a regional tertiary hospital in Taiwan between 1986 and 2010 was performed. Among them, 207 patients were found to have distant metastasis. For a long-term outcome survey, 126 patients that had received at least 5 years (mean 9·6 ± 5·2 years) of follow-up after the diagnosis of distant metastasis were analysed for this study. Prognostic factor analysis included age, sex, histology, disease stage, type of surgical procedure, site of metastatic foci, 131I avidity of tumour, thyroglobulin (Tg) level and accumulated therapeutic dose of radioiodine (RAI). Results The mean age at diagnosis of distant metastasis was 46·4 ± 17·2 years. The female-to-male ratio was 2·1:1. The 10- and 15-year survival rates were 70·6% and 64·9%, respectively. The independent predictors of survival were younger age, surgical dissection of neck lymph nodes (LNs) and low TSH-stimulated Tg level ( 600 mCi of 131I. The mean cumulative doses of 131I in both deceased and living patients were similar. Conclusion The prognosis of patients with distant metastasis from DTC within this study was found to be favourable. Survival may be improved by surgical dissection of neck LNs, but repeated 131I therapy >600 mCi is not advised unless there is a high probability that it would benefit the patient.

Eur J Clin Invest 2012; 42 (3): 245–253 Abstract Background Elevations in blood pressure and visit-to-visit variability have been found to significantly increase the risk of cardiovascular morbidity and mortality in nondiabetic individuals. This study has assessed the association between all-cause mortality and blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP) and visit-to-visit variability] in patients with type 2 diabetes. Materials and methods A longitudinal cohort study of 2161 patients with type 2 diabetes and a mean follow-up period of 66·7 ± 7·5 months. Using Cox regression models, blood pressure parameters were related to the risk of all-cause mortality. Results Visit-to-visit variability in SBP [HR: 1·048 (95% CI: 1·005–1·092; P = 0·03)], DBP [HR: 1·090 (95% CI: 1·021–1·163; P = 0·01)] and MAP [HR: 1·099 (95% CI: 1·033–1·170; P = 0·003)] significantly predicted all-cause mortality in patients with type 2 diabetes after adjusting for baseline data, mean follow-up blood pressure profiles and HbA1c. Visit-to-visit variability in PP [HR: 1·139 (95% CI: 1·030–1·258; P = 0·01)] significantly predicted cardiovascular mortality. Neither baseline nor follow-up SBP, DBP, PP nor MAP was significantly associated with all-cause and cardiovascular mortality after adjusting for blood pressure variability. The risk of all-cause mortality with a mean follow-up SBP has a U-shaped distribution. Patients with a mean follow-up DBP > 90 mmHg were at higher risk of mortality than those with DBP < 90 mmHg. Conclusions Visit-to-visit variability in blood pressure was significantly associated with all-cause mortality independent of mean BP in patients with type 2 diabetes. The data for blood pressure variability might be regarded as a potentially important therapeutic target in the management of type 2 diabetes.