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Introduction Trends on glycemic control and diabetes complications are known for high-income countries, but comprehensive data from low- and middle-income countries (LMIC) are lacking. Methods This is an expert opinion based on two retrospective studies. Here we examine the recent subset analysis of relevant data from the IDMPS Wave 7 (International Diabetes Management-Practices Study, 2015-2016) and the GOAL study conducted in multiple LMICs. Results Wave 7 sub-analysis was performed in 6113 people with type 2 diabetes from 24 LMIC. Poorly controlled diabetes (hemogloblin A1c [HbA1c] >= 7%) was found in 58.6, 73.0 and 78.3% of participants with diabetes duration of < 5, 5-12 and > 12 years, respectively (in association with a high prevalence of macro- and microvascular complications). Moreover, 37.7% of participants with diabetes duration of 5-12 years were treated only with oral antihyperglycemic drugs. The GOAL study investigated the efficacy of insulin in 2704 poorly controlled participants (mean HbA1c 9.7%; diabetes duration 10.1 +/- 6.7 years; 10 LMIC). A significant 2% reduction in mean HbA1c levels was observed after 12 months of treatment. Only 7.2% of participants experienced a symptomatic episode of hypoglycemia (nocturnal or severe hypoglycemia events were infrequent). Conclusion The rate of well-controlled participants (HbA1c < 7.0%) in the Wave 7 sub-analysis was lower than that observed in the USA (NHANES survey) or in European countries (GUIDANCE study), and the incidence of microvascular complications was higher. The GOAL study showed that insulin treatment improves glycemic control and reduces this gap. The Expert Panel recommends intensifying diabetes treatment as soon as possible, as well as patients' education and other preventive measures, initiatives which require modest costs compared to hospitalization and treatment of diabetes complications.

Since bone and fat mass are derived from mesenchyme in early development, adipokines secreted by adipose tissue may have an effect on bone metabolism. The relationship between adiponectin and bone mineral density (BMD) has been inconsistent in previous reports, with results being dependent on age, gender, menopausal status and bone sites. We investigated the relationship between serum adiponectin levels and the BMD of proximal femur and vertebrae bones in a 96-week longitudinal study of post-menopausal women with repeated measures of both. Linear regression models were used to determine the relation between adiponectin and BMD at each time point cross-sectionally, and a generalized estimating equation (GEE) model was used to investigate the longitudinal trends. Among 431 subjects, 376 (87%) provided baseline adiponectin measurements and 373 provided more than two measurements for longitudinal analysis. The means of serum adiponectin and BMD decreased with time. In linear regression models, adiponectin at baseline, the 48th week and the 96th week appeared to be inversely associated with BMD of proximal femur bone, but not lumbar spine after adjusting for age and various confounders. However, they all turn insignificant with further adjustment of body mass index. The inverse association between adiponectin and BMD of proximal femur is substantiated by all generalized equation models. Before adding the BMI in the model, the increase of 1 mg/dL of adiponectin can accelerate the decrease of proximal femur BMD by 0.001 (SE = 0.0004, p = 0.008). With BMI in the model, the drop rate was 0.0008 (SE = 0.0004, p = 0.026) and remained similar with further adjustment of two bone turnover markers. In this longitudinal analysis with both adiponectin and BMD measured at three time points, we demonstrate that with the increase of adiponectin level, the decline of proximal femur BMD in postmenopausal women accelerated during a period of 96 weeks.

Longitudinal data on the association between smoking and glycemic control in men with newly diagnosed type 2 diabetes (T2DM) is scarce. Therefore, this study aimed to examine the extent of the association between smoking and glycemic control in this population.The retrospective cohort study identified 3044 eligible men with T2DM in a medical centre in Taiwan between 2002 and 2017. Smokers (The estimated maximal difference in HbA1c reduction between smokers and non-smokers was 0.33% (95% CI, 0.05-0.62%) at 3 months of follow-up. For patients with body mass index (BMI)25 kg/mOur findings show that smoking was independently associated with unfavourable glycemic control among men with newly diagnosed T2DM, and such a detrimental association could be stronger in men with a lower BMI.

BACKGROUND: Adult patients cared for by cardiologists, neurologists, and diabetologists are highly vulnerable to cardiovascular diseases (CVDs), which are worsened by smoking. In the past, physicians of these three specialties at major hospitals in Taiwan always referred patients to family medicine and chest medicine departments for smoking cessation programs. However, the participation rate in these programs was unsatisfactory. OBJECTIVES: To encourage cardiologists, neurologists, and diabetologists to provide smoking cessation treatment services (SCTSs) to their patients through an annual contest. METHODS: Sequential expert meetings, group training, a contest to reward service quantity and abstinence rate, and an annual awards ceremony were held over the past 3 years. RESULTS: More than 350 cardiologists, neurologists, and diabetologists were certified to provide SCTSs, and in the second half of 2020, 3716 high CVD risk patients entered smoking cessation treatment programs, with an abstinence rate exceeding 30% at 3 months. CONCLUSIONS: The strategy used in this study was effective in overcoming physician inertia to provide SCTSs and encourage high CVD risk smokers to quit smoking.

The 2019 Diabetes Atlas delineated both accomplishments and challenges in diabetes care in Taiwan between 2005 and 2014. The series reported that Taiwan had significantly improved aspects of care quality for patients with diabetes. For example, the mortality rate decreased, the difference between the life expectancies of patients with diabetes and those of the general population decreased, and the rates of hospitalization because of heart diseases, cerebrovascular diseases, chronic kidney diseases, and unsatisfactory glycemic control decreased. However, despite these achievements, the 2019 Diabetes Atlas also reported some substantial challenges that have not been overcome. For example, the incidence of diabetes among women aged

Background: We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D). Methods: We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level. Results: A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [β coefficient 0.199, 95% confidence interval (CI) 0.074–0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7–28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6–34.6 ± 17.0 mg/dl, p = 0.776). Conclusion: Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.

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.

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.

Background The prevalence of diabetes is growing, and diabetes is an independent risk factor for both atrial fibrillation (AF) and stroke. However, the relative effectiveness and safety of different oral anticoagulants for diabetic patients with non-valvular AF remain unclear. We aimed to compare thromboembolic events, bleeding and mortality in diabetic AF patients treated with rivaroxaban, dabigatran and warfarin. Methods and Results Diabetic AF patients taking dabigatran (n = 322), rivaroxaban (n = 320) or warfarin (n = 1,899) were identified from the nationwide diabetes pay-for-performance program (n = 814,465) in Taiwan. Outcomes and comorbidities were evaluated by linking with Taiwan National Health Insurance Research Database. Propensity score weighting method was used to balance covariates across study groups. Patients were followed up until the first occurrence of any study outcome or the study end date. Compared with warfarin, dabigatran significantly decreased the risk of all-cause mortality (hazard ratio [HR] = 0.348, 95% confidence interval [CI] = 0.157–0.771) and gastrointestinal bleeding (HR = 0.558, 95% CI = 0.327–0.955). Relative effectiveness and safety outcomes between rivaroxaban and warfarin were comparable. Compared with rivaroxaban, dabigatran significantly decreased the risk of all-cause mortality (HR = 0.310, 95% CI = 0.121–0.798) and was associated with a borderline reduced risk for composite safety end points (HR = 0.670, 95% CI = 0.421–1.067). Conclusion In diabetic AF patients, dabigatran and rivaroxaban showed a superior or non-inferior effectiveness and safety profile compared with warfarin. Dabigatran was associated with a significantly lower risk of mortality than rivaroxaban.

Background/Purpose: Diabetes mellitus has become a major cause of death worldwide. Many technologies have become available for managing diabetes and its complications. This study investigated the mortality trends in people with diabetes in Taiwan between 2005 and 2014. Methods: We used data from Taiwan's National Health Insurance Research Database, which is linked to the National Death Registry. Patients with at least three outpatient visits in 1 year or at least one hospital admission with the diagnosis of diabetes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 250.x) were defined as diabetic patients. The main causes of death were classified using ICD-9-CM or ICD-10-CM. Results: In 2005–2014, the number of diabetic patients increased from 1.3 to 2.2 million in Taiwan, and all-cause mortality in the patients decreased continuously across sexes and age groups (all, 3.45%–3.00%; women, 3.07%–2.70%; men, 3.82%–3.28%, all p

Background/Purpose: Several new antidiabetic drugs have been introduced in Taiwan. However, the trends in antidiabetic treatment remain unexamined. Methods: We studied data from the Taiwan National Health Insurance Database to identify outpatient prescriptions for antidiabetic drugs from 2005 to 2014. The patterns in antidiabetic treatment and the number of different classes of antidiabetic drugs were analyzed. The proportions of prescriptions of antidiabetic monotherapy, combination therapy, or insulin therapy were further analyzed. Results: The total and mean prescriptions gradually increased during the study period. Prescription of oral antidiabetic drugs (OADs) only or insulin-only therapy decreased slightly. Prescriptions of monotherapy and dual therapy decreased, whereas those of triple or higher order combinations increased. Prescriptions of sulfonylureas (SUs) decreased, whereas those of metformin and dipeptidyl peptidease-4 (DPP4) inhibitors increased. Insulin prescriptions increased but accounted for only 13.07% of prescriptions in 2014. Among monotherapy prescriptions, SU prescriptions decreased, but metformin and DPP4 inhibitor prescriptions increased. Among dual OAD prescriptions, those including SUs decreased, and those of metformin and DPP4 inhibitors increased. Although prescriptions of the metformin–SU combination decreased, they remained the most common among all dual OAD prescriptions, followed by the metformin–DPP4 inhibitor combination. Prescriptions of human insulin decreased and those of insulin analogs increased considerably; those of basal insulin increased, and those of mixed insulin decreased. However, mixed insulin was prescribed more than basal–bolus insulin. Conclusion: Antidiabetic treatment has become complex in Taiwan. Although combination therapy would become the major treatment strategy gradually, the underuse of insulin therapy must improve. Keywords: Antidiabetic drugs, Diabetes, Insulin, Oral antidiabetic drugs

Background: Heart failure is a frequent complication of type 2 diabetes mellitus (T2DM). Plasma cholesterol, particularly the proatherogenic low-density lipoprotein (LDL) cholesterol, impairs heart function by promoting atheroma formation and ventricular dysfunction. Considering the established effect of cholesterol on the cardiovascular system, we hypothesized that plasma LDL cholesterol may influence left ventricular function in individuals with T2DM. Methods: This cross-sectional study was conducted at a tertiary care hospital in Taiwan. Enrollment criteria were patients exceeding 21 years of age with T2DM who received antidiabetic and cholesterol-lowering medications. Candidates were excluded if they had heart failure, acute cardiovascular events, or familial hypercholesterolemia. Participants received blood sampling for plasma lipids after a 12-h fast, followed by transthoracic echocardiography in the cardiology clinic. Results: The study enrolled 118 participants who were divided into two groups according to their plasma LDL cholesterol levels. Demographic characteristics including age (69.7 vs. 66.9 years, P = 0.159), body mass index (26.2 vs. 25.9 kg/m2, P = 0.66), diabetes duration (5.4 vs. 5.1 years, P = 0.48), hemoglobin A1c (7.2 vs. 7.5%, P = 0.225), and systolic blood pressure (129 vs. 130 mm Hg, P = 0.735) were similar between these groups. Moreover, all participants received similar antihypertensive medications. Participants with lower plasma LDL cholesterol levels had better heart function, as measured by the left ventricular ejection fraction (LVEF), than patients with higher LDL cholesterol levels (58.0 vs. 50.5%, P = 0.022). Multivariate regression analysis also showed an inverse correlation between plasma LDL cholesterol and left ventricular function (β coefficient: −0.110, P = 0.024). Conclusion: This study observed an inverse correlation between plasma LDL cholesterol and heart function in individuals with T2DM. Patients with higher levels of plasma LDL cholesterol had worse left ventricular function. Therefore, plasma LDL cholesterol may be a modifiable risk factor of heart failure in diabetes, but prospective studies are necessary to confirm this finding.

Background Diabetes patients who fail to achieve early glycemic control may increase the future risk of complications and mortality. The aim of the study was to identify factors that predict treatment failure (TF) during the first year in adults with newly diagnosed type 2 diabetes mellitus (T2DM). Methods This retrospective cohort study conducted at a medical center in Taiwan enrolled 4,282 eligible patients with newly diagnosed T2DM between 2002 and 2017. Data were collected from electronic medical records. TF was defined as the HbA1c value >7% at the end of 1-year observation. A subgroup analysis of 2,392 patients with baseline HbA1c ≥8% was performed. Multivariable logistic regression analysis using backward elimination was applied to establish prediction models. Results Of all study participants, 1,439 (33.6%) were classified as TF during the first year. For every 1% increase in baseline HbA1c, the risk of TF was 1.17 (95% CI 1.15–1.20) times higher. Patients with baseline HbA1c ≥8% had a higher rate of TF than those with HbA1c p Conclusions Newly diagnosed diabetes patients with baseline HbA1c ≥8% did have a much higher rate of TF during the first year. Subgroup analysis for them highlights the important predictors of TF, including medication adherence, performing SMBG, regular exercise, and gender, in achieving glycemic control.

Background The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). Methods Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0–11.0 % (53–97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c – post-treatment HbA1c)/baseline HbA1c × 100. Results Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (β = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P

Aims Our aims were to investigate the prevalence of diabetes mellitus (DM) among patients with newly-diagnosed tuberculosis (TB) and to determine its associated factors in an Asian population. Methods The data were obtained from the National Health Insurance Research Database and included 9831 newly-diagnosed TB individuals in the period of 2000–2010. The data were divided into a DM group and a non-DM group. We measured the prevalence and the associated comorbidities of DM. Results During 2000–2010, the prevalence of DM progressively increased, with an average prevalence rate of 27.9%. The patients with ages of 55–64 years had the highest association of DM (OR = 3.53) compared with those under 45 years. TB patients with heart failure, ischemic heart disease, cerebral vascular disease, hypertension, dyslipidemia, chronic kidney disease, and liver disease were more likely to associate with DM (ORs = 1.27, 1.23, 1.30, 2.32, 3.26, 1.6, and 1.68, respectively) compared to those without the variables. Conclusions The prevalence of DM among TB patients in Taiwan was high and tended to increase in the past decade. Clinically, inquiring about DM history and screening routinely for those without DM history among TB patients should be carried out in Taiwan.

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

Aim: Addition of 1-3 dose of bolus insulin is recommended by ADA/EASD guidelines when basal insulin (BI) therapy becomes insufficient for T2DM patients to achieve HbA1c target of Method: 328 T2DM patients completed 48 weeks of stepwise intensification of PI + BI therapy (Main group). The primary objective of the study was to determine the mean change in HbA1c. Secondary objectives included; evaluation of change in FPG, 2h-PPG, PI and BI dose and the rate of HbA1c Result: Mean HbA1c was 9.16% in Main group at baseline. At week 48, significant difference in mean HbA1c change (-0.59 ± 1.16% vs. -0.07 ± 1.06%; p Conclusion: This study demonstrated the introduction of stepwise intensification of prandial insulin leads to greater improvements in HbA1c levels than basal insulin monotherapy in T2DM patients in Taiwan and this effect can be maintained during the study period of 48 weeks. Disclosure Y. Hung: Advisory Panel; Self; Sanofi. Y. Huang: Research Support; Self; Sanofi. H. Chen: Research Support; Self; Sanofi. R. Liu: Research Support; Self; Sanofi. N.C. Yu: None. H. Lam: None. C. Huang: Research Support; Self; Sanofi. C. Chen: Research Support; Self; Sanofi. P. Hsiao: Advisory Panel; Self; Sanofi. H. Chen: None. M. Chien: Research Support; Self; Sanofi. T. Lee: None. C.Y. Yang: None. C. Chen: Advisory Panel; Self; Sanofi-Aventis. S. Tu: None. H. Chen: None. W. Sheu: Advisory Panel; Self; Sanofi.

Background/Purpose Estrogen in hormone replacement therapy causes homeostatic changes. However, little is known regarding the safety of high-dose phytoestrogen on coagulation and hematological parameters in healthy postmenopausal women. This study evaluated the effects of high-dose soy isoflavone (300 mg/day) on blood pressure, hematological parameters, and coagulation functions including circulating microparticles in healthy postmenopausal women. Methods The original study is a 2-year prospective, double-blind, placebo-controlled study. In total, 431 postmenopausal women (from 3 medical centers) were randomly assigned to receive either high-dose isoflavone or placebo for 2 years. At baseline, 6 months, 1 year, and 2 years after treatment, blood pressure, body weight, liver function tests, hematological parameters, and lipid profiles were measured. The 1 st year blood specimens of 85 cases of 144 eligible participants (from one of the three centers) were analyzed as D-dimer, von Willebrand factor antigen, factor VII, plasminogen activator inhibitor type 1, and circulating cellular microparticles, including the measurement of monocyte, platelet, and endothelial microparticles. Results In the isoflavone group, after 1 year, the changes in liver function tests, hematological parameters, and coagulation tests were not different from those of the control. Triglyceride levels were significantly lower after 6 months of isoflavone treatment than the placebo group, but the difference did not persist after 1 year. Endothelial microparticles increased steadily in both groups during the 1-year period but the trend was not affected by treatment. Conclusion The results of the present study indicate that high-dose isoflavone treatment (300 mg/day) does not cause hematological abnormalities or activate coagulation factors.

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.

To provide continuous, accessible, and quality care, a diabetes share-care program has been in place in Taiwan for several years. Lukang Christian Hospital, a member of the diabetes share-care network, endeavors to provide "patient-centered" care aimed at increasing care quality and reducing diabetic complications. Information technology has been employed by the hospital for monitoring care quality and analyzing cost-effectiveness. Structured health-care programs have also been developed to ensure the completeness of diabetes care and to encourage self-management of individuals at high risk for diabetes. The implementation of these strategies has led to progressive improvement in quality measures and spawned novel and creative ways to deliver care services.

ObjectiveTo investigate the association between diabetes and latent tuberculosis infections (LTBI) in high TB incidence areas.DesignCommunity-based comparison study.SettingOutpatient diabetes clinics at 4 hospitals and 13 health centres in urban and rural townships. A community-based screening programme was used to recruit non-diabetic participants.ParticipantsA total of 2948 patients with diabetes aged older than 40 years were recruited, and 453 non-diabetic participants from the community were enrolled.Primary and secondary outcome measuresThe interferon-gamma release assay (IGRA) and the tuberculin skin test were used to detect LTBI. The IGRA result was used as a surrogate of LTBI in logistic regression analysis.ResultsDiabetes was significantly associated with LTBI (adjusted OR (aOR)=1.59; 95% CI 1.11 to 2.28) and age correlated positively with LTBI. Many subjects with diabetes also had additional risk factors (current smokers (aOR=1.28; 95% CI 0.95 to 1.71), comorbid chronic kidney disease (aOR=1.26; 95% CI 1.03 to 1.55) and history of TB (aOR=2.08; 95% CI 1.19 to 3.63)). The presence of BCG scar was protective (aOR=0.66; 95% CI 0.51 to 0.85). Duration of diabetes and poor glycaemic control were unrelated to the risk of LTBI.ConclusionThere was a moderately increased risk of LTBI in patients with diabetes from this high TB incidence area. This finding suggests LTBI screening for the diabetics be combined with other risk factors and comorbidities of TB to better identify high-risk groups and improve the efficacy of targeted screening for LTBI.

Dyslipidemia is a major risk factor for cardiovascular complications in people with diabetes. Lowering low-density lipoprotein cholesterol (LDL-C) levels is effective in the primary and secondary prevention of diabetic vascular complications. However, LDL-C levels do not reflect all aspects of diabetic dyslipidemia, which is characterized by hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C). Statins, nicotinic acid, and fibrates play a role in treating diabetic dyslipidemia. Atherosclerosis is a major disorder of the blood vessel wall in patients with diabetes. A number of antihyperlipidemic agents may be beneficial and exhibit effects at the actual site of vascular disease and not only on plasma lipoprotein concentrations. Several novel therapeutic compounds are currently being developed. These include additional therapeutics for LDL-C, triglycerides, HDL-C, and modulators of inflammation that can be used as possible synergic agents for the treatment of atherosclerosis and irregularities in plasma lipoprotein concentrations.

Background Although it is known that the prevalence of type 2 diabetes and obesity is increasing in China, there is little research into how obese or non-obese patients may differ in their attainment of treatment goals for type 2 diabetes. To do this, we assessed the attainment of American Diabetes Association (ADA)-recommended goals in Chinese with type 2 diabetes stratified by body mass index (BMI). Methods This cross-sectional study enrolled 520 Chinese with type 2 diabetes to find out if they had attained the following ADA-recommended goals: HbA1c 40 mg/dl for men and > 50 mg/dl for women. Results Only 44.4% of all participants achieved the blood pressure goal, 20.8% the HbA1c goal, 44.8% the LDL-C goal, 43.3% the HDL-C goal, and 66.8% the triglyceride goal. Obese patients were less likely than normal weight patients to achieve the blood pressure goal (OR, 0.474; 95% CI, 0.231–0.973; p = 0.01), the HDL goal (OR, 0.365; 95% CI, 0.163–0.817; p = 0.01), or the triglyceride goal (OR, 0.416; 95% CI, 0.212–0.817; p = 0.01), after adjusting for confounders. Compared to normal weight participants, the obese patients had a significantly higher prescription rates for statin, metformin and anti-hypertensive drugs. Conclusion Obese diabetic patients were less likely to achieve the blood pressure, LDL-C, HDL-C and triglyceride targets even when they were receiving several drugs to help them meet their target treatment goals. More strategies are needed to improve the treatment of Chinese with type 2 diabetes, particularly those who are obese.

Although sulfonylurea added to metformin is the first oral drug combination regimen for patients with type 2 diabetes recommended by the American Diabetes Association/European Association for the Study of Diabetes consensus statement, it does not allow for individualizing and optimizing therapy with respect to sustaining glycemic control and the reduction of glucose variability. We therefore sought to investigate acarbose as an alternative to glibenclamide in combination with metformin and compare the effects on metabolic control and glucose variability.Type 2 diabetic patients 30-70 years of age with glycosylated hemoglobin 7.0%-11.0% while treated with one or two oral antidiabetic drugs were successively enrolled. After 8 weeks of run-in with metformin 500 mg thrice daily, either acarbose 50 mg or glibenclamide 2.5 mg three times daily was randomly added on and force titrated to acarbose 100 mg or glibenclamide 5.0 mg three times daily for the subsequent 16 weeks. Demographic data, biochemical data and continuous glucose monitoring system data were recorded upon randomization and at the end of the study. Various parameters that measure glucose variability were derived from the continuous glucose monitoring system data.Of the 51 type 2 diabetes patients enrolled, data from 40 subjects, 20 in each group, were analyzed after excluding those unqualified information. Both drug combinations improved glycemic control. Glucose variability, expressed as mean amplitude of glycemic excursion or continuous overall net glycemic action and mean of daily differences, decreased significantly (all P.05) after the addition of acarbose but not glibenclamide. The acarbose-metformin combination has the additional benefits of weight reduction and shorter durations of hyperglycemia compared with metformin monotherapy.This study suggests that both intraday and interday glucose variability are more effectively reduced by the acarbose-metformin combination than by the glibenclamide-metformin combination, while both combinations reduce the overall glucose level equally.

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.

Eur J Clin Invest 2011; 41 (8): 870–878 Abstract Background Asian has higher prevalence of diabetic nephropathy (DN) and end-stage renal disease when compared to Caucasian. No study to date has evaluated whether multifactorial intervention was associated with remission of microalbuminuria in type 2 diabetic Asian population. We evaluated the effect of tightly controlling multiple factors on the remission of DN in type 2 diabetic Chinese with microalbuminuria. Materials and methods A longitudinal cohort study was collected 587 type 2 diabetic patients with microalbuminuria. Cohort members received intensified treatment to meet the following ADA recommended goals: HbA1c 40 mg dL−1 for men and > 50 mg dL−1 for women. Remission of microalbuminuria was defined as shift of albumin–creatinine ratio from mircoalbuminuria to normoalbuminuria. Results During the 4·5-year period, 210 (35·8%) patients achieved remission to normoalbuminuria. A significant association was found between the achievement of ADA goals, including HbA1c

We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma; Pro12Ala) and in PPAR-gamma coactivator-1(PGC-1; Gly482Ser) genes on the response to pioglitazone in Chinese with type 2 diabetes mellitus. A total of 250 patients with type 2 diabetes mellitus were treated with pioglitazone (30 mg/d) for 24 weeks without a change in previous medications. All patients were genotyped for the PPAR-gamma Pro12Ala and PGC-1 Gly482Ser polymorphisms. The Ala12Ala and Pro12Ala genotypes (26.0% vs 13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P = .008) were significantly more frequent in pioglitazone responders than in nonresponders. The distribution of PGC-1 genotypes and alleles was not significantly different between responders and nonresponders. The decrease in fasting glucose (50.4 +/- 52.2 vs 43.3 +/- 51.7 mg/dL, P.001) and hemoglobin A(1c) (0.57% +/- 1.44% vs 0.35% +/- 1.10%, P = .004) levels was significantly greater in subjects with the Ala12 carriers (Pro12Ala and Ala12Ala) than in those without the allele (Pro12Pro). Baseline fasting glucose and triglyceride levels were related to the response of pioglitazone. Only the PPAR-gamma Pro12Ala polymorphism was found to be associated with the response of pioglitazone by multiple logistic regression analysis. The PPAR-gamma Pro12Ala gene polymorphism is associated with the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. These findings may be helpful for targeted treatment of diabetes by identifying patients who are likely to respond to pioglitazone.

Objective We assessed the correlation between intima-media thickness (IMT) and stiffness and test whether they are independent risk factors for atherosclerotic diseases. Methods We enrolled 2333 participants from the general population. Among the study subjects, 197 subjects had a history of stroke or myocardial infarction (MI) and were treated as patients, and the rest were the control subjects. Intima-media thickness was measured at the common carotid artery (CCA), bifurcation, and internal carotid artery. Three parameters (arterial stiffness [β], elastic modulus, and pulse wave velocity) were measured for carotid stiffness. Correlation between IMT and stiffness was first calculated. Multivariate regression model was used to evaluate whether inclusion of both IMT and stiffness can increase the prediction of cardiovascular events. Results Only CCA and bifurcation IMTs were significantly and positively correlated with stiffness. After adjusting for age and sex, the correlations were substantially attenuated. Common carotid artery IMT was most significantly associated with stroke and MI ( P = 2.6 × 10−8) followed by bifurcation IMT ( P = 5.5 × 10−6), and internal carotid artery IMT was least significant ( P = 0.02). For stiffness, β was most significant ( P = 3.6 × 10−8) for stroke and MI, followed by elastic modulus ( P = 1.1 × 10−6) and pulse wave velocity ( P = 6.8 × 10−6). The best model for the combined effect was from β ( P < 0.03) and CCA ( P = 0.056) or bifurcation IMT ( P = 0.057). Conclusions Carotid IMT and stiffness represent different properties of atherosclerotic vessel wall. Measuring both traits provides a better characterization of atherosclerosis.

The risk for peripheral arterial disease (PAD) is increased in patients with chronic kidney disease. We investigated the effects of renal function on PAD in Chinese with type 2 diabetes mellitus. This study enrolled a total of 2983 (1342 men and 1641 women) Chinese adults with diabetes. The mean age was 63.2 +/- 11.9 years. Peripheral arterial disease was diagnosed by an ankle-brachial index less than 0.9. Renal function was evaluated by serum creatinine (SCr), estimated glomerular filtration rate, and urinary albumin-creatinine ratio (ACR). Risk factors for PAD were evaluated using multiple logistic regression analysis. Age, cholesterol, and high-density lipoprotein cholesterol (HDL-C) (inverse association) were significant risk factors in men, whereas age, body mass index (inverse association), low-density lipoprotein cholesterol, and HDL-C (inverse association) were significant risk factors for diabetic women. After adjustment for age, body mass index, blood pressure, glycosylated hemoglobin, cholesterol, HDL-C, low-density lipoprotein cholesterol, and triglyceride levels, we found that SCr levels greater than 1.5 mg/dL, estimated glomerular filtration rate less than 60 mL/min, and urinary ACR greater than 30 mg/g were independent risk factors for PAD in diabetic men and that SCr levels greater than 1.4 mg/dL and urinary ACR greater than 30 mg/g were independently associated with PAD in diabetic women. The risk factors for PAD are somewhat different between men and women with diabetes in Chinese population in Taiwan. Diabetic nephropathy is significantly associated with PAD in this patient population.

The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D).Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c - post-treatment HbA1c)/baseline HbA1c × 100.Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (β = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P 0.05 for all models).In patients with T2D on metformin monotherapy, baseline MAGE was positively correlated with relative HbA1c reduction from baseline after treatment with acarbose, but not glibenclamide. These findings highlight the importance of glycemic excursions in individualized treatment for patients with T2D.

The clinical efficacy of applying a western model for managing hyperglycemia in hospitalized patients in Asia has not been studied.For this observational case-control study, we divided six medical wards into two groups, an intervention group and a control group. The intervention group, consisting three medical wards on the same floor, received care under a computer-assisted consulting model in which special care was automatically indicated for patients who had two successive high glucose measurements in 1 day. The control group, consisting of another three medical wards distributed on different floors, received regular care. Outcome measures were baseline and post-intervention patient-day weighted mean glucose, percentage of patient-day weighted glucose ≥180 mg/dL, proportion of glucose level 100-180 mg/dL, and prevalence of inpatient hyperglycemia (180 mg/dL) and hypoglycemia (individual measurement70 mg/dL and patient-day with any measurement70 mg/dL).At baseline, the patient-day weighted mean glucose level was 181.6 mg/dL. All parameters were comparable between the intervention and control groups with the exception of prevalence of hypoglycemia, which was found to be higher in the intervention group. After intervention, patient-day weighted mean glucose levels for intervention and control groups were 169.9 mg/dL and 176.7 mg/dL, respectively (p0.001). The intervention group had a reduction in hypoglycemia and the control group an increase.This computer-assisted consulting model was found to be potentially very workable for the management of inpatient hyperglycemia in hospitals with high patient volumes in Asia.

Little scientific evidence exists to support the numerous herbs used to improve diabetes-related metabolic disorders. Cordyceps, a Chinese herbal medicine with fruiting body and carcass, has been proposed to have multiple medicinal activities. The objective of this study was to investigate the effects of fruiting body and carcass of Cordyceps on hyperglycemia. Male Wistar rats administered with placebo (STZ group), 1 g of fruiting body (FB group), 1 g of carcass (CC group), or 1g of fruiting body plus carcass (CF group) of Cordyceps for four weeks (d1 to d28) were injected with nicotinamide (200 mg/kg) and streptozotocin (65 mg/kg) on d15. Animals fed with placebo and injected with saline acted as the controls (CON group). The results showed that water intake (d15 to d29), changes in fasting blood glucose concentration (d15 to d26), and serum concentrations of fructosamine (d29) were significantly greater in the STZ, CC and CF groups than in the CON and FB groups (one-way ANOVA, P < 0.05). The diabetic rats had significantly lower weight gain and higher blood glucose response in oral glucose tolerance test than the control rats; and these changes were significantly reduced by administrating the fruiting body of Cordyceps. Our results revealed that fruiting body, not carcass, of Cordyceps attenuated the diabetes-induced weight loss, polydipsia and hyperglycemia, and these improvements suggest that fruiting body of Cordyceps has a potential to be the functional food for diabetes.

Background Hypoglycemia occurs in an appreciable number of individuals with type 2 diabetes mellitus (T2DM) who are receiving glycemic therapy. Iatrogenic hypoglycemia induces not only complications but also a substantial medical expense. Intervention for relevant risk factors may help avert severe hypoglycemia and enhance quality of life in at-risk individuals. This study investigates the relationship between body mass index (BMI) and plasma glucose concentration during iatrogenic hypoglycemia in people with T2DM. Methods Enrollment criteria were people above 20 years of age, with existing diagnosis of T2DM, a documented plasma glucose level ≤70 mg/dL, and acute cognitive impairment requiring hospitalization. Participants were classified into two groups according to their BMI. Specifically, lower BMI subgroup denotes individuals whose BMI fall within lower half of the study population, and vice versa. Plasma glucose concentration, length of hospital stay, and serum electrolyte level at hospitalization were compared between these BMI subgroups. Moreover, multivariate regression analysis was performed to identify covariates associated with plasma glucose level during iatrogenic hypoglycemia. Results This study enrolled 107 participants for whom 54 were assigned to a higher BMI subgroup and the remainder to a lower BMI subgroup. People with lower BMI harbored substantially reduced plasma glucose concentration during iatrogenic hypoglycemia compared to those with higher BMI (30.1 ± 9.6 mg/dL vs. 38.4 ± 12.3 mg/dL, P P = 0.77) and serum potassium level (3.7 ± 0.9 meq/L vs. 3.9 ± 0.8 meq/L, P = 0.14) were comparable between subgroups. Multivariate regression analysis identified BMI as a determinant of plasma glucose concentration in diabetic individuals with iatrogenic hypoglycemia (β coefficient: 0.72, P = 0.008). Discussion In individuals with T2DM who experience severe iatrogenic hypoglycemia, BMI influences the plasma glucose level at hospitalization. People with lower BMI harbored appreciably reduced plasma glucose concentration relative to their higher BMI counterparts. In lower weight people, therefore, appropriate dosing of antidiabetic medications, frequent self-monitoring of blood glucose level and adequate nutritional support may help avert more severe hypoglycemia. Overall, BMI potentially influences the severity of iatrogenic hypoglycemia in people with T2DM.

Background This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. Methods Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-β, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index). Results At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p

Due to the lack of radiation isolation wards in most hospitals in Taiwan, high-dose (exceeding 30 mCi) radioiodine therapy is usually performed in a fractionated manner (successively administering multiple low doses). This study compared the ablating efficacies of post-operative thyroid remnants using a single low dose (30 mCi) and fractionated doses (four doses of 30 mCi given at weekly intervals) in 59 patients with differentiated thyroid cancer who received total or near-total thyroidectomy. Successful ablation was obtained in 20 of 38 patients (52.6%) treated with a single low dose compared with 14 of 21 patients (66.7%) treated in a fractionated manner. There was no statistically significant difference between these two treatment protocols (P = 0.296). As the fractionated-dose protocol has the drawbacks of a much longer hypothyroid state and a higher total expense, we suggest that a single low dose is more feasible than fractionated doses for outpatient ablation therapy.

Type 2 diabetes mellitus is a global health issue. Patients with poor glycemic control often suffer from cardiovascular, cerebrovascular, neuropathic, and nephropathic complications as well as other chronic conditions. Therapeutic guidelines recommend that diabetic patients should maintain their HbA(1c) level below a certain target in order to minimize the risk of developing complications. However, hypoglycemia is recognized as a major impediment to the adequate control of type 2 diabetes. Hypoglycemia can manifest symptoms of varying degrees of severity. Moreover, an association between hypoglycemia and cardiovascular morbidity and mortality has been reported. Here, we present a post hoc Taiwan subgroup analysis of these data collected in the RECAP-DM study to indicate probably more emphasis and concern on hypoglycemia in type 2 diabetic patients in Taiwan. In this analysis, we found no significant difference was observed in treatment-related satisfaction between Taiwanese patients with or without hypoglycemia. Another finding of our study further shows that varying order of hypoglycemic symptoms or severity has no effect on patients' assessment of health-related quality of life scores. We need to pay more attention to this issue because of its enduring impact on compliance and concerns about hypoglycemia in type 2 diabetic patients. Nevertheless, socio-demographic characteristics are also important factors influencing glycemic control and patients' health-related quality of life. Future interventions and therapeutic algorithms should emphasize the probable patients' unawareness or neglect on hypoglycemia in diabetic patients.

Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM.This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin.T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. β-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded.A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P0.01) and serum adiponectin increased (P0.05) after treatment with acarbose, whereas HDL-C decreased (P0.01) after treatment with glibenclamide. β-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12).In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729.

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.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.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 DBP90 mmHg were at higher risk of mortality than those with DBP90 mmHg.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.

Asian has higher prevalence of diabetic nephropathy (DN) and end-stage renal disease when compared to Caucasian. No study to date has evaluated whether multifactorial intervention was associated with remission of microalbuminuria in type 2 diabetic Asian population. We evaluated the effect of tightly controlling multiple factors on the remission of DN in type 2 diabetic Chinese with microalbuminuria.A longitudinal cohort study was collected 587 type 2 diabetic patients with microalbuminuria. Cohort members received intensified treatment to meet the following ADA recommended goals: HbA1c7%, systolic blood pressure (SBP)130mmHg, diastolic blood pressure80 mmHg, low-density lipoprotein cholesterol100mgdL(-1) , triglyceride 150mgdL(-1) , high-density lipoprotein cholesterol40mgdL(-1) for men and50mgdL(-1) for women. Remission of microalbuminuria was defined as shift of albumin-creatinine ratio from mircoalbuminuria to normoalbuminuria.During the 4·5-year period, 210 (35·8%) patients achieved remission to normoalbuminuria. A significant association was found between the achievement of ADA goals, including HbA1c 7% [hazard ratio (HR)=1·345; 95% confidence interval (CI), 1·010-1·792; P=0·04] and SBP130mmHg (HR, 1·516; 95% CI, 1·100-2·089; P=0·01) and remission of microalbuminuria. The intensive SBP control (120mmHg) was significantly associated with remission of microalbuminuria (HR, 2·076; 95% CI, 1·347-3·198; P0·001).The remission of DN could be achieved under multifactorial intervention. Therapeutic focus on remission by tight glycemic and blood pressure control should be considered in Asian population with diabetes and microalbuminuria.

Background/Aims: Three different apo E alleles (E2, E3 and E4) produce apo E isoproteins, which regulate the metabolism of lipoproteins. This study investigated the apo E polymorphisms as a prognostic factor for the development of diabetic nephropathy (DN). Methods: A total of 525 type 2 diabetic patients were enrolled to participate in this prospective observational study. Apo E gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study. Results: The mean follow-up period was 42.4 months. The patients whose DN progressed had significantly higher urine albumin/creatinine ratios and fewer used diuretics than those in whom DN did not progress. In the Cox regression analysis, the apo E4 carriers were found to be at greater risk of progression of DN than non-apo E4 carriers (p = 0.007, hazard ratio 2.252). After adjusting for confounding factors, apo E4 carriers remained at increased risk of progression to more severe DN (p = 0.002, hazard ratio 2.820). Conclusion: Our study suggests the apo E4 carrier might serve as a predictor of DN progression in Taiwan.

BACKGROUND previous studies examining the contributions of fasting glucose (FG) and postprandial glucose (PPG) to glycated haemoglobin (HbA(1c)) have yielded conflicting results. We aimed to clarify the contributions of PPG to hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring. METHODS continuous glucose monitoring was conducted in 121 non-insulin-using type 2 diabetic outpatients, who were divided into five groups according to quintiles of HbA(1c) (ranging from 5.7 to 12.7%). Glucose area under the curve (AUC) above a glucose value of 5.5 mmol/L 24 or 4 h after meals was defined as AUC(total). Glucose AUC above FG or preprandial glucose levels was defined as AUC(PPG). The contribution of PPG to hyperglycaemia was calculated as (AUC(PPG)/AUC(total) × 100%. The contribution of FG or preprandial glucose was calculated as [(AUC(total) - AUC(PPG))/AUC(total)] × 100%. RESULTS the contribution of PPG to either 24-h hyperglycaemia or 4-h hyperglycaemia after meals was significantly higher than FG and preprandial glucose in the lowest quintile of HbA(1c) (both p < 0.001). However, no difference was observed in the other four quintiles. Peak PPG and glucose excursions were higher after breakfast than those after lunch and dinner (p < 0.01 for all comparisons). CONCLUSIONS in Asian patients with type 2 diabetes, PPG 24 and 4 h after meals was a predominant contributor to excess hyperglycaemia in well-controlled patients and was equally important as FG or preprandial glucose in moderately to poorly controlled patients with mean HbA(1c) up to 10%.

AIM This study assesses the impact of serum carboxy-terminal collagen crosslinks (CTX) bone marker feedback (BMF) on adherence to ibandronate treatment in Asian postmenopausal women with osteoporosis. METHODS This was a 12-month (6-monthly phased), randomized, prospective, open-label, multi-center study conducted in 596 (of 628 enrolled) postmenopausal women with osteoporosis (< or = 85 years old) who were naive, lapsed, or current bisphosphonate users. Patients were randomized into two arms: serum CTX BMF at 3 months versus no-BMF. Once-monthly 150 mg ibandronate tablet was administered for 12 months and adherence to therapy was assessed at 6 and 12 months. In addition, patient satisfaction and safety of ibandronate treatment were also assessed. RESULTS Serum CTX BMF at 3 months showed no impact on adherence. The proportions of adherent patients were comparable in the BMF versus no-BMF arms (92.6%vs. 96.0%, P = 0.16); overall, serum CTX levels were similar for adherent and non-adherent patients. However, BMF patients felt more informed about their osteoporosis (P < 0.001) and more satisfied (P < 0.01) than no-BMF patients. CONCLUSIONS The Asian postmenopausal osteoporosis patients in this study had a high adherence rate to once-monthly ibandronate therapy. Use of serum CTX BMF had no further impact on increasing adherence, but increased treatment satisfaction.