Effect of a Web-Based Management Guide on Risk Factors in Patients With Type 2 Diabetes and Diabetic Kidney Disease: A JADE Randomized Clinical Trial.

Importance: Diabetic kidney disease (DKD) and its comorbidities can be prevented by treating multiple targets. Technology-assisted team-based care with regular feedback and patient empowerment can improve the attainment of multiple targets and clinical outcomes in patients with type 2 diabetes, but the effects of this intervention on patients with DKD are unclear. Objective: To evaluate the effect of the Joint Asia Diabetes Evaluation (JADE) web portal, nurse reminders, and team-based care on multiple risk factors in patients with DKD. Design, Setting, and Participants: This 12-month multinational, open-label randomized clinical trial was conducted between June 27, 2014, and February 19, 2019, at 13 hospital-based diabetes centers in 8 countries or regions in Asia. All patients who participated had DKD. The intention-to-treat data analysis was performed from April 7 to June 30, 2020. Interventions: Patients were randomized in a 1:1:1 ratio at each site to usual care, empowered care, or team-based empowered care. All patients underwent a JADE web portal-guided structured assessment at baseline and month 12. Patients in the usual care and empowered care groups received a medical follow-up. Patients in the empowered care group also received a personalized JADE report and nurse telephone calls every 3 months. Patients in the team-based empowered care group received additional face-to-face reviews every 3 months from a physician-nurse team. Main Outcomes and Measures: The primary outcome was the proportion of patients who attained multiple treatment targets (defined as ≥3 of 5 targets: HbA1c level <7.0% [53 mmol/mol], blood pressure <130/80 mm Hg, low-density lipoprotein cholesterol level <1.8 mmol/L, triglyceride level <1.7 mmol/L, and/or persistent use of renin-angiotensin-aldosterone system inhibitors). Results: A total of 2393 patients (mean [SD] age, 67.7 [9.8] years; 1267 men [52.9%]) were randomized to the usual care group (n = 795), empowered care group (n = 802), and team-based empowered care group (n = 796). At baseline, 34.7% patients (n = 830) were on 3 treatment targets. On intention-to-treat analysis, the team-based empowered care group had the highest proportion of patients who had further increase in attainment of multiple treatment targets (within-group differences: usual care group, 3.9% [95% CI, 0.0%-7.8%]; empowered care group, 1.3% [95% CI, -2.8% to 5.4%]; team-based empowered care group, 9.1% [95% CI, 4.7%-13.5%]). The team-based empowered care group was more likely to attain multiple treatment targets than the usual care group (risk ratio [RR], 1.17; 95% CI, 1.00-1.37) and the empowered care group (RR, 1.25; 95% CI, 1.06-1.48) after adjustment for site. Compared with the group that did not attain multiple treatment targets, the group that attained multiple treatment targets reported a lower incidence of cardiovascular, kidney, and cancer events (8.4% [n = 51] vs 14.5% [n = 134]; P = .004). Analysis of the per-protocol population yielded similar results. Conclusions and Relevance: This trial found that technology-assisted team-based care for 12 months improved the attainment of multiple treatment targets as well as empowerment in patients with DKD. Trial Registration: ClinicalTrials.gov Identifier: NCT02176278.

Estimating direct medical costs of type 2 diabetes mellitus in the Philippines: a protocol.

INTRODUCTION: Diabetes and its complications are a major cause of morbidity and mortality in the Philippines. The prevalence of diabetes in the Philippines has increased from 3.4 million in 2010 to 3.7 million in 2017. The government has formulated strategies to control this increase, for example, through its non-communicable disease prevention and control plan. However, there is scarce research on the financial burden of diabetes. Filling this gap may further help policymakers to make informed decisions while developing and implementing resource planning for relevant interventions. The primary objective of the current study is to estimate the direct medical costs associated with type 2 diabetes mellitus (T2DM). METHODS AND ANALYSIS: This is a 1-year retrospective cohort study of patients with T2DM in 2016. Data will be collected from: (1) hospital databases from public institutions to estimate the cost of diabetes treatment and (2) physician interviews to estimate the cost of management of diabetes in outpatient care. We will perform descriptive and comparative analyses on direct medical costs and healthcare resource utilisation, stratified by the presence of diabetes-associated complications. ETHICS AND DISSEMINATION: Research ethics board approval has been obtained from the Department of Health Single Joint Research Ethics Board and Cardinal Santos Medical Center Research Ethics Review Committee. Findings from the study will be reported in peer-reviewed scientific journals and local researcher meetings.

Initial combination therapy with vildagliptin plus metformin in drug-naïve patients with T2DM: a 24-week real-life study from Asia.

AIMS: To assess the effectiveness and safety of vildagliptin/metformin initial combination therapy in drug-naïve patients with type 2 diabetes mellitus (T2DM). METHODS: INITIAL was a 24-week prospective, observational study in T2DM patients with glycated hemoglobin (HbA1c) ≥ 7.5%, and prescribed vildagliptin/metformin as initial combination therapy. The primary endpoint was change in HbA1c from baseline to week 24. Key secondary endpoints were HbA1c change from baseline to week 12, proportion of patients achieving HbA1c ≤7.0%, change in body weight at 12 and 24 weeks, change in HbA1c by sub-groups (baseline HbA1c, age, body mass index [BMI], dosage strength, co-morbidities) from baseline to week 24, and safety. RESULTS: A total of 532 patients were enrolled. The mean age, HbA1c, and BMI were 49.6 ± 11.27 years, 9.3 ± 1.57%, and 26.7 ± 4.50 kg/m2, respectively. Cardiovascular risk factors present at baseline were dyslipidemia (30.1%), hypertension (29.7%), and obesity (20.9%). The mean reductions in HbA1c from baseline to week 12 (-1.6 ± 1.59%) and 24 (-1.9 ± 1.70%) were statistically significant (p < .001). At 24 weeks, 39.6% of patients achieved HbA1c ≤ 7.0%, and the mean body weight reduction was -1.1 ± 2.62 kg. HbA1c reductions were consistently seen from baseline to weeks 12 and 24 in the various sub-groups. Overall, 48 (9.0%) patients reported adverse events, including one hypoglycemic episode. There were no serious adverse events or deaths. CONCLUSIONS: Overall, in a relatively young drug-naïve T2DM Asian study population with high baseline HbA1c and often associated with cardiovascular risk factors, vildagliptin/metformin combination therapy was associated with significant and clinically relevant HbA1c reduction from baseline. This effect was seen at week 12, was maintained over 24 weeks, and was accompanied by good tolerability.

Cross-sectional survey of biosimilar insulin utilization in Asia: The Joint Asia Diabetes Evaluation Program.

AIMS/INTRODUCTION: Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register. MATERIALS AND METHODS: We carried out a cross-sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events. RESULTS: Amongst 81,531 patients, 20.5% (n = 16,738) were insulin-treated. In four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%; the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non-significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures. CONCLUSIONS: Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes.

Self-Reported Hypoglycemia in Insulin-Treated Patients with Diabetes: Results from the Philippine Cohort of the International Operations Hypoglycemia Assessment Tool (IO HAT) Study.

OBJECTIVE: To determine the frequency of hypoglycemia in insulin-treated patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in the non-interventional International Operations Hypoglycemia Assessment Tool (IO HAT) study. METHODOLOGY: This sub-analysis included Filipino patients with T1DM or T2DM, aged 18 years and older, treated with insulin for more than 12 months, who completed the two-part self-assessment questionnaires (SAQ1 and SAQ2) and patient diaries that recorded hypoglycemia during retrospective (6 months/4 weeks before baseline) and prospective period (4 weeks after baseline) (ClinicalTrials.gov number: NCT02306681). RESULTS: A total of 671 patients were enrolled and completed the SAQ1 (62 patients with T1DM and 609 patients with T2DM). Almost all patients (100% in T1DM and 99.3% in T2DM) experienced at least 1 hypoglycemic event prospectively. The incidence of any hypoglycemia was also high in the prospective period compared to retrospective period (72.6 [95% CI: 64.8, 80.9] events PPY and 43.6 [95% CI: 37.8, 49.9] events PPY; p=0.001, respectively) in T1DM patients. CONCLUSION: Among insulin-treated patients, higher rates of hypoglycemia were reported prospectively than retrospectively. This indicates that the patients in real-life setting often under-report hypoglycemia. Patient education can help in accurate reporting and appropriate management of hypoglycemia and diabetes.

Self-reported hypoglycemia in insulin-treated patients with diabetes: Results from an international survey on 7289 patients from nine countries.

AIMS: Hypoglycemia constitutes a significant barrier to achieving glycemic control with insulin in both type 1 and type 2 diabetes. Historically, it has been difficult to accurately verify the rates of hypoglycemia within a clinical setting and there is a need for high-quality, real-world data to ascertain the true rates of hypoglycemia in clinical practice. The global Hypoglycemia Assessment Tool (HAT) study was designed to assess the global incidence of hypoglycemia in patients with insulin-treated diabetes, and the results have indicated that the overall incidence of hypoglycemia is high, with large variations between geographical regions. METHODS: The International Operations HAT (IO HAT) study retrospectively and prospectively assessed the incidence of hypoglycemia in patients with insulin-treated diabetes in Bangladesh, Colombia, Egypt, Indonesia, Philippines, Singapore, South Africa, Turkey, and United Arab Emirates. RESULTS: During the prospective period, hypoglycemic events were reported by 97.4% of patients with type 1 diabetes and 95.3% of those with type 2 diabetes, with an estimated rate of 6.86 events per patient per month (PPPM) for patients with type 1 diabetes and 2.37 events PPPM for patients with type 2 diabetes. CONCLUSIONS: These results represent the first patient-reported dataset on hypoglycemia in the participating countries and confirm that hypoglycemia is under-reported and more widespread than previously believed. Although the incidence of hypoglycemia was variable among patients on different treatment regimens, there were substantial impacts on both productivity and healthcare utilization following an episode of hypoglycemia. This trial is registered at clinicaltrials.gov: NCT02306681.

A Consensus of Key Opinion Leaders on the Management of Pre-diabetes in the Asia-Pacific Region.

The Asia-Pacific region carries a high disease burden, with over half of the global diabetic population residing in this region. Increasing evidence shows that without targeted intervention, the progression from impaired glucose tolerance (IGT) to type 2 diabetes occurs more frequently in Asians compared with Caucasians. Furthermore, IGT is independently associated with an increased risk of cardiovascular disease, and should be managed as early as possible. Because diabetes is now a major public health issue, strategies aimed at prevention and treatment are urgently required. Lifestyle modification, including weight loss, dietary changes and increased physical activity, play a major role in controlling the disease. Significant evidence also supports the effectiveness of a combination of lifestyle modification and pharmacologic therapy, such as metformin, in delaying the onset of diabetes. Although the importance of lifestyle interventions is well recognized throughout Asia, many countries do not have formal recommendations to guide the diagnosis and management of individuals at risk of progression to diabetes. At a recent regional meeting, experts from the Asian region convened to develop consensus recommendations to guide clinicians in the management of Asian patients with pre-diabetes. These consensus recommendations provide a clear and concise approach to the management of individuals with IGT based on the available evidence and current best clinical practice.

Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

OBJECTIVE: Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. METHODS: Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. RESULTS: Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P<.001). Target HbA1c of <7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm. CONCLUSION: Patient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

Consensus statement: appropriate consumer education and communication programs for weight- loss agents in Asia.

BACKGROUND AND AIM: The increasing prevalence of overweight and obesity worldwide demands increased efforts in the prevention and management of obesity. This article aims to present consensus statements promoting appropriate consumer education and communication programs for weight-loss agents in Asia. METHODS: Panel members from various disciplines developed consensus statements based on an expert meeting on the benefits of consumer education and communication programs for over-the-counter weight-loss agents. Key opinion leaders discussed relevant data that served as the basis of the recommendations. RESULTS: Obesity is a growing epidemic in Asia, turning the region into a potential market for weight-loss products and services. Current trends in direct-to-consumer advertising demonstrate the pervasiveness of false representations lacking adequate substantiation. Relevant issues and recommendations were established. CONCLUSIONS: Public education on weight management is a shared responsibility; there is a need to raise public awareness of obesity and its health-related consequences. Advertising guidelines should ensure responsible direct-to-consumer advertising of weight-loss agents.

Parathyroidectomy for refractory secondary hyperparathyroidism with severe bone disease / Journal of the ASEAN Federation of Endocrine Societies

Advances in the medical management of secondary hyperparathyroidism due to renal failure have decreased the use of parathyroidectomy as a treatment option. However, some patients with end-stage renal disease still progress to refractory hyperparathyroidism and debilitating bone disease, for which parathyroidectomy may be warranted. We describe a case of a 35-year-old female on chronic hemodialysis who presented with bone pains, deformities, decrease in height and recurrent pathologic fractures. She had markedly elevated parathyroid hormone (PTH), vitamin D deficiency, persistent hyperphosphatemia and hypocalcemia despite therapeutic measures. Subtotal parathyroidectomy was done with eventual improvement of biochemical abnormalities, resolution of bone pains and healing of fractures.

The diagnostic accuracy of ultrasound guided fine-needle aspiration biopsy and intraoperative frozen section examination in nodular thyroid disease / Journal of the ASEAN Federation of Endocrine Societies

OBJECTIVES:To determine the diagnostic accuracy of combined ultrasound-guided fine needle aspiration biopsy (USG-FNAB) and intraoperative frozen section examinationin (FSE) in diagnosing malignant thyroid nodules.METHODOLOGY:Retrospective review of patients undergoing thyroidectomy with intraoperative frozen section examination following ultrasound guided fine-needle aspiration biopsy. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated with respect to final histology.RESULTS: A total of 2,239 nodules were subjected to USG-FNAB at the Diabetes, Thyroid and Endocrine Center, St. Luke's Medical Center between January 2007 and December 2009. Two hundred fifty-one nodules were surgically excised following USG-FNAB. Frozen section examinations were taken from 90 of 251 nodules. The USG-FNAB yielded 90.3% (n=1,721) adequate specimens and 9.7% (n=185) inadequate specimens. The histologic examination of the 251 surgically excised nodules revealed 182 (73%) benign and 69 (27%) malignant nodules. The sensitivity, specificity, positive and negative predictive values and accuracy rate of USG-FNAB cytology are 70.3%, 92.8%, 76.5%, 90.4% and 87.2%, respectively. The diagnosis by frozen section was benign in 56 cases (62%), malignant in 10 cases (11%) and deferred in 24 cases (27%). By FSE, the sensitivity, specificity, positive and negative predictive values and accuracy rate are 83.3%, 100%, 100%, 96.4% and 96.7%, respectively. A diagnostic accuracy of up to 97.2% was achieved when USG-FNAB and FSE were combined and when their findings were concordant. When USG-FNAB and FSE diagnoses were discordant, the FSE showed superior accuracy (83.3%) than cytology (16.7%). In the group of nodules with indeterminate or inadequate cytology, the diagnostic accuracy of frozen section is 100%.CONCLUSION:Ultrasound guided fine-needle aspiration biopsy is an accurate preoperative test for the evaluation of nodular thyroid disease. It helps to distinguish malignant from benign lesions. The intraoperative frozen section is a valuable test for confirming the cytologic diagnosis. It is especially important in identifying malignant thyroid nodule in cases with indeterminate cytology. The combination of USG-FNAB and FSE greatly improves the accuracy rate in thyroid cancer detection.

Comparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women.

We evaluated adherence with raloxifene therapy compared with daily bisphosphonate in Asian postmenopausal women at increased risk of osteoporotic fractures. In this 12-month observational study conducted in Asia (Hong Kong, Malaysia, Pakistan, Philippines, Singapore, Taiwan), 984 postmenopausal women (aged 55 years or older) were treated with raloxifene 60 mg/day (n = 707; 72%) or daily bisphosphonate (alendronate 10 mg/day; n = 206; 21%, or risedronate 5 mg/day; n = 71; 7%) during their normal course of care. Patients were assessed at baseline, 6, and 12 months. Baseline characteristics (including age, race, education, menopausal status, and baseline fractures) were comparable between the raloxifene and bisphosphonate groups. More women on raloxifene completed the study compared with those on bisphosphonate (50.2% versus 37.5%; P < 0.001). Patients also took raloxifene for a longer period than bisphosphonate (median, 356 versus 348 days; P = 0.011). Compared with those taking bisphosphonate, significantly fewer patients taking raloxifene discontinued the study because of stopping treatment (5.7% versus 10.1%, P = 0.017) or changing treatment (2.8% versus 9.7%, P < 0.001). Inconvenient dosing was reported as a primary reason for discontinuation due to stopping or changing treatment in 19 (6.9%) bisphosphonate patients compared with 0 raloxifene patients. The percentage of patients who had consumed 80% or more of their study medication was similar for raloxifene patients (48-56 weeks; 95.2%) and bisphosphonate patients (48-56 weeks; 93.3%). More raloxifene patients responded that they were satisfied with their medication than bisphosphonate patients at 48-56 weeks (P = 0.002). We concluded that Asian postmenopausal women at increased risk of osteoporotic fractures showed a greater propensity to remain on raloxifene compared with bisphosphonate. The women on raloxifene exhibited lower discontinuation rates and higher treatment satisfaction.