Search

BackgroundDiabetes is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease. This study aims to develop and validate different risk predictive models for incident CKD and CKD progression in people with type 2 diabetes (T2D).MethodsWe reviewed a cohort of people with T2D seeking care from two tertiary hospitals in the metropolitan cities of the state of Selangor and Negeri Sembilan from January 2012 to May 2021. To identify the 3-year predictor of developing CKD (primary outcome) and CKD progression (secondary outcome), the dataset was randomly split into a training and test set. A Cox proportional hazards (CoxPH) model was developed to identify predictors of developing CKD. The resultant CoxPH model was compared with other machine learning models on their performance using C-statistic.ResultsThe cohorts included 1992 participants, of which 295 had developed CKD and 442 reported worsening of kidney function. Equation for the 3-year risk of developing CKD included gender, haemoglobin A1c, triglyceride and serum creatinine levels, estimated glomerular filtration rate, history of cardiovascular disease and diabetes duration. For risk of CKD progression, the model included systolic blood pressure, retinopathy and proteinuria. The CoxPH model was better at prediction compared with other machine learning models examined for incident CKD (C-statistic: training 0.826; test 0.874) and CKD progression (C-statistic: training 0.611; test 0.655). The risk calculator can be found at https://rs59.shinyapps.io/071221/.ConclusionsThe Cox regression model was the best performing model to predict people with T2D who will develop a 3-year risk of incident CKD and CKD progression in a Malaysian cohort.

Background: Due to several limitations in the study designs of sulfonylurea pharmacogenomics studies, we investigated the clinical and genetic predictors of secondary sulfonylurea failure in Type 2 diabetes patients. Materials & methods: Patients receiving the maximum sulfonylurea and metformin doses for >1 year were enrolled. Secondary sulfonylurea failure was defined as HbA1c >7.0% (>53 mmol/mol) after a 12-month follow-up. Results: By multivariate analysis, increased insulin resistance (HOMA2-IR), baseline HbA1c >7.0%, residing in eastern Peninsular Malaysia, and the CC genotype of rs757110 ABCC8 gene polymorphism were independent predictors of secondary sulfonylurea failure (p

Objectives. The COVID-19 pandemic has made a major impact on hospital services globally, including the care of persons with diabetes and endocrine disorders. The aim of this study is to describe the epidemiology of COVID-19 in the ASEAN Federation of Endocrine Societies (AFES) member countries; to describe challenges, changes and opportunities in caring for patients with endocrine diseases, as well as in fellowship training programs, and endocrine-relatedresearch in the AFES countries. Methodology. The AFES ASEAN Survey Of Needs in Endocrinology (AFES A.S.-O.N.E.) was an open-ended questionnaire that was sent to the presidents and representatives of the AFES member countries by email. Responses from Societies were collated and synthesized to obtain perspectives on the emergent issues in endocrinology in the Southeast Asian region during this pandemic. Results. The burden of COVID-19 cases varied widely across the AFES member countries, with the least number of cases in Vietnam and Myanmar, and the greatest number of cases in either the most populous countries (Indonesia and the Philippines), or a country with the highest capability for testing (Singapore). The case fatality rate was also the highest for Indonesia and the Philippines at around 6%, and lowest for Vietnam at no fatalities. The percentage with diabetes among patients with COVID-19 ranged from 5% in Indonesia to 20% in Singapore, approximating the reported percentages in China and the United States. The major challenges in managing patients with endocrine diseases involved inaccessibility of health care providers, clinics and hospitals due to the implementation of lockdowns, community quarantines or movement control among the member countries. This led to disruptions in the continuity of care, testing and monitoring, and for some, provision of both preventive care and active management including surgery for thyroid cancer or pituitary and adrenal tumors, and radioactive iodine therapy. Major disruptions in the endocrine fellowship training programs were also noted across the region, so that some countries have had to freeze hiring of new trainees or to revise both program requirements and approaches to training due to the closure of outpatient endocrine clinics. The same observations are seen for endocrine-related researches, as most research papers have focused on the pandemic. Finally, the report ends by describing innovative approaches to fill in the gap in training and in improving patient access to endocrine services by Telemedicine. Conclusion. The burden of COVID-19 cases and its case fatality rate varies across the AFES member countries but its impact is almost uniform: it has disrupted the provision of care for patients with endocrine diseases, and has also disrupted endocrine fellowship training and endocrine-related research across the region. Telemedicine and innovations in training have been operationalized across the AFES countries in an attempt to cope with the disruptions fromCOVID-19, but its over-all impact on the practice of endocrinology across the region will only become apparent once we conquer this pandemic.

To compare Saudi Arabia with other countries regarding patient attitudes towards fasting Ramadan and complications related to fasting during the COVID-19 pandemic.Data collected from Saudi Arabia and 12 other mostly Muslim majority countries, via physician administered questionnaire within post Ramadan 2020.1485 Type1 diabetes (T1DM) patients analyzed; 705 (47.5%) from Saudi Arabia vs. 780 (52.5%) from other countries. 1056 (71.1%) fasted Ramadan; 636 (90.2%) of Saudi patients vs. 420 (53.8%) of other countries. Experiencing Ramadan during the COVID-19 pandemic did not affect the Saudi T1DM patients' decision to fast while it significantly influenced their decision in other countries (1.4 vs 9.9%, P 0.001). More Saudi patients needed to break the fast due to a diabetes related complication compared to other countries (67.4% vs. 46.8%, p=0.001). The mean number of days fasted in Saudi and other countries was 24 ± 7 and 23 ± 8 days respectively. Hypoglycemic events were more common among Saudi patients during Ramadan compared to other countries 72% and 43.6% (p 0.001) respectively. There was a significant difference in timing; the largest peak for Saudi Arabia patients was after dawn (35% vs 7%, p 0.001), while it was pre-sunset for the other countries (23 vs 54%, p = 0.595). Day time-hyperglycemia was also more common among Saudi patients (48.6% vs. 39%, p 0.001), however it was a less likely cause to break the fast (25.6% vs 38.3%, p 0.001).Observing the fast of Ramadan is extremely common among Saudi T1DM patients compared to other Muslim countries and was not affected by the COVID-19 pandemic. However, it was associated with higher frequency of hypoglycemic and hyperglycemic episodes.

Patients with type 2 diabetes (T2D) carry higher risk of glycaemic variability during Ramadan. Glucose-lowering medications such as SGLT2 inhibitors are also associated with genitourinary infection, acute kidney injury, and euglycaemic diabetic ketoacidosis. Limited data is available on the effects of SGLT2 inhibitors on T2D patients during Ramadan. We investigated effects of empagliflozin use in fasting T2D patients.This was a prospective cohort study in a single diabetes centre in Malaysia. Empagliflozin group were on study drug for at least three months. For control group, subjects not receiving SGLT2 inhibitors were recruited. Follow-up were performed before and during Ramadan fasting. Anthropometric measurements, blood pressure, renal profile, and blood ketone were recorded during visits. Hypoglycaemia symptoms were assessed via hypoglycaemia symptom rating questionnaire (HypoSRQ).We recruited a total of 98 subjects. Baseline anthropometry, blood pressure, and renal parameters were similar in two groups. No significant changes in blood pressure, weight, urea, creatinine, eGFR, or haemoglobin levels during Ramadan was found in either group. Likewise, no difference was detected in blood ketone levels (empagliflozin vs control, 0.17 ± 0.247 mmol/L vs 0.13 ± 0.082 mmol/L, p = 0.304) or hypoglycaemia indices (empagliflozin vs control, 19.1% vs 16%, p = 0.684).Ramadan fasting resulted in weight loss and reduction in eGFR levels in patients with T2D. Empagliflozin use during Ramadan is safe and not associated with increased risk of dehydration, ketosis, or hypoglycaemia. Therefore, empagliflozin is a viable glucose-lowering drug for patients with T2D planning for Ramadan fasting.

To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes.MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322).We included 38 trials from seven classes of glucose-lowering therapies. Both sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty).SGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.

Fasting during Ramadan is one of the five pillars of Islam and is obligatory for all healthy Muslims from the age of puberty. Though individuals with some illness and serious medical conditions, including some people with diabetes, can be exempted from fasting, many will fast anyway. It is of paramount importance that people with diabetes that fast are given the appropriate guidance and receive proper care. The International Diabetes Federation (IDF) and Diabetes and Ramadan (DaR) International Alliance have come together to provide a substantial update to the previous guidelines. This update includes key information on fasting during Ramadan with type 1 diabetes, the management of diabetes in people of elderly ages and pregnant women, the effects of Ramadan on one's mental wellbeing, changes to the risk of macrovascular and microvascular complications, and areas of future research. The IDF-DAR Diabetes and Ramadan Practical Guidelines 2021 seek to improve upon the awareness, knowledge and management of diabetes during Ramadan, and to provide real-world recommendations to health professionals and the people with diabetes who choose to fast.

Aim: This study investigated the incidence of sulfonylurea-induced hypoglycemia and its predictors in Type 2 diabetes (T2D) patients. Patients & methods: In this prospective, observational study, T2D patients on maximal sulfonylurea-metformin therapy >1 year were enrolled. Hypoglycemia was defined as having symptoms or a blood glucose level 0.05). Prior history of hypoglycemia admission (odds ratio = 16.44; 95% CI: 1.74–154.33, p = 0.014) independently predicted its risk. Conclusion: Sulfonylurea-treated T2D patients who experienced severe hypoglycemia are at increased risk of future hypoglycemia episodes.

Aim To develop an evidence-based expert group opinion on the role of insulin motivation to overcome insulin distress during different stages of insulin therapy and to propose a practitioner’s toolkit for insulin motivation in the management of diabetes mellitus (DM). Background Insulin distress, an emotional response of the patient to the suggested use of insulin, acts as a major barrier to insulin therapy in the management of DM. Addressing patient-, physician- and drug-related factors is important to overcome insulin distress. Strengthening of communication between physicians and patients with diabetes and enhancing the patients' coping skills are prerequisites to create a sense of comfort with the use of insulin. Insulin motivation is key to achieving targeted goals in diabetes care. A group of endocrinologists came together at an international meeting held in India to develop tool kits that would aid a practitioner in implementing insulin motivation strategies at different stages of the journey through insulin therapy, including pre-initiation, initiation, titration and intensification. During the meeting, emphasis was placed on the challenges and limitations faced by both physicians and patients with diabetes during each stage of the journey through insulinization. Review Results After review of evidence and discussions, the expert group provided recommendations on strategies for improved insulin acceptance, empowering behavior change in patients with DM, approaches for motivating patients to initiate and maintain insulin therapy and best practices for insulin motivation at the pre-initiation, initiation, titration and intensification stages of insulin therapy. Conclusions In the management of DM, bringing in positive behavioral change by motivating the patient to improve treatment adherence helps overcome insulin distress and achieve treatment goals.

Objectives The DAR Global survey of Ramadan-fasting during the COVID-19 pandemic aimed to describe the characteristics and care in participants with type 2 diabetes (T2D) with a specific comparison between those < 65years and > 65 years. Methods Participants were consented to answer a physician-administered questionnaire following Ramadan 2020. Impact of COVID-19 on the decision of fasting, intentions to fast and duration of Ramadan and Shawal fasting, hypoglycaemia and hyperglycaemia events were assessed. Specific analysis comparing age categories of 65years were performed. Results Among the 5865 participants, 22.5% were > 65 years old. Concern for COVID-19 affected fasting decision for 7.6% ( > 65years) vs 5.4% ( 65 years old did not fast (28.8% vs 12.7%, 15 days and 12.6% had to break fast due to diabetes-related illness. The average number of days fasting within and post-Ramadan were 27 and 6 days respectively, regardless of age. Hypoglycaemia and hyperglycaemia occurred in 15.7% and 16.3% of participants respectively, with 6.5% and 7.4% requiring hospital care respectively. SMBG was performed in 73.8% of participants and 43.5% received Ramadan-focused education. Conclusion During the COVID-19 pandemic, universally high rates of Ramadan-fasting were observed regardless of fasting risk level. Glycemic complications occurred frequently with older adults requiring higher rates of acute hospital care. Risk stratification is essential followed by pre-Ramadan interventions, Ramadan-focused diabetes education and self-monitoring to reduce and prevent complications, with particular emphasis in older adults.

OBJECTIVES: The DaR Global survey was conducted to determine the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in

Various data have demonstrated inadequate glycemic control amongst Asians with type 2 diabetes mellitus (T2DM), possibly on account of suboptimal titration of basal insulin—an issue which needs to be further examined. Here we review the available global and Asia-specific data on titration of basal insulin, with a focus on the use of insulin glargine 100 U/mL (Gla-100). We also discuss clinical evidence on the efficacy and safety of titrating Gla-100, different approaches to titration, including some of the latest technological advancements, and guidance on the titration of basal insulin from international and local Asian guidelines. The authors also provide their recommendations for the initiation and titration of basal insulin for Asian populations. Discussion of the data included in this review and in relation to the authors’ clinical experience with treating T2DM in Asian patients is also included. Briefly, clinical studies demonstrate the achievement of adequate glycemic control in adults with T2DM through titration of Gla-100. However, studies investigating approaches to titration, specifically in Asian populations, are lacking and need to be conducted. Given that the management of insulin therapy is a multidisciplinary team effort involving endocrinologists, primary care physicians, nurse educators, and patients, greater resources and education targeted at these groups are needed regarding the optimal titration of basal insulin. Technological advancements in the form of mobile or web-based applications for automated dose adjustment can aid different stakeholders in optimizing the dose of basal insulin, enabling a larger number of patients in Asia to reach their target glycemic goals with improved outcomes. Electronic supplementary material The online version of this article (doi:10.1007/s13300-017-0322-z) contains supplementary material, which is available to authorized users.

Although the incidence of diabetes is rising in Southeast Asia, there is limited information regarding the incidence and manifestation of insulin‐associated hypoglycemia. The aim of the present review was to discuss what is currently known regarding insulin‐associated hypoglycemia in Southeast Asia, including its known incidence and impact in the region, and how the Southeast Asian population with diabetes differs from other populations. We found a paucity of data regarding the incidence of hypoglycemia in Southeast Asia, which has contributed to the adoption of Western guidelines. This might not be appropriate, as Southeast Asians have a range of etiological, educational and cultural differences from Western populations with diabetes that might place them at greater risk of hypoglycemia if not managed optimally. For example, Southeast Asians with type 2 diabetes tend to be younger, with lower body mass indexes than their Western counterparts, and the management of type 2 diabetes with premixed insulin preparations is more common in Southeast Asia. Both of these factors might result in higher rates of hypoglycemia. In addition, Southeast Asians are often poorly educated about hypoglycemia and its management, including during Ramadan fasting. We conclude there is a need for more information about Southeast Asian populations with diabetes to assist with the construction of more appropriate national and regional guidelines for the management of hypoglycemia, more closely aligned to patient demographics, behaviors and treatment practices. Such bespoke guidelines might result in a greater degree of implementation and adherence within clinical practice in Southeast Asian nations.

BACKGROUND: Most metastatic pheochromocytoma (PCC) and paraganglioma (PGL) express somatostatin receptors (SSTR) similar to neuroendocrine tumors, which may benefit from peptide radionuclide receptor therapy (PRRT), a molecular targeted therapy to SSTR avid tumors. We describe 5 cases of progressive metastatic PCC/PGL who had PRRT from year 2015 to 2018. RESULTS: The patients were aged 18-51 years at diagnosis of PCC/PGL, with mean duration of disease to PRRT of 9.6 (4 - 19) years. Four patients with functional disease were on alpha-blockade prior to PRRT. All patients had surgery as first line therapy, with 3 had repeated surgeries prior to PRRT. One patient had trans-arterial chemo-embolization and one patient had alcohol ablation therapy prior PRRT. All patients underwent induction treatment of PRRT, consisting 4 cycles of Lu-177 DOTATATE given at 8-16 weeks apart, with dose ranged 68.8 - 207mCi (2.5 - 7.66 GBq). Two patients with functioning PCC/PGL experienced paroxysm during PRRT, requiring adjustment of infusion rate and anti-hypertensives. Three patients had partial response and the other 2 had mixed response at interim imaging assessment. The subsequent imaging post PRRT showed stable disease. One patient had transient worsening of disease clinically and biochemically at the treatment interim which improved with subsequent cycles of therapy. All patients with functioning disease showed improvement in symptoms and catecholamine levels upon completion of PRRT, of which, 2 of them had their antihypertensive agents stopped. CONCLUSION: PRRT helps in disease control in particularly the symptoms, blood pressure and biochemical parameters in patients with SSTR avid metastatic PCC/PGL. Further review required for long term outcome of PRRT. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Introduction: Antithyroid drugs (ATDs) are recommended effective treatment for uncontrolled Graves’ disease but achieves maximal antithyroid effects between 6 to 12 weeks. Cholestyramine sequesters thyroid hormones in the intestine and enhances its fecal excretion. Steroids inhibits the conversion of thyroxine to triiodothyronine peripherally and blocks thyroid hormone production. We hypothesize that adjunctive cholestyramine or prednisolone to ATDs may reduce circulating thyroid hormones and improve biochemical control. Methods: In this multicenter, open labelled, parallel-group trial, we randomly assigned in a 1:1:1 ratio, adult Graves’ disease patients with moderate to severe hyperthyroidism (FT4 levels > 40 pmol/L) to receive either adjunctive cholestyramine 4g twice daily or prednisolone 30 mg daily in tapering down doses in addition to standard treatment or standard treatment alone for 4 weeks. Standard treatment was carbimazole 30mg daily and propanolol 40mg BD for 4 weeks. The primary endpoint was change from baseline for FT4 and FT3 levels at the end of 2 and 4 weeks of intervention. Safety endpoints including gastrointestinal adverse events, hypokalemia, hypothyroid and hyperglycemia were recorded. Results: A total of 107 patients were screened and 97 patients randomised. Baseline demographics, clinical and biochemical characteristics were similar between the groups. The baseline median FT4 levels were 51.6 pmol/L (42.2-71.1) and FT3 levels 22.5 pmol/L (5.7-30.8). Both FT4 and FT3 declined at two and four weeks from baseline but were no different between the three groups. At week 2, median FT4 levels declined by 43.3% (25.8-53.3), 39.8% (19.1-55.1) and 33.4% (20.1-62.0) (p=0.988) and at 4 weeks, 50.9% (33.3-63.8), 57.8% (39-70.9), 55.8% (36.2-72.0) (p =0.362) in the cholestyramine, prednisolone and standard treatment group respectively. Median FT3 levels reduced by 51.2% (22.8- 58.9), 59.9% (38.9-69.3) and 50.9% (26.9-63.9) (p=0.084) at week 2 and 60% (39.2-67.9), 67.5% (38.4-78.4), 63.1% (45.7-69.3) (p=0.387) in the corresponding cholestyramine, prednisolone and standard treatment only group. A higher number of gastrointestinal adverse events: constipation, bloating, diarrhea, abdominal pain and vomiting were observed in the cholestyramine group in the first 2 weeks of treatment and no difference in the incidence of hypokalemia between groups. Conclusion: Adjunctive cholestyramine or prednisolone did not improve the biochemical control of uncontrolled moderate to severe Graves’ disease when added to ATDs. The additional use of cholestyramine resulted in a higher number of gastrointestinal adverse events but were mild and self-limiting.

For ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), when surgery is not feasible, or in cases of severe biochemical disturbances, immunosuppression or mental instability, medical therapy with agents such as etomidate is indicated. We present our experience in using etomidate for a 41-year old female with EAS secondary to a malignant mediastinal paraganglioma. We were able to demonstrate that etomidate can be used effectively to control severe hypercortisolism in a lower dose than previously described.

Objective Eating self-efficacy behavior is an important predictor of successful lifestyle intervention. This secondary analysis evaluated the changes in eating self-efficacy behavior in patients with type 2 diabetes (T2D) and overweight/obesity following structured lifestyle intervention based on the Malaysian customized transcultural Diabetes Nutrition Algorithm (tDNA). Methods Patients with T2D and overweight/obesity (n = 230) were randomized either into the tDNA group which included a structured low-calorie meal plan using normal foods, incorporation of diabetes-specific meal replacements, and an exercise prescription or usual T2D care (UC) for 6 months. Patients in the tDNA group also received either counseling with motivational interviewing (tDNA-MI) or conventional counseling (tDNA-CC). The UC group received standard dietary and exercise advice using conventional counseling. Eating self-efficacy was assessed using a locally validated Weight Efficacy Lifestyle (WEL) questionnaire. All patients were followed up for additional 6 months’ post-intervention. Results There was a significant change in WEL scores with intervention over one-year [Group X Time effect: F = 51.4, df = (3.4, 318.7), p Conclusion Eating self-efficacy improved in patients with T2D and overweight/obesity who maintained their weight loss and glycemic control following a structured lifestyle intervention based on the Malaysian customized tDNA and the improvement was further enhanced with motivational interviewing. Clinical trial This randomized clinical trial was registered under National Medical Research Registry, Ministry of Health Malaysia with registration number: NMRR-14-1042-19455 and also under ClinicalTrials.gov with registration number: NCT03881540.

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Purpose To evaluate the diagnostic performance of 68Ga-DOTATATE 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT), 18F-FDG PET/CT and 131I-MIBG scintigraphy in the mapping of metastatic pheochromocytoma and paraganglioma.

Background Increasing prevalence and disease burden has led to an increasing demand of programs and studies focused on dietary and lifestyle habits, and chronic diseases such as type 2 diabetes mellitus (T2DM). We evaluated the effects of a 6-month web-based dietary intervention on Dietary Knowledge, Attitude and Behaviour (DKAB), Dietary Stages of Change (DSOC), fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c) in patients with uncontrolled HbA1c (> 7.0%) in a randomised-controlled trial (myDIDeA) in Malaysia. Methods The e-intervention group (n = 62) received a 6-month web-delivered intensive dietary intervention while the control group (n = 66) continued with their standard hospital care. Outcomes (DKAB and DSOC scores, FBG and HbA1c) were compared at baseline, post-intervention and follow-up. Results While both study groups showed improvement in total DKAB score, the margin of improvement in mean DKAB score in e-intervention group was larger than the control group at post-intervention (11.1 ± 0.9 vs. 6.5 ± 9.4,p

To gain insight into type-2 diabetic patients’ perceptions and beliefs about the use of insulin, to explore barriers to initiation of insulin and to evaluate the impact of a short educational intervention regarding patients’ resistance to using insulin injections. This is an exploratory qualitative study. One-to-one in-depth interviews were conducted with a purposive sample of type-2 diabetic patients. Then, a short educational intervention was conducted with the participants. After the intervention, the participants were interviewed to evaluate their acceptance of insulin initiation. The interviews were audio-taped and transcribed verbatim. Thematic content analysis was conducted and the analysis was reviewed independently by two researchers. A total of 13 diabetic patients were included in the study. Before the intervention, 11 subjects refused initiation of insulin. Resistance to initiation of insulin was influenced by misconceptions about insulin therapy, psychological barriers and fear, lack of self-efficacy and fear of adverse effects. All subjects perceived that insulin should only be initiated in very severe diabetes. Some participants demonstrated lack of belief in insulin efficacy. Psychological barriers and fears such as fear of self-injection and personal phobia about blood, needle and pain as well as perceived side effects also hindered insulin acceptance. The study findings revealed that misconceptions about insulin use and psychological barriers played a major role in patients’ resistance to initiation of insulin therapy. The study demonstrated, however, that a short educational intervention could dispel patients’ fears and erroneous beliefs and help them to start insulin therapy.

AimsThe aim of this A1chieve sub-group analysis was to examine populations beginning insulin aspart together with any basal insulin, all ± oral glucose lowering drugs: insulin aspart added to existing basal insulin (n=519); switched from biphasic insulin (n=947); switched from NPH plus human meal-time insulins (n=586); and insulin-naïve begun with basal plus insulin aspart (n=1594).MethodsA1chieve was a 24-week non-interventional study evaluating insulin analogues in 66,726 people with type 2 diabetes in routine clinical care in 28 non-Western countries. Major endpoints were analysed as change from baseline using Student's paired t-test.ResultsBaseline glycaemic control was poor (mean HbA1c: 9.4–10.1% [79–87 mmol/mol]). HbA1c, FPG and PPPG improved significantly from baseline in all groups (mean change from baseline in HbA1c: −2.8 to −1.8% [−31 to −20 mmol/mol]; FPG: −4.9 to −2.9 mmol/L; PPPG: −6.7 to −3.9 mmol/L; p

Introduction Hypoglycemia is a complication in the management of type 2 diabetes, and elderly people are at greater risk of experiencing hypoglycemia events than younger patients. Insulin analogs achieve glycemic control with minimal risk of hypoglycemia and may therefore be a good treatment option for all patients. Methods A1chieve was an international, multicenter, prospective, open-label, non-interventional, 24-week study in people with type 2 diabetes who started/switched to therapy with biphasic insulin aspart 30, insulin detemir or insulin aspart (alone/in combination) in routine clinical practice. This sub-analysis evaluated clinical safety and effectiveness of insulin aspart as part of a basal-bolus regimen (±oral glucose-lowering drugs) in three age-groups (≤40, >40–65, and >65 years) of insulin-experienced and insulin-naive people with type 2 diabetes. Results In total, 4,032 patients were included in the sub-analysis. After 24 weeks of insulin aspart treatment, significant improvements versus baseline were observed in all age-groups for: proportion of people with ≥1 hypoglycemia events (18.3–27.1% and 11.0–12.7%, at baseline and 24 weeks, respectively), ≥1 major hypoglycemia events (3.3–6.7% and 0–0.2%), and ≥1 nocturnal hypoglycemia events (9.2–13.7% and 2.9–4.9%); glycated hemoglobin (9.6–9.8% and 7.4%); fasting plasma glucose (change from baseline ranged from −3.6 to −4.4 mmol/l); and post-breakfast post-prandial plasma glucose (change from baseline ranged from −5.5 to −5.9 mmol/l). Fourteen serious adverse drug reactions were reported. Health-related quality of life was significantly improved for all age-groups (all, p

Aim To evaluate the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in ASEAN type 2 diabetes (T2D) patients switched from biphasic human insulin (BHI) in the non-interventional 24-week A 1 chieve study. Methods Indonesian, Malaysian, Filipino and Singaporean patients switched from BHI to BIAsp 30 at their physicians' discretion were included. The incidence of serious adverse drug reactions (SADRs), including major hypoglycaemia was the primary endpoint. Changes in hypoglycaemia, glycated haemoglobin A 1c (HbA 1c ), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), lipids, body weight and systolic blood pressure were also evaluated. Quality of life (QoL) was measured using the EQ-5D questionnaire. Results For the 465 patients included (mean±SD age: 56±10.3 years, diabetes duration: 9.7±7.1 years, baseline HbA 1c : 9.4±1.8%), the mean pre-study BHI dose was 0.62±0.28 IU/kg and 63.4% were dosing BHI twice daily (bid). The mean baseline BIAsp 30 dose was 0.65±0.27U/kg, titrated up to 0.71±0.28U/kg over 24 weeks, and most patients continued bid dosing. No SADRs or major hypoglycaemic episodes were reported. The proportion of patients reporting overall hypoglycaemia decreased significantly from 10.8% at baseline to 3.4% at Week 24 (p 1c : –1.4±1.7%, FPG: –56.7±72.5 mg/dL, post-breakfast PPPG: –84.8±82.8 mg/dL, p Conclusion BIAsp 30 was well-tolerated and significantly increased glycaemic control in this ASEAN subgroup poorly controlled on BHI.

Aims The present Malaysian cohort analysis determined the prevalence of hypoglycemia among patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) attending primary care- or hospital-based diabetes clinics in Malaysia and their awareness of the symptoms of hypoglycemia. Methods The Hypoglycemia Assessment Tool (HAT) study was a non-interventional, 6-month retrospective and 4-week prospective analysis of hypoglycemic events in 24 countries, using self-assessment questionnaires and diaries among patients with T1DM/T2DM aged ≥18 years, using insulin for >12 months. This report focuses on prospective data, as they are less prone to recall bias. Results There were 1153 participants in the Malaysian cohort (114 T1DM; 1039 T2DM). In the prospective period, 50.4% and 33.4% of patients reported ≥1 hypoglycemic events, with estimated rates of 20.3 and 13.1 events per patient-year of exposure in patients with T1DM and T2DM, respectively. 24.8% and 16.1% of patients with T1DM or T2DM, respectively, reported ≥1 nocturnal hypoglycemic event. The majority of patients (96.5%, T1DM; 91.8%, T2DM) knew what hypoglycemia was prior to the study. Impaired awareness was present in 48.0% (T1DM) and 36.9% (T2DM) of patients. In the prospective period, 50% of patients with T1DM or T2DM consulted a doctor or nurse following a hypoglycemia episode. Conclusions Half of patients with T1DM and a third of patients with T2DM reported ≥1 hypoglycemic event during the prospective period. Although the majority of patients knew the typical features of hypoglycemia, many reported impaired ability to recognize symptoms in real life. The present findings highlight the importance of patient education and physician awareness in dealing with hypoglycemia, in particular the burden of hypoglycemic unawareness. Clinical trial number This trial was registered at www.clinicaltrials.gov as NCT01696266 on 26 September 2012.

Ectopic thyroid or thyroid ectopia is a rare developmental anomaly with the prevalence of 1 per 100,000-300,000 population. Even rarer, such an anomaly manifests as dual thyroid ectopia. To our best knowledge, only one case has been reported on dual thyroid ectopia with Graves' disease in the English literature. We present here a case of dual thyroid ectopia complicated by Graves' disease, whereby the diagnosis was rendered through judicious use of various diagnostic modalities coupled with a close clinical follow-up. In this case, therapeutic consideration should be personalized with proper informed consent of the patient.

Thyroid disorders are amongst one of the most common endocrine diseases in Malaysia. In 1998, a taskforce consisting of experts in the field of thyroidology was set up to develop consensus recommendations for the management of thyroid disorders in the country based on available scientific evidence at that point in time. The following article summarizes the recommendations put together by the task force incorporating some of the recent available evidence with regards to the treatment of thyroid disorders.

In response to Dr. Maja Baretic’s letter, we would like to give an update on our patient’s clinical outcome. 1 After the first dose of denosumab, she continued to receive subcutaneous denosumab every 4–8 weekly depending on her calcium levels. She did not have any further admissions for hypercalcemic crisis. The …

Objective: The aim of this study was to evaluate Glycemic Variability (GV) among older adults with type 2 diabetes in a tertiary center (Putrajaya Hospital) using the Continuous Glucose Monitoring System (CGMS) and to compare the GV between patients with optimal versus suboptimal glycemic control. Research designs and methods: A total of 138 patients (69 with HbA1c