Cost of cardiovascular disease events in patients with and without type 2 diabetes and factors influencing cost: a retrospective cohort study.

BACKGROUND: Cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) are non-communicable diseases that impose a significant economic burden on healthcare systems, particularly in low- and middle-income countries. The purpose of this study was to evaluate the hospital treatment cost for cardiovascular disease events (CVDEs) in patients with and without diabetes and identify factors influencing cost. METHOD: We conducted a retrospective, cross-sectional study using administrative data from three public tertiary hospitals in Malaysia. Data for hospital admissions between 1 March 2019 and 1 March 2020 with International Classification of Diseases 10th Revision (ICD-10) codes for acute myocardial infarction (MI), ischaemic heart disease (IHD), hypertensive heart disease, stroke, heart failure, cardiomyopathy, and peripheral vascular disease (PVD) were retrieved from the Malaysian Disease Related Group (Malaysian DRG) Casemix System. Patients were stratified by T2DM status for analyses. Multivariate logistic regression was used to identify factors influencing treatment costs. RESULTS: Of the 1,183 patients in our study cohort, approximately 60.4% had T2DM. The most common CVDE was acute MI (25.6%), followed by IHD (25.3%), hypertensive heart disease (18.9%), stroke (12.9%), heart failure (9.4%), cardiomyopathy (5.7%) and PVD (2.1%). Nearly two-thirds (62.4%) of the patients had at least one cardiovascular risk factor, with hypertension being the most prevalent (60.4%). The treatment cost for all CVDEs was RM 4.8 million and RM 3.7 million in the T2DM and non-T2DM group, respectively. IHD incurred the largest cost in both groups, constituting 30.0% and 50.0% of the total CVDE treatment cost for patients with and without T2DM, respectively. Predictors of high treatment cost included male gender, non-minority ethnicity, IHD diagnosis and moderate-to-high severity level. CONCLUSION: This study provides real-world cost estimates for CVDE hospitalisation and quantifies the combined burden of two major non-communicable disease categories at the public health provider level. Our results confirm that CVDs are associated with substantial health utilisation in both T2DM and non-T2DM patients.

An update on the current characteristics and status of care for Muslims with type 2 diabetes fasting during Ramadan: the DAR global survey 2022.

BACKGROUND: Managing diabetes during Ramadan fasting is a challenge due lifestyle changes. We described the characteristics and patterns of care for type 2 diabetes mellitus (T2DM) during Ramadan 2020 and 2022. METHODS: Our study included multinational Muslims with T2DM who were during routine consultation. We collected data on demographics, fasting characteristics, and complications. Descriptive statistics, chi-square test, and multiple testing were performed. RESULTS: 12,529 patients participated. Mean age was 55.2 ± 11.8 years; 52.4% were females. Mean diabetes duration was 9.9 ± 7.4 years; 27.7% were with HbA1c >9% (75 mmol/mol) and 70% had complications. Metformin was the most used medication followed by insulin. 85.1% fasted ≥1 day; fasting mean duration was 27.6 ± 5.6 days. Hypoglycemia occurred in 15.5% of whom 11.7% attended emergency department or were hospitalized; this was significantly associated with age and/or duration of diabetes. Hyperglycemia occurred in 14.9% of whom 6.1% attended emergency department or were hospitalized and was also associated with age or duration of diabetes. 74.2% performed SMBG during fasting. 59.2% were educated on Ramadan fasting, with 89.7% receiving it during routine consultation. CONCLUSIONS: Ramadan fasting in T2DM is high. Multidisciplinary approach is required to mitigate complications. Our findings support current recommendations for safe fasting.

The goal of this survey was to describe the characteristics and current ways of care for Muslim patients with type 2 diabetes mellitus fasting during and after Ramadan 2020 and 2022. Most of the participants fasted a minimum of one day during Ramadan (85.1%). Overall, 15.5 and 14.9% reported low blood sugar levels or high blood sugar levels during fasting, respectively. Low blood sugar level was more reported in patients with older age, patients with longer diabetes duration, and women. High blood sugar level was more reported in patients with longer diabetes duration. Educational programs focusing on the risks occurring with fasting and practices that improve control of the disease will raise knowledge and awareness among patients with diabetes. Improving blood sugar control during Ramadan fasting remains a major need for both patients and healthcare providers who should collaborate to reduce the risk of diabetes-related problems.

Real-world evaluation of care for type 2 diabetes in Malaysia: A cross-sectional analysis of the treatment adherence to guideline evaluation in type 2 diabetes (TARGET-T2D) study.

AIM: Given a lack of data on diabetes care performance in Malaysia, we conducted a cross-sectional study to understand the clinical characteristics, control of cardiometabolic risk factors, and patterns of use of guideline-directed medical therapy (GDMT) among patients with type 2 diabetes (T2D), who were managed at publicly-funded hospitals between December 2021 and June 2022. METHODS: Patients aged ≥18 years with T2D from eight publicly-funded hospitals in the Greater Kuala Lumpur region, who had ≥2 outpatient visits within the preceding year and irrespective of treatment regimen, were eligible. The primary outcome was ≥2 treatment target attainment (defined as either HbA1c <7.0%, blood pressure [BP] <130/80 mmHg, or low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L). The secondary outcomes were the individual treatment target, a combination of all three treatment targets, and patterns of GDMT use. To assess for potential heterogeneity of study findings, all outcomes were stratified according to prespecified baseline characteristics namely 1) history of atherosclerotic cardiovascular disease (ASCVD; yes/no) and 2) clinic type (Diabetes specialist versus General medicine). RESULTS: Among 5094 patients (mean±SD age 59.0±13.2 years; T2D duration 14.8±9.2 years; HbA1c 8.2±1.9% (66±21 mmol/mol); BMI 29.6±6.2 kg/m2; 45.6% men), 99% were at high/very high cardiorenal risk. Attainment of ≥2 treatment targets was at 18%, being higher in General medicine than in Diabetes specialist clinics (20.8% versus 17.5%; p = 0.039). The overall statin coverage was 90%. More patients with prior ASCVD attained LDL-C <1.4 mmol/L than those without (13.5% versus 8.4%; p<0.001). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors (13.2% versus 43.2%), glucagon-like peptide-1 receptor agonists (GLP1-RAs) (1.0% versus 6.2%), and insulin (27.7% versus 58.1%) were lower in General medicine than in Diabetes specialist clinics. CONCLUSIONS: Among high-risk patients with T2D, treatment target attainment and use of GDMT were suboptimal.

Impact of COVID-19 Lockdown on Glycemic, Weight, Blood Pressure Control and Medication Adherence in Patients with Type 2 Diabetes.

Medication adherence profoundly affects blood glucose management in patients with type 2 diabetes. Measures to contain the COVID-19 pandemic have affected disease management and medication adherence, owing to limited access to healthcare facilities. This study aimed to examine the impact of the COVID-19 lockdown on adherence to glucose-lowering and lipid-lowering therapies (statins), and glycemic, weight, and systolic blood pressure control measures. A retrospective chart review was conducted one year pre- and post- March 18, 2020, for patients receiving glucose-lowering medications and lipid-lowering therapies (statins) in two major public hospitals in Malaysia. We compared the proportion of days covered by medication, HbA1c level, weight, and systolic blood pressure (SBP) values pre- and after the index date. A total of 1985 patients were included in this study. The adherence rate significantly increased for metformin, sulfonylureas dipeptidyl peptidase 4 inhibitors (DPP4i) and statin after the index date (metformin (PDC: 0.985 vs 0.978, p < 0.001), sulfonylureas (PDC: 0.988 vs 0.979, p < 0.01), DPP4i (PDC: 0.987 vs 0.98, p < 0.001), and statins (PDC: 0.983 vs 0.978, p < 0.05)). HbA1c levels were significantly reduced after the index follow-up (Mean difference: -0.43%, p < 0.001), while there was a 2.5 mmHg (p = 0.03) significant increase in SBP post-index follow-up. No significant changes in weight were observed during the post-index follow-up period. In this study, we observed better medication adherence and glycemic control among patients during the lockdown, but not for weight and systolic blood pressure control.

Cost-Effectiveness of Glucose-Lowering Therapies as Add-on to Standard Care for People With Type 2 Diabetes in Malaysia.

OBJECTIVES: This study aims to evaluate the cost-effectiveness of various glucose-lowering therapies as add-on to standard care for people with type 2 diabetes (T2D) in Malaysia. METHODS: A state-transition microsimulation model was developed to compare the clinical and economic outcomes of 4 treatments: standard care, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists. Cost-effectiveness was assessed from a healthcare provider's perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of people with T2D. Data input were informed from literature and local data when available. Outcome measures include costs, quality-adjusted life-years, incremental cost-effectiveness ratios, and net monetary benefits. Univariate and probabilistic sensitivity analyses were performed to assess uncertainties. RESULTS: Over a lifetime horizon, the costs to treat a person with T2D ranged from RM 12 494 to RM 41 250, whereas the QALYs gains ranged from 6.155 to 6.731, depending on the treatment. Based upon a willingness-to-pay threshold of RM 29 080 per QALY, we identified SGLT2i as the most cost-effective glucose-lowering treatment, as add-on to standard care over patient's lifetime, with the net monetary benefit of RM 176 173 and incremental cost-effectiveness ratios of RM 12 279 per QALY gained. The intervention also added 0.577 QALYs and 0.809 LYs compared with standard care. Cost-effectiveness acceptability curve showed that SGLT2i had the highest probability of being cost-effective in Malaysia across varying willingness-to-pay threshold. The results were robust to various sensitivity analyses. CONCLUSIONS: SGLT2i was found to be the most cost-effective intervention to mitigate diabetes-related complications.

Ramadan fasting in people with diabetes and chronic kidney disease (CKD) during the COVID-19 pandemic: The DaR global survey.

BACKGROUND AND AIMS: The DaR Global survey was conducted to observe the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in people with diabetes and chronic kidney disease (CKD). METHODS: Muslim people with diabetes and CKD were surveyed in 13 countries shortly after the end of Ramadan 2020, using a simple Survey Monkey questionnaire. RESULTS: This survey recruited 6736 people with diabetes, of which 707 (10.49%) had CKD. There were 118 (16.69%) people with type1 diabetes (T1D), and 589 (83.31%) were with type2 diabetes (T2D). 62 (65.24%) people with T1D and 448 (76.06%) people with T2D had fasted with CKD. Episodes of hypoglycaemia and hyperglycaemia were more frequent among people with T1D compared to T2D, 64.52% and 43.54% vs 25.22% and 22.32% respectively. Visits to the emergency department and hospitalization were more frequent among people with CKD, however no significant difference was found between people with T1D and T2D. CONCLUSION: The COVID-19 pandemic had only a minor effect on the intention to fast during Ramadan in people with diabetes and CKD. However, hypoglycaemia and hyperglycaemia were found to be more frequent, as well as emergency visits and hospital admissions among people with diabetic kidney disease. Prospective studies are needed in future to evaluate the risk indicators of hypoglycaemia and hyperglycaemia among fasting people with CKD, especially in the context of different stages of kidney disease.

Patient Characteristics, Disease Burden, Treatment Patterns and Outcomes in Patients with Acromegaly: Real-World Evidence from the Malaysian Acromegaly Registry.

Objective: This study aims to report the demographic features of patients with acromegaly, the disease burden, and the corresponding treatment patterns and outcomes in Malaysia. Methodology: This is a retrospective study that included patients from the Malaysian Acromegaly registry who were diagnosed with acromegaly from 1970 onwards. Data collected included patient demographics, clinical manifestations of acromegaly, biochemical results and imaging findings. Information regarding treatment modalities and their outcomes was also obtained. Results: Registry data was collected from 2013 to 2016 and included 140 patients with acromegaly from 12 participating hospitals. Median disease duration was 5.5 years (range 1.0 - 41.0 years). Most patients had macroadenoma (67%), while 15% were diagnosed with microadenoma. Hypertension (49.3%), diabetes (37.1%) and hypopituitarism (27.9%) were the most common co-morbidities for patients with acromegaly. Majority of patients had surgical intervention as primary treatment (65.9%) while 20.7% were treated medically, mainly with dopamine agonists (18.5%). Most patients had inadequate disease control after first-line treatment regardless of treatment modality (79.4%). Conclusion: This registry study provides epidemiological data on patients with acromegaly in Malaysia and serves as an initial step for further population-based studies.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes in Malaysia: Results from a Prospective, Non-interventional Real-World Study.

Objectives: Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings. Methodology: ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS). Results: Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: -1.3% [95% CI: -1.61 to -0.90]) and fasting plasma glucose levels (ED: -1.8 mmol/L [95% CI: -2.49 to -1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients. Conclusion: Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

Comparison of a chronic kidney disease predictive model for type 2 diabetes mellitus in Malaysia using Cox regression versus machine learning approach.

Background: Diabetes 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). Methods: We 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. Results: The 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/. Conclusions: The 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.

Effect of empagliflozin in patients with type 2 diabetes during Ramadan on volume status, ketonaemia, and hypoglycaemia.

BACKGROUND AND AIMS: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Fasting Ramadan in patients with T1DM - Saudi Arabia versus other countries during the COVID-19 pandemic.

BACKGROUND AND AIMS: To compare Saudi Arabia with other countries regarding patient attitudes towards fasting Ramadan and complications related to fasting during the COVID-19 pandemic. METHODS: Data collected from Saudi Arabia and 12 other mostly Muslim majority countries, via physician administered questionnaire within post Ramadan 2020. RESULTS: 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). CONCLUSION: 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.

Safety of sodium-glucose cotransporter 2 inhibitors in Asian type 2 diabetes populations.

The prevalence of type 2 diabetes mellitus continues to increase in many Asian countries, with possible contributing factors, such as younger-onset disease, diabetes development at lower body mass index, higher visceral fat accumulation and poorer ß-cell function, among Asian populations. Sodium-glucose cotransporter 2 inhibitors have been shown to confer favorable effects in type 2 diabetes mellitus patients, such as improved glycemic control, weight and blood pressure reduction, and importantly, cardiorenal benefits. Sodium-glucose cotransporter 2 inhibitors are generally well-tolerated, and have a well-defined safety profile based on evidence from numerous clinical trials and post-marketing pharmacovigilance reporting. To our knowledge, this review is the first to provide a comprehensive coverage of the adverse events of sodium-glucose cotransporter 2 inhibitors, as well as their management and counseling aspects for Asian type 2 diabetes mellitus populations.

Fenofibrate for the prevention of progression of non-proliferative diabetic retinopathy: review, consensus recommendations and guidance for clinical practice.

The prevalence of diabetic retinopathy (DR), and associated morbidity is high in the Asia-Pacific region. Emerging evidence suggests a potential role for fenofibrate in the prevention of progression of DR, especially in patients with cardiovascular risk, and pre-existing mild-to-moderate DR. Fenofibrate has also been found to reduce maculopathy, and the need for laser treatment in these patients. Considering these benefits of fenofibrate, a group of experts from the fields of endocrinology and ophthalmology convened in May 2017, to discuss on the the mechanism of action, and clinical efficacy of fenofibrate in DR. The findings from key clinical studies on fenofibrate in DR were reviewed by the experts, and consensus statements were derived to define the role of fenofibrate in the prevention and treatment of DR. The statements were rated based on the GRADE criteria. An algorithm was also developed for the screening and treatment of DR in patients with type 2 diabetes (T2D), and the place of fenofibrate was defined in the algorithm. The expert recommendations, and the algorithm provided in this review will serve as a guide to the clinicians to reconsider the adjunctive use of fenofibrate for preventing the progression of DR in selected T2D patients.

Use of Combination of Oral Levothyroxine and Liothyronine in Severe Hypothyroidism With Massive Pericardial Effusion.

Thyroid hormone plays an important role in cardiovascular function. Pericardial effusions are commonly seen in cases of severe hypothyroidism. However, large to massive pericardial effusions with cardiac tamponade are exceptionally rare. Herein, we present two cases of severe hypothyroidism with massive pericardial effusion. Our first case demonstrates that a patient with large pericardial effusion can be managed conservatively with aggressive thyroid hormone replacement therapy. In our second case, pericardiocentesis was performed in addition to thyroid hormone replacement therapy as the underlying aetiology of effusion could not be reasonably limited to hypothyroidism. These two cases served to highlight and demonstrate rapid normalisation of thyroid function test by using aggressive oral thyroid hormone replacement therapy using liothyronine, in combination with levothyroxine, which led to resolution of pericardial effusion and prevent its re-accumulation.

Diabetes and Ramadan: Practical guidelines 2021.

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.

Comparative effectiveness of cardiovascular, renal and safety outcomes of second-line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta-analysis of randomised controlled trials.

AIMS: To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Pharmacogenetics of sulfonylurea-induced hypoglycemia in Type 2 diabetes patients: the SUCLINGEN study.

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 <3.9 mmol/l. Results: Of the 401 patients, 120 (29.9%) developed sulfonylurea-induced hypoglycemia during the 12-month follow-up. The ABCC8 rs757110, KCNJ11 rs5219, CDKAL1 rs7756992 and KCNQ1 rs2237892 gene polymorphisms were not associated with sulfonylurea-induced hypoglycemia (p > 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.

Ectopic Cushing's Syndrome secondary to Recurrent Thymic Neuroendocrine Carcinoma with Bilateral Ovarian Metastases: A Case Report.

Cushing's syndrome due to ectopic adrenocorticotrophic hormone (ACTH) secretion is uncommon, accounting for 9 to 18% of cases; approximately 10% of ACTH producing tumours are caused by thymic carcinomas.1 We describe a young lady who presented with Cushing's syndrome secondary to a primary neuroendocrine tumour (NET) arising from the thymus. She had surgical resection of her primary tumour with remission of her Cushing's syndrome however subsequently went on to have locoregional recurrence followed by distant metastases to her bilateral ovaries. She underwent 6 surgeries including bilateral adrenalectomy and had 3 cycles of chemotherapy over the course of the 8 years since her diagnosis. Due to the rarity and highly aggressive nature of this disease, we highlight the need for a multidisciplinary team approach and use of multiple modalities in the management of our patient. Timely use of bilateral adrenalectomy particularly in young patients is important to prevent further complications and facilitate other treatment modalities.

Giant Parathyroid Adenoma versus Parathyroid Carcinoma: Differentiating Two Entities.

Giant parathyroid adenoma (GPA) is defined as adenoma larger than 3.5 g. Twenty-one cases of parathyroid mass >3.5 g in patients with primary hyperparathyroidism who underwent parathyroidectomy in Hospital Putrajaya, Malaysia were identified. Most cases presented with nephrolithiasis. Two cases are reported as parathyroid cancer. GPA has significantly higher serum calcium and iPTH levels and can be asymptomatic. Parathyroid carcinoma patients are frequently symptomatic, with large tumors. Differentiating GPA from parathyroid cancer is important as it determines the subsequent surgical intervention.

Diabetes emergencies around Ramadan study (DEARS) - A multi-center study of diabetes emergencies admitted before, during and after Ramadan in Malaysia.

OBJECTIVE: The objective of this study was to determine admissions for diabetes emergencies among patients who fasted or planned to fast one month before, during and one month after Ramadan 2019 in public hospitals in Malaysia. MATERIALS AND METHODS: This was a cross sectional prospective study done in 18 public hospitals in Malaysia from 7/4/2019 to 2/7/2019. Data was collected prospectively with universal sampling. All adult Muslim patients with previous diagnosis of diabetes, who were admitted for hypoglycemia, DKA or HHS were included if they had fasted and had intentions to fast. RESULTS: 295 admissions for diabetes emergencies were analyzed. The pre-Ramadan period recorded the highest number of admissions (119) followed by during (106) and post-Ramadan (70). Admissions for hyperglycemic emergencies accounted for 2/3 of total admissions. 37% of admissions for hypoglycemia occurred during pre-Ramadan period compared to 32.1% during Ramadan. Contributing factors included use of sulphonylurea (59.6%), presence of nephropathy (54.5%) and past history of hypoglycemia (45.5%). Admissions for DKA were more common than HHS (119 versus 77) and highest during Ramadan period (36.1%). Most of the admissions for hyperglycemic emergencies were among those with Type 2 diabetes (75.9% for DKA and 97.4% for HHS). Only 31.5% of patients admitted for diabetes emergencies recalled having received Ramadan advice in the past. DISCUSSION: Admissions for diabetes emergencies were highest during pre-Ramadan period followed by Ramadan and post-Ramadan period. This suggests that fasting during Ramadan does not increase admissions for diabetes emergencies.