The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease.

BACKGROUND: graves' disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves' disease in Indonesia. METHODS: this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. RESULTS: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves' ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). CONCLUSION: genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in patients with Graves' disease.

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.

Expert Opinion on Diabetes Management Challenges and Role of Basal Insulin/GLP-1 RA Fixed-Ratio Combination in People with Type 2 Diabetes from Indonesia.

Indonesia is struggling with a rapidly growing burden of diabetes due to rapid socioeconomic transition. People with type 2 diabetes mellitus (T2DM) need appropriate treatment strategies to maintain glycemic control. New modalities with simplicity, such as fixed-ratio combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA), further referred to as FRC, have proven to be an effective and practical therapeutic approach that may address this issue. In January 2021, a scientific expert meeting was held with the participation of endocrinologists from Indonesia to provide expert opinions regarding the optimal practical use of the FRC basal insulin/GLP1-RA. Topics discussed in the meeting included the challenges in diabetes management, clinical inertia with insulin therapy, local and international guideline positioning, initiation, titration, and switching of basal insulin and GLP-1 RA, including FRC, and the management of T2DM.

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.

AADMA as a marker of endothelial dysfunction in prediabetic women.

AIM: to determine the correlation between glycohemoglobin (HbA1c) with level of asymmetric dimethylarginine (ADMA) in serum, between HbA1c and value of brachial artey flow-mediated dilatation (FMD) by ultrasound study, and between ADMA serum and FMD in prediabetes women. METHODS: the study was done in prediabetes women aged between 30-55 years of age in Cipto Mangunkusumo Hospital Jakarta (RSCM). Prediabetes was based on PERKENI criteria. Subject with fasting blood glucose less than 126 mg/dL and 2-hours blood glucose less than 200 mg/dL met the criteria. Laboratory test of HbA1c and ADMA plasma were performed. To asses brachial FMD, the left brachial artery diameter was measured both at rest and during reactive hyperemia. Increased flow was induced by inflation of pneumatic tourniquet around the forearm to a pressure of 50 mm Hg upper systolic pressure for 5 minutes, followed by release. Measurements of arterial diameter were performed at end diastole at rest and 60 seconds after cuff release. The vessel diameter in scans after reactive hyperemia was expressed as the percentage relative to resting scan (100%). All ultrasound scans were analyzed by a single reader. RESULTS: from 41 prediabetes subjects could be found correlation between ADMA serum with 2-hours post prandial blood glucose (p 0,003 and r 0,457) and HbA1c (p <0,001 and r 0,720). We also found correlation between FMD value with 2-hours post prandial blood glucose (p 0,01 and r -0.487) and HbA1c (p <0,001 and r -0.763). Besides that, there was correlation between ADMA serum with FMD value (p <0,001 and r -0,617). From multivariate analysis, we could determine that HbA1c is the influential factor of ADMA serum and FMD. CONCLUSION: in prediabetes women there was correlation between HbA1c with ADMA, between HbA1c with FMD and between ADMA serum with FMD.

Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel.

AIM: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. BACKGROUND: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. REVIEW RESULTS: After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. CONCLUSION: Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

Euthymia in Diabetes: Clinical Evidence and Practice-Based Opinion from an International Expert Group.

AIM: To develop an evidence-based expert group opinion on various types of euthymia associated with diabetes mellitus (DM) and its management. BACKGROUND: Diabetes mellitus is a metabolic syndrome characterized by diverse biomedical and psychosocial features. Emotional health disturbances may lead to psychological and psychiatric dysfunction and may negatively influence glycemic control. Patients with DM may experience diabetes distress (DD) associated with burden of self-care, interpersonal issues, and emotional worries regarding the ability to cope with the illness. Euthymia or a state of positive mental health and psychological well-being should be considered a key outcome of diabetes care. Therefore, to achieve optimal outcomes, the consideration and measurement of psychological and psychiatric aspects along with glycemic levels are very important. A group of multidisciplinary clinical experts came together in an international meeting held in India to develop a workable concept for euthymia in diabetes care. A multidisciplinary approach was suggested to enhance the clinical outcomes and facilitate patient-centered care. During the meeting emphasis was given to the concept of a euthymia model in diabetes care. This model focuses on enhancement of self-care skills in diabetic patients and preventative health awareness among diabetes care providers. Euthymia also encompasses patient-provider communication to aid enhancement of coping skills. RESULTS: After due discussions and extensive deliberations, the expert group provided several recommendations on implementing the concept of euthymia in DM care. CONCLUSIONS: Introduction of the concept of euthymia in routine clinical practice is important to improve the quality of life and coping skills in patients with DM. A timely clinical assessment of psychological and psychiatric aspects along with patient-reported outcomes of diabetes contributes to overall health and well-being of affected individuals. FUNDING: Sanofi India.

Glucocrinology of Modern Sulfonylureas: Clinical Evidence and Practice-Based Opinion from an International Expert Group.

AIM: The primary objective of this document is to develop practice-based expert group opinion on certain important but less discussed endocrine and metabolic effects of modern sulfonylureas (SUs) and their usage in the management of diabetes mellitus (DM). BACKGROUND: Modern SUs may be considered a panacea in DM care with their beneficial extra-pancreatic, pleiotropic, and cardiovascular effects. Safe glycemic control with SUs could be achieved with appropriate patient selection, drug and dosage selection, and patient empowerment. Additionally, sulfonylureas also exhibit certain endocrine and metabolic effects, which could be considered beneficial in the management of DM. In this regard, a group of international clinical experts discussed the less known beneficial aspects of SUs and safe and smart prescription of modern SUs in DM care. RESULTS: The concept of glucocrinology or the relationship of glycemia with the endocrine system was emphasized during the meetings. Clinical experts arrived at a consensus for the usage of modern SUs in the presence of other endocrine dysfunction and the impact of these drugs on endocrine health. The beneficial pleiotropic and cardiovascular effects of modern SUs were also discussed. The key discussion points were considered to develop clinical expert opinions for the use of modern SUs in persons with DM. Clinical expert opinions were developed for indications, pleiotropic benefits, cardiovascular outcomes, adherence, and safe use of modern SUs. CONCLUSIONS: Appropriate clinical judgement coupled with a patient-centered approach is crucial to achieve the best outcome in persons with DM. Owing to their safety, efficacy, extra-pancreatic benefits including effects on endocrine and metabolic aspects, and low cost of therapy, modern SUs could be considered as drugs/agents of choice for the treatment of diabetes. FUNDING: Sanofi India.

Consensus Recommendations on Sulfonylurea and Sulfonylurea Combinations in the Management of Type 2 Diabetes Mellitus - International Task Force.

For decades, sulfonylureas (SUs) have been important drugs in the antidiabetic therapeutic armamentarium. They have been used as monotherapy as well as combination therapy. Focus on newer drugs and concerns about the risk of severe hypoglycemia and weight gain with some SUs have led to discussion on their safety and utility. It has to be borne in mind that the adverse events associated with SUs should not be ascribed to the whole class, as many modern SUs, such as glimepiride and gliclazide modified release, are associated with better safety profiles. Furthermore, individualization of treatment, using SUs in combination with other drugs, backed with careful monitoring and patient education, ensures maximum benefits with minimal side effects. The current guidelines, developed by experts from Africa, Asia, and the Middle East, promote the safe and smart use of SUs in combination with other glucose-lowering drugs.

Iron deposit state and risk factors for anemia in the elderly.

AIM: To determine the type of anemia, iron deposit and risk factors for anemia in the elderly. METHODS: A cross-sectional study was conducted among 84 patients admitted to the geriatric inpatient ward of dr. Cipto Mangunkusumo Hospital. The patients underwent anamnesis, administration of a dietary questionnaire which included SQFF and food recording, physical examination, laboratory investigations (blood, urine and benzidine test), chest x-ray, ECG and spirometry. Anemic elderly patients also underwent iron store measurements, including serum iron (SI), total iron binding capacity (TIBC) and serum ferritin (SF). RESULTS: The proportion of anemia was 54.76%. Increased anemia was inversely correlated with increased body mass index (OR 0.870; 95% CI 0.762-0.994), serum albumin (OR 0.285; 95% CI 0.090-0.907) and calorie intake (OR 0.998; 95% CI 0.996-0.999), and positively correlated with renal impairment (OR 2.647; 95% CI 1.084-6.467). Anemia due to chronic disease (ACD) accounted for 21 subjects, 5 subjects with iron deficiency coexisting with ACD, 1 subject with megaloblastic anemia, and the cause of anemia in 19 patients could not be identified due to diagnostic procedural limitation. Most of the anemic elderly subjects had normal iron deposits. As many as 42.1% of the men and 44.4% of the women had elevated iron deposits. The level of hemoglobin, SI, TIBC in ACD patients were lower than in non-ACD patients (Hb 10.4 vs 10.8 g/dl, SI 58.71 vs. 92.38 ug/dl, TIBC 283.11 vs. 288.95 microg/dl). In contrast, serum ferritin levels in ACD patients were higher than in non-ACD (178.26 vs. 111.35 ng/ml). CONCLUSION: Body mass index, serum albumin, calorie intake and renal impairment are risk factors for anemia in the elderly. Normal iron deposits accounted for 57.9% and 55.6% of anemic elderly men and women with elevated iron deposits.