Consensus Guidelines for Influenza Vaccination in Patients with Diabetes.

Influenza is a prevalent health issue encountered in daily practice. Patients with diabetes mellitus face a higher risk of infections, including influenza, owing to the compromised immune system associated with diabetes. This susceptibility arises from the potential of diabetes mellitus to weaken the immune system. Moreover, elevated blood glucose levels can create a conducive environment for the growth of bacteria and viruses. This consensus is formulated by a multidisciplinary team to serve as practical guidance for the administration of influenza vaccinations to patients with diabetes mellitus in daily practice.

Similar Blood Glucose Pattern with Highest Peak at Minute 45 on Oral Glucose Tolerance Test Despite Higher Fasting Insulin and Insulin Resistance in Healthy Obese than Non-Obese Subject.

BACKGROUND: Obesity increase the risk for type 2 diabetes through induction of insulin resistance. Diagnosis of diabetes were based on blood glucose level. However, insulin resistance may had happened far before diagnosis itself. This study aimed to compare fasting insulin level, insulin resistance, and blood glucose pattern during oral glucose load in healthy obese and non-obese subject. METHODS: This semi-experimental study was conducted at Department of Internal Medicine, Sanglah Hospital, Denpasar. Sixteen subjects in each obese and non-obese group were matched by age and sex. Obesity was defined based on body mass index (BMI) of ≥25kg/m2 and waist circumference (WC) ≥80cm (female) or ≥90cm (male). The non-obese group was defined by BMI of 18-25kg/m2 and WC <80cm (female) or <90cm (male). Fasting insulin level and blood glucose was measured at minute 0, 15, 30, 45, 60, 75, 90, 120 after glucose load of 75 grams. Insulin resistance was calculated based on homeostasis model assessment of insulin resistance (HOMA-IR) with the following formula: HOMA-IR = (FPI×FPG)/22.5. Normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) subject was defined by American Diabetes Association (ADA) criteria. RESULTS: Fasting insulin level in obese subjects was higher than non-obese subjects with median 12.75 (range 3.70 - 41.30) vs 3.80 (1.80 - 36.80) µU/mL, p=0.041. HOMA IR was also higher in obese subjects compared to non-obese subjects: 2.45 (0.70 - 8.00) vs 0.80 (0.40 - 8.50), p=0.001. Fasting insulin level was correlated with BMI (r=0.559, p=0.001) and WC (r=0.633, p<0.001). A significant correlation was also detected between HOMA IR with BMI (r=0.528, p=0.002) and WC (r=0.600, p<0.001). Blood glucose pattern in four groups: obese IGT, obese NGT, non-obese IGT, and non-obese NGT, were typically similar, in particular two peaks of blood glucose. The first peak was the highest blood glucose, shown in minute 45 in both obese and non-obese subjects. The second peak was lower than the first peak, found in minute 75 among NGT and minute 90 among IGT subject. Blood glucose level for each measurement point was consistently higher in obese than non-obese subjects. CONCLUSION: Fasting insulin level and HOMA-IR were higher in obese than in non-obese subjects. BMI and WC were significantly correlated with fasting insulin level and HOMA IR, so that high BMI and WC can be an earlier clinical sign of insulin resistance and prediabetes. Pattern of blood glucose level after oral glucose load were similar with two peaks, and blood glucose consistently higher in obese compared to non-obese subjects. The highest peak of blood glucose, shown in minute 45 in both obese and non-obese subjects.

Early Recognition of Type 2 Diabetes Complications and Use of SGLT2i in Multidisciplinary Approach: Indonesian Perspective - An Expert Opinion.

Indonesia ranks seventh with the highest number of cases of type 2 diabetes mellitus (T2DM). T2DM is associated with major undesirable complications including cardiovascular disease and chronic kidney disease. Kidneys play a major role in maintaining glucose homeostasis, leading the development of sodium glucose transporter inhibitors (SGLT2i). These inhibitors block renal sodium and glucose reabsorption. Several cardiovascular trials proved that SGLT2i have cardioprotective and renoprotective roles and have been suggested  as a drug of choice in primary and secondary prevention and management of cardiorenal complications associated with T2DM. This review highlights the need for a multidisciplinary recommendation for T2DM management in Indonesian population. Additionally, it is vital to provide the perspective of Indonesian medical experts in terms of screening, diagnosis and treatment as the outcome differs geographically. An expert panel of 6 members from Indonesia was convened to review the existing literature and develop an expert-based review/ summary on this topic. Members were chosen for their proficiency in diabetes, kidney disease and cardiovascular disease. The experts opined that the early use of SGLT2i will be effective in preventing and minimising the progression of cardiorenal complications. Moreover, a consistent multidimensional approach is necessary for improved outcomes.

Use of sodium-glucose co-transporter-2 inhibitors in Asian patients with type 2 diabetes and kidney disease: An Asian perspective and expert recommendations.

Early onset of type 2 diabetes and a high prevalence of co-morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin-angiotensin system inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT-2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA-CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT-2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end-stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose-lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.

Use of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations.

Diabetes mellitus in Asia accounts for more than half of the global prevalence. There is a high prevalence of cardiovascular disease (CVD) in the region among people with type 2 diabetes mellitus (T2DM) and it is often associated with multiple risk factors including hypertension, renal disease and obesity. The early onset of T2DM and the eventual long disease duration portends an increasing proportion of the population to premature CVD. In addition to lowering blood glucose, sodium-glucose co-transporter-2 (SGLT-2) inhibitors exert favourable effects on multiple risk factors (including blood pressure, body weight and renal function) and provide an opportunity to reduce the risk of CVD in patients with T2DM. In this article, we consolidated the existing literature on SGLT-2 inhibitor use in Asian patients with T2DM and established contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, published data from clinical trials in the Asian population (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin and tofogliflozin), CVD outcomes trials (EMPAREG-OUTCOME, CANVAS and DECLARE-TIMI 58) and real-world evidence studies (CVD-REAL, EASEL, CVD-REAL 2 and OBSERVE-4D). A series of clinical recommendations on the use of SGLT-2 inhibitors in Asian patients with T2DM was deliberated among experts with multiple rounds of review and voting. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.

Transcription factor 7-like 2 single nucleotide polymorphisms are associated with lipid profile in the Balinese.

Transcription factor 7-like 2 (TCF7L2) protein plays an important role in glucose and lipid metabolisms. Single nucleotide polymorphisms (SNPs) in the TCF7L2 gene contribute to increased fasting plasma glucose (FPG) and body mass index (BMI), and altered lipid concentrations in various population. We investigated whether the TCF7L2 SNPs were associated with obesity, high FPG and altered lipid profile in the Balinese. A total of 608 Balinese from rural and urban Bali, Indonesia, were recruited. Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and FPG were measured, and BMI was calculated. Ratios of TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were determined. Genotyping of SNPs rs7903146, rs10885406, and rs12255372 were done in all samples. Genetic association analyses under a dominant model showed that the rs7903146 (OR 5.50, 95% CI 2.34-12.91, p = 8.5 × 10-5), rs12255372 (OR 4.15, 95% CI 1.66-10.33, p = 0.003) and rs10885406 (OR 2.43, 95% CI 1.39-4.25, p = 0.003) were significantly associated with high TC/HDL-C ratio. The rs10885406 also presented a significant association with high TG (OR 2.21, 95% CI 1.29-3.81, p = 0.004) and low HDL-C (OR 3.02, 95% CI 1.58-5.80, p = 0.001) concentrations, as well as high TG/HDL-C ratio (OR 1.95, 95% CI 1.16-3.27, p = 0.013). None of the SNPs exhibited significant association with obesity or high FPG. SNPs in the TCF7L2 gene are associated with altered lipid profile in the Balinese.

Glucagon-like peptide-1 receptor agonist and new-onset diabetes in overweight/obese individuals with prediabetes: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) is incretin-based therapy that possessed significant glucose lowering and weight loss properties. The present study aims to analyze the efficacy of GLP-1RA in the management of overweight/obese individuals with prediabetes. METHODS: A thorough search was carried out on the Cochrane Library, ClinicalTrials.gov, Scopus, and Medline databases until April 3rd, 2024, using a mix of pertinent keywords. This review incorporates randomized clinical trials (RCTs) concerning the efficacy of GLP-1RA for prediabetes. The primary outcome was regression to normoglycemia and/or progression to type 2 diabetes (T2D). We used random-effect models to examine the odds ratio (OR) and mean difference (MD). RESULTS: A total of eight RCTs were incorporated. The results of our meta-analysis indicated that GLP-1RA therapy was associated with higher odds of regression to normoglycemia (OR 4.80; 95%CI: 3.40-6.77, p < 0.00001, I2 = 67 %) and lower risk of progression into T2D (OR 0.27; 95%CI: 0.18-0.42, p < 0.00001, I2 = 0 %) in overweight/obese individuals with prediabetes. Administration of GLP-1RA was also associated with higher reduction in HbA1c (MD -0.28 %; p < 0.00001), fasting glucose (MD -0.45 mmol/L; p < 0.00001), and BMI (MD -1.71 kg/m2; p < 0.00001) in comparison to placebo. However, the administration of GLP-1RA was associated with higher incidence of total adverse events (TAEs), treatment discontinuation due to AEs, hypoglycemia, and gastrointestinal AEs. CONCLUSIONS: This study indicates that while GLP-1RA is a potent therapeutic agent for prediabetes, its adverse effects are concerning, thereby precluding its recommendation as a prediabetes therapy.

Different doses of imeglimin for management of type 2 diabetes mellitus: a systematic review, meta-analysis, and meta-regression of randomized clinical trials.

BACKGROUND: A new medication for type 2 diabetes mellitus (T2DM) called imeglimin can target all three organs involved in the pathogenesis of DM, namely the liver, skeletal muscles, and pancreas. This research seeks to examine the most efficacious and safe dose of imeglimin for the management of T2DM. RESEARCH DESIGN AND METHODS: Using particular keywords, we searched the CENTRAL, Medline, Scopus, and ClinicalTrials.gov databases for pertinent literature. The results of continuous variables were pooled into the mean difference (MD) and dichotomous variables into odds ratio (OR) along with their 95% confidence intervals (95% CI) using fixed-effect models. RESULTS: Our pooled analysis revealed that imeglimin 1000 mg twice daily [MD -0.90% p < 0.00001] and 1500 mg twice daily [MD -0.84% p = 0.0003] as monotherapy was associated with a higher reduction in the HbA1c compared to placebo. This superiority was still maintained when given as combination therapy. Regrettably, there was an observed escalation in gastrointestinal AEs as the dosage of imeglimin was raised, despite the absence of a corresponding improvement in its efficacy in decreasing HbA1c levels. CONCLUSIONS: Our study suggests that imeglimin 1000 mg twice daily may offer the most optimum therapeutic effects for glycemic control without compromising its safety profiles.

The role of probiotics and synbiotics on treatment of gestational diabetes: systematic review and meta-analysis.

OBJECTIVE: This review investigated the efficacy of probiotics and/or synbiotics in gestational diabetes mellitus treatment by targeting insulin resistance, lipid metabolism, and anti-inflammatory effects in an updated trial. DATA SOURCES: The literature review was performed using the key words "Probiotics," "Synbiotics," and "Gestational Diabetes" in several databases, including PubMed, ScienceDirect, and the Cochrane Central Register of Controlled Trials. STUDY ELIGIBILITY CRITERIA: Eligible publication was screened independently by 2 reviewers. Studies included provided at least 1 of the following outcomes: (1) blood glucose marker, including fasting blood glucose level, fasting serum insulin level, and homeostasis model assessment insulin resistance; (2) blood lipid profiles, including triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol; and (3) nitric oxide and C-reactive protein. METHODS: All studies were reviewed using the critical appraisal Cochrane risk-of-bias tool for randomized trials. The descriptions of the extracted data were guided by the Preferred Reporting Items for Systematic Reviews 2020 statement with the Grading of Recommendations Assessment, Development, and Evaluation approach. This study was registered on the International Prospective Register of Systematic Reviews database (identification number: CRD42022375665). RESULTS: From 13 randomized controlled trials involving 896 patients, individuals with probiotic had significant reduction on homeostasis model assessment insulin resistance (mean difference, -0.72; 95% confidence interval, -1.07 to -0.38; I2, 96%; P=.00), fasting blood glucose level (mean difference, -3.79; 95% confidence interval, -6.24 to -1.34; I2, 93%; P=.00), and insulin level (mean difference, -2.43 mg/dL; 95% confidence interval, -3.37 to -1.48; I2, 54%; P=.00). Meanwhile for profile lipid, significant reduction of the mean difference was observed in the triglyceride (mean difference, -17.73 mg/dL; 95% confidence interval, -29.55 to - 5.9; P=.003) and C-reactive protein (mean difference, -1.93 dL; 95% confidence interval, -2.3 to -1.56; P=.00). CONCLUSION: Probiotic and synbiotic supplementations reduced the risk of insulin resistance and improved glycemic control, blood lipid profiles, and inflammation in women with gestational diabetes mellitus. Probiotics may be a viable option for gestational diabetes mellitus treatment; however, large-scale, well-designed randomized controlled trials with longer follow-up periods are required before they can be recommended to patients.

Utility of non-invasive liver fibrosis markers to predict the incidence of chronic kidney disease (CKD): A systematic review, meta-analysis, and meta-regression.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) share common risk factors and pathogenesis mechanisms. However, the association between the degree of liver fibrosis and the incidence of CKD remains unclear. This study aims to examine the utility of non-invasive fibrosis markers to predict the occurrence of CKD. METHODS: Cochrane Library, Scopus, and Medline were searched up to May 20th, 2023 using combined keywords. Literature that analyzes FIB-4, NFS, and APRI to predict CKD incidence was included in this review. We used random-effect models of odds ratio (OR) with 95% confidence intervals (CI) to express the outcomes in this review. RESULTS: Twenty-one studies were included. Our meta-analysis showed that high FIB-4 was associated with a higher incidence of CKD (OR 2.51; 95%CI: 1.87-3.37, p < 0.00001, I2 = 96%). Further regression analysis revealed that this association was significantly influenced by hypertension (p = 0.0241), NAFLD (p = 0.0029), and body mass index (BMI) (p = 0.0025). Our meta-analysis also showed that high NFS (OR 2.49; 95%CI: 1.89-3.30, p < 0.00001, I2 = 96%) and high APRI (OR 1.40; 95%CI: 1.14-1.72, p = 0.001, I2 = 26%) were associated with a higher incidence of CKD. CONCLUSIONS: This study suggests that these non-invasive liver fibrosis markers can be routinely measured both in NAFLD patients and the general population to enable better risk stratification and early detection of CKD.

MIRNA146a And Diabetes-Related Complications: A Review.

Diabetes mellitus, defined as long-standing hyperglycemic conditions caused by a defect in insulin production and activity, has become a major healthcare burden as the number of catastrophic and life-threatening complications rises. Microvascular complications (neuropathy, retinopathy, and nephropathy), and also diabetes-related macrovascular complications are common problems that arise as the life expectancy of diabetic patients has increased despite improved treatment options. While it is impossible to pinpoint the specific crucial timing when the complications become fully entrenched, looking for novel sensitive biomarkers to identify physiological changes in the initial stages would be needed. An increasing amount of data shows that miRNAs, particularly miRNA146a, are stable in a range of body fluids and can be used to identify pathogenic changes at the cellular or tissue level. In this brief review, we highlight the important functioning of miRNA146a and its putative target of action in diabetic microvascular and cardiovascular complications. A decrease in miRNA146a levels may play a critical role in the onset and development of diabetes complications, whereas its anti-inflammatory properties were revealed to be associated with the pathogenesis of numerous diabetic complications, including diabetic nephropathy, retinopathy, neuropathy, and diabetes-related cardiovascular disorders, even tending to be a potential biomarker of the disease's inflammatory status.

The Important Role of Intermuscular Adipose Tissue on Metabolic Changes Interconnecting Obesity, Ageing and Exercise: A Systematic Review.

As age increases, adipose tissue infiltrates muscle tissue and leads to sarcopenia. When excessive accumulation of adipose tissue accompanied progressive decrease in lean body mass especially visceral fat, termed as sarcopenic obesity (SO) and related metabolic intermuscular adipose tissue (IMAT) is an ectopic tissue found between muscle groups, and is distinct from subcutaneous adipose tissue. Until now, the association between IMAT and metabolic health was not understood. This study is the first systematic review assessing the association between IMAT and metabolic health. The PubMed, Science Direct and Cochrane databases were searched for studies reporting IMAT and metabolic risk. The descriptions of the extracted data are guided by the Preferred Reporting Items for Systematic Reviews (PRISMA) statement with a Grading of Recommendations Assessment, Development and Evaluation approach. This study is registered at PROSPERO (identifier: CRD42022337518). Six studies were pooled and reviewed using critical appraisal by the Newcastle Ottawa Scale and Centre for Evidence-Based Medicine checklist. Two clinical trials and four observational trials were included. Our results reveal that IMAT is associated with metabolic risk, especially in older adults and patients with obesity. However, in a person with abdominal obesity, VAT has a more significant role in metabolic risk than IMAT. The largest decrease in IMAT was achieved by combining aerobic with resistance training.

Expert Opinion on Addressing the Gap in Injection Technique and Needle Reuse for People with Diabetes in Indonesia.

The use of insulin for patients with diabetes mellitus in Indonesia appears to be under expectation; moreover, there are gaps in knowledge regarding the proper injection technique and pen needle reuse by both healthcare professionals (HCPs) and patients. To address these issues, a scientific expert meeting was held with the participation of endocrinologists and public health specialist from many different organizations in Indonesia to identify the challenges and problem related to injection technique, high pen needle reuse rate, and the need of all stakeholders. The experts agreed that it is necessary to ensure physicians to start the initiation phase as early as indicated, continue optimizing its dosage to reach targeted blood sugar based on guideline, and involve all relevant stakeholders to improve insulin distribution and patient access in every primary care facility in order to optimize the use of insulin or other injectable diabetes medications in Indonesia. Additionally, the experts believed that education on proper injection technique and improved reuse rate of pen needle is necessary. To date, Indonesian Diabetes Educators Association (IDEA/PEDI) has established guideline on injection technique. There are also recommendations on injection technique and needle reuse from Indonesian Society of Endocrinology (PERKENI) and Forum for Injection Technique & Therapy: Expert Recommendations (FITTER); however, this guideline/recommendation should be disseminated more widely among HCPs. In addition, cost-effectiveness studies based on local data are needed to propose and convince the Payors and other stakeholders. This article can be used as a guidance for HCPs and policymakers to improve current practice on injection technique, pen needle reuse, needle prescription and reimbursement policy in Indonesia and elsewhere.

Effectiveness, safety, initial optimal dose, and optimal maintenance dose range of basal insulin regimens for type 2 diabetes: A systematic review with meta-analysis.

AIMS: To investigate the effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins in insulin-naïve patients with type 2 diabetes mellitus. METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched from January 2000 to February 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was adopted. The registration ID is CRD42022319078 in PROSPERO. RESULTS: Among 11 163 citations retrieved, 35 publications met the planned criteria. From meta-analyses and network meta-analyses, we found that when injecting basal insulin regimens at bedtime, the optimal choice in order of most to least effective might be glargine U-300 or degludec U-100, glargine U-100 or detemir, followed by neutral protamine hagedorn (NPH). Injecting glargine U-100 in the morning may be more effective (ie, more patients archiving glycated hemoglobin < 7.0%) and lead to fewer hypoglycemic events than injecting it at bedtime. The optimal starting dose for the initiation of any basal insulins can be 0.10-0.20 U/kg/day. There is no eligible evidence to investigate the optimal maintenance dose for basal insulins. CONCLUSIONS: The five basal insulins are effective for the target population. Glargine U-300, degludec U-100, glargine U-100, and detemir lead to fewer hypoglycemic events than NPH without compromising glycemic control.

Use of basal insulin in the management of adults with type 2 diabetes: An Asia-Pacific evidence-based clinical practice guideline.

The objective of this study was to provide recommendations regarding effectiveness, safety, optimal starting dose, optimal maintenance dose range, and target fasting plasma glucose of five basal insulins (glargine U-300, degludec U-100, glargine U-100, detemir, and insulin protamine Hagedorn) in insulin-naïve adult patients with type 2 diabetes in the Asia-Pacific region. Based on evidence from a systematic review, we developed an Asia-Pacific clinical practice guideline through comprehensive internal review and external review processes. We set up and used clinical thresholds of trivial, small, moderate, and large effects for different critical and important outcomes in the overall certainty of evidence assessment and balancing the magnitude of intervention effects when making recommendations, following GRADE methods (Grading of Recommendations, Assessment, Development, and Evaluation). The AGREE (Appraisal of Guidelines, Research and Evaluation) and RIGHT (Reporting Items for practice Guidelines in HealThcare) guideline reporting checklists were complied with. After the second-round vote by the working group members, all the recommendations and qualifying statements reached over 75% agreement rates. Among 44 contacted external reviewers, we received 33 clinicians' and one patient's comments. The overall response rate was 77%. To solve the four research questions, we made two strong recommendations, six conditional recommendations, and two qualifying statements. Although the intended users of this guideline focused on clinicians in the Asia-Pacific region, the eligible evidence was based on recent English publications. We believe that the recommendations and the clinical thresholds set up in the guideline can be references for clinicians who take care of patients with type 2 diabetes worldwide.

Device-supported automated basal insulin titration in adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.

Background: Technological advances make it possible to use device-supported, automated algorithms to aid basal insulin (BI) dosing titration in patients with type 2 diabetes. Methods: A systematic review and meta-analysis of randomized controlled trials were performed to evaluate the efficacy, safety, and quality of life of automated BI titration versus conventional care. The literature in Medline, Embase, Web of Science, and the Cochrane databases from January 2000 to February 2022 were searched to identify relevant studies. Risk ratios (RRs), mean differences (MDs), and their 95% confidence intervals (CIs) were calculated using random-effect meta-analyses. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Findings: Six of the 7 eligible studies (889 patients) were included in meta-analyses. Low- to moderate-quality evidence suggests that patients who use automated BI titration versus conventional care may have a higher probability of reaching a target of HbA1c <7.0% (RR, 1.82 [95% CI, 1.16-2.86]); and a lower level of HbA1c (MD, -0.25% [95% CI, -0.43 to -0.06%]). No statistically significant differences were detected between the two groups in fasting glucose results, incidences of hypoglycemia, severe or nocturnal hypoglycemia, and quality of life, with low to very low certainty for all the evidence. Interpretation: Automated BI titration is associated with small benefits in reducing HbA1c without increasing the risk of hypoglycemia. Future studies should explore patient attitudes and the cost-effectiveness of this approach. Funding: Sponsored by the Chinese Geriatric Endocrine Society.

2021 Asia-Pacific Graves' Disease Consortium Survey of Clinical Practice Patterns in the Management of Graves' Disease.

AIM: Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe. METHODS: A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions. RESULTS: A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and ß-blockers and adjunctive ATD-treatment during RAI in the APAC-group. CONCLUSION: Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts.

Uncoupling protein 2 gene polymorphisms are associated with obesity.

BACKGROUND: Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(-866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. METHODS: A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(-866)A and Ala55Val polymorphisms of the UCP2 gene. RESULTS: Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(-866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D' = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. CONCLUSIONS: We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population.

Direct Medical Cost of Type 2 Diabetes Mellitus and Its Associated Complications in Indonesia.

OBJECTIVES: To estimate the direct medical cost of type 2 diabetes mellitus (T2DM) and its complications in the Indonesian population from a payer perspective using a prevalence-based approach. METHODS: The direct medical costs in 2016 were estimated using the database of Indonesia's National Health Insurance, known as Jaminan Kesehatan Nasional, which included diagnosis-related group costs and unbundled costs for patients accessing advanced care. The study population included people aged 30 years or older having a diagnosis of T2DM. T2DM and its related complications were identified using the International Classification of Diseases, 10th Revision, code. Hypoglycemia and all complications listed in the Diabetes Severity Complications Index were included. Descriptive analysis was conducted. Costs were converted to 2016 US dollar equivalent. RESULTS: Of the 18.9 million Jaminan Kesehatan Nasional members who accessed secondary and tertiary care, 812 204 (4%) were identified with T2DM, of which 57% had complications. The most common complication was cardiovascular diseases (24%). The total direct medical cost was US $576 million, with 56% spent on hospitalization, 38% on specialist visits, 4% on unbundled non-diabetes-related medication, and 2% on unbundled anti-hyperglycemic medications. Approximately 74% of the total costs was used for the management of people with complications. People with complications (US $930/person/year ± US $1480/person/year) incurred twice the cost of those without complications (US $421/person/year ± US $745/person/year). CONCLUSION: The direct medical cost for management of people with T2DM in Indonesia was high. Early diagnosis and optimal management of T2DM to prevent complications may reduce the costly sequelae and have a possibility of cost savings.

Transcription factor 7-like 2 single nucleotide polymorphisms rs290487 and rs290481 are associated with dyslipidemia in the Balinese population.

Background: Dyslipidemia is one of the major risks for the development of cardiovascular diseases which has been the leading cause of death in developing countries. Previously, common polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been associated with altered lipid profiles. In this study, we investigated the associations of TCF7L2 SNPs, rs290487 and rs290481, with dyslipidemia and altered lipid profile in the Balinese. Methods: A total of 565 subjects from four locations in the Bali Province, Indonesia, were recruited. Serum lipid concentrations (triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)) were measured using standard protocol. SNP genotyping was done using the amplification refractory system mutation polymerase chain reaction (ARMS-PCR) method. Results: We found the shifted major/minor allele frequencies of both SNPs (0.56 for rs290487 T allele, 0.53 for rs290481 T allele) in the Balinese, as compared to dbSNP. The rs290487 and rs290481 C alleles were significantly associated with dyslipidemia, particularly high TC and high LDL-C. These associations were independent of age, sex, population, obesity, diabetes mellitus, and high TyG index as a proxy for insulin resistance. The haplotype CC also showed similar association with these traits. Our findings indicate that TCF7L2 polymorphisms are associated with dyslipidemia and altered lipid profile in the Balinese.