Immunogenicity and Safety of Half-Dose Heterologous mRNA-1273 Booster Vaccination for Adults Primed with the CoronaVac® and ChAdOx1-S Vaccines for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection.

Increased risk of poor clinical outcome in COVID-19 patients with diabetes mellitus and in-hospital mortality predictors: A retrospective cohort from a tertiary hospital in Indonesia.

AIM: To determine association between diabetes in confirmed cases of COVID-19 and intensive care admission and in-hospital mortality, evaluate several laboratory parameters as mortality predictor and develop predictors of in-hospital mortality among diabetics with COVID-19. METHODS: This retrospective cohort recruited all cases of COVID-19 hospitalized in Fatmawati General Hospital from March to October 2020. Inclusion criterion was RT-PCR confirmed cases of COVID-19 who aged 18 years and older while exclusion criteria were incomplete medical record or cannot be found and pregnant women. RESULTS: We enrolled 506 participants to this study with median age of 51 years (IQR:22), female (56.32%), and diabetes (28.46%). Diabetes increased intensive care admission (adjusted OR: 2.57; 95% CI: 3.52-10.43) and in-hospital mortality (adjusted OR: 2.50; 95% CI: 1.61-3.89). In predicting in-hospital mortality, ferritin and lactate dehydrogenase offered an acceptable discrimination, AUC: 0.71 (95% CI: 0.62-0.79) and AUC: 0.70 (95% CI: 0.61-0.78), respectively. The optimal cut-off of predicting mortality for ferritin was 786 g/mL and for LDH was 514.94 u/L. Factors include age above 70 years old, RBGs level on admission above 250 mg/dL or below 140 mg/dL, ferritin level above 786 ng/mL and presence of ARDS increased the odds of mortality among individuals with diabetes. CONCLUSIONS: Diabetes increases risk intensive care admission and in hospital mortality in COVID-19. Multivariate analysis showed that older age, RBG on admission, high ferritin level, presence of ARDS increased the odds of mortality among individuals with diabetes.

Dysregulation of adipokines levels among healthy first-degree relatives of type 2 diabetes patients.

Background: Leptin, adiponectin and its ratio (L/A), as well as adipocyte fatty acid binding protein (A-FABP) have shown association to type 2 diabetes and atherosclerosis. Since first degree relatives (FDR) of type 2 diabetes are known to have higher risks of developing aforementioned diseases, this study aimed to see differences in adipokines profiles between FDR of type 2 diabetes and non-FDR counterpart. Methods: Age, sex and body mass index (BMI)-matched normotensive-normoglycemic subjects, aged 19-39 years with BMI<30 kg/m2, were included in this cross-sectional study. Serum adiponectin, leptin, and A-FABP levels were measured by sandwich ELISA while HOMA-IR was calculated from fasting blood glucose and insulin levels. Results: Of 116 subjects recruited, there were significant difference of insulin level (6.00 vs 5.00 µIU/mL, P = 0.029) and HOMA-IR (1.27 vs 1.10, P = 0.028). Adiponectin, leptin, L/A ratio, and A-FABP levels were not statistically different between FDR and non-FDR groups. Stratified by BMI, non-obese FDR had higher L/A ratio (0.83 vs 0.49, P = 0.020) compared to those of corresponding non-FDR. In multivariate analysis, after adjusting for age, sex, waist circumference, BMI, and metabolic profiles (HbA1C, HOMA-IR, LDL-C, HDL-C, and triglyceride levels), FDR status became significantly associated with adiponectin level, and in non-obese subgroup, remained its significance with L/A ratio. Conclusion: The FDR status was independently associated with adiponectin level. Furthermore, higher L/A ratio was more pronounced in non-obese FDR than those of non-FDR subjects, suggesting that FDR status may already contribute to the development of adipokines dysregulation before obesity occurs.

Differential effect of ramadan fasting on intercellular adhesion molecule-1 (ICAM-1) in diabetes mellitus and non-diabetes mellitus patients.

Background: The month of Ramadan is a holy month for Muslims. During this month, Muslims do not eat, drink, or smoke from sunrise to sunset. Patients with type 2 diabetes mellitus (T2DM) will also fast from dawn to dusk, creating a unique opportunity to study the effects of dietary changes during fasting period. One of the interesting results of Ramadan fasting is its effect on endothelial dysfunction, measured using Intercellular Adhesion Molecule-1 (ICAM-1) as a biological marker of endothelial function. Aim: To determine the changes ICAM-1 levels in T2DM and non-DM patients during Ramadan fasting. Methods: A retrospective cohort study was performed on 26 T2DM patients and 21 non-DM, age-matched patients (aged 19-60 years). Measurement of metabolic parameters (systolic and diastolic blood pressure, total calorie intake, and intensity of physical activity), anthropometry (body weight, body mass index (BMI) and abdominal circumference), total dietary intake, and laboratory analysis (blood glucose fasting, HbA1c, lipid profile, ICAM-1) were done at 4 weeks before (T0) and 14 days after Ramadan fasting (T1). Result: The median ICAM-1 level in T2DM patients at T0 was 340.9 (193-505) ng/mL and at T1 was 312.3 (158-581) ng/mL, while the ICAM-1 level in non-DM patients at T0 was 482 (305-653) and at T1 was 398.4 (202-526) ng/mL. There was no significant difference of ICAM-1 level between study groups at both T0 and T1 (p > 0.05). Both T2DM and non-DM patients had lower ICAM-1 level following Ramadan fasting. However, only non-DM patients had significantly lower post Ramadan ICAM-1 (p = 0.008). Conclusion: There was a significant decrease in ICAM-1 level in both T2DM and non-DM patients after Ramadan fasting.

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. METHODS: A pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). RESULTS: The primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60' (p = 0.07) and 90' (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. CONCLUSION: Intraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

Challenges in the diagnosis of insulin resistance: Focusing on the role of HOMA-IR and Tryglyceride/glucose index.

BACKGROUND AND AIMS: Metabolic Syndrome (MS) prevalence is increasing worldwide in line with the growing prevalence of obesity. The underlying mechanism of MS is insulin resistance which can be diagnosed by measuring Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Triglyceride/Glucose (TyG) Index. This review will focus on comparing studies assessing the HOMA-IR and TyG index cut-off points. METHODS: We carried out a comprehensive review of the literature using suitable keywords on the search engines of PubMed, Scopus, Research Gate, and Google Scholar in the month of October 2020. RESULTS: There is a high degree of variability in determining threshold levels of HOMA-IR for defining insulin resistance. The distribution of the HOMA-IR varies according to the demographic characteristics of the subjects, such as age, sex, and race, making it difficult to estimate the optimal cut-off point. Another simpler method without requiring the use of insulin assays is TyG Index. Similar to HOMA-IR, the TyG Index cut-off point from existing data shows varying results. CONCLUSION: The HOMA-IR and the TyG index are simple and widely used methods for determining insulin resistance. However, an issue that arises is determining the insulin resistance cut-off point for both methods. Further studies are needed to assess the cut-off point of insulin resistance for various ethnicities associated with the risk of developing MS later in life.

Effect of calorie restriction diet on levels of C reactive protein (CRP) in obesity: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Chronic inflammation in obese patients can be managed through a calorie-restricted diet, characterized by reduced C - reactive protein (CRP). This study aims to assess the role of such diet on CRP. METHODS: Literature searches were performed using search engines. Randomized controlled trials were included. Calorie-restricted diets in combination with non-diet interventions were excluded. RESULTS: Calorie restriction decreased CRP in obese patients with a mean difference of -0.22 (95% CI -0.40 to -0.04, p 0.006). CONCLUSIONS: Calorie-restricted diet reduces CRP. Diet administration >12 weeks had a beneficial effect.

The urgency in proposing the optimal obesity cutoff value in Indonesian population: A narrative review.

In developing nations such as Indonesia, obesity and central obesity have emerged as major public health issues. Many studies have revealed that morbidity and death from obesity-related diseases are already significant in some "Asian" communities at low body mass index (BMI) levels. A recent study showed that the obesity prevalence in Indonesia is underestimated when using the current BMI cutoff (obese ≥ 27.0). Indonesia faced an increase in obesity-related chronic diseases despite having a lower obesity prevalence than developed countries, which may be explained by the underestimation of obesity levels in Indonesia. This creates a huge global health problem, as well as an economic burden. Another recent study on the Indonesian population depicted the new proposed cutoff of waist circumference (WC), which is lower than the World Health Organization (WHO) standard for detecting the early detection of type 2 diabetes mellitus (T2DM), one of the comorbidities and a strong correlation with obesity. An analysis of 58 studies in 2021 that included Indonesian adult subjects revealed enormous differences and ambiguities in defining obesity cutoffs values among Indonesian researchers. Additionally, we advocate adding the Edmonton Obesity Staging System (EOSS) staging to the anthropometric classification for a better clinical evaluation of obesity. Considering the urgency of obesity determination in Indonesia for clinical application and study purposes, this review highlights the need to revise the optimal cutoff value for obesity to warrant early prevention and control of diabetes complications.

Non-vascular contributing factors of diabetic foot ulcer severity in national referral hospital of Indonesia.

PURPOSE: Diabetic foot ulcer (DFU) is a common chronic complication of type 2 diabetes mellitus (T2DM) in Indonesia, with a prevalence of 7.3%. However, the characteristics of these patients remain unclear. We investigated the characteristics of patients with DFU without peripheral arterial disease (PAD) and analyzed non-vascular factors related to severity of DFU in a tertiary care national referral hospital in Indonesia. METHODS: This was a cross-sectional study including 123 hemodynamically stable DFU patients without PAD recruited from Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia from 2010-2015. RESULTS: DFU patients were predominantly over 50 years old (75.6%) and diagnosed with T2DM for 5 years with poor glycemic control (82.7%) and peripheral neuropathy (91.3%). Most patients had anemia (86.7%), leukocytosis (84.6%), and were undernourished, as characterized by a low lipid profile (90.8%) and hypoalbuminemia (83.7%). Most had extensive size of ulcer at the initial visit, with a median size of 16.23 (2.92-60.16) cm2. Ulcers were mostly located of the forefoot (62.5%) and were caused by mechanical trauma (46.2%). Bivariate analysis revealed that significant factors for the development of DFU were related to DFU size, including duration of T2DM (p = 0.04), leukocyte levels (p = < 0.01), and thrombocyte levels (p = < 0.01). Multivariate analysis showed leucocyte (p = 0.03) and thrombocyte (p = 0.023) had significantly correlated with DFU severity. CONCLUSION: Leucocyte and thrombocyte may be the greatest contributing non-vascular factors for severity of DFU in Indonesia.

New proposed cut-off of waist circumference for central obesity as risk factor for diabetes mellitus: Evidence from the Indonesian Basic National Health Survey.

BACKGROUND: Waist circumference (WC) measurement is practical to define central obesity. However, WC cut-off point might be differ based on different race or ethnicity. This study aims to analyze the optimal WC cut-off point to identify T2DM risk among Indonesian population. METHOD: We analyzed the secondary data of national based cross-sectional study of the Indonesian Basic National Health Research 2013, comprising 24,660 adults aged ≥ 18 years who were assessed for fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). The new proposed cut-off point for WC was calculated using ROC curve analysis and Youden index. The odds ratio of having T2DM was calculated using logistic regression analysis. RESULTS: Increased WC was associated with worsening dysglycemia status among men and women (p<0.001). The optimal cut-off point of WC for detecting T2DM from ROC analysis was 76 for men and 80 for women. Based on this WC cut-off point, the odds ratio for having T2DM was 1.64 [95% CI 1.45-1.86, p<0.01] for men and 1.90 [95% CI 1.71-2.11 p<0.01] for women. CONCLUSION: The newly proposed WC cut-off point of 76 for men and 80 women can be used to screen the risk of T2DM among Indonesian population.

The Role of Butyrate on Monocyte Migration and Inflammation Response in Patient with Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2DM) is a very serious global problem. In Indonesia, this disease attacks at the most productive age; consequently, it can reduce economic status and life expectancy. The pathogenesis of T2DM is very closely related to inflammation and macrophage accumulation. However, no anti-inflammatory agent has been proven to play a role in the management of T2DM. Butyrate is a short chain fatty acid produced from resistant starch fermentation in the intestinal lumen. It is able to bind to GPR41 and GPR43 receptors on monocytes, so that it can change the pattern of cytokine expression, activation, migration and cell differentiation. Hence, it is interesting to examine the anti-inflammation effect of butyrate and the effect on monocyte migration. A total of 37 subjects were examined in this study. They were divided into two groups, with and without butyrate treatment. We analyzed two pro-inflammatory cytokines (Tumor Necrosis Factor TNF-α and Interleukin IL-6) and one anti-inflammatory cytokine, IL 10. Monocytes were isolated in type 1 collagen gel for migration testing using the µ-slide chemotaxis IBIDI. Image analysis used ImageJ and Chemotaxis tool software. There was a significant difference in the TNFα/IL 10 ratio between healthy groups and T2DM. Butyrate also appears to suppress TNFα cytokine production and increase IL10 production. It also decreases the accumulation distance of monocyte migration in T2DM.

Diagnostic Approach for Thyroid Nodules.

Thyroid nodule is a health problem which commonly found in daily practice, therefore clinical guidance is needed. This guideline was compiled by a multidisciplinary team and expected to be a guideline in diagnosing thyroid nodules on daily clinical practice.

Gastroschisis Following Treatment with High-Dose Methimazole in Pregnancy: A Case Report.

Hyperthyroidism in pregnancy is associated with a increased incidence of low birth weight, preterm birth and admission to the neonatal intensive care unit. However, available treatment options are limited. In this report, we present a case of fetal gastroschisis with a history of intrauterine exposure to methimazole. A 37-year-old woman was diagnosed with Grave's disease 3 years before her pregnancy. She had a poor response to propylthiouracil and required high-dose methimazole before her pregnancy. During the first trimester, she received methimazole 120 mg/day. After her 12th week of pregnancy, she received block-and-replace therapy (levothyroxine [LT4] 50 µg/day) because of the risk of hypothyroidism, and the dose of methimazole was downtitrated to 60 mg/day. Fetal ultrasonography showed fetal growth retardation and gastroschisis at gestational week 33. The relationship between the very high doses of methimazole in the first trimester of pregnancy and the incidence of gastroschisis in this patient was not fully understood because evidence of a relationship between the use of antithyroid drugs in the first trimester and congenital abnormalities in the fetus is lacking. Furthermore block-and-replace therapy is not recommended in pregnancy because it requires a higher dose of methimazole. We recommend preconception counseling and early screening of thyroid function. The counseling should include the best timeline for pregnancy and a discussion of the risks and benefits of hyperthyroidism treatment options.

Practical Guidelines Management of Graves Ophthalmopathy.

Graves' ophthalmopathy is the most common extra-thyroid manifestation in patients with Graves' disease, based on inflammatory and autoimmune conditions in orbital tissue. This practical guideline was formed by a multidiciplinary team, and is intended to provide guidance for diagnosis and management of Graves' ophthalmopathy in daily clinical practice to improve quality of care and treatment outcome.

Thyroid Dysfunction in Type 2 Diabetes Mellitus Patients.

BACKGROUND: thyroid dysfunction is more likely to occur in diabetes mellitus patients than general population. Until now, no study has been done to find prevalence of hypothyroidism and hyperthyroidism in Indonesian diabetics. This study aimed to find the proportion and characteristics of thyroid dysfunction in Indonesian type 2 diabetes mellitus patients. METHODS: a cross-sectional study was conducted in Endocrine and Diabetes Polyclinic, Department of Internal Medicine, Cipto Mangunkusumo Hospital from July to September 2015. This study include type 2 diabetes mellitus patients, age ≥ 18 year-old, willing to undergo thyroid laboratory testing. In this study, hypothyroidism defined as TSH more than 4.0 mIU/L, while hyperthyroidism is defined as TSH less than 0.4 mIU/L with eCLIA. RESULTS: from 364 subjects who were recruited from Endocrine and Diabetes Polyclinic, Cipto Mangunkusumo Hospital, 303 subjects underwent this study until analysis. Two hundred and three (273) subjects (90.1%) were euthyroid, 7 subjects (2.31%) were hyperthyroid, and 23 subjects (7.59%) were hypothyroid. Majority of the patients had subclinical hypothyroidism (56.5% based on Zulewski and Billewicz Score and 65.2% based on fT4 laboratory result), while 42.9% and 71.4% subjects had clinical hyperthyroidism based on clinical appearance and fT4 laboratory result respectively. CONCLUSION: proportion of hypothyroidism was 7.59% and hyperthyroidism was 2.31%, while the proportion of total thyroid dysfunction was 9.9% among diabetics. It is suggested that screening for thyroid dyscfunction can be done in high risk condition as a part of comprehensive management in type 2 diabetes mellitus patients.