Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; ••: ••-••.

Challenges in Diagnosis and Treatment of Male Hypogonadism.

Hypogonadism is a condition characterized by diminished or absent production of sex hormones by the testicles in men and the ovaries in women. Hypogonadism is classified into primary and secondary hypogonadism. Each type of hypogonadism can be caused by congenital and acquired factors. There are many factors that contribute to the occurrence of hypogonadism, including genetic and developmental disorders, infection, kidney disease, liver disease, autoimmune disorders, chemotherapy, radiation, surgery, and trauma. This represents the considerable challenge in diagnosing hypogonadism.The goals of treatment include restore sexual functionality and well-being, initiating and sustaining virilization, osteoporosis prevention, normalize growth hormone levels in elderly men if possible, and restoring fertility in instances of hypogonadotropic hypogonadism. The main approach to treating hypogonadism is hormone replacement therapy. Male with prostate cancer, breast cancer, and untreated prolactinoma are contraindicated for hormone replacement therapy. When selecting a type of testosterone therapy for male with hypogonadism, several factors need to be considered, such as the diversity of treatment response and the  type of testosterone formulation. The duration of therapy depends on individual response, therapeutic goals, signs and symptoms, and hormonal levels. The response to testosterone therapy is evaluated based on symptoms and signs as well as improvements in hormone profiles in the blood. Endocrine Society Clinical Practice Guideline recommend therapeutic goals based on the alleviation of symptoms and signs, as well as reaching testosterone levels between 400 - 700 ng/dL (one week after administering testosterone enanthate or cypionate) and maintaining baseline hematocrit.Hormone therapy is the primary modality in the management of hypogonadism. The variety of signs and symptoms makes early diagnosis of this condition challenging. Moreover, administering hypogonadism therapy involves numerous considerations influenced by various patient factors and the potential for adverse effects. This poses a challenge for physicians to provide targeted hypogonadism therapy with minimal complications.

Physio-cognitive decline syndrome among middle-aged diabetes patients: Handgrip strength significantly correlates with glycaemic control and cognitive score.

Aims: To investigate the correlation between glycaemic control with component of Physio-Cognitive Decline Syndrome (PCDS) and among each component of PCDS itself. Methods: A cross sectional study was conducted (January 2021-November 2022) at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia on consecutively recruited T2DM outpatients aged 40-59 years old. Data on the latest three months HbA1c, hand grip strength (HGS), usual gait speed (GS), and Indonesian Montreal Cognitive Assessment (MoCA-Ina) were evaluated. Pearson or Spearman's test was used to analyse the correlations. Results: There were 133 subjects with median age 53 (40-59) years. The PCDS was found in 48.1 % subjects, of which 64.1 % with uncontrolled glycaemia. Significant correlations were found between HGS and HbA1c (r = -0.24, R2 = 0.06, p < 0.01) and MoCA-Ina score (r = 0.21, R2 = 0.04, p < 0.05). Conclusion: The higher HbA1c and the lower MoCA-Ina score, the weaker handgrip strength was.

Therapeutic Plasma Exchange as a Bridging Therapy for the Definitive Treatment of a Patient with Graves' Disease and Methimazole-Induced Liver Injury.

Introduction: Graves' disease (GD) is an autoimmune condition affecting the thyroid gland. The aim of treating GD is to control the symptoms of hyperthyroidism and achieve long-term remission. Antithyroid drugs (ATDs) are the medications of choice among newly-diagnosed GD patients as they are easy to be delivered and cause remission in more than 50% of patients. However, ATDs increase the risk of hepatotoxicity, especially among patients with liver abnormalities. Patients who cannot tolerate ATDs should receive definitive therapy such as radioactive iodine (RAI) or surgery. In order to minimize the risk of thyroid storm during these procedures, patients should be in euthyroid condition and receive bridging therapy. Therapeutic plasma exchange (TPE), which aims to remove thyroid hormones from plasma, is one of the modalities that can be considered as a bridging therapy during the perioperative period among GD patients who cannot tolerate ATD. Case Presentation: A 35-year-old man with general weakness and thyrotoxicosis symptoms was admitted to the emergency room. Lid retraction, diffuse Goiter, and tremors were evident. Laboratory findings revealed TSH = 0.005 µIU/mL, FT4 = 7.77 ng/dL, TRAb = 9.90 IU/L, ALT = 123 U/L, total bilirubin = 23.94 µmol/L, and direct bilirubin = 10.26 µmol/L. Ultrasonographic examination showed the enlargement of the thyroid gland, and abdomen ultrasonographic evaluation showed mild hepatomegaly with mild fatty infiltration. The patient was diagnosed with GD, suspected thyroid storm, elevated liver transaminases, and fatty liver disease. The patient then received methimazole, propranolol, and glycyrrhizin. During observation, the patient developed drug-induced liver injury (DILI) evidenced by an increase in liver enzymes (ALT up to 1023 U/L) and the elevation of total bilirubin to 258.21 µmol/L, so methimazole was stopped. After discontinuing methimazole, liver injury improved. However, thyrotoxicosis symptoms returned, so the patient underwent a total thyroidectomy. In order to achieve a euthyroid status before surgery, five sessions of therapeutic plasma exchange were performed, which improved the signs and symptoms of hyperthyroidism and retained the thyroxine hormone within the normal range. Thyroidectomy was then performed successfully without serious complications (e.g., thyroid storm, etc.). Conclusions: Therapeutic plasma exchange is a safe and effective bridging therapy for GD patients who require thyroidectomy but cannot tolerate ATDs.

The role of high fat diet on serum uric acid level among healthy male first degree relatives of type 2 diabetes mellitus.

First-degree relatives (FDR) of type 2 diabetes mellitus have increased risk of developing insulin resistance-related disorders including hyperuricemia. We investigated metabolic profile and serum uric acid (SUA) metabolism in response to high-fat diet among healthy male FDR in comparison to those without family history of diabetes. A total of 30 FDR and 30 non-FDR subjects completed a 5-days-hypercaloric diet with fat added to regular daily intake. Despite similar insulin response, FDR displayed different changes in SUA compared to non-FDR subjects (0.26 ± 0.83 mg/dL vs - 0.21 ± 0.78 mg/dL, p = 0.028). In subgroup analyses stratified by body mass index and waist circumference, significant different SUA changes between FDR and non-FDR subjects were only found in obese (0.48 ± 0.87 mg/dL vs - 0.70 ± 0.71 mg/dL, p = 0.001) and centrally obese (0.59 ± 0.83 mg/dL vs - 0.55 ± 0.82 mg/dL, p = 0.011) subgroups. In multivariate analysis, visceral adiposity seemed mediating the different response in SUA metabolism between FDR and non-FDR subjects induced by short-term obesogenic diet.

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.

Vitamin D Levels in Pre-frail Older Adults and Its Correlation with Hand Grip Strength.

BACKGROUND: Vitamin D deficiency is frequent in older adults and associated with poor musculoskeletal function. The prevalence of pre-frailty is also high in older persons, who may proceed to a frail state. This study aimed to determine the vitamin D levels in pre-frail older adults and its correlation with hand grip strength. METHODS: A cross-sectional study was conducted on older adults (age > 60 years) with a pre-frail condition who were visiting the outpatient geriatric clinic at Cipto Mangunkusumo Hospital in Jakarta, Indonesia. Serum levels of vitamin D, measured as 25(OH)D, were determined by enzyme-linked immunosorbent assay (ELISA), and hand grip strength was measured using a Jamar hydraulic dynamometer. Correlations between vitamin D levels and hand grip strength were evaluated by Spearman's rank correlation coefficient. Multiple linear regression analysis was carried out to assess contribution of variables that influence hand grip strength. RESULTS: Of 95 pre-frail older adults (mean age 70.08 ± 5.35 years), 67.4% were female,  and the median vitamin D level was 17.91 (interquartile range/IQR 13.68-26.36) ng/mL. Overall, 11.6% of the participants had normal vitamin D levels, whereas 34.7% and 53.7% had insufficient and deficient levels, respectively. Females were more likely to have inadequacy of vitamin D than males.  Those with vitamin D deficiency tended to have a higher body mass index (BMI) and lower vitamin D intake than normal levels. A significant correlation between serum vitamin D levels and hand grip strength was observed (r = 0.283; P = 0.006). After adjusting for age, comorbidities, nutritional status, functional status, BMI, protein intake, and sun exposure score, regression analysis between hand grip strength and vitamin D levels gave standard coefficient beta = 0.255 (P = 0.013). CONCLUSION: In this study, pre-frail older adults had a high proportion of deficient and insufficient vitamin D levels, and a significant correlation was found between serum vitamin D levels and hand grip strength.

In-hospital malnutrition among adult patients in a national referral hospital in Indonesia.

BACKGROUND/OBJECTIVES: Malnutrition during hospitalization is linked to increased morbidity and mortality, but there are insufficient studies observing clinical factors contributing to weight loss during hospitalization in Indonesia. This study was therefore undertaken to determine the rate of weight loss during hospitalization and the contributing factors. SUBJECTS/METHODS: This was a prospective study involving hospitalized adult patients aged 18-59 yrs, conducted between July and September 2019. Body weight measurement was taken at the time of admission and on the last day of hospitalization. The factors studied were malnutrition at admission (body mass index < 18.5 kg/m2), immobilization, depression (Beck Depression Inventory-II Indonesia), polypharmacy, inflammatory status (neutrophil-lymphocytes ratio; NLR), comorbidity status (Charlson Comorbidity Index; CCI), and length of stay. RESULTS: Totally, 55 patients were included in the final analysis, with a median age of 39 (18-59 yrs) yrs. Of these, 27% had malnutrition at admission, 31% had a CCI score > 2, and 26% had an NLR value of ≥ 9. In all, 62% presented with gastrointestinal symptoms, and depression was documented in one-third of the subjects at admission. Overall, we recorded a mean weight loss of 0.41 kg (P = 0.038) during hospitalization, with significant weight loss observed among patients hospitalized for 7 days or more (P = 0.009). The bivariate analysis revealed that inflammatory status (P = 0.016) was associated with in-hospital weight loss, while the multivariate analysis determined that the contributing factors were length of stay (P < 0.001) and depression (P = 0.019). CONCLUSIONS: We found that inflammatory status of the patient might influence the incidence of weight loss during hospitalization, while depression and length of stay were independent predictors of weight loss during hospitalization.

Increased intestinal-fatty acid binding protein in obesity-associated type 2 diabetes mellitus.

BACKGROUND: Obesity is a traditional risk factor for type 2 diabetes mellitus (T2DM). However, recent studies reported that metabolically unhealthy obesity (MUO) exerts a higher risk of developing T2DM than metabolically healthy obesity (MHO) because of its higher state of insulin resistance. This may happen due to metabolic endotoxemia through gut dysbiosis and increased intestinal permeability. Our study aimed to know the association of intestinal permeability using intestinal fatty acid-binding protein (I-FABP) with obesity-related T2DM patients in Indonesia. METHODS: This was a cross-sectional study that recruited 63 participants with obesity defined using body mass index (BMI) classification for the Asia-Pacific population (BMI ≥25 kg/m2). All participants were then grouped into T2DM and non-T2DM based on American Diabetes Association (ADA) diagnostic criteria. The I-FABP levels were measured using the enzyme-linked immunosorbent assay method. RESULTS: The I-FABP level of T2DM group was higher compared to non-T2DM group, namely 2.82 (1.23) ng/mL vs. 1.78 (0.81) ng/mL (p<0.001; mean difference 1.033 with 95% CI 0.51-1.55). This difference was not attenuated even after adjustment for age. The fitted regression model using linear regression was: i-FABP = 1.787+1.034*(DM) (R2 = 18.20%, standardized ß = 0.442, p<0.001). CONCLUSIONS: This study underscores the association of intestinal permeability with T2DM in people with obesity and supports the evidence of the potential role of intestinal permeability in the pathogenesis of obesity-related T2DM.

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.

Sarcopenia and Chronic Complications of Type 2 Diabetes Mellitus.

Sarcopenia, defined as the loss of skeletal muscle mass and strength and/or a decrease in physical performance, is classically related to aging. However, chronic disease, including type 2 diabetes mellitus (T2DM), may accelerate the development of sarcopenia. Previous studies found strong association between T2DM and sarcopenia. Insulin resistance that exists in T2DM is thought to be the key mediator for impaired physical function and mobility which may lead to sarcopenia. T2DM may cause sarcopenia through the mediation of insulin resistance, inflammation, accumulation of advanced glycation end-products, and oxidative stress that may affect muscle mass and strength, protein metabolism, and vascular and mitochondrial dysfunction. On the other hand, loss of muscle in sarcopenia may play a role in the development of T2DM through the decreased production of myokines that play a role in glucose and fat metabolism. This review highlights the findings of existing literature on the relationship between T2DM and sarcopenia which emphasize the pathophysiology, chronic vascular complications, and the course of macrovascular and microvascular complications in T2DM.

Effect of Cholecalciferol Supplementation on Disease Activity and Quality of Life of Systemic Lupus Erythematosus Patients: A Randomized Clinical Trial Study.

BACKGROUND: Increase in the prevalence and survival rates has led to the assessment of disease activity and quality of life of SLE patients as targets in treatment. Cholecalciferol was considered as having a role in reducing disease activity and improving quality of life. METHODS: A double blind, randomized, controlled trial was conducted on female  outpatients aged 18-60 years with SLE, consecutively recruited from September to December 2021 at Cipto Mangunkusumo Hospital. Sixty subjects who met the research criteria were randomized and equally assigned into the cholecalciferol and placebo groups. The study outcomes were measured at baseline and after 12 weeks of intervention. RESULTS: Out of 60 subjects, 27 subjects in cholecalciferol group and 25 subjects in placebo group completed the intervention. There was a significant improvement on the level of vitamin D (ng/ml) after intervention in the cholecalciferol group, from an average of 15,69 ng/ml (8.1-28.2) to 49,90 ng/ml (26-72.1), and for the placebo group from 15,0 ng/ml (8.1-25,0) to 17.35 ng/ml (8.1-48.3) (p<0,000). Results of the MEX-SLEDAI score showed significant differences in both groups after the intervention, with a significant decrease in the cholecalciferol group from 2,67 (0-11) to 1,37 (0-6), compared to the placebo group from 2,6 (0-6) to  2,48 (0-6) (p<0,001). There were no significant differences on the quality of life in both groups. CONCLUSION: Supplementation of cholecalciferol 5000 IU/day for 12 weeks was statistically significant in increasing vitamin D levels and improving disease activity, but did not significantly improve the quality of life of SLE patients.

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.

Characteristics of Diabetic Foot Ulcer Patients Pre- and During COVID-19 Pandemic: Lessons Learnt From a National Referral Hospital in Indonesia.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most terrifying diabetic complications for patients, due to the high mortality rate and risk for amputation. During the COVID-19 pandemic, many diabetic patients limited their visits to the hospital, resulting in delays for treatment especially in emergency cases. OBJECTIVE: This study aimed to compare the characteristics of patients with DFU pre- and during COVID-19 pandemic period. Methods: This study was a retrospective cohort study using foot registry data. We compared our patients' characteristics pre-COVID-19 pandemic period (1 March 2019-28 February 2020) and during COVID-19 pandemic period (1 March 2020-28 February 2021). RESULTS: Cohorts of 84 and 71 patients with DFU pre- and during COVID-19 pandemic period, respectively, were included in this study. High infection grade (66.7% vs 83.1%, P = .032), osteomyelitis event (72.6% vs 87.3%, P = .04), leukocyte count (15 565.0/µL vs 20 280.0/µL, P = .002), neutrophil-to-lymphocyte ratio (7.7 vs 12.1, P = .008), waiting time-to-surgery (39.0 h vs 78.5 h, P = .034), and number of major amputation (20.2% vs 39.4%, P = .014) were significantly higher during the COVID-19 pandemic period. CONCLUSION: During the COVID-19 pandemic, patients with DFU had more severe infection, higher proportion of osteomyelitis, longer waiting time for getting surgical intervention, and higher incidence of major amputation.

Comparison of insulin-like growth factor-1 and sclerostin levels between premenopausal women with and without diabetes mellitus.

OBJECTIVES: This study assesses the serum levels of insulin-like growth factor-1 (IGF-1) and sclerostin as markers of decreased bone formation in premenopausal women with type 2 diabetes mellitus. METHODS: A cross-sectional study was conducted to measure serum levels of IGF-1 and sclerostin in 40 premenopausal women with and without diabetes mellitus using an enzyme-linked immunosorbent assay. The levels of IGF-1 and sclerostin were compared between the groups using the Mann Whitney test and unpaired t-test, respectively. RESULTS: The median IGF-1 serum levels were 40.60 ng/mL and 42.7 ng/mL in the diabetic and non-diabetic groups, respectively, with no significant difference. The serum levels of sclerostin were significantly higher in the diabetic group than in the non-diabetic group (132.1 pg/mL and 96.0 pg/mL, respectively; p < 0.001). CONCLUSION: The levels of sclerostin were significantly higher in premenopausal women with diabetes mellitus than in the non-diabetic group. Since sclerostin influences the differentiation and maturation of osteoblasts, serum sclerostin might potentially be useful as a marker of decreased bone formation in premenopausal women with diabetes.

The Correlation Between Iron Overload and Endocrine Function in Adult Transfusion-Dependent Beta-Thalassemia Patients with Growth Retardation.

BACKGROUND: Iron overload is a major problem in patients with transfusion-dependent beta-thalassemia (TDT). Reports on the correlation between iron overload and endocrine function with growth retardation in such a population in Indonesia have not been established. Therefore, this study aims to obtain a profile of iron load and endocrine function of adult transfusion dependent beta-thalassemia patients and their correlation with growth retardation. METHODS: A cross-sectional study was performed, involving adult homozygous and HbE beta-thalassemia patients receiving blood transfusions at the Cipto Mangunkusumo Hospital, Jakarta. Iron overload was represented by serum ferritin (FS) and transferrin saturation (TS), while the endocrine function was examined by the Thyroid Stimulating Hormone-sensitive (TSHs), free T4 (fT4), and insulin-like growth factor-1 (IGF-1). The results were analyzed using bivariate analysis plus Pearson and Spearman correlation tests. RESULTS: In general, 58 subjects were selected from 224 adult transfusion dependent beta- thalassemia patients, consisting of 31 males (53.4%) and 27 females (46.6%). Furthermore, their median age was 21 (18-24) years, while the subclinical hypothyroid proportion was 32.7% and low IGF-1 levels were detected in 79.3% of the total population. There was a weak negative correlation between FS and fT4 (Spearman rho=-0.361; p=0.003), as well as IGF-1 (Spearman rho=-0.313; p=0.008), but FS and TSHs had no correlation (Spearman rho=0.074; p=0.29). Also, there was no correlation between ST with TSHs (Spearman rho=0.003; p=0.492), fT4 (Spearman rho=0.018; p=0.448), and IGF-1 (Spearman rho=-0.142; p=0.143). CONCLUSION: Based on serum ferritin, iron overload is discovered to have a negative correlation with free T4 and insulin-like growth factor-1.

Effect of atorvastatin on subclinical atherosclerosis in virally-suppressed HIV-infected patients with CMV seropositivity: a randomized double-blind placebo-controlled trial.

Background: Persistent immune activation and inflammation in HIV-infection are linked to excess cardiovascular risk and other non-communicable diseases. Periodic asymptomatic CMV-reactivity in HIV infected patients over a lifetime may contribute to non-AIDS defining morbidity. Despite undetectable levels of HIV and CMV, these patients continue to have increased levels of biomarkers and immune activations. Statin administration is thought to reduce subclinical atherosclerosis by decreasing LDL-C levels. It may also add beneficial effects against CMV infection. Methods: We are conducting a double-blind placebo-controlled trial in which patients are randomized to receive either atorvastatin or placebo with a ratio of 1:1. This trial aims to study the effect of atorvastatin in statin-naive virally-suppressed HIV-infected patients with stable ART and CMV seropositivity on carotid intima media thickness (CIMT), tool that evaluates subclinical atherosclerosis. The study recruits 80 patients at HIV integrated care unit of Cipto Mangunkusumo hospital. All eligible subjects have CIMT evaluation as primary outcome, along with flow mediated vasodilatation (FMD), liver fibrosis and steatosis evaluation, fasting lipid, neurocognitive test, community periodontal index (CPI), and residual immune activation as secondary outcomes in 48 weeks. Ethics and dissemination: This study has received an ethical approval from Health Research Ethics Commitee-Universitas Indonesia and Cipto Mangunkusumo Hospital. Before joining the study, all participants fill in an informed consent form. At the end of study analysis, the trial results will be published and disseminated in peer-reviewed journals. Discussion: The main purpose of our study is to evaluate the effect of atorvastatin administration on CIMT changes in statin naïve virally suppressed HIV-infected patients with stable ART and CMV seropositivity Registration: ClinicalTrials.gov ID NCT04101136; registered on 24 September 2019.

Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus.

AIM: To analyze indoleamine 2,3-dioxygenase (IDO) production in the cell culture supernatant of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from type 2 DM (T2DM) patients and investigate IDO's association to pro- and anti-inflammatory cytokines. SUBJECTS AND METHODS: PBMC samples were collected from 21 T2DM patients and 17 normoglycemic participants, then stimulated with PHA for 3 days. Cytokine and IDO concentrations were measured in the PBMC culture supernatants. In vitro production of TNF-α, IL-6, interferon-γ, and IL-10 were measured using multiplex immunoassay. IDO concentration was assessed using ELISA. To assess how PHA stimulation altered IDO production and to minimize the unstimulated baseline effect of T2DM, we subtracted the PHA-stimulated IDO concentration from the unstimulated one. IBM SPSS version 23 was used for statistical analysis. RESULTS: The IDO concentrations in the PBMC culture supernatants were significantly higher in T2DM patients regardless of whether they were unstimulated (P < .001) or PHA-stimulated (P = .012). Reduced IDO production was observed in 52.8% of T2DM patients and was associated with older age and lower interferon-γ levels. Conversely, 42.8% of T2DM patients showed increased IDO concentrations, which were correlated with the IL-6/IL-10 ratio (r = 0.683, P = .021) and interferon-γ/IL-10 ratio (r = 0.517, P = .077). CONCLUSION: The interferon-γ level was reduced in the PBMC culture supernatant of T2DM patients with reduced IDO production. Reduced IDO production in T2DM patients following PHA stimulation was associated with older age and, notably, higher baseline IDO concentrations. Since IDO is primarily produced by dendritic cells, reduced IDO production after PHA stimulation may indicate dendritic cell dysfunction.

Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus.

PURPOSE: In this study, we analyzed the production of interferon γ (IFN-γ) and interleukin 10 (IL-10) by peripheral blood mononuclear cells (PBMCs) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the capacity of monocytes to produce tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) following IFN-γ stimulation and the associated role of IL-10 in TNF-α and IL-6 production. PATIENTS AND METHODS: In vitro experiments were conducted on PBMCs obtained from 19 patients with T2DM and 17 healthy participants. PBMCs were isolated from venous blood by density gradient centrifugation, followed by 3-day phytohemagglutinin induction. In vitro production of TNF-α, IL-6, IFN-γ, and IL-10 was measured using the multiplex immunoassay. Statistical analysis was performed using IBM SPSS 23 version. RESULTS: IFN-γ concentration in the T2DM group was significantly lower than that in control group (T2DM 7,700.86 ± 3,037.77 vs control 10,672.69 ± 5,625.50 pg/mL; p = 0.048). However, TNF-α, IL-6, and IL-10 levels showed no significant difference between the two groups. The TNF-α/IFN-γ and IL-6/IFN-γ ratios were significantly higher in T2DM than in the control group (p = 0.026 and p = 0.048, respectively). In T2DM, the high TNF-α/IFN-γ ratio was consistent, with the low baseline IL-10 level (p = 0.022). CONCLUSION: In T2DM, T-cell response is impaired with significantly reduced IFN-γ production, and simultaneously, circulatory monocytes show enhanced cellular responsiveness to inflammatory stimuli. The low baseline IL-10 level likely contributes to such an immune response.

Subclinical Atherosclerosis in Young Adult Population with First Degree Relatives of Type 2 Diabetes Mellitus.

Cardiovascular disease (CVD) remain a leading cause of death globally. The concept of acute myocardial infarction in young adults was uncommon. Atherosclerosis is the leading cause of CVD, including myocardial infarction, stroke, heart failure and peripheral artery disease. This condition is initiated early in childhood and progressive in nature. CVD risk factors includes hypertension, dyslipidemia and obesity play a role in the development of atherosclerosis and  components in insulin resistance syndrome.One of many risk factors for insulin resistance in healthy individuals is a first-degree relative (FDR) of Type 2 Diabetes Mellitus (T2DM) patients. This group shows a higher risk of insulin resistance and pancreatic beta cells disruption even in adolescence, although they often remains asymptomatic. Clinical manifestations of metabolic disorders and atherosclerosis will appear earlier in the FDR T2DM group who have sedentary lifestyles and obesity, when compared to the non-FDR group. Several studies have attempted to detect metabolic disorders and subclinical atherosclerosis that might occur; therefore an early prevention can be carried out in these high-risk groups.  Unfortunately, factors that affect the onset and the severity of the prospective clinical manifestations from the previous studies remained inconclusive.