Proportion of Hypogonadism in Transfusion-Dependent Thalassemia Patients and Its Contributing Factors.

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

Secretome of Hypoxia-Preconditioned Mesenchymal Stem Cells Enhance Angiogenesis in Diabetic Rats with Peripheral Artery Disease.

Background: Lower limb peripheral artery disease (PAD) is the main risk of diabetes mellitus which result to high mortality rate. Approximately, 50% of patients who receive several treatments have passed away or lost limbs at a year's follow-up. Secretome of hypoxia mesenchymal stem cells (S-MSCs) contains several active soluble molecules from hypoxia MSCs (H-MSCs) that capable inducing anti-inflammatory and vascular regeneration in PAD. Objective: In this study, we investigated the therapeutic potential of S-MSCs in improving dynamic function and angiogenesis of PAD diabetic rats. Methods: The PAD was established by the incision from the groin to the inner thigh and distal ligation of femoral arteries in rats with diabetes. Rats were administered with 200 µL and 400 µL S-MSCs that successfully filtrated using tangential flow filtration (TFF) system based on various molecular weight cut-off categories intravenously. ELISA assay was used to analyze the cytokines and growth factors contained in S-MSCs. Tarlov score were examined at day 1, 3, 5, 7, 10 and 14. The rats were sacrificed at day 14 and muscle tissues were collected for immunohistochemistry (IHC) and gene expression analysis. Results: ELISA assay showed that S-MSCs provides abundant level of VEGF, PDGF, bFGF, IL-10 and TGFß. In vivo administration of S-MSCs remarkably enhanced the Tarlov score. S-MSCs improved angiogenesis through enhancing VEGF gene expression and significantly increasing CD31 positive area in muscle tissue of PAD diabetic rats. Conclusion: Our findings suggest that S-MSCs could improves dynamic function and angiogenesis in PAD diabetic rats.

The Effect of Drug-Related Problems on Blood Glucose Level in the Treatment of Patients with Type 2 Diabetes Mellitus.

AIM: The study aimed to investigate the effect of drug-related problems (DRPs) on changes in blood glucose level (BGL) in the treatment of type 2 diabetes mellitus (T2DM) patients. METHODS: This three-month prospective cross-sectional study was conducted to patients of T2DM with complications hospitalised in Haji Adam Malik (HAM) Hospital, Medan, Indonesia period from July to October 2018. DRPs were identified and classified by using Cipolle DRP classification and trustable literature. The data obtained were analysed by Chi-Square test (p < 0.05 implied that there was a significant relationship). RESULTS: This study involved 81 T2DM patients, 52 (64.2%) of the patients were male, and 29 (35.8%) of them were female. Most (30.9%) of patients were at the age of 51-60 years. Combination of rapid-acting and long-acting insulin was the most frequently provided antidiabetic drugs (69.1%). There were 68 DRPs experienced by 32 (39.5%) of the patients. Percentage of DRP experienced by the 32 patients by number: 1 DRP, 53.1; 2 DRPs, 28.1; 3 DRPs, 3.1; 4 DRPs, 3.1; 5 DRPs, 3.1; 7 DRPs, 9.3. This study showed that 27.2% and 12.3 % of the patients had hyperglycemia and hypoglycemia, respectively. There was no significant relationship between BGL and indication without drug therapy (p = 0.064), ineffective provided drug (p = 0.079), and there was a significant relationship between BGL and irrational dose (p = 0.000). Furthermore, there was a significant relationship between hypoglycemia and adverse drug reaction (p = 0.000). CONCLUSION: DRPs are common among T2DM patients and still required the attention and appropriate actions of healthcare providers.

Correlations between Insulin Receptor Substrate-1 with Phosphoinositide 3-Kinase and P38 Mitogen-Activated Protein Kinase Levels after Treatment of Diabetic Rats with Puguntano (Curanga Fel-Terrae [Merr.]) Leaf Extract.

BACKGROUND: Defects in post-receptor insulin signalling are the major cause of insulin resistance in type 2 diabetes mellitus (T2DM). AIM: This study aimed to investigate the correlations between insulin receptor substrate (IRS)-1 with phosphoinositide 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) levels after puguntano (Curanga fel-terrae [Merr.]) leaf extract treatment in a rat model of T2DM. METHODS: A combination of high-fat diet-feeding (HFD) and multiple low dose intraperitoneal injections of streptozotocin was used to induced T2DM in 48 Wistar rats, which were then randomly divided into control and treatment groups (n = 24 per group). Puguntano leaf extract was administered to the treatment group once daily (200 mg/kg.bw) for 10 days. IRS-1, PI3K and p38 MAPK levels were measured in skeletal muscle using sandwich ELISAs in control group after becoming T2DM and in the treatment group after 10 days of puguntano treatment. Data were analysed using the Wilcoxon test and Spearman's correlation. RESULTS: IRS-1, PI3K and p38 MAPK levels were significantly higher in the treatment group than in the control group. There were also significant positive correlations between IRS-1 with PI3K and p38 MAPK levels (r = 0.375, p = 0.035; r = 0.552, p = 0.003; respectively) after the treatment. CONCLUSION: This study demonstrated significant positive correlations between IRS-1 with PI3K and p38 MAPK levels after puguntano leaf extract treatment of T2DM rats.

The Effect of Puguntano Leaf Extract (Curanga Fel - Terrae Merr.) On P38 Mapk Levels and Glut-4 Expression in Type 2 Diabetic Rat Muscle.

BACKGROUND: Puguntano (Curanga feel-terrae Merr.) contains flavonoids, saponins, tannins, and steroids/ terpenoids which improved post-receptor insulin signalling in rats model of type 2 diabetes mellitus (T2DM). AIM: This study aimed to determine the effect of puguntano leaf extract on p38 mitogen-activated protein kinase (MAPK) levels and glucose transporter-4 (GLUT-4) expression in diabetic rats muscle. METHODS: Forty-eight male Wistar rats had T2DM induced using a combination of feeding a high-fat diet for 5 weeks and multiple intraperitoneal injections of low-dose streptozotocin (30 mg/kg). The diabetic rats were randomly divided into control and treatment groups, and 200 mg/kg/day puguntano extract was administered orally for 10 days to treatment group. Subsequently, p38 MAPK levels were measured by Sandwich Elisa and plasma membrane GLUT-4 expression was evaluated by Immunohistochemistry in their gastrocnemius muscles. RESULTS: There were significantly higher p38 MAPK levels and GLUT-4 expression in the treatment group than in the control group. CONCLUSION: These data suggest that a puguntano leaf extract can improve post-receptor insulin signalling by enhancing p38 MAPK levels and GLUT-4 expression in a rat model of T2DM.

Neck Circumference in Overweight/Obese Subjects who Visited the Binjai Supermall in Indonesia.

BACKGROUND: Neck circumference (NC) is a simple screening measure for identifying overweight and obesity, it reflects upper-body fat distribution and central obesity. AIM: To determine whether a single measure of NC might be used to identify overweight/obesity. MATERIAL AND METHODS: An observational, analytical, cross-sectional study was done. The subjects consisted of all consecutive subjects who visited Binjai Supermall (North Sumatera Province, Indonesia) between 23rd and 29th September 2015 and agreed to participate in the study. NC, weight, height, body mass index (BMI), and waist circumference (WC) were measured. Overweight and obesity were defined as BMIs of 23.0-24.9 and ≥ 25 kg/m2, respectively. RESULTS: In total, 1554 subjects participated. Of these, 1238 (79.7%) were overweight/obese. NC correlated significantly with weight, height, BMI, and WC. Receiver operating characteristic (ROC) analysis showed that for all men and women, the area under the curve of overweight/obesity for NC was 0.83 and 0.79, respectively. The best NC cutoff points for males and females that indicated overweight/obesity were ≥ 37 cm (sensitivity, 78.3% and specificity, 75.5%) and ≥ 33.5 cm (sensitivity, 76.6% and specificity, 66.7%), respectively. CONCLUSION: The NC cutoffs that were identified may be useful for screening for overweight/obesity and related co-morbidities.