Indonesia DIA-RAMADAN Study: A Real-life, Prospective and Observational of Gliclazide MR in Type-2 Diabetes Patients During Ramadan Fasting.

BACKGROUND: Sulfonylureas (SUs) have been widely used in many countries for T2DM treatment. Gliclazide is one of the SUs with the lowest risk of hypoglycemia; however, the safety and effectiveness of gliclazide MR during Ramadan has not yet been reported in Indonesia. This study aimed to assess safety, efficacy, and tolerability of gliclazide modified release (MR) during Ramadan fasting. METHODS: The study was a part of DIA-RAMADAN study, a prospective observational study with subjects of T2DM patients aged >18 years, who had either controlled or sub-optimally controlled blood glucose level, performed Ramadan fasting. Subjects had been treated with gliclazide MR for at least 90 days prior the study, and were examined for their body mass index (BMI), fasting plasma glucose (FPG) and HbA1c levels 6 to 8 weeks before Ramadan (V0) and 4 to 6 weeks after the end of Ramadan (V1). RESULTS: Out of 198 subjects participating in the study, there were only two subjects (1.0%) who reported symptomatic HEs (either confirmed or not confirmed) and no severe HEs had been reported. There were no significant changes in HbA1c and FPG levels (p>0.05). Interestingly, there was a reduction of bodyweight (-0.4kg) from pre- to post-Ramadan (p < 0.001). Almost no subjects reported discontinuation of gliclazide MR throughout the entire study; however, there was one subject who reported a change of diabetic treatment into diet only. CONCLUSION: gliclazide MR is safe, well tolerated and can maintain glycemic control effectively for Indonesian patients with T2DM who perform Ramadan fasting.

A high-fat and high-fructose diet lowers the cecal digesta's weight and short-chain fatty acid level of a Sprague-Dawley rat model.

BACKGROUND: This study aimed to analyze the effect of a high-fat and high-fructose diet (HFFD) on the digesta weight and shortchain fatty acid (SCFA) levels of cecal digesta in rats. METHODS: This study was an experimental study with a posttest-only control group design with male Sprague-Dawley strain rats as the samples. A total of 36 rats were divided into two groups with normal diet (N) and modified HFFD. The data of energy intake, nutrients and fiber, body weight, Lee index, abdominal circumference, digesta weight, and SCFA levels of cecal digesta were collected. RESULTS: The results showed an 11.94% increase in body weights of rats with HFFD. The total energy intake of the HFFD group was significantly higher than that of N (p = 0.000). The fiber intake and cecal digesta weight in group N were higher than that in the HFFD group (p = 0.00 and p = 0.02, respectively). The concentrations of acetate, butyrate, propionate, and total SCFA in the N group were significantly higher than in the HFFD (p = 0.041,,p = 0.004, p = 0.040, p = 0.013, respectively). A significant negative relationship was observed between the abdominal circumference and cecal digesta concentration (p = 0.029; r = -0.529) and between the Lee index and the SCFA concentration of cecal digesta (p = 0.036, r = -0.206).

The Effect of Physical Activity on Social Isolation in Elderly.

BACKGROUND: Elderly people who have poor social relationships have a higher risk of death than those who have strong social networks. Loneliness and social isolation are associated with an increased risk of coronary heart disease and stroke. Physical activity can reduce social isolation, diverting feelings of loneliness by socializing with other people and expanding social networks by participating in the community. This study aimed to determine the effect of physical activity on social isolation in the elderly. METHODS: A Cross-sectional study was conducted to 181 respondents. The data is collected through interviewing respondents with the International Physical Activity Questionnaire (IPAQ) and social isolation questionnaires. The data was then analyzed descriptively and calculated using Fisher's exact test. SETTING: Ardirejo and Panggungrejo villages, Kepanjen District, Malang Regency. RESULTS: Based on the Fisher's exact between  physical activity and social isolation results were obtained p-value 0.000 (PR = 23.407; 95% CI = 3,117-175,800). CONCLUSION: There is a significant relationship between physical activity and social isolation in the elderly in the community.

Effect of Uric Acid on Blood Glucose Levels.

Uric acid as the final result of purine bases metabolism. In high level condition, uric acid enters the cell and act as oxidant, and acts as independent risk factor and predicts the incident of type 2 diabetes mellitus (T2DM). It may directly inactivate or through oxidative reaction that lower the nitric oxide (NO) level. Lower NO level will reduce insulin uptake in tissues and reduce in GLUT4 translocation in cell that will effect the blood glucose level. The High level of uric acid or hyperuricemia makes oxidative stress by inducing the production of reactive oxygen species (ROS) which interferes the insulin signalling pathway,creates inflammatory  state that reduced the insulin sensitivity,blood glucose uptake and metabolism, also reducing the insulin production from pancreatic islet cells.

Indonesia Cohort of IO HAT Study to Evaluate Diabetes Management, Control, and Complications in Retrospective and Prospective Periods Among Insulin-Treated Patients with Type 1 and Type 2 Diabetes.

BACKGROUND: hypoglycemia is a major adverse event of insulin therapy for diabetes mellitus patients. The study was conducted to evaluate the incidence of hypoglycemia among insulin treated patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) in the Indonesian cohort. METHODS: this Indonesian cohort study consisted of retrospective and prospective evaluation of hypoglycemic episodes, using International Operations Hypoglycemia Assessment Tool (IO HAT) in 374 patients with diabetes (T1DM; n=17 or T2DM; n=357). The patients of ≥18 years of age and treated with insulin for >12 months were selected for this study (ClinicalTrials.gov number: NCT02306681). RESULTS: a total of 374 patients were enrolled in this study and completed SAQ1. All patients with T1DM (17 [100%]), and 347 (97.2%) patients with T2DM completed SAQ2. Almost all the patients in the 4-week prospective period reported at least one hypoglycemic event (T1DM 100%, T2DM 99.4%) and the incidence rate of any hypoglycemia was 67.5 events per patient-year (PPY) and 25.7 events PPY for T1DM and T2DM patients, respectively. Among patients with T1DM and T2DM, 5.9% and 36.4%, respectively, did not know what hypoglycemia was at baseline, also high proportion of patients had impaired hypoglycemic awareness in the study (82.4% and 62.7%, respectively). CONCLUSION: overall, high proportion of patients reported hypoglycemic events in the prospective period indicating under reporting during the retrospective period due to recall bias. Therefore, there is a need for patient education program to improve the awareness of hypoglycemia in diabetes patient in Indonesia.

The effect of cacao bean extracts on the prevention of periodontal tissue breakdown in diabetic rats with orthodontic tooth movements.

Objective: Proper management of orthodontic treatment in diabetic patients is essential due to the heightened risk of periodontal tissue breakdown associated with hyperglycemia. Cacao bean extracts (CBE) are known to reduce the inflammatory response and increase synthesis and angiogenesis in periodontitis. Therefore, this study aims to examine the effect of CBE on preventing periodontal tissue breakdown in diabetes with orthodontic force. Methods: A total of 25 Wistar rats were divided randomly into 5 groups, including non-diabetes, diabetes, diabetes cacao 125, 250, and 500 mg/kg BW. Diabetic rats were induced with the stratified dose of Streptozotocin, and a 30-g-force from orthodontic device was applied in all groups. Diabetes cacao group was given CBE for 7 days using a gastric probe. GCF samples were used to analyze the eNOS level through the ELISA method. NFκB, Collagen-1, and FGF-2 expression were then assessed using the immunohistochemical method, while the number of fibroblasts and blood vessels was observed using hematoxylin-eosin stained tissue. The data obtained were analyzed with one-way ANOVA and post hoc tests, with p < 0.05. Results: CBE at a dose of 250 mg/kg BW significantly increased eNOS level, Collagen-1, and FGF-2 expression, and the number of fibroblasts and blood vessels in diabetes groups. Meanwhile, the treatment decreased NFκB expression in diabetes groups (p < 0.05). Conclusion: This study proved that CBE increased periodontal ligament synthesis and angiogenesis and decreased inflammatory response, thereby preventing periodontal tissue breakdown in diabetic rat models with tooth movement.

Cognitive status and low sun exposure as frailty major risk factor among older people in a rural area of East Java, Indonesia: A cross-sectional study.

AIM: To reveal the prevalence of frailty and factors that strongly affected the frailty condition among older adults in East Java, Indonesia. METHOD: We conducted a cross-sectional study carried out among 400 older adults aged ≥60 years without any acute illness. Data were collected from rural area in two locations in Malang and Pasuruan, East Java, Indonesia, in 2019-2020. For data collection, we used the sociodemographic profile assessment, Fried frailty phenotype, Geriatric Depression Scale, Mini Mental State assessment, sun exposure, handgrip strength, International Physical Activity Questionnaire, walk score, and body mass index. We used logistic regression statistics for data analysis. RESULTS: The result showed that 2.5% were robust, 83% were prefrail, and 14.5% were frail. A higher proportion of subjects were aged 60-74 years (83.3%), women (70.3%), with lower educational status (84.5%). Multivariate analysis showed that the intrinsic factors low cognitive status (odds ratio [OR], 3.052 [95% confidence interval (CI), 1.691-5.508]) and older age (OR, 3.073 [95% CI, 1.637-5.767]) were associated with frailty among the older adults in a rural area. Depression was also associated with frailty (OR, 2.458 [95% CI, 0.465-12.985]). From extrinsic factors, we also found that low sun exposure (OR, 2.931 [95% CI, 1.650-5.204]) and unemployment (OR, 1.997 [95% CI, 1.112-3.588]) were associated with frailty. CONCLUSION: For the Indonesian elderly in this study, low cognitive status, older age, depression, low sun exposure, and unemployment were associated with frailty. Understanding the modifiable risk factors of frailty can provide a valuable reference for future prevention and intervention. Geriatr Gerontol Int 2024; 24: 170-175.

Comparative analysis of short-chain fatty acid levels in non-alcoholic steatohepatitis rat model: Impact of high-fat high-fructose (HFHF), high fat, and Western diets.

The evidence on the role of diets in the production of short-chain fatty acids (SCFAs) was limited. The aim of this study was to assess the potential effects of high-fat high-fructose (HFHF), high-fat, and Western diets on the levels of SCFA. A research experiment employing a post-test-only control group design was carried out from January to April 2022. A total of 27 rats were randomly allocated to each study group. SCFA was measured two weeks after diet administration. Analysis of variance (ANOVA) test was used to analyze the differences among groups, and the effect estimate of each group was analyzed using post hoc Tukey. The concentrations of SCFAs post HFHF diets were recorded as follows: acetic acid at 54.60±10.58 mmol/g, propionic acid at 28.03±8.81 mmol/g, and butyric acid at 4.23±1.68 mmol/g. Following the high-fat diet, acetic acid measured 61.85±14.25 mmol/gr, propionic acid measured 25.19±5.55 mmol/gr, and butyric acid measured 6.10±2.93 mmol/gr. After the administration of Western diet, the levels of SCFA were 68.18±25.73, 29.69±12.76, and 7.48±5.51 mmol/g for acetic acid, propionic acid, and butyric acid, respectively. The level of butyric acid was significantly lower in HFHF diet group compared to the normal diet (mean difference (MD) 6.34; 95%CI: 0.61, 12.04; p=0.026). The levels of acetic acid (p=0.419) and propionic acid (p=0.316) were not statistically different among diet types (HFHF, high-fat, and Western diet). In conclusion, HFHF diet is associated with a lower level of butyric acid than the normal diet in a rat model.

Effects of Lombok Island's local moringa (Moringa oleifera) leaf powder on the decrease of liver fructose levels and GLUT5 expression in albino rats (Rattus novergicus) fed a high fructose diet.

Background: Consumed fructose enters enterocytes of the intestinal epithelial apical membrane mediated by glucose transporter 5 (GLUT5). Aim: To determine the effects of Lombok Island's local Moringa leaf powder on reducing liver fructose levels and GLUT5 expression in the small intestine of albino rats (Rattus novergicus) fed a high-fructose diet. Methods: Moringa leaf (Moringa oleifera) was obtained from Lombok Island, Indonesia. Subsequently, 30 male albino rats (R. novergicus) were used, divided into the normal group (NG), treatment group 1 (T1G), treatment group 2 (T2G), Quercetin group (QG), Moringa group (MG). Quercetin and moringa leaf powder (M. oleifera) was administered at 50 and 500 mg/kgbw for 28 days. Enzyme-linked immunosorbent assay (Elisa) method was used to examine liver fructose levels. The observation of GLUT5 expression in the small intestine was performed by the Immunofluorescence method. Results: The ANOVA test proved that there are significant differences (p < 0.005) in liver fructose levels in all groups. Further post hoc tests show no significant difference (p > 0.005) in liver fructose levels in rats fed a high fructose diet in T1G and T2G with QG and MG rats. However, Moringa leaf powder reduces liver fructose levels by 32.1% and 17.2% in T1G and T2G rats, respectively. The ANOVA test showed a significant difference (p < 0.005) in the expression of GLUT5 in all groups. Further post hoc tests showed a significant difference (p < 0.005) in the expression of GLUT5 in the duodenum, jejunum, and ileum between the NG and the T1G rats. Meanwhile, in T2G rats, significant differences were only found in the jejunum. Moringa leaf powder reduces GLUT5 expression in T1G rats by 44.5%, 59.5%, and 57.2% in the duodenum, jejunum, and ileum, whereas in T2G rats is by 33.5%, 50.2%, and 48.1%, respectively. Conclusion: The administration of local moringa (M. oleifera) leaf powder in Lombok Island had an effect on reducing GLUT5 expression in the small intestine, however, did not in liver fructose levels of albino rats (R. novergicus) fed a high-fructose diet.

Impact of multiple different high-fat diets on metabolism, inflammatory markers, dysbiosis, and liver histology: study on NASH rat model induced diet.

Background: The spectrum of non-alcoholic fatty liver disease (NAFLD), known as non-alcoholic steatohepatitis (NASH), can lead to advanced liver disease. It is known that a variety of diets play a significant role in the development of NAFLD/NASH. The goal of this study was to determine the most appropriate composition of diet to induce NASH in an animal model. Methods: This research used Rattus norvegicus strain Wistar (n=27), which were divided into four groups and given each diet for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7), and high-fat-high-fructose diet (HFHFD, n=7). Subjects were monitored for changes in body weight. Blood samples were collected for biochemical analysis, including low-density lipoprotein (LDL), triglyceride, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatic lipase, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and lipopolysaccharide (LPS). Fecal samples were taken for short-chain fatty acid (SCFA) analysis. Liver histology was assessed using NAS (NAFLD activity score). A statistical comparison test was carried out using the one-way ANOVA or Kruskal-Wallis test. Results: The highest average body weight was observed in the WD group (346.14 g). Liver enzymes, LDL, triglyceride, propionic acid, and acetic acid did not show significantly differences among the groups. TNF-α, IL-6, and hepatic lipase were significant (p = 0.000; p = 0.000; p = 0.004) and the highest level recorded in the HFD group. Butyrate acid level also showed significances (p = 0.021) with the lowest concentration seen in the HFHFD group (4.77 mMol/g). Only WD and HFHFD had a NAS ≥ 5 (14% and 14%). The highest percentage of borderline NAS was found in WD (57%). Conclusions: WD feeding is the most appropriate diet type to induce NASH in rats as it influences metabolic, inflammatory, dysbiosis, and liver histology of rats.

DLBS3233 enhances nephrin and podocin expression also reduces oxidative stress marker and insulin receptor serine diabetic rats' podocytes.

Numerous oxidative stresses are detected in patients with diabetic kidney disease, resulting in insulin resistance that damages the pancreas and kidney. Renal podocytes insensitive to insulin lead to decreased nephrin and podocin and increased insulin receptor serine. The authors did an experiment on diabetic rats to examine the effect of DLBS3233 on repairing insulin resistance. Materials and Methods: Thirty adult male Wistar rats were randomly divided into six groups (n=5 per group): group of nondiabetic rats as a negative control (group 1); untreated diabetic rats (group 2); diabetic rats treated with DLBS3233 4.5 mg/kg BB (group 3); 9 mg/kg BB (group 4); 18 mg/kg BB (group 5); and diabetic rats treated with pioglitazone (group 6). The authors checked Homeostatic Model Assessment for Insulin Resistance to corroborate insulin resistance prior to DLBS3233 administration in diabetic rats. Immunohistochemistry was performed to examine the expression of renal antimalondialdehyde (MDA) antibodies, nephrin, podocin, and insulin receptor serine. The data were analyzed using analysis of variance and the t-test. Result: In the DBLS3233 group, immunohistochemistry showed enhanced expression of renal nephrin and podocin, as well as diminished expression of anti-MDA antibody, along with decreased insulin receptor serine. From statistical analysis, anti-MDA antibodies and insulin receptor serine showed lower expression, whereas the expression of nephrin and podocin were enhanced compared to untreated groups (P<0.05). Conclusion: DLBS3233 reduces oxidative stress by decreasing MDA and improves insulin resistance by increasing the expression of renal nephrin and podocin as well as decreasing insulin receptor serine.

Effects of mobile phone electromagnetic radiation on thyroid glands and hormones in Rattus norvegicus brain: An analysis of thyroid function, reactive oxygen species, and monocarboxylate transporter 8.

The aim of this study was to investigate the effects of mobile phone electromagnetic radiation (MP-EMR) on the thyroid glands and hormones in Rattus norvegicus brain in term of thyroid function, reactive oxygen species (ROS), and monocarboxylate transporter 8 (MCT8) concentration. Forty rats were divided into different groups: control (without EMR exposure), EMR1 (120-min/day exposure), EMR2 (150-min), and EMR3 (180-min). The levels of serum thyroid stimulating hormone (TSH), thyroxine (T4), and malondialdehyde (MDA) and brain and MCT8 were measured using enzyme-linked immunosorbent assay. One-way analysis of variance followed by the Duncan test was used to analyze the data. Our data indicated that the levels of serum TSH and T4 in all the EMR groups were lower significant postexposure compared to the control with P < 0.01 (EMR1 and EMR2) and P < 0.001 (EMR3), suggesting hypothyroidism due to MP-EMR exposure. Increased MDA and decreased MCT8 levels were also observed following the intervention; however, the changes in both concentrations were notably significant after being subjected to 150-min and 180-min of exposure. In conclusion, a significant reduction in TSH, T4, and MCT8 levels indicated thyroid dysfunction due to MP-EMR exposure.

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.

Knowledge and behavior changes in clinician after training of partnership for Diabetes Control in Indonesia.

BACKGROUND AND AIMS: One of the main determinants of successful diabetes management is the quality of healthcare provider including general practitioner and internist which can be increased through medical training. This study aimed to describe the changes of clinician's knowledge and behavior of comprehensive diabetes management training program around Indonesia. METHOD: We conducted a three-day training program for general practitioners and internists for 3.5 years, 2013 to 2016. All clinicians invited as voluntary participant to send their patient data from medical record. Each participant was expected to submit a minimum of 25 type 2 diabetes (T2DM) set patient data before and 6 months after training program to analyze the impact of program in physician knowledge and behavior related to diabetes management. RESULT: 120 of 489 voluntary participants submitted completed baseline data with 4676 patient data. Meanwhile, only 32 participants that submitted completed data of 6 months before after training with 886 patient data. Most of parameters were improve before and after program. The greatest and lowest improvement were on A1c measurement (21%) and smoking assessment (2%). CONCLUSION: Intensive seminar and training was not enough to empower diabetes management. This research might push the creation of clinical practice program that were tailored to each care facilities and integrated within routine care aimed at continual improvement of its healthcare worker.

Substitution of local Indonesian varieties of brown rice on anthropometry and blood glucose level improvement in type 2 DM patients: a pilot project.

BACKGROUND: Diabetes mellitus is a metabolic disorder whose prevalence increases globally. Medical nutrition therapy (MNT) is one of the DM management pillars to control blood glucose. Local Indonesian brown rice is proven to contain high fiber and magnesium levels thus could improve obesity, fasting blood glucose, and HbA1c This study aims to prove the benefits of brown rice on anthropometric parameters and blood glucose control. DESIGN AND METHODS: Respondents were overweight women older than 40 years with type 2 diabetes who were given three main meals and three snacks six days a week for 12 weeks. Anthropometric and blood glucose control data were collected before and after the intervention. Diet and intake data before the intervention were obtained through a semi quantitate food frequency questionnaire. Intake data during the intervention were recorded using the 24-hour food record and analyzed using modified NutriSurvey 2007 software. RESULTS: Brown rice intervention significantly reduced body weight, BMI, body fat percentage, and abdominal circumference (p<0.05), also in fasting blood glucose (FBG), 2-h postprandial blood glucose (PBG), and HbA1c (p<0.05). From the Pearson's test results, an increase in fiber intake correlated with a decrease in BMI and abdominal circumference (p=0.03; r = -0.511 and p=0.006; r = -0.619, respectively). Meanwhile, magnesium intake and changes in BMI showed a negative correlation. CONCLUSIONS: The substitution of brown rice as a staple food for 12 weeks improves anthropometric parameters and blood glucose control in respondents with type 2 diabetes.

Descriptive Regional Subanalysis of a Real-World Study in Patients with Type 2 Diabetes Treated with Gliclazide MR During Fasting: DIA-RAMADAN.

INTRODUCTION: To analyse the safety and effectiveness of gliclazide modified release (MR) in adults with type 2 diabetes mellitus participating in Ramadan from three geographically and culturally different regions of the world included in the DIA-RAMADAN study. METHODS: DIA-RAMADAN was a real-world, observational, international, non-comparative study. The global study population was divided into three regional subgroups, with data gathered at inclusion 6-8 weeks prior to Ramadan (V0), during Ramadan (4.5 weeks) and 4-6 weeks after Ramadan (V1). Primary endpoint was the proportion of patients reporting ≥ 1 symptomatic hypoglycaemic events (HE), which were collected using a patient diary along with other adverse events. RESULTS: Patient numbers from the three regions were n = 564 (46.5%; Indian sub-continent), n = 354 (29.1%; Middle East) and n = 296 (24.4%; South-East Asia). Patient baseline characteristics, demographics, fasting habits and antidiabetic treatments varied between regions. There were similar proportions of symptomatic HE between regions, with no severe HE. Significant weight reductions were observed in all regions following Ramadan, along with reductions in HbA1c and fasting plasma glucose. CONCLUSION: These real-world study data indicate that gliclazide MR is safe and effective for management of type 2 diabetes during Ramadan in all three regions studied as part of DIA-RAMADAN. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04132934. INFOGRAPHIC.

Calcium channel blocker (diltiazem) inhibits apoptosis of vascular smooth muscle cell exposed to high glucose concentration through lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) pathway.

AIM: to examine the role of diltiazem in the prevention of VSMC apoptosis exposed to high glucose through inhibition of LOX-1 expression. METHODS: we performed experimental study on the primary culture of VSMCs. Expression LOX-1, and Caspase-3 activity (a key regulatory protease at which many signaling pathways merge for the execution of apoptosis) were measured by Elisa. Data were expressed as mean ± SEM. The statistical significance was assessed by one-way analysis of variance (ANOVA) followed by post hock analysis by Turckey test, p<0.05 was considered statistically significant. RESULTS: chronic exposed VSMC to high glucose concentration (25 mM), increase cytosolic Ca++ concentration (3127 ± 413.89 v.s. 2011.81 ± 410.93 unit/cell, p<0.01), expression of LOX-1 ((506.80 ± 10.47 v.s. 458.40 ± 36.49 ng/ml, p<0.05), and caspase-3 activity (129.98 ± 5.97 v.s. 114.73 ± 10.84%, p<0.05) respectively, compare exposed to 5mM glucose concentration. LOX-1 was related to caspase-3 activity, pre-treated with inhibitor LOX-1 activity, k-carragenan before being exposed to glucose 25 mM, prevents the increasing of caspase-3 activity (96.41 ± 5.11 v.s. 129.98 ± 5.98 %, p<0.01). Pre incubation with 10µM of diltiazem before being exposed to 25 mM glucose concentration significantly inhibits the elevation of cytosolic Ca++ concentration (2149.61 ± 339.49 v.s. 3127 ± 413.89 unit/cell, p<0.01), LOX-1 expression (468,60 ± 14.44 v.s. 506.80 ± 10.47 ng/ml, p < 0.05), and caspase-3 activity (82.50 ± 9.90 v.s. 129.98 ± 5.97%, p<0.01). CONCLUSION: overall, these results demonstrate that high glucose induces VSMCs apoptosis through caspase-3 pathway. This effect appears to be inhibited by diltiazem through decreasing LOX-1 expression and activity.

A real-world study in patients with type 2 diabetes mellitus treated with gliclazide modified-release during fasting: DIA-RAMADAN.

AIMS: To explore the real-world safety and effectiveness of gliclazide modified release (MR) in patients with type 2 diabetes mellitus (T2DM) fasting during Ramadan. METHODS: DIA-RAMADAN (NCT04132934) was a prospective, international, observational study conducted in nine countries. Patients >18 years of age with T2DM (N = 1244) were examined at an inclusion visit (V0) occurring 6-8 weeks before the start of Ramadan. Patients received a diary to report treatment changes, hypoglycaemic events (HEs), and other adverse events. Gliclazide MR was taken once daily for 14-18 weeks. A second visit (V1) was conducted 4-6 weeks after the end of Ramadan. The primary endpoint was the proportion of patients reporting ≥1 symptomatic HE. Changes in HbA1c, fasting plasma glucose (FPG), and body weight were secondary endpoints. RESULTS: The proportion of patients reporting ≥1 symptomatic HE during Ramadan was low (2.2%) with no reported severe HEs. There was a significant reduction in HbA1c (-0.3%), FPG (-9.7 mg/dL), body weight (-0.5 kg) and body mass index (-0.2 kg/m2) between V0 and V1 (p < 0.001). CONCLUSIONS: Patients with T2DM treated with gliclazide MR during Ramadan have a low risk of hypoglycaemia and maintain glycaemic control and weight while fasting.

Rosmarinic acid monotherapy is better than the combination of rosmarinic acid and telmisartan in preventing podocyte detachment and inhibiting the progression of diabetic nephropathy in rats.

BACKGROUND: Podocyte injury and its subsequent detachment play a critical role in the development and progression of diabetic nephropathy (DN). The objective of this study was to investigate the effect of rosmarinic acid (RA) in preventing podocyte detachment and inhibiting the progression of DN in streptozotocin (STZ)-induced diabetic in rats. METHODS: We used 20 adult male Wistar rats as experimental animals, which were randomly divided into 5 groups (n=4 per group): nondiabetic rat group (negative control) and 4 groups of STZ-induced diabetic rats, namely, 1 group untreated diabetic rats (positive control) and 3 groups treated diabetic rats with RA 75 mg/kg, telmisartan (TMS) 1 mg/kg and combination of RA 75 mg/kg with TMS 1 mg/kg), respectively. After 8 weeks of therapy, urinary levels of podocin, nephrin and albumin and also serum cystatin C levels were examined by ELISA. The expression of p65 nuclear factor-kB by immunohistochemistry whereas expression of podocin and nephrin glomerulus were examined by immunofluorescence. RESULTS: In the treated diabetic groups, we found that urinary level of podocin and nephrin, albumin urine excretion and serum cystatin C levels were significantly lower than the positive control group. Compared to negative controls, the group of treated diabetic rats did not differ significantly in preventing increased excretion of urinary nephrin and podocin. Meanwhile, treatment with RA monotherapy was significantly better than TMS or a combination of RA with TMS in reducing albumin excretion and preventing decreased kidney function. CONCLUSION: In STZ-induced diabetic rats, RA can prevent podocyte detachment. Treatment with RA and TMS either monotherapy or in combination can inhibit the development and progression of DN. However, the combination of both did not show a synergistic effect, even have higher urinary albumin excretion and worse kidney function compared to the RA monotherapy.

Hypoglycaemia among Insulin-Treated Patients with Diabetes: Southeast Asia Cohort of IO HAT Study.

OBJECTIVE: To provide real-world data on hypoglycaemia incidence in patients with type 1 (T1D) or type 2 diabetes (T2D) from the Southeast Asian cohort of the International Operations Hypoglycaemia Assessment Tool (IO HAT) study. METHODOLOGY: IO HAT was a non-interventional, multicentre, 6-month retrospective and 4-week prospective study of hypoglycaemic events among insulin-treated adults with T1D or T2D, including four countries in Southeast Asia (Singapore, Philippines, Indonesia, and Bangladesh). Data were collected using a two-part self-assessment questionnaire (SAQ1 for retrospective and SAQ2 for prospective). The primary endpoint was the percentage of patients experiencing at least one hypoglycaemic event during the 4-week prospective observational period (ClinicalTrials.gov Identifier: NCT02306681). RESULTS: A total of 2594 patients completed SAQ1. Nearly all patients reported experiencing any hypoglycaemic event in the 4-week prospective period (T1D, 100%; T2D, 97.3%), with all patients reporting higher rates in the prospective versus retrospective period. Severe hypoglycaemia was also reported higher prospectively (57.2% and 76.9%) than retrospectively (33.9% and 12.2%) in both T1D and T2D, respectively. Nocturnal hypoglycaemia was reported higher retrospectively than prospectively. CONCLUSION: Incidence of any and severe hypoglycaemia in the Southeast Asian cohort of IO HAT was higher prospectively versus retrospectively, suggesting hypoglycaemia has previously been under-reported in this region.