AIMS: To investigate P. niruri leaves aqueous extract (PN) effects on kidney functions, histopathological changes and levels of oxidative stress, inflammation, fibrosis, apoptosis and proliferation in DM.
METHODS: PN was orally administered to streptozotocin-nicotinamide-induced male diabetic rats for 28 days. At the end of the treatment, fasting blood glucose (FBG) and kidney functions were measured. Kidney somatic index, histopathological changes and levels of RAGE, Nrf2, oxidative stress markers (TBARS, SOD, CAT and GPx), inflammatory markers (NFkβ-p65, Ikk-β, TNF-α, IL-1β and IL-6), apoptosis markers (caspase-3, caspase-9 and Bax), fibrosis markers (TGF-β1, VEGF and FGF-1) and proliferative markers (PCNA and Ki-67) were determined by biochemical assays, qPCR, Western blotting, immunohistochemistry or immunofluorescence.
RESULTS: Administration of PN helps to maintain near normal FBG, creatinine clearance (CCr), blood urea nitrogen (BUN), BUN/Cr ratio, serum electrolytes, uric acid and urine protein levels in DM. Decreased RAGE, TBARS and increased Nrf2, SOD-1, CAT and GPx-1 were observed in PN-treated diabetic rat kidneys. Expression of inflammatory, fibrosis and apoptosis markers in the kidney reduced but expression of proliferative markers increased following PN treatment. Lesser histopathological changes were observed in the kidney of PN-treated diabetic rats.
CONCLUSION: PN helps to preserve near normal kidney function and prevents histopathological changes via ameliorating oxidative stress, inflammation, fibrosis and apoptosis while enhancing proliferation of the kidney in DM.
METHODS: This was a prospective cohort study in a single diabetes centre in Malaysia. Empagliflozin group were on study drug for at least three months. For control group, subjects not receiving SGLT2 inhibitors were recruited. Follow-up were performed before and during Ramadan fasting. Anthropometric measurements, blood pressure, renal profile, and blood ketone were recorded during visits. Hypoglycaemia symptoms were assessed via hypoglycaemia symptom rating questionnaire (HypoSRQ).
RESULTS: We recruited a total of 98 subjects. Baseline anthropometry, blood pressure, and renal parameters were similar in two groups. No significant changes in blood pressure, weight, urea, creatinine, eGFR, or haemoglobin levels during Ramadan was found in either group. Likewise, no difference was detected in blood ketone levels (empagliflozin vs control, 0.17 ± 0.247 mmol/L vs 0.13 ± 0.082 mmol/L, p = 0.304) or hypoglycaemia indices (empagliflozin vs control, 19.1% vs 16%, p = 0.684).
CONCLUSIONS: Ramadan fasting resulted in weight loss and reduction in eGFR levels in patients with T2D. Empagliflozin use during Ramadan is safe and not associated with increased risk of dehydration, ketosis, or hypoglycaemia. Therefore, empagliflozin is a viable glucose-lowering drug for patients with T2D planning for Ramadan fasting.
METHODS: This study included 168 non-diabetic patients (58% males, 69% of Chinese ethnicity) who received renal transplantation between 1st January 1994 to 31st December 2014, and were followed up in two major renal transplant centres in Malaysia. Fasting blood glucose levels were used to diagnose NODAT in patients who received renal transplantation within 1 year. Two single nucleotide polymorphisms (SNPs), namely; rs1494558 (interleukin-7 receptor, IL-7R) and rs2232365 (mannose-binding leptin-2, MBL2) were selected and genotyped using Sequenom MassArray platform. Cox proportional hazard regression analyses were used to examine the risk of developing NODAT according to the different demographics and clinical covariates, utilizing four time-points (one-month, three-months, six-months, one-year) post-transplant.
RESULTS: Seventeen per cent of patients (n = 29, 55% males, 69% Chinese) were found to have developed NODAT within one-year of renal transplantation based on their fasting blood glucose levels. NODAT patients had renal transplantation at an older age compared to non-NODAT (39.3 ± 13.4 vs 33.9 ± 11.8 years, p = 0.03). In multivariate analysis, renal-transplanted patients who received a higher daily dose of cyclosporine (mg) were associated with increased risk of NODAT (Hazard ratio (HR) =1.01 per mg increase in dose, 95% confidence interval (CI) 1.00-1.01, p = 0.002). Other demographic (gender, ethnicities, age at transplant) and clinical factors (primary kidney disease, type of donor, place of transplant, type of calcineurin inhibitors, duration of dialysis pre-transplant, BMI, creatinine levels, and daily doses of tacrolimus and prednisolone) were not found to be significantly associated with risk of NODAT. GA genotype of rs1494558 (HR = 3.15 95% CI 1.26, 7.86) and AG genotype of rs2232365 (HR = 2.57 95% CI 1.07, 6.18) were associated with increased risk of NODAT as compared to AA genotypes.
CONCLUSION: The daily dose of cyclosporine and SNPs of IL-7R (rs1494558) and MBL2 (rs2232365) genes are significantly associated with the development of NODAT in the Malaysian renal transplant population.
METHODS: Muslim people with T1DM were surveyed in 13 countries between June and August 2020, shortly after the end of Ramadan (23rd April-23rd May 2020) using a simple questionnaire.
RESULTS: 71.1% of muslims with T1DM fasted during Ramadan. Concerns about COVID-19 were higher in individuals ≥18 years (p = 0.002). The number of participants who decided not to fast plus those who received Ramadan-focused education were significantly higher in the ≥18-year group (p
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.
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
METHODS: Participants were consented to answer a physician-administered questionnaire following Ramadan 2020. Impact of COVID-19 on the decision of fasting, intentions to fast and duration of Ramadan and Shawal fasting, hypoglycaemia and hyperglycaemia events were assessed. Specific analysis comparing age categories of <65 years and ≥65 years were performed.
RESULTS: Among the 5865 participants, 22.5% were ≥65 years old. Concern for COVID-19 affected fasting decision for 7.6% (≥65 years) vs 5.4% (<65 years). More participants ≥65 years old did not fast (28.8% vs 12.7%, <65 years). Of the 83.6%, participants fulfilling Ramadan-fasting, 94.8% fasted ≥15 days and 12.6% had to break fast due to diabetes-related illness. The average number of days fasting within and post-Ramadan were 27 and 6 days respectively, regardless of age. Hypoglycaemia and hyperglycaemia occurred in 15.7% and 16.3% of participants respectively, with 6.5% and 7.4% requiring hospital care respectively. SMBG was performed in 73.8% of participants and 43.5% received Ramadan-focused education.
CONCLUSION: During the COVID-19 pandemic, universally high rates of Ramadan-fasting were observed regardless of fasting risk level. Glycemic complications occurred frequently with older adults requiring higher rates of acute hospital care. Risk stratification is essential followed by pre-Ramadan interventions, Ramadan-focused diabetes education and self-monitoring to reduce and prevent complications, with particular emphasis in older adults.
METHODS: Muslim people with diabetes and CKD were surveyed in 13 countries shortly after the end of Ramadan 2020, using a simple Survey Monkey questionnaire.
RESULTS: This survey recruited 6736 people with diabetes, of which 707 (10.49%) had CKD. There were 118 (16.69%) people with type1 diabetes (T1D), and 589 (83.31%) were with type2 diabetes (T2D). 62 (65.24%) people with T1D and 448 (76.06%) people with T2D had fasted with CKD. Episodes of hypoglycaemia and hyperglycaemia were more frequent among people with T1D compared to T2D, 64.52% and 43.54% vs 25.22% and 22.32% respectively. Visits to the emergency department and hospitalization were more frequent among people with CKD, however no significant difference was found between people with T1D and T2D.
CONCLUSION: The COVID-19 pandemic had only a minor effect on the intention to fast during Ramadan in people with diabetes and CKD. However, hypoglycaemia and hyperglycaemia were found to be more frequent, as well as emergency visits and hospital admissions among people with diabetic kidney disease. Prospective studies are needed in future to evaluate the risk indicators of hypoglycaemia and hyperglycaemia among fasting people with CKD, especially in the context of different stages of kidney disease.