Labisia pumila standardized extract (SKF7®) reduces percentage of waist circumference and waist-to-height ratio in individuals with obesity.

AIM: Evidence from the literature points towards a viable choice of utilizing Labisia pumila to improve the metabolic profile in animal studies. To that end, this prospective study was designed to assess the health impact of the consumption of L. pumila standardized extract (SKF7®) on key parameters of obesity in humans such as body weight (BW), body mass index (BMI), waist circumference (WC) and waist-to-height ratio (WHtR). MATERIALS AND METHODS: A dose-ranging analysis using SKF7® was conducted through a randomized, double-blind, multicentre, placebo-controlled, phase 2 clinical trial involving individuals with obesity (N = 133) between January 2020 and April 2021. The potential percentage of change was assessed in relation to BW, BMI, WC and WHtR. RESULTS: Average treatment effect estimates (treatment group vs. placebo) show a statistically significant reduction in the percentage of change for BW (mean = -2.915; CI: -4.546, -1.285), BMI (-2.921; CI: -4.551, -1.291), WC (mean = -2.187; CI: -3.784, -0.589) and WHtR (mean = -2.294, CI: -3.908, -0.681) in the group with a total of 750 mg of SKF7® (p < .01). An incremental reduction in WC and WHtR was consistent with the gradual increase in the total daily concentration of SKF7® from 375 to 750 mg. WC and WHtR had higher effect size (f 2 = 0.11 and f 2 = 0.13 respectively) in comparison with BW and BMI. CONCLUSIONS: SKF7® is potentially a novel therapeutic treatment for obesity, reflected by reductions in BW, BMI, WC and WHtR. The use of SKF7® suggests a dose-dependent reduction in abdominal obesity, exemplified by a decline in WC and WHtR.

Impact of COVID-19 Lockdown on Glycemic, Weight, Blood Pressure Control and Medication Adherence in Patients with Type 2 Diabetes.

Medication adherence profoundly affects blood glucose management in patients with type 2 diabetes. Measures to contain the COVID-19 pandemic have affected disease management and medication adherence, owing to limited access to healthcare facilities. This study aimed to examine the impact of the COVID-19 lockdown on adherence to glucose-lowering and lipid-lowering therapies (statins), and glycemic, weight, and systolic blood pressure control measures. A retrospective chart review was conducted one year pre- and post- March 18, 2020, for patients receiving glucose-lowering medications and lipid-lowering therapies (statins) in two major public hospitals in Malaysia. We compared the proportion of days covered by medication, HbA1c level, weight, and systolic blood pressure (SBP) values pre- and after the index date. A total of 1985 patients were included in this study. The adherence rate significantly increased for metformin, sulfonylureas dipeptidyl peptidase 4 inhibitors (DPP4i) and statin after the index date (metformin (PDC: 0.985 vs 0.978, p < 0.001), sulfonylureas (PDC: 0.988 vs 0.979, p < 0.01), DPP4i (PDC: 0.987 vs 0.98, p < 0.001), and statins (PDC: 0.983 vs 0.978, p < 0.05)). HbA1c levels were significantly reduced after the index follow-up (Mean difference: -0.43%, p < 0.001), while there was a 2.5 mmHg (p = 0.03) significant increase in SBP post-index follow-up. No significant changes in weight were observed during the post-index follow-up period. In this study, we observed better medication adherence and glycemic control among patients during the lockdown, but not for weight and systolic blood pressure control.

Cost-Effectiveness of Glucose-Lowering Therapies as Add-on to Standard Care for People With Type 2 Diabetes in Malaysia.

OBJECTIVES: This study aims to evaluate the cost-effectiveness of various glucose-lowering therapies as add-on to standard care for people with type 2 diabetes (T2D) in Malaysia. METHODS: A state-transition microsimulation model was developed to compare the clinical and economic outcomes of 4 treatments: standard care, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists. Cost-effectiveness was assessed from a healthcare provider's perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of people with T2D. Data input were informed from literature and local data when available. Outcome measures include costs, quality-adjusted life-years, incremental cost-effectiveness ratios, and net monetary benefits. Univariate and probabilistic sensitivity analyses were performed to assess uncertainties. RESULTS: Over a lifetime horizon, the costs to treat a person with T2D ranged from RM 12 494 to RM 41 250, whereas the QALYs gains ranged from 6.155 to 6.731, depending on the treatment. Based upon a willingness-to-pay threshold of RM 29 080 per QALY, we identified SGLT2i as the most cost-effective glucose-lowering treatment, as add-on to standard care over patient's lifetime, with the net monetary benefit of RM 176 173 and incremental cost-effectiveness ratios of RM 12 279 per QALY gained. The intervention also added 0.577 QALYs and 0.809 LYs compared with standard care. Cost-effectiveness acceptability curve showed that SGLT2i had the highest probability of being cost-effective in Malaysia across varying willingness-to-pay threshold. The results were robust to various sensitivity analyses. CONCLUSIONS: SGLT2i was found to be the most cost-effective intervention to mitigate diabetes-related complications.

Effects of metformin on glycaemic variability in combination with insulin in overweight/obese patients with type 1 diabetes.

BACKGROUND: The prevalence of overweight and obesity in type 1 diabetes mellitus (T1DM) individuals is increasing. Overweight people with T1DM may be insulin resistant. Glycaemic variability (GV) is an emerging measure of glycaemic control. The aim of this study is to investigate whether metformin, in adjunct to insulin, would have any favourable effect on GV. METHODS: This was a multi-centre, open-label randomised crossover study. Twenty-four overweight/obese T1DM patients aged ⩾18 years old with HbA1c ⩾ 7.0% (53 mmol/mol) were recruited and randomised into two study arms. For first 6-week, one arm remained on standard of care (SOC), the other arm received metformin, adjunctive to SOC. After 2-week washout, patients crossed over and continued for another 6 weeks. Glycaemic variability, other glycaemic parameters and metabolic profile were monitored. RESULTS: There were significant reduction in metformin group for GV: mean (0.18 ± 1.73 vs -0.95 ± 1.24, p = 0.014), %CV (-15.84 (18.92) vs -19.08 (24.53), p = 0.044), glycemic risk assessment of diabetes equation (-0.69 (3.83) vs -1.61 (3.61), p = 0.047), continuous overlapping net glycaemic action (0.25 ± 1.62 vs -0.85 ± 1.22, p = 0.013), J-index (-0.75 (21.91) vs -7.11 (13.86), p = 0.034), time in range (1.13 ± 14.12% vs 10.83 ± 15.47%, p = 0.032); changes of systolic blood pressure (2.78 ± 11.19 mmHg vs -4.30 ± 9.81 mmHg, p = 0.027) and total daily dose (TDD) insulin (0.0 (3.33) units vs -2.17 (11.45) units, p = 0.012). Hypoglycaemic episodes were not significant in between groups. CONCLUSION: Metformin showed favourable effect on GV in overweight/obese T1DM patients and reduction in systolic blood pressure, TDD insulin, fasting venous glucose and fructosamine.

Comparison of a chronic kidney disease predictive model for type 2 diabetes mellitus in Malaysia using Cox regression versus machine learning approach.

Background: Diabetes is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease. This study aims to develop and validate different risk predictive models for incident CKD and CKD progression in people with type 2 diabetes (T2D). Methods: We reviewed a cohort of people with T2D seeking care from two tertiary hospitals in the metropolitan cities of the state of Selangor and Negeri Sembilan from January 2012 to May 2021. To identify the 3-year predictor of developing CKD (primary outcome) and CKD progression (secondary outcome), the dataset was randomly split into a training and test set. A Cox proportional hazards (CoxPH) model was developed to identify predictors of developing CKD. The resultant CoxPH model was compared with other machine learning models on their performance using C-statistic. Results: The cohorts included 1992 participants, of which 295 had developed CKD and 442 reported worsening of kidney function. Equation for the 3-year risk of developing CKD included gender, haemoglobin A1c, triglyceride and serum creatinine levels, estimated glomerular filtration rate, history of cardiovascular disease and diabetes duration. For risk of CKD progression, the model included systolic blood pressure, retinopathy and proteinuria. The CoxPH model was better at prediction compared with other machine learning models examined for incident CKD (C-statistic: training 0.826; test 0.874) and CKD progression (C-statistic: training 0.611; test 0.655). The risk calculator can be found at https://rs59.shinyapps.io/071221/. Conclusions: The Cox regression model was the best performing model to predict people with T2D who will develop a 3-year risk of incident CKD and CKD progression in a Malaysian cohort.

Hypercalcaemia associated with disseminated cryptococcosis.

We report an elderly man who presented with giddiness and right-sided weakness, constipation and constitutional symptoms for 6 months duration. Blood investigations indicated hypercalcaemia with normal serum phosphate and acute kidney injury. Serum intact parathyroid hormone was suppressed. CT revealed bilateral tiny lung nodules with right upper lobe tree in bud appearance and incidental findings of bilateral adrenal lesion. Tuberculosis was ruled out. CT adrenal showed multiseptated hypodense rim enhancement adrenal lesion bilaterally. Adrenal function tests were normal except for low dehydroepiandrosterone (DHEA). Right-sided cervical lymph node biopsy confirmed fungal infection with the presence of intracellular and extracellular fungal yeast. Serum cryptococcus antigen titre was positive. Our final diagnosis was disseminated cryptococcosis with lungs, bilateral adrenal gland and lymph nodes involvement. The patient was then treated with antifungal treatment. Serum calcium was normalised after 1 month with marked clinical improvement.

Rare Presentation of Right Adrenal Mass: Extramedullary Haematopoiesis in a Patient with Thalassaemia Intermedia.

Extramedullary hematopoiesis (EMH) is a rare cause of adrenal mass. We present a 44-year-old woman who has thalassaemia intermedia, referred to Endocrinology clinic for huge adrenal mass. Along with a paraspinal lesion discovered in this patient, the leading diagnosis was EMH. The patient was treated with hypertransfusion and hydroxyurea, which led to a reduction in the size of the right adrenal mass and paraspinal mass. This case highlights the challenges in managing this rare condition. Although EMH is a rare cause of adrenal mass, the diagnosis must be considered in any patient with a history of a congenital hemolytic disorder, to avoid unnecessary surgical procedures.

CNDP1, NOS3, and MnSOD Polymorphisms as Risk Factors for Diabetic Nephropathy among Type 2 Diabetic Patients in Malaysia.

Type 2 diabetes mellitus (T2DM) is associated with a high incidence of nephropathy. The aim of this study was to investigate the association of a genetic polymorphism of carnosinase (CNDP1-D18S880 and -rs2346061), endothelial nitric oxide synthase (NOS3-rs1799983), and manganese superoxide dismutase (MnSOD-rs4880) genes with the development of diabetic nephropathy among Malaysian type 2 diabetic patients. A case-control association study was performed using 652 T2DM patients comprising 227 Malays (without nephropathy = 96 and nephropathy = 131), 203 Chinese (without nephropathy = 95 and nephropathy = 108), and 222 Indians (without nephropathy = 136 and nephropathy = 86). DNA sequencing was performed for the D18S880 of CNDP1, while the rest were tested using DNA Sequenom MassARRAY to identify the polymorphisms. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models, and the best mode of inheritance was chosen based on the least p value. The rs2346061 of CNDP1 was significantly associated with diabetic nephropathy among the Indians only with OR = 1.94 and 95% CI = (1.76-3.20) and fitted best the multiplicative model, while D18S880 was associated among all the three major races with the Malays having the strongest association with OR = 2.46 and 95% CI = (1.48-4.10), Chinese with OR = 2.26 and 95% CI = (1.34-3.83), and Indians with OR = 1.77 and 95% CI = (1.18-2.65) in the genotypic multiplicative model. The best mode of inheritance for both MnSOD and NOS3 was the additive model. For MnSOD-rs4880, the Chinese had OR = 2.8 and 95% CI = (0.53-14.94), Indians had OR = 2.4 and 95% CI = (0.69-2.84), and Malays had OR = 2.16 and 95% CI = (0.54-8.65), while for NOS3-rs1799983, the Indians had the highest risk with OR = 3.16 and 95% CI = (0.52-17.56), followed by the Chinese with OR = 3.55 and 95% CI = (0.36-35.03) and the Malays with OR = 2.89 and 95% CI = (0.29-28.32). The four oxidative stress-related polymorphisms have significant effects on the development of nephropathy in type 2 diabetes patients. The genes may, therefore, be considered as risk factors for Malaysian subjects who are predisposed to T2DM nephropathy.

Association of CCL2, CCR5, ELMO1, and IL8 Polymorphism with Diabetic Nephropathy in Malaysian Type 2 Diabetic Patients.

The unique variants or biomarkers of individuals help to understand the pathogenesis as well as the potential risk of individuals or patients to diabetic nephropathy (DN). The aim of this study was to investigate the association of a genetic polymorphism of monocyte chemoattractant protein-1 (CCL2-rs3917887), chemokine receptor 5 (CCR5-rs1799987), engulfment and cell mortality (ELMO1-rs74130), and interleukin-8 (IL8-rs4073) with the development of DN among Malaysian type 2 diabetes mellitus (T2DM) patients. More than one thousand diabetic patients were examined and a total of 652 T2DM patients were tested comprising 227 Malays (nonnephrotic=96 and nephrotic=131), 203 Chinese (nonnephrotic=95 and nephrotic=108), and 222 Indians (nonnephrotic=136 and nephrotic=86). DNA Sequenom mass ARRAY was employed to identify polymorphisms in CCL2, CCR5, ELMO1, and IL8 genes. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models and the best mode of inheritance was chosen. CCR5 rs1799987 (G>A) showed strong association with the development of diabetic nephropathy only among the Chinese with OR=6.71 (2.55-17.68) 95% CI while IL8 rs4073 (T>A) showed association with nephropathy only among the Indians with OR=1.57 (0.66-3.71) 95% CI. The additive model was the best model for the mode of inheritance of all the genes. The contribution of genetic variants differs across ethnic groups or background. Further studies which involve environmental risk factors should be taken into consideration.