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Evaluation of Efficacy and Safety of Empagliflozin in Bangladeshi Patients with Type 2 Diabetes Mellitus (EFFISAEM Study)

Abstract Background: Empagliflozin is a relatively newer glucose-lowering drug (GLD) with many extra-glycemic benefits. To date, no study has evaluated the efficacy and safety of empagliflozin in Bangladeshi patients with type 2 diabetes mellitus (T2DM). Objectives: To assess the efficacy and safety of empagliflozin as an add-on to ongoing GLDs in Bangladeshi adults with uncontrolled T2DM. Materials and Methods: This real-world, multicenter, open-label, prospective study was carried out at 21 sites throughout Bangladesh from 1 February 2022 to 31 July 2022. Patients with T2DM who met the criteria had Empagliflozin added to their existing GLD treatment, with necessary modifications to their ongoing medication regimen. The efficacy and safety data were collected 12 weeks after empagliflozin initiation. Results: Out of 1449 subjects initiating empagliflozin, 1340 subjects [age 50.3 ± 9.0 years, male 52.5%, overweight/obese 94.4%, insulin-treated 25.7%, baseline hemoglobin A1c (Hba1c) 9.9 ± 1.4%] completed the study. At 12 weeks, the reduction in HbA1c was 1.6% (95% CI 1.5-1.6, P < 0.001); 12.5% of the study subjects achieved HbA1c < 7%. There were also significant (P < 0.001 in all instances) reductions in fasting plasma glucose (3.0 mmol/L), plasma glucose 2 hours after breakfast (4.8 mmoL/L), body weight (1.9 kg), body mass index (0.8 kg/m2), systolic blood pressure (BP) (10 mmHg), diastolic BP (7 mmHg), insulin dose (3 U), serum creatinine (0.06 mg/dL), total cholesterol (18 mg/dL), low-density lipoprotein cholesterol (13 mg/dL), high-density lipoprotein cholesterol (1 mg/dL), and triglyceride (42 mg/dL) and an increase in estimated glomerular filtration rate (4.2 mL/min/1.73 m2) from the baseline values. 6.62% experienced adverse events (lightheadedness 2.21%, genital tract infection 0.97%, urinary tract infection 1.24%, generalized weakness 0.48%, and nocturia 0.48%). 1.1% of subjects experienced hypoglycemia, and other 0.12% reported severe hypoglycemic events. Conclusion: Empagliflozin is effective, safe, and tolerable for treating Bangladeshi patients with uncontrolled T2DM as add-on therapy in routine clinical practice with favorable effects on body weight, BP, lipid profile, and renal function.

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The Effects of Prolonged Use of Caffeine on Thyroid and Adrenal Glands: A Retrospective Cohort Study

Abstract Background: Caffeine consumption has skyrocketed in recent decades as we try to match the pace with the machines. Studies have been conducted on animals and a few on humans, mainly on the acute effects of high-dose caffeine intake. Almost none have been conducted on the chronic effects of caffeine consumption. This study involved medical professionals as case subjects, who consumed caffeine daily. Methods: This study, for 3 months, involved 96 volunteers (chosen randomly w.r.t. gender and field in the medical fraternity), including people who drank >500 mg of caffeine a day and people who consumed none. People with any comorbidities at all were excluded straight away. Two sets of blood samples were drawn and assessed. Three groups were created: group 1 (>200 mg caffeine/day), group 2 (15–200 mg caffeine/day) and group 3 (<200 mg caffeine/day). Results: The result of the study found that exposure to caffeine at doses >200 mg/day for more than 6 months leads to a significant difference in circulating free T3 ((-0.96 pmol/L ± 0.07) = (-18.5%), 95% confidence interval (CI), P = .000024) and cortisol ((-123 nmol/L ± 9.8) = (-46.8%), 95% CI, P = .00029) hormones but shows an insignificant effect on circulating thyroid-stimulating hormone (TSH) (0.4 mIU/L, 95% CI, P = .37) and adrenocorticotrophic hormone (ACTH) ((-3.2 pg/ml ± 0.3), 95% CI, P = .53) hormones, which stay within normal physiological ranges, irrespective of the daily dose of consumption. Results also highlight that women are more susceptible to a decrement in fT3 than men (relative risk = 1.58, analysis of variance (ANOVA) F-static = 7.15, P = 0.0105). Conclusions: Caffeine consumption in excess of 200 mg/day, for more than or equal to 6 months, causes significant derangement in basal fT3 and cortisol hormone levels, without affecting the TSH and ACTH (regulatory) hormone levels, indicating disturbance of action at the peripheral and/or cellular levels, possibly via the paraventricular nucleus (PVN)–leptin–CAR–adenosine interactions. Women are more susceptible to a decrement in fT3 levels than men (at the same dose of caffeine).

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The Hidden Battle Within: Shedding Light on the Co-existence of Sarcopenia and Sarcopenic Obesity among Participants with Type 2 Diabetes in a Tertiary Care Hospital, Gujarat.

Type 2 diabetes (T2DM) is characterised by chronic hyperglycaemia due to abnormal insulin secretion and/or utilisation. Currently, sarcopenia has emerged as a new complication of T2DM, which increases the risk of physical disability, and even death. The study aims to estimate the prevalence of sarcopenia and sarcopenic obesity (SO) as well as their association with various other factors related to T2DM. The study was an observational hospital-based cross-sectional study conducted among diabetic patients who came to the non-communicable diseases (NCD) clinic of a tertiary care hospital in Gujarat, India, from April 2023 to June 2023. Adult patients with T2DM attending follow-ups were included, with a diagnosis of T2DM for at least 1 year from the date of their electronic medical records, regardless of their mode of therapeutic treatment. They were on regular medical reviews with two or more visits to the study site in the past 1 year. Then a self-structured standard questionnaire was used to collect the data, containing socio-demographic characteristics, clinical profiles, anthropometric assessment (comprising weight, height and body mass index [BMI]), bio-impedance indices like body fat%, skeletal muscle% and handgrip by hand dynamometer. In the study, a total of 404 participants participated. Their mean age was 55 ± 13.5 years and their mean body fat (BF) % was 30 ± 7.4%. BF%-defined obesity was found in 260 (64.4%) participants. A total of 362 (89.6%) had possible sarcopenia, 183 (45.3%) had sarcopenia and 124 (30.7%) had SO. Age (OR: 2.6, CI: 1.7-3.9), duration of diabetes for more than 7 years (OR: 7.5, CI: 3.65-15.4) and BF%-defined obesity (OR: 2.2, CI: 3.6-15) were statistically associated with Sarcopenia, in similar pattern age (OR: 2.4, CI: 1.5-3.7), and duration of diabetes more than 7 years (OR: 18.9, CI: 5.7-62) were associated with SO (P < 0.05). Older age, longer diabetes duration and BF%-defined obesity are associated with an increased likelihood of developing sarcopenia and sarcopenic obesity. Healthcare providers should prioritise regular screening for sarcopenia and SO in elderly individuals with diabetes to facilitate early detection and intervention.

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Accuracy of a Non-Invasive Home Glucose Monitor for Measurement of Blood Glucose.

Patients with diabetes mellitus monitor their blood glucose at home with monitors that require a drop of blood or use a continuous glucose monitoring device that implants a small needle in the body. However, both cause discomfort to the patients which may inhibit them for regular blood glucose checks. Photoplethysmogram (PPG) sensing technology is an approach for non-invasive blood glucose measurement and PPG sensors can be used to predict hypoglycaemic episodes. InChcek is a PPG-based non-invasive glucose monitor. However, its accuracy has not been checked yet. Hence, this study aimed to evaluate the accuracy of InCheck, a non-invasive glucose monitor for the estimation of blood glucose. In a tertiary care hospital, patients who came for blood glucose estimation were tested for blood glucose non-invasively on the InCheck device and then by the laboratory method (glucose oxidase-peroxidase). These two readings were compared. We used International Organization for Standardization (ISO) 15197:2013 (95% of values should be within ± 15 mg/dL of reference reading if reference glucose <100 mg/dL or within ± 15% of reference reading if reference glucose ≥100 mg/dL and 99% of the values should be within zones A and B in consensus error grid), and Surveillance Error Grid for analyzing the accuracy. A total of 1223 samples were analyzed. There was a significant difference between the reference method glucose level (135 [Q1-Q3: 97 - 179] mg/dL) and monitor-measured glucose level (188.33 [Q1-Q3: 167.33-209.33] mg/dL) (P < 0.0001). A total of 18.5% of readings were following ISO 15197:2013 criteria and 67.25% of coordinates were within zone A and zone B of the consensus error grid. In the surveillance error grid analysis, about 29.4% of values were in the no-risk zone, 51.8% in slight risk, 18.6% in moderate risk, and 0.2% were in the severe risk zone. The accuracy of the InCheck device for the estimation of blood glucose by PPG signal is not following the recommended guidelines. Hence, further research is necessary for programming or redesigning the hardware and software for a better result from this optical sensor-based non-invasive home glucose monitor.

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Utility of Colour Flow Doppler Ultrasonography to Differentiate Gestational Transient Thyrotoxicosis and Graves Disease in Pregnancy.

Accurate diagnosis of the etiology of thyrotoxicosis in pregnancy is important to guide appropriate treatment. The role of thyroid blood flow velocities by color Doppler to differentiate between Graves' disease (GD) in pregnancy and gestational transient thyrotoxicosis (GTT) is not well explored. This study evaluated inferior thyroid artery (ITA)-peak systolic velocity (PSV) as a marker for differential diagnosis of thyrotoxicosis in pregnancy. Fifty-six pregnant patients with thyrotoxicosis (30 with GTT and 26 with GD) along with 30 age-matched healthy euthyroid pregnant subjects were enrolled. Thyroid ultrasound examinations and color Doppler was performed by an ultrasound scanner. The studies of the right and left ITAs were performed with Doppler, and the PSV and End diastolic velocity (EDV) values were obtained from the right and left ITA. The mean total T4 value in GD and GTT were almost similar (25.04 ± 2.43 vs 23.25 ± 2.81, P value = 0.14). Beta HCG levels were significantly higher in cases of GTT as compared to GD (152946 ± 26694 vs 120608 ± 21244 mIU/ml, P < 0.0001). The ITA-PSV and EDV in patients with GTT were significantly lower than those of pregnant patients with GD (right: 22.5 ± 6.8 and 8.3 ± 2.3; left: 22.97 ± 6.3 and 8.13 ± 2.01; P < 0.001). receiver-operating-characteristic (ROC) curve demonstrated an optimal cutoff value of mean right ITA-PSV of 35 cm/sec to differentiate GTT from GD during pregnancy, with 84.6% and 93.3% sensitivity and specificity. Thyroid artery velocities can help to differentiate between GD and GTT. The cutoff point of mean ITA-PSV at 35 cm/s had an excellent value in differentiating between the two, with good sensitivity and specificity.

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Screening of Individuals with Type 2 Diabetes on Anti-Diabetic Agents for Probable Hypoglycaemia Using the Stanford Hypoglycemia Questionnaire (SHQ) in Outpatient Settings: A Cross-Sectional Study from Outpatient Diabetes Care Centres in North India.

The study was aimed at identifying the incidence of unreported probable hypoglycaemia in individuals with type 2 diabetes (T2DM) on anti-diabetic medications, using the screening Stanford Hypoglycemia Questionnaire (SHQ) in real-world situations. It was a multicentre cross-sectional study on consecutive individuals attending 10 diabetes care centres in Lucknow, Uttar Pradesh, India. The inclusion criteria were as follows: known individuals with T2DM, literate, age greater than or equal to 18 years, on at least one anti-diabetic agent for more than a month and not engaged in regular self-monitoring of blood glucose (SMBG). This study was conducted from August 2017 to April 2018, involving 1198 participants. The mean age of the individuals enrolled was 53.45 years (±10.83), with males comprising 55.3% of the population. It was found that 63.6% of patients were on sulphonylurea (SU), 14.5% were on pioglitazone, 92.2% on metformin, 62.3% on Dipeptidyl peptidase (DPP4i) and 12.8% on Sodium-glucose cotransporter (SGLT2i). The mean SHQ score was 1.81 (±1.59). Probable hypoglycaemia was mild in 57.59%, moderate in 14.69% and severe in 1.41%. Those with diabetic neuropathy (P = <0.001), retinopathy (P = <0.001) and nephropathy (P = <0.001) had significantly higher SHQ scores. Insulin or SU use was associated with a significantly higher SHQ score. Concomitant statin use was associated with a lower incidence of mild, moderate and severe hypoglycaemia (P = 0.01). On multivariate analysis, we found that age, sex, systolic blood pressure (SBP), insulin use and fasting blood sugar were the most important factors associated with an increased risk of hypoglycaemia with an R2 cut-off of 0.7. SHQ was discovered to be a simple and cost-effective screening tool for outpatient detection of hypoglycaemia in an Indian setting, and it can add value to management.

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Association of Protein Tyrosine Phosphatase Receptor Type D and Serine Racemase Genetic Variants with Type 2 Diabetes in Malaysian Indians.

Type 2 diabetes (T2D) candidate genes, protein tyrosine phosphatase receptor type D (PTPRD), and serine racemase (SRR) were suggested by a genome-wide association study (GWAS) in the Chinese population. Association studies have been replicated among East Asian populations. The association of PTPRD and SRR genetic variants with T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of PTPRD and SSR genetic variants with T2D in Malaysian Indian subjects. The single nucleotide polymorphisms (SNPs) of PTPRD (rs649891 and rs17584499) and SRR (rs4523957, rs391300, and rs8081273) were genotyped in 397 T2D and 285 normal Malaysian Indian subjects. The homozygous dominant genotype of rs17584499 is frequent in diabetic patients (56.5%) compared to normal subjects (47.3%). In contrast, the homozygous recessive genotype of rs8081273 is more frequent among normal subjects (12.5%) than diabetic patients (5.6%). The dominant genetic model showed that PTPRD rs17584499 (CC) is a risk factor for T2D (OR = 1.42, P = 0.029), whereas the recessive genetic model showed that SRS SNP rs8081273 was protective for T2D (OR = 0.42, P = 0.003). This study confirmed the association of PTPRD rs17584499 genetic variations with T2D in Malaysian Indians. While the SRR rs8081273 (TT) genotype showed protection against T2D, more investigation in different populations is required to confirm this protection.

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Heterophilic Interference of Rheumatoid Factor in TSH Immunometric Assay: A Cross-Sectional Observational Study.

Considering the inherent vulnerability of immunoassays for heterophilic interference and the potential of Rheumatoid Factor (RF) to act as a heterophile-like antibody, we conducted this study to investigate if RF leads to any such heterophilic interference in seropositive rheumatoid arthritis (RA) patients. The study was done on the TSH assay as it is a noncompetitive, double antibody sandwich assay, which is known to be vulnerable to heterophilic interference. In this cross-sectional observational study, eighty-four consecutive newly diagnosed RF-positive RA patients underwent TSH, Free T4, and anti-TPO estimation using the chemiluminescence technique (CLIA) on Siemens Immulite 1000 platform. The samples were screened for TSH interference using four methods: 1) analysis on a different platform, 2) assessment of linearity using doubling dilutions, 3) polyethylene glycol (PEG) precipitation, and 4) addition of a commercial blocker. Ten samples had a loss of linearity on serial dilution, indicating potential interference. After heterophile blocker treatment, five cases exhibited interference. One patient had diagnostic interpretation discordance on the second platform. No sample on PEG precipitation suggested the influence of antibodies. It is worth noting that even in cases where interference was suspected, the clinical interpretation was largely unaffected by the correction of TSH values based on mean dilution or measurement after heterophile blocker treatment. RF can cause heterophilic interference in TSH immunoassays used commercially. However, in most cases, this interference does not affect clinical decision-making.

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