Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.

Sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus and moderate to severe hepatic fibrosis: A retrospective study.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to decrease hepatic transaminases, steatosis, and in some studies, hepatic fibrosis. However, the safety and efficacy of SGLT2i has not been tested in patients who have moderate to severe hepatic fibrosis. METHODS: In a retrospective study of sixty patients with moderate to severe hepatic fibrosis (kPa estimated by Fibroscan > 10), SGLT2i were prescribed on top of other oral anti-hyperglycemic medications. The safety and efficacy of SGLT2i were evaluated. Using the Fibroscan, CAP scores (decibel/meter), and liver stiffness measurement (LSM) (kPa, kilopascals) were examined before and after treatment. RESULTS: The mean age of the T2DM patients was 54.7 ± 10.3 years, and the mean duration of T2DM was 8.3 ± 7.1 years. SGLT2i were given from 3 to 36 months. After treatment, a decrease in glycated hemoglobin (HbA1c), and hepatic transaminases (SGOT and SGPT) was recorded. Upon follow up, CAP and kPa scores decreased significantly. Importantly, no adverse drug reaction, such as balanoposthitis, vulvovaginitis, urosepsis, and postural drop in blood pressure, were reported in any patient. CONCLUSION: In this retrospective cohort study, patient with T2DM and moderate to severe hepatic fibrosis, use of SGLT2i is safe with respect to common adverse effects & may have contributed to improved hepatic profile.

Role of Cytokines in Chemotherapy-related Cognitive Impairment of Breast Cancer Patients: A Systematic Review.

BACKGROUND: Cognitive impairment is one of the most common problems experienced by patients receiving chemotherapy, and evidence suggests that cytokines might play an important role. Various studies were conducted to evaluate the role of cytokines in chemotherapy-related cognitive impairment (CRCI). However, the association between CRCI due to cytokines is not well-established. Thus, this systematic review aims to assess the role of cytokines in CRCI in breast cancer patients. METHODS: This systematic review was conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis (PRISMA) guidelines. An intense literature search was carried out for inclusion criteria in major databases, including PubMed and Clinicaltrials.gov, in August 2021. Studies assessing cognitive parameters through objective and subjective assessment in breast cancer patients receiving chemotherapy were included. RESULTS: A total of 4052 studies were identified, and 15 studies were included in this systematic review. We found that IL-6, IL-1ß, and TNF-α were associated with varying degrees of cognitive impairment in breast cancer patients receiving chemotherapy. CONCLUSION: This systematic review showed a correlation between various cytokines and chemotherapy- associated cognitive decline in breast cancer patients.

Dapagliflozin Improves Body Fat Patterning, and Hepatic and Pancreatic Fat in Patients With Type 2 Diabetes in North India.

CONTEXT: Excess hepatic and pancreatic fat may contribute to hyperglycemia. OBJECTIVE: The objective of this study was to examine the effect of dapagliflozin (an SGLT2 inhibitor) on anthropometric profile, liver, and pancreatic fat in patients with type 2 diabetes mellitus (T2DM). METHODS: This is an observational interventional paired study design without a control group. Patients (n = 30) were given dapagliflozin 10 mg/day (on top of stable dose of metformin and/or sulfonylureas) for 120 days. Changes in anthropometry (circumferences and skinfold thickness), surrogate markers of insulin resistance, body composition, liver, and pancreatic fat (as measured by magnetic resonance imaging (MRI)-derived proton density fat fraction [FF]) were evaluated. RESULTS: After 120 days of treatment with dapagliflozin, a statistically significant reduction in weight, body mass index (BMI), body fat, circumferences, and all skinfold thickness was seen. A statistically significant reduction in blood glucose, glycated hemoglobin A1c, hepatic transaminases, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and postprandial C-peptide was noted, while HOMA-ß, postprandial insulin sensitivity, and fasting adiponectin were statistically significantly increased. There was no change in lean body mass. Compared to baseline there was a statistically significant decrease in mean liver FF (from 15.2% to 10.1%, P < .0001) and mean pancreatic FF (from 7.5% to 5.99%, P < .0083). Reduction in liver fat was statistically significant after adjustment for change in body weight. CONCLUSION: Dapagliflozin, after 120 days of use, reduced pancreatic and liver fat and increased insulin sensitivity in Asian Indian patients with T2DM.

Breakthrough COVID19 infections after vaccinations in healthcare and other workers in a chronic care medical facility in New Delhi, India.

BACKGROUND AND AIMS: Vaccinations for COVID19 are now open to all adults in India. However, spread of COVID19 infection continues unabated. We aimed to ascertain number of breakthrough COVID19 infections after vaccinations in a chronic care, diabetes-centric healthcare facility. METHODS: We reviewed rigorously maintained data of vaccinations, health status, symptoms of COVID19 & RT-PCR testing of all staff (doctors, nurses, paramedical workers, and other staff) in our health care facility from January 16, 2021 till date. RESULTS: Out of 123 employees, 113 were vaccinated (Covaxin, 28, Covishield, 85). Second dose was completed in 107 (94.7%) and first dose in 6 persons (5.3%). Symptomatic COVD19 infections occurred in 19 persons (16.9%) post any dose of vaccine. Symptomatic breakthrough infections > 14 days after second dose occurred in 15 persons (13.3%). Except one (required hospitalization), all 14 had mild COVID19 disease. CONCLUSIONS: We report mild symptomatic breakthrough infections as seen in our health care facility. Research in breakthrough infections in India should be extended to other institutions and community to obtain larger data.

Glycemic parameters in patients with new-onset diabetes during COVID-19 pandemic are more severe than in patients with new-onset diabetes before the pandemic: NOD COVID India Study.

BACKGROUND AND AIMS: It is not known if new onset diabetes during Coronavirus-19 disease (COVID-19; NOD COVID) is phenotypically or biochemically different than new onset diabetes before COVID-19 (NOD). METHODS: All adults diagnosed with new onset diabetes from during the time of COVID-19 were compared with new onset diabetes prior to COVID-19 from two tertiary care hospitals in Chennai and Delhi. RTPCR test for SARS-CoV-2 virus was done as appropriate, and COVID-19 antibody test was done in all other NOD COVID patients. RESULT: A total of 555 patients with new onset diabetes were included in the study (282 NOD and 273 NOD COVID patients). Patients with NOD COVID had higher fasting and post prandial blood glucose and glycated hemoglobin levels vs. NOD patients. Both the groups had high average body mass index; ∼28 kg/m2. Interestingly, fasting C-peptide levels were significantly higher in the NOD COVID group vs. NOD group. There was no difference in C-peptide levels or glycemic parameters between the COVID-19 antibody positive and negative NOD COVID cases. CONCLUSION: Individuals who were diagnosed with diabetes during COVID-19 epidemic (NOD COVID) do not significantly differ from those diagnosed before COVID-19 in symptomatology, phenotype, and C-peptide levels but they had more severe glycemia.

About 1/3rd of north Indian patients less than 50 years of age with type 2 diabetes have high pulse wave velocity indicating high risk of atherosclerosis.

BACKGROUND AND AIMS: Asian Indian patients with type 2 diabetes mellitus (T2DM) have a high cardiovascular risk even at young age. There is a need to assess this increased risk and identify atherosclerosis early so that appropriate measures for risk reduction can be taken. We aimed to study carotid-femoral pulse wave velocity (Cf-PWV), a non-invasive indicator of atherosclerosis, in patients with diabetes below 50 years of age and its correlation with markers of obesity and other cardiovascular risk factors. METHODS: Patients (n, 299) with T2DM below 50 years of age underwent measurement of Cf-PWV by applanation tonometry. Anthropometric parameters, blood pressure, liver span, glycosylated hemoglobin, serum lipid profile, urinary microalbumin, ankle brachial index and carotid intima media thickness were measured. RESULTS: Data show that 32.4% of patients had high Cf-PWV, with mean values higher in males than females. On stepwise multiple linear regression analysis, the significant independent determinants of PWV were age, systolic blood pressure, waist circumference, microalbumin and liver span. CONCLUSION: About one third patients with T2DM less than 50 years of age, in north India have increased arterial stiffness which correlates with blood pressure, abdominal obesity, liver size and microalbumin, indicating increased risk for coronary artery disease.

Marked erythrocytosis during treatment with sodium glucose cotransporter-2 inhibitors-report of two cases.

SGLT-2 inhibitors are known to increase hematocrit. We present two cases with marked asymptomatic erythrocytosis developing after taking SGLT-2 inhibitors. No other predisposing or causative factor was found and SGLT-2 inhibitor drug was the most likely cause in both cases. Both patients underwent phlebotomy and haematocrit came down after withdrawing the offending drug.

Dipeptidyl peptidase 4 inhibitors linked bullous pemphigoid in patients with type 2 diabetes mellitus: A series of 13 cases.

BACKGROUND: Dipeptidyl peptidase 4 (DPP4) inhibitors have increasingly been linked to bullous pemphigoid, but there is paucity of data from India where about 1.85 million patients have been estimated to use these drugs. METHODS: In 30,000 patients with T2DM seen by us in two tertiary care centres since 2015, we detected 13 cases of bullous pemphigoid linked to DPP4 inhibitors. We used WHO-UMC (World Health Organisation-Uppsala Monitoring Centre) causality assessment system for assessment. RESULTS: Lesions of bullous pemphigoid appeared at varied intervals (within 1 weeks-2 years) after start of DPP4 inhibitors. Implicated drugs were Linagliptin (n, 8), Vildagliptin (n, 4) and Sitagliptin (n, 1). Mostly, lesions were seen after 60 years age, and over trunk and extremities. Skin biopsy was compatible with bullous pemphigoid in two patients. Lesions regressed within a month of stopping DPP4 inhibitors in 9 patients while delayed regression up to 6 months in 4 patients. Overall, skin lesions remitted in all patients and did not recur. CONCLUSION: Any new bullous lesion appearing while patient is on DPP4 inhibitors should be considered as bullous pemphigoid and should necessitate prompt withdrawal of the drug.