Effect of Teneligliptin 20 mg Twice Daily on Glucagon-Like Peptide-1 Levels and Its Influence on Non-Glycemic Components in Non-Diabetic Obese Individuals.

Background and Aims: Teneligliptin is an oral antidiabetic agent, it can persevere glucagon-like peptide-1 (GLP-1) by inhibiting dipeptidyl peptidase enzyme. In addition, it has rare incidence of hypoglycemia. Hence, this study aimed to test the effect of teneligliptin 20 mg twice daily along with low carbohydrate diet and physical exercise on change of body weight and insulin resistance in nondiabetic obese subjects. Materials and Methods: It is a prospective, randomized, double-blind, placebo-controlled, parallel group study carried out at outpatient department of an endocrinology hospital over the period of 48 weeks. Teneligliptin 20 mg twice daily 30 min before food (low carbohydrate diet [LCD]) with regular physical exercise, and control group was kept with placebo twice daily 30 min before food LCD with regular physical exercise. This study was registered in clinical trial registry of India [CTRI/2020/02/023329]. Results: A total of 150 nondiabetic obese subjects were randomized into test (n = 75) and control groups (n = 75). At the end of 48 weeks there was significant improvement in GLP-1, simplified nutrition assessment questionnaire (SNAQ) score, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and body weight. The mean difference and 95% confidence interval of GLP-1 (pg/mL) was 76.42 (44.42-148.41) (P = 0.37); SNAQ score, -1.64 (-2.48 to -0.81) (P = 0.000); HOMA-IR, -0.9 (-0.59 to -0.38) (P = 0.000); TG (mg/dL) -29.37 (-44.46 to -14.07) (P = 0.000); reduction of body weight (kilograms) -3.09 (-6.11 to -0.07) (P = 0.043). Conclusion: Findings of this study reveals that teneligliptin-treated group showed significant improvement in GLP-1 levels, reduced insulin resistance, body weight, TG, appetite, and metabolic syndrome. Teneligliptin is well tolerated, except in upper respiratory tract infections. CTR number: CTRI/2020/02/023329.

Topical Esmolol Hydrochloride as a Novel Treatment Modality for Diabetic Foot Ulcers: A Phase 3 Randomized Clinical Trial.

Importance: Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs). Objective: To study the efficacy of topical esmolol for healing of uninfected DFUs. Design, Setting, and Participants: A randomized, double-blind, multicenter, phase 3 clinical trial was conducted from December 26, 2018, to August 19, 2020, at 27 referral centers across India. Participants included adults with DFUs. Interventions: Participants were randomized after a run-in phase (1 week) to receive esmolol, 14%, gel with standard of care (SoC), SoC only, or vehicle with SoC (3:3:1 proportion) for 12 weeks (treatment phase) and followed up subsequently until week 24. Main Outcomes and Measures: The primary outcome was the proportion of wound closure within the 12-week treatment phase in the esmolol with SoC and SoC only groups. Analysis was conducted using an intention-to-treat safety evaluable population, full analysis set or efficacy-evaluable population, and per-protocol population comparing the esmolol plus SoC and SoC only treatment groups. Results: In the study, 176 participants (122 men [69.3%]; mean [SD] age, 56.4 [9.0] years; mean [SD] hemoglobin A1c level, 8.6% [1.6%]) with DFUs classified as University of Texas Diabetic Wound Classification system grade IA and IC (mean [SD] ulcer area, 4.7 [2.9] cm2) were randomized to the 3 groups. A total of 140 participants were analyzed for efficacy. The proportion of participants in the esmolol with SoC group who achieved target ulcer closure within 12 weeks was 41 of 68 (60.3%) compared with 30 of 72 (41.7%) participants in the SoC only group (odds ratio [OR], 2.13; 95% CI, 1.08-4.17; P = .03). A total of 120 participants completed the end of study visit which were analyzed. Target ulcer closure by the end of the study (week 24) was achieved in 44 of 57 (77.2%) participants in the esmolol with SoC group and 35 of 63 (55.6%) participants in the SoC only group (OR, 2.71; 95% CI, 1.22-5.99; P = .01). The median time for ulcer closure was 85 days for the esmolol with SoC group and was not estimable for SoC only group. Significant benefits of Esmolol with SoC were seen in patients with factors that impede the healing of DFU. Treatment-emergent adverse events were noted in 18.8% of the participants, but most (87.3%) of these events were not attributable to the study drug. Conclusions and Relevance: In this multicenter, randomized, double-blind clinical trial, the addition of esmolol to SoC was shown to significantly improve the healing of DFUs. With these results, topical esmolol may be an appropriate addition to SoC for treating DFUs. Trial Registration: ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.

Association between physical activity knowledge and attitude on diabetes among normal weight and overweight/obese type-2 diabetic patients: a rural community-based cross-sectional study.

Background: Physical activity is one of the most important regimens for the treatment of diabetes. Hence, we aimed to examine the association between physical activity knowledge (PAK), knowledge and attitude on diabetes among rural T2DM patients. Objectives: The PAK, knowledge and attitude on diabetes were targeted to evaluate in rural Indian T2DM patients. Methodology: A cross-sectional community-based survey was carried out with eighty-four patients with known T2DM in rural population of India. Results: Among 84 patients, 46 were overweight/obese and 38 patients with normal weight were participated in our study. The odds of smoking were found to be a significant socio-demographic risk factor (OR: 4.42, 95% CI 0.93-20.33 and P<0.001) compared to non-smokers. The PAK categories such as A, B & D had associated with BMI. The OR, 95% CI and P. Value are (5.610, 2.18-14.38 and P<0.001; 1.72, 0.72-4.12 and P 0.030; 2.55, 1.05-6.20 and P 0.047) except in category C. Iilliterates, low annual income, poor knowledge on T2DM and negative attitude, OR (4.50; 12.87; 10.80 and 47.66) were reported disagree or don't know with PAK questionnaire. Conclusion: The results have impact on the design of new education programs will assist in preventing and managing complications related to T2DM.

The role of body mass index or metabolic syndrome components causing depression in women: An observation from weight reduction clinical trial.

WHAT IS KNOWN AND OBJECTIVE: Depression is most important psychological problem that is much prevalent in women than men. Obesity and depression are the leading causes of both physical and mental disability and the link between these disorders had not explored well. The present study evaluated the link between the depression, Body mass index (BMI) and the components of metabolic syndrome (MetS) in subjects with, without insulin resistance. METHODS: A total of 150 subjects, vital and biochemical parameters were measured for eligible screened subjects in the trial of weight loss intervention at first visit. A self-reported Patient Health Questionnaire (PHQ-9) scale was used to assess the depression among the participants. The association of BMI and MetS components with risk of depression was analysed using multiple logistic regression analysis in subjects with and without insulin resistance. RESULTS: Obesity was associated with highly significant increase in risk of depression (OR = 13.01, 95% CI 4.40-38.49) as compared to overweight subjects. Female subjects with obesity had a greater risk for depression (ß: 3.725, OR: 42.62, 95% CI: 5.74-316.3 and p < 0.0001) than male subjects (ß: 1.922, OR: 6.83, 95% CI: 1.8-26 and p = 0.005), and it was statistically significant. There was no association between other models (IR and MetS) and depression in both genders (p < 0.05). WHAT IS NEW AND CONCLUSION: The odds of depression was 42.62 times more in obese women and 6.83 time more in obese men compared to overweight subjects. Subjects those who are having ≥3 metabolic syndrome (MetS) components, increased the risk of depression by 0.75 times in women and 1.50 times in men. In view of these results of our study, we conclude that the body mass index is an individual strong predictor of depression whereas metabolic syndrome and insulin resistance had no significant association with depression.

Persistent Elevation of Parathormone Levels after Surgery for Primary Hyperparathyroidism.

BACKGROUND: Persistent elevation of serum parathyroid hormone (PTH) despite normocalcemia have been documented in 8- 40% of patients after parathyroidectomy. We hereby report our experience from different centers across India to determine clinical significance of postoperatively elevated PTH levels and review relevant literature. METHODS: We conducted a retrospective case series study and reviewed all the patients who underwent surgery for primary hyperparathyroidism (PHPT) from April 2010 to January 2020. RESULTS: Total of 201 patients was diagnosed as PHPT. Out of available follow-up data of 180 patients, a total of 54 patients (30%) had persistently elevated PTH (PePTH) at 1 month. Patients with PePTH were older with higher preoperative serum calcium, iPTH, alkaline phosphatase and lower serum phosphate and 25-hydroxy vitamin D3 levels. Creatinine clearance was found to be significantly lower in patients with PePTH. Multiple linear regression analysis revealed that preoperative 25-OH D3 concentration, creatinine clearance and iPTH are the factors influencing persistent elevation of PTH levels. Significantly lower serum calcium and higher alkaline phosphatase levels were observed in PePTH patients with preoperative 25-OH D3 levels <20 ng/mL. Thirty patients at 6 months, 24 patients at 1 year, 18 patients at 2 years and 9 patients at 3 years had eucalcemic PTH elevation. Nine out of 126 (7%) patients with normal initial postoperative calcium and iPTH levels developed PePTH, with none culminating into recurrent hyperparathyroidism. CONCLUSION: Though the pathogenesis of such a phenomenon still remains to be elucidated, a multifactorial mechanism appears to play a role.

Surgical excision of hypothalamic hamartoma in a twenty months old boy with precocious puberty.

A twenty months old boy presented to our department with true precocious puberty due to hypothalamic hamartoma. Total surgical excision of pedunculated hypothalamic hamartoma was done successfully by the pterional trans-sylvian approach as he could not afford medical management. Patient had uneventful post-operative course with normalization of serum testosterone levels and regression of secondary sexual characters.

Etiology of early-onset type 2 diabetes in Indians: islet autoimmunity and mutations in hepatocyte nuclear factor 1alpha and mitochondrial gene.

CONTEXT: Indians are at high risk of developing type 2 diabetes mellitus (T2DM) at an early age, despite their lower body mass index. Studies on the etiology of patients presenting as early-onset T2DM in this racial group are not available. OBJECTIVE: The objective was to delineate the clinical features in young Indian patients with T2DM and to determine the role of mutations in the hepatocyte nuclear factor 1alpha (HNF1alpha) gene [MODY3 (maturity-onset diabetes of the young, type 3)], mitochondrial A3243G mutation, and islet autoimmunity in its etiology. DESIGN: This was an observational cohort study. SETTING: The setting was an outpatient diabetes clinic in a teaching hospital. PATIENTS: Ninety-six consecutive young patients with T2DM (onset,