Indian Journal of Endocrinology and Metabolism最新文献

Introduction: Maturity-onset diabetes of the young (MODY) is a rare group of disorders characterised by impaired functions or development of pancreatic islets and monogenic diabetes at a young age. Diagnosing MODY can be rewarding for both clinicians and patients as it can change the management from generic to targeted therapy.

Methods: This study reports the retrospective analysis of data collected from four clinics between March 2016 and February 2023 from Lucknow, a city in northern India. Fifty-three individuals are suspected to be affected by MODY based on ISPAD guidelines. Following a detailed clinical evaluation, they were referred for genetic diagnostic testing.

Results: The cohort consists of 19 females and 34 males with a mean age of diagnosis of 25.3 years and a body mass index of 22.3 Kg/m². Genetic testing detected variants in 13/53 (~24.5%) individuals. Five cases had significant pathogenic/likely pathogenic variants, HNF1A gene in two [(p.Phe268LeufsTer74) (p.Arg200Gln)], one each in HNF4A (Arg311His), PDX1(p.Ala228GlyfsTer33), and a case with suggestive digenic variants in HNF1A gene (p.Arg200Gln) and HNF1B [(p.Leu13Met)]. Variants of uncertain significance (VUSs) with inconclusive evidence of pathogenicity were reported in eight patients, and five were considered to be clinically significant as they are lean young onset, sulfonylurea-responsive, and presented with diabetes without acanthosis nigricans and with high pretest probability. These individuals harboured variants in HNF1A (p.Thr425_Thr429delinsPro), HNF1B (p.Ser19Phe), CEL (p.Val681ArgfsTer6), ABCC8 (p.Ile872Met), and KCNJ11 (p.Arg221Cys) genes.

Conclusion: We found a diagnostic yield of around 10% of pathogenic or likely pathogenic variants in individuals who were suspected to have MODY. As it is a field that is still evolving, we might consider starting with oral agents under close supervision in those individuals who have VUS; there are some proportions of individuals who might not have classical sulfonylurea-responsive genetic variants, but they might respond to it.

Obesity is a heterogeneous, complex, and chronic disease that has a detrimental impact on disability-adjusted life years across the globe. Recent advancements in our understanding of gut-brain communication at the molecular level have driven the development of next-generation anti-obesity medications (AOMs). Glucagon-like peptide-1 receptor agonists (GLP1RAs) remain the front-runners in this rapidly evolving landscape of hormone-based AOMs. Two GLP1RAs, namely Liraglutide and Semaglutide, have been approved by the Food and Drug Administration (FDA) and European Medicine Agency (EMA) for use in clinical practice for weight loss. Three oral GLP1RAs, namely Semaglutide, Danuglipron, and Orforglipron, are undergoing advanced clinical trials in individuals with obesity. Amylin receptor agonist (AMYRA) Cagrilintide, when used alone or in combination with Semaglutide, has demonstrated substantial weight reduction in clinical trials. Tirzepatide, a dual agonist for the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, has been observed to be associated with a significant placebo-subtracted weight reduction of 17.8% in a 72-week randomized controlled trial. Novel approaches targeting glucagon signalling have also yielded promising preliminary results. Three long-acting GLP1R/glucagon receptor (GCGR) dual agonists, namely Survodutide, Mazdutide, and Pemvidutide, exhibited significant weight loss in clinical trials. Retatrutide, a GLP1R/GCGR/GIPR tri-agonist, has been associated with a placebo-subtracted weight reduction of -22.1% in a 48-week phase-II trial. As a note of caution, long-term data on such medications' safety and cardiovascular benefits is yet to be ascertained. Our review provides a comprehensive overview of the approved and emerging hormone-based AOMs, highlighting the diversity of options that might become available in the near future.

Colours of India is an annual cultural phenomenon that transcends the boundaries of professional conferences, uniting endocrinologists through the universal language of music and dance. Since its inception in 2016, this vibrant event has brought together teams from across India and other participating countries, showcasing diverse dance forms while fostering friendships, promoting wellness, and celebrating cultural diversity within the medical community.

No meta-analysis has analysed role of cagrilintide as weight-loss medication in obese individuals. Electronic databases were searched for RCTs involving obese individuals receiving cagrilintide or cagrilintide-2.4 mg with semaglutide-2.4 mg combination (Cagrisema) compared to placebo/active comparator. Primary outcomes were changes in body weight; secondary outcomes were alterations in glycemia, lipids, and adverse events. From 678 articles, data from 3 RCTs involving 430 individuals were analysed. At 20-32 weeks, patients receiving Cagrisema weekly had significantly greater percentage [mean difference (MD)-9.07% (95%CI: -11.91, -6.23); P < 0.00001;I ² = 96%] and absolute [MD-9.11 kg (95%CI: -12.84, -5.39); P < 0.00001; I ² = 98%] weight-loss, compared to semaglutide 2.4 mg weekly. At 26-32 weeks, cagrilintide 2.4 mg had a similar percentage [MD - 1.83% (95%CI: -4.08, -0.42); P = 0.11; I ² = 98%] and absolute [MD - 1.88 kg (95%CI: -4.23,0.47); P = 0.12; I ² = 98%] weight-loss, compared to semaglutide/liraglutide. Treatment-emergent and serious adverse events were comparable between groups. Gastrointestinal adverse events and vomiting were significantly higher with Cagrisema compared to semaglutide. Vomiting was significantly lower with cagrilintide compared to semaglutide/liraglutide. Cagrisema outperforms semaglutide regarding weight loss. Cagrilintide shows comparable weight loss to semaglutide/liraglutide with significantly lower vomiting.

Introduction: Hypogonadism is a common comorbidity associated with several metabolic disorders including type 2 diabetes (T2D) that can remain undetected without proper screening. Here, we evaluated the prevalence of hypogonadism in Indian male patients with T2D with or without obesity.

Methods: In this prospective, observational study, male patients with T2D and hypogonadism were evaluated symptomatically using the androgen deficiency in ageing male (ADAM) questionnaire at baseline and confirmed on the basis of total testosterone (TT) levels (<300 ng/dL) at Days 5-7 (Visit 2) and 9-14 (Visit 4) assessed after 12 hours of fasting between 8 AM and 10 AM. Prevalence of hypogonadism was presented as proportion of patients.

Results: Of 598 enrolled patients, 526 completed the study. Mean (standard deviation [SD]) age was 50.4 (9.12) years. The percentage of patients with TT <300 ng/dL at visit 2 was 18.4%, while upon repeat confirmation, it reduced to 8.6%. Thus, the prevalence of true hypogonadism was 8.6%. Prevalence of hypogonadism in patients with BMI range of >30 kg/m² (obese) was 11.1%. At screening, 81.4% (487 of 598) patients had positive ADAM questionnaire results.

Conclusions: Prevalence of hypogonadism in Indian patients with T2D was found to be 8.6% upon repeat evaluation of testosterone. Symptomatic (ADAM questionnaire) as well as biochemical (total testosterone levels with repeat evaluation) confirmation is vital in the definite diagnosis of male hypogonadism.

Introduction: Childhood obesity is associated with chronic low-grade systemic inflammation, which results in obesity-related comorbidities. This study compared the inflammatory markers between obese and normal children and assessed obesity-related comorbidities.

Methods: In this cross-sectional analytical study, 40 obese children between 5-18 years of age were recruited as cases, and an equal number of age and gender-matched normal children as the control. The inflammatory markers-high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and adiponectin were compared between the groups. Hypothyroidism, dyslipidemia, insulin resistance, hypertension, and nonalcoholic fatty liver disease (NAFLD) were screened among obese children.

Results: We observed a male-female ratio of 1.5:1 in each group. The median hs-CRP between obese and normal children were 2.53 mg/L (0.94,6.85) and 0.77 mg/L (0.19,7.19), and the median IL-6 levels were 3.56 pg/ml (2.17,5.48) and 3.76 pg/ml (1.08,7.91) respectively. The median IL-10 levels between obese and control groups were 2.06 pg/ml (0.35,6.3) and 1.82 pg/ml (0.41,6.5), and the median adiponectin levels between the groups were 8.6 mcg/ml (6.65,16.04) and 9.79 mcg/ml (8.45,11.91) respectively. We didn't observe significant differences in the markers between the groups. Dyslipidemia, insulin resistance, and metabolic syndrome were seen in 80%, 52.5%, and 45% of obese children, respectively. Other comorbidities-NAFLD, hypertension, and hypothyroidism, were observed in 27.5%, 25%, and 7.5% of obese children, respectively. IL-6 had a significant positive correlation with total cholesterol (r = 0.40), LDL levels (r = 0.50), and HDL (r = 0.32).

Conclusion: There was no difference in inflammatory markers between obese and normal children. Dyslipidemia and insulin resistance were the most common comorbidities.

Introduction: Parietal cell antibody (PCA)-mediated auto-immune gastritis is known to increase the risk of iron-deficiency and pernicious anaemia in adults with type 1 diabetes mellitus. However, in children and young adults with type 1 diabetes, these data are scarce. We aimed to study the prevalence of parietal cell antibodies (PCAs) and its clinical associations in people with type 1 diabetes with onset below 30 years.

Methods: In a cross-sectional study, 224 children and young adults with type 1 diabetes and 171 healthy controls were enrolled. We measured haemoglobin, serum ferritin, vitamin B12, PCA, thyroid peroxidase, and anti-tissue transglutaminase antibodies in all patients. Mann-Whitney U test for continuous data and Chi square test for categorical data were used. Linear regression analysis was performed with haemoglobin as a dependent variable.

Results: The prevalence of PCA was significantly higher in patients than in controls (22% vs 10.2%; P = 0.002). Patients with PCA had a higher frequency of anaemia (60% vs 30%, P < 0.001), lower haemoglobin [7.3 (1.6) vs 7.8 (1.1) mmol/L; P = 0.002], and lower serum ferritin [46.9 (70.8) pmol/L vs 66.0 (105.3) pmol/L; P = 0.04], as compared to those without PCA. On multivariate analysis, haemoglobin was associated with PCA (β = -0.174, P = 0.005) and serum ferritin (β =0.247, P < 0.001).

Conclusion: Presence of PCA was an independent risk factor for iron deficiency and anaemia in children and young adults with type 1 diabetes.

Introduction: Diabetes mellitus is a global health burden, and India is regarded as the diabetes capital of the world. Glycaemic variability (GV) is an established risk factor for hypoglycaemia (plasma glucose concentration <70 mg/dL) and a notorious risk factor for diabetes complications. The primary aim of the study was to assess the correlation between the GV indices, HbA1c levels, and measures of hypoglycaemia in patients with type 2 DM (T2DM).

Methods: In this cross-sectional study, continuous glucose monitoring (CGM) was done for a period of 14 days in T2DM patients (n = 50). The GV indices were determined from the readings obtained from the CGM monitor. Spearman's rank correlation coefficient was used for correlation analyses. The area under the receiver operating characteristics (ROC) curve was used to assess the effectiveness of the various GV indices in predicting hypoglycaemia.

Results: A total of 50 T2DM patients had a mean (SD) age of 61.84 ± 11.88 years. Among the GV indices, high blood glucose index (HBGI), average daily risk range (ADRR), and continuous overall net glycaemic action (CONGA) had a significantly positive correlation with HbA1c levels. Average episodes of nocturnal hypoglycaemia in 8 hours of night-time had a statistically significant negative correlation with the HbA1c levels (correlation coefficient: -0.301, P = 0.034). In addition, low blood glucose index (LBGI) was found to be the best predictor for the risk of hypoglycaemia in 24 hours and nocturnal hypoglycaemia.

Conclusion: Various GV indices are associated with HbA1c levels and are better predictors of hypoglycaemia.