Background: HNF1A-MODY (MODY3) is a monogenic form of diabetes caused by pathogenic variants in the HNF1A gene, a transcription factor essential for pancreatic β-cell development and function. Objectives: Since there are no functional studies of the truncation mutation, we aimed to understand the functional basis of the novel p.Ser471Profs*14 mutation in a MODY patient using different techniques. Materials and Methods: We had previously identified a novel frameshift variant, c.1411delT (p.Ser471Profs*14), in a 13-year-old MODY patient. Functional characterization of this mutation was done by creating the mutation using conventional site-directed mutagenesis. Transcriptional activation was performed in three cell lines. Furthermore, DNA-binding assay, Western blotting, and nuclear colocalization of the mutant were assessed along with the glucose-stimulated insulin secretion assay. Results and Conclusion: We identified a novel heterozygous frameshift variant, c.1411delT (p.Ser471Profs*14), in a clinically suspected MODY patient, a 13-year-old female presenting with hyperglycemia and negative pancreatic autoantibodies. The variant introduces a premature termination codon (PTC) 14 amino acids downstream of the mutation site within exon 7. As the PTC is positioned upstream of the final exon–exon junction, the mutant transcript is predicted to undergo nonsense-mediated mRNA decay, leading to haploinsufficiency. Variant interpretation classifies the variant as pathogenic. The patient demonstrated clinical responsiveness to sulfonylurea therapy, further supporting the diagnosis of pathogenicity. This study highlights the importance of combining clinical, genetic, and functional evidence for accurate interpretation of novel HNF1A variants.
Background: Different types of weight training affect blood glucose (BG) and blood lactate levels differently. Muscular endurance training, a form of aerobic exercise, relies on adequate oxygen delivery to meet energy demands, whereas strength, hypertrophy, and power training are primarily anaerobic and depend on glycolysis. Currently, there are no weight-training guidelines specifically designed for adolescents with type 1 diabetes (T1D). Objectives: This study evaluated the effects of different weight-training methods on glycemic control and examined the relationship between BG and blood lactate levels in adolescent athletes with T1D. Materials and Methods: Adolescents aged 13–17 years with T1D for at least 2 years, a hemoglobin A1c ≤10%, and current continuous glucose monitor (CGM) use were recruited from a pediatric endocrinology clinic. Participants completed four 60-min training sessions, each focused on a specific exercise modality: aerobic (endurance) or anaerobic (strength, hypertrophy, and power) training. Body fat, BG, blood lactate, and CGM data were collected at each visit. Paired-sample t-tests were used to evaluate the relationships between changes in BG and blood lactate levels. Results: Fifteen participants were enrolled, of which 13 completed the study and two withdrew. Aerobic exercise resulted in significant changes in BG (−19.87 ± 40.71 mg/dL) and blood lactate (4.75 ± 2.68 mmol/dL). During anaerobic exercise, significant changes in BG and blood lactate were observed for strength training (−14.07 ± 25.44 mg/dL and 3.23 ± 2.08 mmol/dL, respectively; P = 0.022) and hypertrophy training (−12.47 ± 26.16 mg/dL and 5.23 ± 2.09 mmol/dL, respectively; P = 0.022). BG decreased more during endurance than during strength training (P = 0.006). Strength training produced greater increases in blood lactate than hypertrophy training (P = 0.009). Conclusion: BG decreased during all exercise modalities, with the largest decline occurring during aerobic exercise. Higher blood lactate levels were not associated with increased BG levels.
Introduction: Insulin degludec is an ultra-long-acting basal insulin characterized by low day-to-day variability compared to first-generation basal insulins. While its pharmacological advantages are well established in type 1 and type 2 diabetes, real-world data on its use in hyperglycemia in pregnancy (HIP) remain limited. This study aimed to evaluate maternal glycemic control, insulin requirements, and pregnancy outcomes in HIP treated with insulin degludec under real-world clinical conditions. Materials and Methods: This retrospective observational study included 97 pregnant women with HIP. Participants received basal–bolus insulin, with insulin degludec as the basal component and faster-acting insulin aspart (Fiasp) as the most frequently used bolus insulin (taken thrice a day). Data on demographics, glycemic parameters, and maternal and neonatal outcomes were extracted from medical records and analyzed using appropriate statistical methods. Results: The mean maternal age was 32.5 ± 4.47 years, and body mass index was 30.6 ± 5.98 kg/m2. Hemoglobin A1c significantly decreased from 7.58% at baseline to 6.30% at delivery (P < 0.001). Fasting plasma glucose dropped from 134.6 to 93.9 mg/dL (P < 0.001). Postprandial glucose (PPG) at 2 h post-lunch reduced from 161.7 ± 14.2 to 91.7 ± 6.3 mg/dL, and PPG after dinner reduced from 162.8 ± 12.8 to 92.6 ± 5.9 mg/dL (both P < 0.001). Degludec dose increased from 13.6 ± 3.09 to 21.8 ± 4.25 units/day (P < 0.001), and the premeal dose of bolus insulin increased from 6.84 ± 1.79 to 12.07 ± 2.26 units/meal (P < 0.001). Maternal hypoglycemia was infrequent (Level 1: four cases, Level 2: three cases, and Level 3: one case). Neonatal outcomes were favorable with a 90% live birth; neonatal hypoglycemia and jaundice occurred in 10.7% and 19.7%, respectively. Conclusion: Insulin degludec was associated with effective glycemic control, low hypoglycemia rates, and favorable maternal and neonatal outcomes in HIP. Supported by EXPECT trial data and endorsed by national and international clinical recommendations, degludec emerges as a viable basal insulin option in pregnancy.
Type 2 diabetes mellitus (T2DM) in Indian women represents a growing and complex public health challenge, driven by a combination of biological, sociocultural, and metabolic factors. Throughout their life stages including reproductive years, pregnancy, perimenopause, and menopause, Indian women exhibit increased susceptibility to central adiposity, insulin resistance, and cardiometabolic risk. Even so, treatment methods often focus only on weight or glucose, which does not help people who are both overweight and have high blood sugar levels, which is a problem that affects this group more than others. Semaglutide, a glucagon-like peptide-1 receptor agonist administered weekly, provides a mechanism-based approach aimed at achieving glycemic control and significant weight loss. In addition to lowering HbA1c levels, innovator semaglutide has shown benefits in managing weight and cardiovascular risk reduction. These are especially important for Indian women who often have abdominal obesity and early cardiometabolic problems. This review seeks to contextualize the role of semaglutide in Indian women with T2DM, emphasizing gender-specific factors, practical challenges, and the necessity for customized medical education. The article aims to promote a more cohesive, gender-sensitive therapeutic strategy that effectively tackles the interconnected metabolic and cardiometabolic risks encountered by Indian women with T2DM, by amalgamating existing clinical evidence and Indian practice viewpoints.
Background: Diabetes mellitus (DM) is a prevalent chronic disease associated with high morbidity and mortality. Current therapeutic strategies remain limited in achieving sustained metabolic control and preventing long-term complications. Mesenchymal stem cell (MSC) based therapies have shown promising regenerative and immunomodulatory potential. Therefore, we conducted a systematic review to evaluate the clinical efficacy of stem cell-based therapies in the management of DM. Materials and Methods: A systematic search was conducted using electronic databases from January 2015 to December 2024. Eligible studies included randomized controlled trials (RCTs) and controlled experimental studies in humans or animal models that investigated a single stem cell-based intervention for type 1 DM (T1DM) or type 2 DM (T2DM). The process involved extracting data and evaluating study quality with the Cochrane Risk of Bias 2 tool; statistical analyses were conducted in RevMan 5.4.1. Results: Sixteen studies (seven human and nine animal) were included. Stem cell therapies consistently improved glycemic outcomes, including lower glycated haemoglobin, fasting, and postprandial glucose, with higher C-peptide and β-cell preservation. Clinical studies showed reduced insulin requirements and improved sensitivity, while preclinical models confirmed β-cell regeneration and immunomodulatory effects. Safety profiles were favorable, with no major adverse events reported. Conclusion: Stem cell-based therapies, especially MSCs, demonstrate significant potential as adjunctive treatments for T1DM and T2DM, improving glycemic control and reducing insulin dependence. While preclinical evidence is strong, clinical data remain limited. Larger, multicenter RCTs with extended follow-up are needed to confirm efficacy, standardize protocols, and ensure long-term safety.
