Type II Diabetes Research Articles

Correlating enzymatic reactivity for different substrates using transferable data-driven collective variables

Machine learning (ML) is transforming the investigation of complex biological processes. In enzymatic catalysis, one significant challenge is identifying the reactive conformations (RC) of the enzyme:substrate complex where the substrate assumes a precise arrangement in the active site necessary to initiate a reaction. Traditional methods are hindered by the complexity of the multidimensional free energy landscape involved in the transition from nonreactive to reactive conformations. Here, we applied ML techniques to address this challenge, focusing on human pancreatic α-amylase, a crucial enzyme in type-II diabetes treatment. Using ML-based collective variables (CVs), we correlated the probability of being in a RC with the experimental catalytic activity of several malto-oligosaccharide substrates. Our findings demonstrate a remarkable transferability of these CVs across various compounds, significantly streamlining the modeling process and reducing both computational demand and manual intervention in setting up simulations for new substrates. This approach not only advances our understanding of enzymatic processes but also holds substantial potential for accelerating drug discovery by enabling rapid and accurate evaluation of drug efficacy across different generations of inhibitors.

Clinical utility of novel diabetes subgroups in predicting vascular complications and mortality: up to 25 years of follow-up of the HUNT Study

IntroductionCluster analysis has previously revealed five reproducible subgroups of diabetes, differing in risks of diabetic complications. We aimed to examine the clusters’ predictive ability for vascular complications as compared with...

BS SO10 - Predictive Factors in the Development of Dumping Syndrome After Bariatric Surgery

Abstract Background Dumping syndrome (DS) is a recognised complication of Roux En-Y Gastric Bypass (RYGB) and rarely Sleeve Gastrectomy (SG). The prevalence of DS is unclear, with current literature ranging from 10-50%. The condition is characterised by gastrointestinal and vasomotor symptoms resulting in a significant impact on quality of life. This study aimed to prospectively utilise Sigstad scoring to evaluate post-operative patients, investigating the timing of symptom onset and its correlation with pre-existing diabetes, revision surgery, and percentage of Total Body Weight Loss (TBWL). Method We used the Sigstad scoring questionnaire, administered by our bariatric Clinical Nurse Specialists (CNS) at outpatient clinics to assess patients for DS between January to May 2024. Data collected included patient demographics, surgery type and date, TBWL, Body Mass Index (BMI), and whether the patient had a diagnosis of Diabetes Mellitus type II (DMII). A diagnosis of DS was confirmed if a patients score ³7 points on the Sigstad questionnaire. We explored factors influencing the development of DS. Results In total, 64 patients were evaluated for DS of whom 86% were female and the median age was 44 years (IQR: 35-45). Most patients (67%) had undergone primary RYGB, 19% SG, 11% conversion from SG to RYGB and 70% were assessed within one year of surgery. DS symptoms emerged in 25% of patients, predominantly within the first-year post-operation (60%). The median TBWL was 12% (IQR: 9-22%), showing no correlation to DS onset. Patients with DMII exhibited a higher propensity for DS (66% vs 20%, p=0.029). Patients undergoing revisional surgery also had a higher incidence of DS (33% vs 6%, p=0.117). Conclusion A quarter of patients undergoing bariatric surgery will develop DS, most of whom within the first-year post-surgery. Revisional surgery and pre-existing DMII are the primary predictors in developing DS. There was no observed association between TBWL and DS onset. Further extensive studies are needed to confirm these observations.

The Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Regulates Sirtuin-1-Mediated Neutrophil Extracellular Traps to Improve Diabetes-Induced Bone Metabolism Imbalance

Background: Diabetes mellitus (DM) is a chronic metabolic disorder that disrupts normal bone remodeling. Objectives: This study aimed to investigate how the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LIR) addresses bone metabolism imbalances induced by type-II diabetes. Methods: Type-II diabetic rat models were established through a single intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were measured using a blood glucose meter, and insulin levels were assessed using an assay kit. Bone formation markers [alkaline phosphatase (ALP), osteocalcin (OCN), and procollagen I N-terminal propeptide (PINP)] and bone resorption markers [tartrate-resistant acid phosphatase (TRACP) and CTX-1] were monitored using assay kits. Bone marrow mesenchymal stem cells (BMSCs) were cultured in vitro under high-fat and high-glucose (HFHS) conditions to mimic diabetic bone metabolism dysregulation. Neutrophil extracellular traps (NETs) formation was examined through immunofluorescent staining and Western blot analysis. Results: Liraglutide was found to reduce STZ-induced NETs formation, as indicated by decreased expression of cit-H3 by 36.90% - 53.57%, myeloperoxidase (MPO) by 55.81% - 65.12%, NE by 53.95% - 65.17%, and PAD4 by 46.81% - 63.83%, alongside increased Sirtuin-1 (SIRT1) expression in femur tissue (70.71% - 91.19%). In vitro, LIR enhanced osteogenesis and inhibited apoptosis, effects that were partially reversed by SIRT1 knockdown. Additionally, SIRT1 knockdown partially restored LIR-induced reductions in oxidative stress, inflammation, and NETs formation. Conclusions: LIR mitigates diabetes-induced bone metabolism imbalance by inhibiting NETs formation through SIRT1 mediation.

Gut-Brain Nexus: Mapping Multi-Modal Links to Neurodegeneration at Biobank Scale.

Co-occurring disorders of the gut-brain axis combined with genetic and proteomic data can better predict neurodegenerative risk.

Exploring the Synergistic Effects of Concurrent Exercise for Managing Type-II Diabetes Mellitus: A Meta-Analysis.

The effectiveness of concurrent exercise (CE) as an emerging approach for type-II diabetes mellitus (T2DM) patients was evaluated through a comprehensive search on Google Scholar, PubMed, Pedro, CINAHL, and Medline from 2015 to March 2023. Sixteen RCTs were selected which evaluated CE (aerobic + resistance in the same session) effects on a minimum of three days/week among T2DM patients, and the control group received usual care or no exercise. Studies that evaluated at least one glycaemic variable, i.e. HbA1C, fasting blood glucose level (FBGL), andHomeostatic Model Assessment for Insulin Resistance (HOMA-IR), were eligible. Intervention with a follow-up period of ≥8 weeks, patients of any age and gender, and literature in the English language were included. A rigorous review was performed using the Cochrane Collaboration risk of bias tool (RoB 2) to minimise biases, which include the randomisation process, deviation from intended intervention, missing outcome data, outcome measurement, and selection bias. CE significantly improved HbA1C (95% CI of -0.654 to 0.363, I2 = 84.92% moderate heterogeneity), FBGL (95% CI of -0.239 to 1.145, I2 = 93.74% - high level of heterogeneity), and insulin resistance (HOMA-IR) (95% CI of -0.593 to 0.544, I2 = 92.85% - high level of heterogeneity). Collectively, findings indicate the potential of CE as an intervention to impact glycaemic control in T2DM patients positively. However, the relatively high I² values suggest notable variability among studies, and further research to explore the factors contributing to this heterogeneity, exercise protocol along with progression, and duration of diabetes are needed, which is more challenging to determine a precise dose-response relationship. Therefore, more studies are required to provide thorough insights into these components for T2DM management. Key Words: Glycated haemoglobin, Glycaemic control, Insulin resistance, Physical exercise, Type-II diabetes mellitus.

Exploring the Synergistic Effects of Concurrent Exercise for Managing Type-II Diabetes Mellitus: A Meta-Analysis.

The effectiveness of concurrent exercise (CE) as an emerging approach for type-II diabetes mellitus (T2DM) patients was evaluated through a comprehensive search on Google Scholar, PubMed, Pedro, CINAHL, and Medline from 2015 to March 2023. Sixteen RCTs were selected which evaluated CE (aerobic + resistance in the same session) effects on a minimum of three days/week among T2DM patients, and the control group received usual care or no exercise. Studies that evaluated at least one glycaemic variable, i.e. HbA1C, fasting blood glucose level (FBGL), andHomeostatic Model Assessment for Insulin Resistance (HOMA-IR), were eligible. Intervention with a follow-up period of ≥8 weeks, patients of any age and gender, and literature in the English language were included. A rigorous review was performed using the Cochrane Collaboration risk of bias tool (RoB 2) to minimise biases, which include the randomisation process, deviation from intended intervention, missing outcome data, outcome measurement, and selection bias. CE significantly improved HbA1C (95% CI of -0.654 to 0.363, I2 = 84.92% moderate heterogeneity), FBGL (95% CI of -0.239 to 1.145, I2 = 93.74% - high level of heterogeneity), and insulin resistance (HOMA-IR) (95% CI of -0.593 to 0.544, I2 = 92.85% - high level of heterogeneity). Collectively, findings indicate the potential of CE as an intervention to impact glycaemic control in T2DM patients positively. However, the relatively high I² values suggest notable variability among studies, and further research to explore the factors contributing to this heterogeneity, exercise protocol along with progression, and duration of diabetes are needed, which is more challenging to determine a precise dose-response relationship. Therefore, more studies are required to provide thorough insights into these components for T2DM management. Key Words: Glycated haemoglobin, Glycaemic control, Insulin resistance, Physical exercise, Type-II diabetes mellitus.

Continuous Glucose Monitoring With Remote Telemonitoring-enabled Virtual Educator Visits in Adults With Non-insulin Dependent Diabetes: A Randomized Trial

Continuous Glucose Monitoring With Remote Telemonitoring-enabled Virtual Educator Visits in Adults With Non-insulin Dependent Diabetes: A Randomized Trial

Triazole scaffold-based DPP-IV Inhibitors for the management of Type-II Diabetes Mellitus: Insight into Molecular Docking and SAR.

Diabetes mellitus, characterized as a chronic metabolic disorder or a polygenic syndrome; is increasing at a very fast pace among every group of the population worldwide. It arises due to the inability of the body to produce enough insulin (the hormone responsible for controlling blood sugar levels) or inability to utilize the insulin, leading to hyperglycaemic condition, which, if left uncontrolled gives rise to chronic microvascular and macrovascular complications like retinopathy, neuropathy, nephropathy, coronary artery disease, cognitive impairment, etc. Several therapeutic approaches are available for the treatment of diabetes; among which dipeptidyl peptidase (DPP-IV) inhibitors (gliptins) hold a significant place. DPP-IV is a multifunctional enzyme or a serine exopeptidase that plays an imperative role in cleaving bioactive molecules. DPP-IV causes the breakdown of incretin hormone (GLP-1: Glucagon-like peptide 1 and GIP: Glucose-dependent insulinotropic peptide) that is essential for controlling glycaemic levels in the body. Inhibition of DPP-IV enzyme (DPP-IV inhibitors: Sitagliptin, Saxagliptin, Linagliptin, Alogliptin) prevents this breakdown, thereby controlling blood glucose levels and saving the patients from deleterious effects of prolonged hyperglycaemic conditions. Triazole-based DPP-IV inhibitors are a significant class of drugs used to treat Type 2 diabetes mellitus in a dose-dependent manner. Clinical trials have demonstrated their efficacy as monotherapy or in combination with other antidiabetic agents. This review highlights the molecular docking studies and structure-activity relationship of potential synthetic derivatives that may act as lead molecules for future drug discovery and yield drug molecules with enhanced efficacy, potency and reduced toxicity profile.

The Impact of Trendy Diets on Nutritional Imbalance and Health Risks

In nowadays society people are focusing on their well-being and appearance more than ever. Social media has amplified almost every detail on daily occasions, however, such additional attention may not necessarily be beneficial for everyone. Influencers post pictures of their perfect physique and use them for more attention and followers. Among all the so-called ‘secrets’, people are most curious about what they eat and how they eat to look that stunning. Compared to tiring gym sessions and boring lectures about anatomy and physiology, a brand-new revolutionary recipe is far more appealing. The trendy recipes are beneficial to some people who have special needs such as those who are obese, type-II diabetes patients, people who suffer from cardiovascular diseases, etc. Such recipes greatly altered the proportions of the different essential nutrients to improve some symptoms that are occurring due to an imbalance of nutrition. However, such a diet may be beneficial to the human body in the short run by adjusting the daily calorie intake and controlling the categories of food in each sitting, in the long run, it would lead to another malfunction of the body due to nutrition imbalance.

Subphenotypes of adult-onset diabetes: Data-driven clustering in the population-based KORA cohort.

A data-driven cluster analysis in a cohort of European individuals with type 2 diabetes (T2D) has previously identified four subgroups based on clinical characteristics. In the current study, we performed a comprehensive statistical assessment to (1) replicate the above-mentioned original clusters; (2) derive de novo T2D subphenotypes in the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) cohort and (3) describe underlying genetic risk and diabetes complications. We used data from n = 301 individuals with T2D from KORA FF4 study (Southern Germany). Original cluster replication was assessed forcing k = 4 clusters using three different hyperparameter combinations. De novo clusters were derived by open k-means analysis. Stability of de novo clusters was assessed by assignment congruence over different variable sets and Jaccard indices. Distribution of polygenic risk scores and diabetes complications in the respective clusters were described as an indication of underlying heterogeneity. Original clusters did not replicate well, indicated by substantially different assignment frequencies and cluster characteristics between the original and current sample. De novo clustering using k = 3 clusters and including high sensitivity C-reactive protein in the variable set showed high stability (all Jaccard indices >0.75). The three de novo clusters (n = 96, n = 172, n = 33, respectively) adequately captured heterogeneity within the sample and showed different distributions of polygenic risk scores and diabetes complications, that is, cluster 1 was characterized by insulin resistance with high neuropathy prevalence, cluster 2 was defined as age-related diabetes and cluster 3 showed highest risk of genetic and obesity-related diabetes. T2D subphenotyping based on its sample's own clinical characteristics leads to stable categorization and adequately reflects T2D heterogeneity.

A Comprehensive Review about Risks of Type-II Diabetes on Ocular Tear Film

Millions of people worldwide suffer from diabetes mellitus (DM), which can lead to systemic issues in a number of organs. Ocular problems, such as dry eye syndrome (DES), are among its less well-known side effects. This review delves into the interactions between diabetes and the composition of tear films, emphasizing alterations in the mucin, aqueous and lipid layer. Dry eye symptoms are exacerbated by induced changes in the components of the tear film in diabetes DM, which lead in decrement in tear production, increment in tear evaporation and tear film instability. Lipid layer is a lubricant, that reduces friction between the ocular surface and the eyelids which promotes high-quality, smooth refractive surface. The lacrimal function unit shields the tear film, preserves the normal function of the ocular surface. The mucin layer is secreted by the conjunctival goblet cells, in hyperglycemia the functionality of the cells are reduced thus, the mucin secretion is also altered which causes instability of the tear film. Diabetic patients can have their tear film integrity assessed with the help of diagnostic methods like Schirmer's Test and Tear Break- Up Time (TBUT). In order to relieve symptoms and maintain ocular health, there should be a complete management of diabetes and the induced tear film disorders.

Screening of Pre-Diabetes and Type-II Diabetes Mellitus Among the Personnel of Bangladesh Air Force

Background: Medical Squadron (Med Sqn) of Bangladesh Air Force (BAF) Base Bashar (BSR) has been providing medical support for BAF Base BSR, Air Headquarters, most of the retired officers and their families. It has been observed that the number of Diabetes Mellitus (DM) patient is increasing day by day, and now it becomes a major health problem among the members of BAF, even among the young age group. In view of above, a study was conducted among the BAF uniform members who reported for laboratory investigation to Med Sqn BAF Base BSR. Assessing prevalence of DM among BAF personnel will also help for overall assessment of health problem of BAF personnel to make a preventive guideline. Methods: A descriptive type of cross-sectional study was conducted with available data in the pathological laboratory of Med Sqn BAF Base BSR during the period from 01 July 2021 to 30 Jun 2022. Within this period a total 9269 Air Force uniform members reported for routine as well as diagnostic purpose of checking blood sugar. Associated risk factor like overweight or obesity was also assessed by latest data from personal documents. Age and job pattern wise data were also analyzed. Statistical Package for Social Sciences (SPSS) version 29.0 was used to analyze data. Results: Out of 9269 BAF members a total 683 persons (7.36%) had high (above normal) plasma glucose. Of these 413(60.46%) were diabetic and 270(39.53%) were pre-diabetic (IFG/IGT). Among the 413 diabetic patients 292(42.75%) had fasting plasma glucose (FPG) ≥7 mmol/L as well as post prandial plasma glucose (PPPG) level ≥11.1 mmol/L. Among the 270 pre-diabetic patients 205(30.01%) had FPG level between 6.1-6.9 mmol/L with PPPG level <7.8 mmol/L (Impaired Fasting Glucose/IFG) and 65(9.51%) had FPG level <7 mmol/L with PPPG level between 7.8-11 mmol/L (Impaired Glucose Tolerance/IGT). Conclusion: DM has become a major health concern all over the world. This study attempted to identify the prevalence of age-related factors for DM among BAF uniform members between the ages 30 to 60 years. It has been observed that the prevalence of pre-diabetes is more among the 41 to 45 years age group and Type-II DM among the 46-50 years age group. Bangladesh Armed Forces Med J Vol 57 No (1) June 2024, pp 22-27

COMPARING STAGES OF DIABETIC RETINOPATHY WITH SYSTEMIC VASCULAR STATUS USING FINGER PHOTOPLETHYSMOGRAPHY.

To evaluate systemic vascular fitness measured by finger photoplethysmography (PPG) in diabetic retinopathy (DR). This was a cross sectional observational study on type-II Diabetes Mellitus patients from October 2020 to May 2021. Data collected include systolic/diastolic blood pressure (BP), visual acuity, HbA1c, and central macular thickness (CMT). DR severity was categorised using the ETDRS classification. PPG signals were acquired using pulse-oximeter modules (OEM-60, Dolphin Medical Inc) measured for 90 seconds at 275Hz sampling rate and 16-bits resolution which records photoplethysmography fitness index (PPGF), vascular-risk prediction index (VRPI) and vascular age (VascA). One-hundred-and-forty-one patients were equally distributed into six DR categories. Mean age was 58.8±9.9 years, with female-to-male ratio of 1.27. There were significant differences in mean systolic (125.5±10.0mmHg, p=0.007) and diastolic-BP (80.0±8.8mmHg), mean HbA1c (7.6±1.9%, p=0.005), median LogMAR (0.3, IQR:0.2-0.5, p<0.001) and CMT (p=0.003) across DR severity. Significant differences were also seen in PPGF (p=0.001), VRPI (p<0.001) and VascA (p=0.001), with poorer values in severe compared to mild/moderate DR. After adjusting for age, BP and HbA1c, PPGF reduces by 3.3% (regression coefficient, b= -3.27, p<0.001), VascA increases by 2.5 years (b=2.54, p=0.002) and VRPI increases by 3.1 (b= 3.08, p<0.001) with every DR worsening. More severe DR were associated with poorer PPG vascular markers.

Screening of anti-diabetic potential of the siddha formulation sambirani poo kuligai by in-vitro alpha glucosidase enzyme inhibition assay

Background: Noninsulin-dependent diabetes mellitus (NIDDM) is a common disease of the endocrine system caused by the decreased secretion of insulin by the pancreatic Langerhans beta cell or by the lowering of insulin resistance due to excessive absorption of glucose. The Siddha system of medicine is a traditional medical system that uses a scientific and holistic approach to provide preventive, promotive, curative, rejuvenative and rehabilitative health care. According to Siddha literature, diabetes is known as Innippu Neer, Madhumegam and Neerizhivu. The various reasons for the cause of this disease are attributed to foodhabits and lifestyle changes and also due to hereditary causes. One of the therapeutic approaches is to decrease the postprandial hyperglycemia by retarding the absorption of glucose through the inhibition of carbohydrate-hydrolyzing enzymes, such as a-amylase and ?-glucosidase. ?-Glucosidase are enzyme that catalyze the absorption of digested glucose from dietary polysaccharides in the small intestine. Aim: The aim of the present study is to evaluate the anti-diabetic potential of the siddha formulation of Sambirani Poo Kuligai(SPK) by alpha glucosidase enzyme inhibition assay. Method: The spectrophotometric assay method was used to find alpha glucosidase inhibitory activity. Results: SPK showed presence of alpha glucosidase inhibitory potential with the maximum inhibition of about 41.74 ± 3.578 % and the corresponding IC50 is 606.5 ± 49.51?g/ml. Conclusion: This in-vitro study revealed the presence of the alpha glucosidase activity in the siddha formulation Sambirani Poo Kuligai possesses antidiabetic activity

7531 Spontaneous Coronary Artery Dissection Induced Diabetic Ketoacidosis In A Young Female: A Rare Complication Of Ketosis In A Priorly Non-Insulin Dependent Diabetic

Abstract Disclosure: F. farhat: None. P. Gonzalez: None. A.B. Ravin: None. H. Akhlaq: None. M. hossain: None. K. chalasani: None. S.W. Holland: None. R. Ong: None. J. Cheng: None. Introduction: Spontaneous Coronary Artery Dissection (SCAD) is a poorly understood and underdiagnosed condition that puts healthy young women at risk of Myocardial infarction (MI) and potential death. It occurs when a tear develops in a coronary artery. SCAD can have an atypical presentation especially in diabetic and young females; Diabetic ketoacidosis (DKA) is an uncommon, yet potentially fatal complication and can be the primary presentation in SCAD. We present a case of SCAD complicated by DKA in a non insulin dependent diabetic (NIDD).Case presentation: A 19 year old female with a past medical history of NIDDM presented to the Emergency Department with chest pain. She had troponemia and ECG revealed ST elevations. Patient was found in DKA initially. Insulin drip was started with DKA resolution in 24 hours. Hemoglobin A1c was 12.4% with negative antibody workup. Her course was complicated by SCAD found upon cardiac catheterization with unsuccessful recanalization; she was not a surgical candidate given late presentation and therefore, an intra aortic balloon pump was placed. Subsequently, she developed pericarditis and left ventricular thrombus. Discussion: SCAD is a rare condition, often presenting with acute MI and cardiogenic shock. MI may be complicated with DKA. One proposed mechanism for that is the activation of ketogenic pathways caused by excess catecholamines and cortisol; this increases physiologic stress on the body resulting in increased ketogenesis, lipolysis and free radicals causing further myocardial injury. DKA precipitated by MI increases the mortality rate to nearly 85% since the myocardium is denied glucose uptake. Signs and symptoms of SCAD are similar to MI symptoms including: chest tightness, shortness of breath and sweating. MI and SCAD can be differentiated by cardiac catheterization or by specialized contrasted CT scans. 20% of SCAD patients will experience a second episode within 5 years. Avoiding emotional stress, exercising regularly, following a healthy diet and controlling chronic conditions can help lower the risk for SCAD. Medical management is often preferred. Invasive treatments like coronary stenting or cardiac bypass may be needed if there is a complete blockage in the vessel, clinical instability or ongoing chest pain. Conclusion: SCAD is an important cause of MI in young females and can present initially as DKA in diabetics. For clinicians facing such rare cases, it is worth maintaining a broad approach to the diagnosis and treatment of these patients. The causes of SCAD remain fully unclear and genetic relations are still under investigation. Since DM type I and SCAD occur in young people, it is extremely important for clinicians to consider SCAD in the differential while managing DKA. Presentation: 6/3/2024

9390 Does Znt8a Have An Association With The Duration Of Diabetes? Case Series And Literature Review

Abstract Disclosure: N.M. Rivera Vargas: None. C.S. Botero Suarez: None. S.K. Suryanarayanan: None. S. Saad-Omer: None. Context: Latent autoimmune Diabetes of adults (LADA) is a form of autoimmune diabetes with features of Type 2 Diabetes but positive autoantibodies resembling Type 1 Diabetes. Latent autoimmune diabetes in adults (LADA), has a mixed phenotype with positive islet-cell antibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), protein tyrosine phosphatase autoantibodies (IA2A), insulin autoantibodies (IAA), or zinc transporter-8 autoantibodies (ZnT8A). Since the discovery of ZnT8A, the relevance and clinical utility of this marker has sparked interest. Although ZnT8A is used as a complementary diagnostic aid in children, its utility in adults seems to be unclear. Objective: We report a case series of 26 subjects referred to the Orlando VA Endocrine clinic with measured ZnT8A. We hypothesize that higher ZnT8A will be found in adult autoimmune diabetes with newly diagnosed diabetes rather than those with a longer duration of diabetes. We also explore the association between ZnT8A and family history, duration of diabetes, diabetes complications, and C-peptide levels. Method: A case series of 26 adult patients with diabetes mellitus with a positive ZnT8A (≥15 U/mL). We reviewed medical records of these cases to include ZnT8A levels, years of diabetes diagnosis, C-peptide levels, and diabetes complications. Patients were classified into subgroups based on ZnT8A levels into &amp;lt; 350 U/mL or ≥ 350 U/mL. Results: The 26 patients reviewed had a mean (SD) age of 46 (13) years. The mean (SD) duration of diabetes was 16 (12) years, and HbA1C was 8.4 (1.1) %. Poisson regression analysis showed a statistically significant inverse relationship between ZnT8A and years of diabetes (regression coefficient: -0.028; 95% confidence interval: -0.03 to -0.25; p-value &amp;lt;0.001). Diabetic ketoacidosis was present in 35% of subjects, while diabetic neuropathy was noted in 58% of subjects with positive ZnT8A. Patients with a high ZnT8Ab above 350 U/mL displayed a weak trend towards a lower C-peptide mean (p-value 0.42), and lower prevalence of DKA (p-value 0.42) which was not statistically significant. Conclusion: In this case series of patients with adult-onset diabetes, there seems to be a statistically significant inverse relationship between ZnT8A levels and duration of diabetes suggesting a reduction of ZnT8A levels over time. Although limited by a small number of subjects, this may suggest the need for screening with autoantibodies in the setting of diabetes earlier in the disease process. Presentation: 6/2/2024

8070 Atypical New Onset Diabetes Mellitus in a Young Male: Is this LADA vs Type 1 or Type 2?

Abstract Disclosure: S.K. Devineni: None. S. Shaik: None. J.L. Gilden: None. Background: Recent literature suggests that autoantibody seropositivity is common in new onset autoimmune Diabetes Mellitus (DM), especially in younger patients. Latent autoimmune diabetes of adults (LADA), a form of adult-onset autoimmune DM. is considered a mix of type 1 and type 2 DM, sharing similar immune cell characteristics to both subtypes. Unlike type 1, LADA patients do not require insulin for glycemic control for the first six months after diagnosis. Unlike type 2, LADA patients are positive for single islet autoantibody, glutamic acid decarboxylase (GAD), and anti-gliadin antibodies. Patients with LADA often present with symptoms (polyuria, polydipsia, nocturia, fatigue, and visual changes). We present a case of new onset Diabetes Mellitus in a young male, autoantibody seronegative, at the time of diagnosis. Case report: A 19-year-old Caucasian male was sent to the Emergency Department with a serum blood glucose (BG) level of 579 mg% after routine blood tests. He denied any clinical symptoms and serum levels showed no elevation in ketones, nor bicarbonate levels, ruling out ketoacidosis. His hemoglobin A1c at that time was 14.7%. He denied prior knowledge of personal or family history of DM. or other autoimmune disorders. However, it was discovered that routine labs done 1 ½ months earlier on a Health Screen revealed BG=295 mg% with urine positive for ketones (80 mg/dl) and glucose (&amp;gt;1000 mg/dL). Physical Exam: (HT=178 cm; WT=79 Kg) was unremarkable. Autoantibodies for GAD 65, islet-cell, Zinc transporter 8, and Islet Antigen 2 were all negative. He was hospitalized for 9 days. BG levels were difficult to control and required increasing doses of both long acting and short acting insulin. He was discharged with insulin therapy (30 units of glargine at nighttime and 12 units of premeal aspart). One week later, the patient ate several gummy bears as a nighttime snack and subsequently woke up in the middle of the night feeling shaky and having blurry vision. BG was greater than 300 mg%. In the emergency room, he. received intravenous fluids. No insulin was given as his BG normalized and he was discharged. Later, a continuous glucose monitor revealed multiple hypoglycemic episodes. The patient was living in a situation where he only had limited access to certain foods, and thus his insulin regimen was decreased (28 units glargine and 10 units aspart for meals) Conclusion: We present the case of new onset atypical DM in a young patient whose insulin sensitivity and risk factors seem to resemble a pattern of type 1 DM; despite seronegative autoantibodies We predict that he may eventually seroconvert to type 1 DM. It is also possible that he may have an unusual presentation of LADA or type 2 DM, although he had no hyperglycemic symptoms. Presentation: 6/3/2024

8494 A Case of Diabetic Ketoacidosis in Setting of COVID-19 Infection and SGLT-2 Inhibitor Use

Abstract Disclosure: N. Abrahimi: None. S. Bajpay: None. A. Abrahimi: None. Background: COVID-19 infection can cause endocrine system disruptions leading to the development of diabetic ketoacidosis (DKA) in patients with type 1, 2 or new onset diabetes mellitus. (1) DKA is a side effect of SGLT-2 inhibitor use and its development on the medication can lead to discontinuation of SGLT-2 inhibitor. (2) SGLT-2 inhibitors are part of guideline directed medical therapy for management of heart failure with reduced ejection fraction (HFrEF). (3) Case: 67-year-old female history of non-insulin dependent diabetes mellitus type 2 on Empagliflozin presented with shortness of breath and hypoxia. Initial BMP: Glucose 141 mg/dL, bicarb 24 mmol/L, anion gap of 10 mmol/L. Patient test positive for COVID-19 and was admitted for acute hypoxic respiratory failure in setting of COVID-19 infection. Six hours after patient received first dose of dexamethasone, labs showed BMP: Glucose 582 mg/dL, bicarb 14 mmol/L, anion gap of 20 mmol/L. ABG: pH 7.09, bicarb 13.2 mmol/L, glucose 509 mg/dL, lactate 9.6, beta-hydroxybutyrate 1.15 mmol/L. Patient was diagnosed and treated for DKA. Patient had an echocardiogram which showed new HFrEF. There was initial hesitation to restart patient on home Empagliflozin due to recent development of DKA. Literature review showed cases of DKA associated with COVID-19 infection. Etiology of DKA remained unclear. Ultimately, it was decided to restart patient on home Empagliflozin for management of diabetes and HFrEF. Conclusion: An abundance of evidence support the benefits of SGLT-2 inhibitors for patients with and without type 2 diabetes mellitus. (4) It is important to consider other causes of DKA for patients who develop DKA on SGLT-2 Inhibitors. Furthermore, additional research into endocrinopathies related to COVID-19 infections should be considered.

Maternal vascular indices and hemodynamic parameters at 36 weeks' gestation in gestational and pre-existing diabetes mellitus.

To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by gestational diabetes mellitus (GDM), those with pre-existing diabetes mellitus (DM) and those without GDM or pre-existing DM. This was a prospective observational study in women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, and measurement of vascular indices and hemodynamic parameters using a non-invasive operator-independent device. These included carotid-to-femoral pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. The values in the GDM and pre-existing DM groups were compared to those in the unaffected group. We examined 6746 women, of whom 396 were excluded because they had chronic hypertension or developed pre-eclampsia or gestational hypertension. The study population of 6350 pregnancies contained 99 (1.6%) with pre-existing Type-I or Type-II DM and 617 (9.7%) that developed GDM, including 261 (42.3%) that were treated with diet alone, 239 (38.7%) treated with metformin alone and 117 (19.0%) treated with insulin with or without metformin. Among women with GDM and those with pre-existing DM, compared to those without GDM or pre-existing DM, there was a higher median cardiac output and heart rate, central systolic and diastolic blood pressure and pulse-wave velocity, but there was no significant difference in stroke volume or total peripheral resistance. There were no significant differences within the GDM group according to treatment type, except for higher heart rate in women treated with metformin alone compared to the group treated with diet alone. Women with GDM and those with pre-existing DM have evidence of early vascular disease in the third trimester, and this may contribute to their increased long-term cardiovascular risk. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.