Diagnosis Of Diabetes Research Articles

12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection

Abstract Disclosure: R. Pratibha: None. T.R. Langner: None. Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient. Presentation: 6/3/2024

12395 Continuous Glucose Monitoring In Pseudohypoparathyroidism Type 1a

Abstract Disclosure: J. Tamaroff: None. A.E. Lee: None. A.H. Shoemaker: None. Background: Pseudohypoparathyroidism type 1A (PHP1A), due to heterozygous mutations in GNAS, is a rare disorder that leads to multi-hormone resistance, cognitive impairment, and early-onset obesity. Individuals with PHP1A have dysglycemia on oral glucose tolerance tests and increased rates of type 2 diabetes (T2DM). Individuals with rare diseases, like PHP1A, may travel significant distances for specialized clinical or research care. Wearable technology may alleviate barriers and provide useful information for clinical care or for use as potential biomarkers. The objective of this study is to evaluate glycemia in individuals with PHP1A and feasibility of utilizing continuous glucose monitors (CGMs) in this population. Methods: Observational study of individuals with PHP1A (3R01DK118407-03S1). CGMs (Dexcom Pro, Dexcom Inc, San Diego, CA) were placed on participants’ abdomens, typically by a family member, over secure-video call with study staff. CGMs collected data every 5 minutes for up to 10 days. Results: Seven participants (all female) with PHP1A without a diagnosis of diabetes had available data. Median age was 17 years (IQR: 14, 19; range: 8-23). Body mass index (BMI) categories (by percent of the 95th percentile for those under 18 years and BMI for adults) spanned from overweight to class 3 obesity. In terms of feasibility, 1 individual had to replace a CGM sensor due to an upcoming MRI and 1 individual had a “sensor failure” of unclear etiology. Both were able to place new CGMs. Individuals participated across 5 states in the United States. Median length of wear was 9.8 days (IQR 8.6, 9.9). Participants had a median average glucose of 104mg/dL (IQR 102, 111) and COV of 16% (15, 21). Percent of glucose > 140mg/dL was 5.0% (IQR: 1.8, 10.9; range:1.2-19.4%). One individual had 3.2% of glucose values ≥ 200mg/dL despite a normal hemoglobin A1c (HbA1c) level (5.5%). This level of hyperglycemia is qualitatively higher than published CGM data in healthy individuals. One study found individuals (6-24 years of age) had median percent of glucose values over 140mg/dL ranging from 1.2 to 2.4% with IQR values ranging from 0.3 to 4.4%, based on age categories.1Conclusions: In females with PHP1A, with overweight or obesity, CGM placement at home is a feasible way to collect real-world data. Participants with rare diseases often must travel for clinical and research care and CGMs may provide insight into glycemia without requiring an in-person visit. This “real-world” data mirrors research data reporting glycemia with normal HbA1c levels. The rate of hyperglycemia is higher than expected in some individuals with PHP1A though more data is needed. Ongoing studies will evaluate matched control participants and assess drivers of glycemia including inactivity and decreased sleep duration, as measured by actigraphy.

6889 Potential Impact of Parental Origin of Inheritance in Presentation of Familial Partial Lipodystrophy

Abstract Disclosure: D. Gilio: None. M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. Speaker; Self; Amryt. O. Besci: None. M. Celik Guler: None. A. Neidert: None. I. Yildirim: None. B. Akinci: Advisory Board Member; Self; Amryt. Consulting Fee; Self; Regeneron Pharmaceuticals, Alnylam Pharmaceuticals, Amryt, AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis Pharmaceuticals, Novo Nordisk, Sanofi-Aventis, Servier, Third Rock Ventures. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Fractyl, Ionis Pharmaceuticals Inc., GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Background: Familial partial lipodystrophy Type 2 (FPLD2) caused by autosomal dominant LMNA variants is characterized by partial loss of subcutaneous adipose tissue in the limbs, trunk, and gluteal region with accumulation in other parts of the body, such as the face and neck. It is usually associated with different degrees of insulin resistance and hypertriglyceridemia and body composition patterns. We wanted to know the contributing factors for the different metabolic abnormalities and body composition presentations of FPLD2. We hypothesized that parental inheritance line may be a contributory factor to the expression of the metabolic phenotype and body composition characteristics. Methods: We retrospectively collected clinical data of 77 FPLD2 cases from the Divisions of Metabolism and Endocrinology of 3 different sites: the University of Michigan, the University of São Paulo and The Turkish Lipodystrophy Study Group (TuLip). We further selected 53 published cases curated from 15 studies in the literature. For inclusion of the studies, we used web search tools including PubMed, OMIM and Google Scholar. Only patients where we could assess the genetic inheritance were included in this study. Data collected included demographic information, medical history and laboratory results. Results: 79 patients inherited the LMNA variant from the mother (Group 1; 18 males and 61 females), and 51 patients inherited it from the father (Group 2; 14 males and 37 females). The median age at lipodystrophy diagnosis was lower in Group 1 than in Group 2. Diabetes was reported in more than half of the groups; however, the prevalence rates were not significantly different. The mean age (± SEM) at first diagnosis of diabetes was 30 ± 15 years in Group 1 and 32 ± 11 years in Group 2; the microvascular complications were present in 8 patients with diabetes in Group 1 (36.3%) and in 5 patients in Group 2 (23.8%). Both groups' mean triglycerides levels were >150 mg/dL, with a trend of higher triglycerides in Group 2 than in Group 1. Episodes of acute pancreatitis were identified in 9 patients (19.5%) of Group 1 and 10 patients (31.2%) of Group 2; however, patients in Group 1 showed 1.7 episodes of pancreatitis per person while Group 2 showed 8.1 episodes per person on average. The fatty liver disease was the most common liver abnormality identified and it seemed to be more frequent in Group 2 than in Group 1. There was no difference between the two groups in relation to the body mass index (BMI) and the ratio of percent fat mass of the trunk to percent fat mass of the legs (FMR); however, the DEXA (dual x-ray absorptiometry) showed a higher total fat mass in Group 1 compared to Group 2 (22.2 versus 17.3 Kg, p=0.040) in the presence of comparable total lean mass. Conclusion: Our data suggest that there is a difference in body fat mass according to the genetic inheritance, however the metabolic impact is not completely clear and require more detailed analysis. Presentation: 6/1/2024

12441 Factors Affecting The Evaluation Of Adrenal Incidentalomas

Abstract Disclosure: A. Poloju: None. S.K. Pabich: None. S. Syed: None. A. Krueger: None. A. Chiu: None. Introduction: Adrenal incidentalomas are increasingly being detected, owing to the increasing number of high-resolution radiologic studies performed. While most of the nodules are non-functional, 10-15% are hormonally active and hence merit workup. We assessed the rates of, and factors associated with appropriate workup of these nodules. Methods: A retrospective analysis of CT chest and abdominal scans between Jan 1, 2021, and June 1, 2022, in adults ≥18 years at a single tertiary care center was performed. Reports were screened with key phrases to identify adrenal nodules. A chart review was conducted to confirm the reported nodule, obtain demographic data, obtain data on co-morbid conditions, and evaluate for biochemical and radiologic workup. Exclusion criteria included: patients deceased at the time of our review, previously diagnosed nodules, sub-centimeter lesions, and adrenal hemorrhage. Patients were categorized as being from high or low disadvantaged neighborhoods based on their Area Deprivation Index (ADI) score. ADI above the 50th percentile was categorized as more disadvantaged. Charleston Comorbidity Index (CCI), a 10-year survival predictor based on the presence of common diseases was abstracted. Patients with any biochemical workup were compared to patients with no workup. Bivariate analysis was performed using chi-squared and Student’s t-test analysis. A multivariate logistic regression was performed to evaluate factors associated with biochemical workup. Results: A total of 533 records were reviewed. After applying the above exclusion criteria, a total of 245 patients were included in our analysis. Baseline characteristics included: 58.7% female and 41.2% male. 67.3% had hypertension diagnosis, 22% had sleep apnea diagnosis, and 30.6% had diabetes diagnosis. 86% were White, 5.7% Black, 3.2% Hispanic, 3.2% Asian, and 1.6% Other. 71% of the patients had no biochemical workup, 18% had partial workup, and 11% had full workup. Factors associated with having either partial or full workup compared to no workup included female sex (OR 2.33, CI 1.23-4.41), internal medicine/family medicine provider ordering the scan compared to Emergency Department providers (OR 3.84, CI 1.61-9.14), and ADI scores below the 50th percentile (OR 1.98, CI 1.04-3.78). There was no statistically significant difference based on age, race, ethnicity, and CCI. There was no significant difference in the workup for hypercortisolism based on the presence of co-morbid conditions like diabetes, sleep apnea, and overweight/obesity. Conclusions: In our study population, the rates of guideline-based biochemical workup of adrenal incidentalomas were very low at 11%. Factors associated with having at least partial biochemical workup included less socioeconomic disadvantage, female sex, and studies ordered by primary care providers. Presentation: 6/3/2024

7277 Diabetic Ketoacidosis As The First Manifestation Of Ectopic Cushing’s Syndrome

Abstract Disclosure: R.S. Medeiros: None. Introduction: Ectopic Cushing’s Syndrome (ECS) represents 10-20% of all ACTH-dependent CS, and the majority of cases arise from lung carcinoids. These indolent lesions usually evolve clinically over 6-24 months, whereas carcinomas are associated with faster onset of ECS. Diabetic Ketoacidosis (DKA) as a presenting manifestation of Cushing’s Syndrome (CS) is very rare, with the few cases published to date related to Cushing’s disease. Clinical Case: A 42-year-old woman was admitted in the emergency room with DKA and COVID-19. During stabilization, florid CS was clinically suspected. She reported a 6-month history of secondary amenorrhea, lack of concentration and memory, easy bruising, proximal myopathy with frequent falls evolving to daily life dependency from relatives. She also reported a 2-month diagnosis of dyslipidemia, Diabetes and hypertension, and a diagnosis of atypical pneumonia 6 months ago. Physical exam showed typical cushingoid appearance, especially for marked limb sarcopenia and proximal myopathy. An overnight dexamethasone suppression test (morning cortisol: 25.7 ug/dL), 24h urinary free cortisol (UFC; 1072.5 ug/dL; reference: <176) and serum cortisol at 23h00 (25.5 ug/dL) confirmed CS. ACTH-dependent CS was diagnosed. She had non-suppressible serum cortisol in high dose dexamethasone suppression test, and CRH stimulation test was suggestive of Cushing’s disease only by a 20% rise of cortisol at 30 minutes. Pituitary MRI was normal. Inferior Petrosal Sinus sampling was postponed for several months due to healthcare strikes. The patient started 750 mg of metyrapone in three divided doses but rapidly decreased the dose and stopped it due to clinical resolution of CS, a dramatic improvement of all glucocorticoid-related comorbidities leading to discontinuation of statin, insulin, main oral anti-hyperglycemic and antihypertensive medications, and normal midnight salivary cortisol and 24h UFC. She remained in this eucortisolemic state for 12 months. Thoracic CT scan revealed thymic hyperplasia and a 25x15 mm well-defined nodule in the lingula. A 68Ga-DOTANOC PET/CT showed a single uptake in the same lung region. The patient underwent lingulectomy plus excisional biopsy of interlobar lymph nodes, and pathology revealed a low-grade neuroendocrine tumor (Ki67<2%, <2 mitosis) without involved lymph nodes. The patient is weaning off from physiologic doses of hydrocortisone. Conclusion: DKA can rarely be the presenting manifestation of severe CS, including ECS. Clinicians should suspect on this etiology of DKA based on clinical signs and cumulative morbidity not typical of a young patient. This hint would lead to the expedite implementation of targeted therapies for initial stabilization of the CS patient, and the timely institution of a proper diagnostic approach and definitive treatment of this challenging patients. Presentation: 6/2/2024

7522 Effects of Trikafta On Bone Mineral Density And Body Composition In Patients With Cystic Fibrosis

Abstract Disclosure: N. Mon: None. S.S. Krishnasamy: None. G. Bakeerathan: None. L. Healy: None. E. Favier: None. S. Foushee: None. Background: Cystic fibrosis related bone disease (CFBD) is a common complication of adult Cystic fibrosis (CF) patients due to calcium, vitamin D and K malabsorption from exocrine pancreatic insufficiency, increased inflammatory cytokines, glucocorticoid therapy, delayed puberty, physical inactivity, and hypogonadism. Newer CF transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (Trikafta) has proven benefit in pulmonary and nutritional outcomes. There is limited data on effects of Trikafta on bone health and body composition. The aim is to examine the effects of Trikafta on bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN), and body composition in terms of fat free mass index (FFMI) and fat mass index (FMI) in our CF patients. Method: We conducted a cross sectional and retrospective review of 38 adults with CF (Ages 20-59, 28 males and 10 females) in our CF clinic. Body Mass Index (BMI), Body composition measured by bioelectric impedance analysis, BMD of LS and FN by Dual-energy X-ray absorptiometry, Vitamin D level, and forced expiratory volume in one second (FEV1 % predicted) in patients taking Trikafta were analyzed and compared with control CF group who were not on Trikafta. Results: 38 subjects on Trikafta, aged 33.29 ± 10.36 years with FEV1 % predicted 65.11± 28.14% were studied. Serum 25-hydroxyvitamin D level was 35.92 ± 18.52 ng/dL. Of the 38 study patients, 23 (60.53%) had a diagnosis of CF related diabetes (CFRD). Among the Trikafta cohort, 18 (50%) had low BMD with Z-scores ≤ -2.0 and 7 (19.44%) of them had Z score ≤ -1.0 and > -2.0. Compared with the control group, LS BMD 0.93 ± 0.16 g/cm2 and FN BMD 0.73± 0.13g/cm2 (p >0.05) were not improved significantly. BMI of study population 23.09 ± 4.21 kg/m2 (p <0.05) and FMI 6.11 ± 4.25 kg/m2 (p <0.05) increased significantly; however, there was a decrease in FFMI 9.60 ± 1.44 kg/m2 (p <0.05). Conclusion: Treatment with Trikafta in CF patients was associated with increases in BMI and fat mass index but decrease in fat free mass index. There was no statistically significant difference in BMD at LS and FN in our study cohort. This study has limitations in terms of gender differences within the study cohort, duration of Trikafta use in relation to bone mass, and also extent of glucocorticoid use among the study subjects. Larger prospective clinical trials are needed to study efficacy of Trikafta on CFBD. Presentation: 6/3/2024

8772 Impact of Stress Hyperglycemia on Individuals Hospitalized for COVID-19 with and without Diabetes

Abstract Disclosure: E. Burguera-Couce: None. V.O. Cheng: None. J.G. Monteiro: None. G. Gopalakrishnan: None. Background: Stress hyperglycemia (SH), the physiologic increase in blood glucose during severe illness, has been linked with poor outcomes in certain disease states1. Hyperglycemia in the setting of diabetes (DM) has been well established as a predictor of poor outcomes in Coronavirus disease 2019 (COVID-19) infection2-4. The impact of SH on health outcomes for individuals without DM (NoDM) hospitalized with COVID-19 infection is less clear with studies reporting variable outcomes in this population4-6. Objective: To evaluate the impact of SH on health outcomes among hospitalized individuals with COVID-19Methods: Data from 1001 individuals with SH (defined as ≥ 2 instances of BG above 180 mg/dL) admitted in Rhode Island with COVID-19 infection during the first-wave (March 1-June 30, 2020) and second-wave (July 1, 2020-February 28, 2021) was analyzed. Multivariate logistic regression was conducted to compare DM status for length of stay (LOS), ICU admission, mechanical ventilation (MV) and in-hospital mortality, and was adjusted for age, race/ethnicity, gender, insurance, and wave. Model investigating risk factors associated with poor outcomes (ICU admission, MV or in-hospital mortality) in hospitalized individuals with SH was additionally adjusted to include BMI, Chronic kidney disease (CKD), hypertension (HTN), pulmonary disease, and cardiovascular diseases. Results: 17.0% (170) of the cohort had NoDM. Average age (67.6±13.9), gender (57.1% male) and race/ethnicity (Caucasian/White 48.9%, Hispanic 28.0%, Black 13.2% and Other 10.0%) noted in the overall cohort. Individuals with NoDM were more likely to be Caucasian/White (57.7 vs 47.1%, p-value=0.0122), and more likely to require LOS ≥1-week (OR 2.32[1.57-3.44]), ICU admission (2.26[1.60-3.20]) and MV (3.39[2.35-4.89]). NoDM was also associated with higher in-hospital mortality (3.44[2.39-4.96]). The risk of poor outcomes was significantly higher in NoDM compared to DM (ICU admission 47.7 vs 28.6%, MV 45.3 vs 20.1%, Mortality 41.8 vs. 18.2%). In multivariate analysis, Caucasians/Whites (0.50[0.29-0.87]) were less likely to have poor outcomes than the other races. NoDM (3.55[2.40-5.25]), male gender (1.57[1.16-2.13]), CKD stage 5 (1.94[1.40-2.68]), and admission during the first-wave (2.64[1.89-3.70]) were identified as independent risk factors for poor outcomes in SH associated with COVID-19. Conclusion: Our study showed that individuals without a known diagnosis of diabetes hospitalized with COVID-19 who experienced SH during their hospital course had worse outcomes when compared to individuals with diabetes and hyperglycemia. NoDM, male gender, nonwhite race/ethnicity, CKD stage 5 and admission during the first wave were identified as independent risk factors for poor outcomes in COVID-19 hospitalizations with hyperglycemia. Presentation: 6/1/2024

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 < 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 <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

Biosensor development for diabetes diagnosis: Determining relevant miRNA using a newly developed N-annulated perylene fluorescent dye

MicroRNAs (miRNAs) have emerged as essential biomarkers for disease diagnosis, and several techniques are available to determine type 2 diabetes (T2D) relevant miRNAs. However, detecting circulating miRNAs can be challenging due to their small size, low abundance, and high sequence similarity, often requiring sensitive detection approaches combined with additional amplification processes. Laser-induced fluorescence (LIF) is a classic analytical method suitable for sensitively detecting trace amounts of nucleotide acid. Duplex-specific nuclease (DSN)-mediated amplification recently gained attention due to its catalytic activity based on target recycling, demonstrating a promising approach for miRNA amplification. This work developed a novel N-annulated perylene fluorescent dye to create a biosensor to analyze the miRNA (miR-223) relevant to T2D. The amine-reactive fluorescent dye assists the amidation reaction for nucleotide labeling, giving the oligonucleotide probe a high fluorescence quantum yield and sufficient water solubility. By combining the locked nucleic acid (LNA) modified oligonucleotide fluorescent probe to enhance the stability of LNA/RNA hybrids, thereby improving the DSN-mediated target miR-223 recycling for signal amplification, the proposed biosensor can highly selectively determine miR-223 with a limit of detection (LOD, S/N = 3) of 9.5 pM. When applied to real-world samples, the biosensor demonstrated its potential to distinguish between T2D patients and healthy controls.

12548 Mammary De Novo Lipogenesis During A Hyperinsulinemic-euglycemic Clamp

Abstract Disclosure: T.M. Fordham: None. M. Ramos-Roman: None. E.J. Parks: Consulting Fee; Self; Simply Good Foods. Stock Owner; Self; Sagimet Biosciences. Other; Self; Past President of The Obesity Society. Introduction: The mammary produces large amounts of medium-chain saturated fatty acids. Long-chain saturated fatty acids found in human milk primarily derive from the maternal diet or from the mobilization of stored triglycerides. Previous studies have established the importance of insulin in stimulating mammary differentiation, milk synthesis, and lipogenesis. However, no studies have assessed how changes in insulin concentrations alter human mammary de novo lipogenesis (DNL) nor what effect gestational diabetes may have on insulin’s relationship to lipogenesis during lactation. Through the utilization of stable isotopes and the hyperinsulinemic-euglycemic clamp technique, we tested the differing concentrations of insulin to stimulate mammary DNL. Methods: Eight women (32±4 yrs) with (GDM, n=4) or without (NGT, n=4) recent gestational diabetes and overweight or obesity (28.2±2.9 kg/m2) were recruited to participate in this study at 6 weeks postpartum. The night before the study, participants orally consumed 3 doses of 70% deuterated water to label newly made fatty acids. Participants arrived in the morning for IV placement and immediately pumped milk contralaterally for 20 minutes. Milk was pumped two hours later, again at the end of step 1 of the clamp (10 mU/m2/min) and once more after step 2 (either 20 or 40 mU/m2/min). Milk triglycerides were extracted and prepared for analysis by gas chromatography-mass spectrometry. The incorporation of deuterium into milk triglyceride-fatty acids was the primary outcome. Results: Fasting insulin concentrations were significantly associated with newly-made 16:0 in milk triglycerides (r=0.85, P=0.01). Of all measured triglyceride 16:0, 1.6±1.0% were made de novo. This percentage increased 1.5-fold by the end of step 2 of the clamp (P=0.06). Fasting milk DNL 14:0 was 12.3±4.8% which was significantly greater than DNL 16:0 (P<0.01). DNL 14:0 increased 1.7-fold during step 2 (P=0.04). For both milk triglyceride 12:0 and 14:0 derived from DNL, a significant effect across clamp-stage was observed (P<0.001 for both), but not an effect of group (P=0.12, P=0.11, respectively). Bonferroni posthoc analyses revealed that the insulin effect was significant for both groups for 12:0 (GDM, P=0.02; NGT, P <0.01) and 14:0 (GDM, P<0.01; NGT, P=0.01). Interpretation: The present study is the first to assess the acute effect of a hyperinsulinemic-euglycemic clamp on the synthesis of newly-made triglyceride fatty acids in human milk. These results suggest that the increases in mammary DNL may be fatty acid specific, favoring that of lauric and myristic acids, but not longer chain fatty acids like palmitate. Mammary lipogenesis was stimulated by insulin in all subjects regardless of recent gestational diabetes diagnosis. The role mammary DNL plays in overall milk fat content deserves further investigation. Presentation: 6/3/2024

8527 The Role Of SGLT2 Inhibitors In Outcomes After LVAD Implantation

Abstract Disclosure: L. Carafone: None. S. McNitt: None. I. Goldenberg: None. J. Alexis: None. Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important medications in the treatment of diabetes mellitus, however they offer several additional benefits, including improved heart failure outcomes in patients with and without diabetes. The role of SGLT2i in heart failure outcomes for patients who receive left ventricular assist device (LVAD) implantation is not known. Right heart failure, in particular, is a frequent complication and major contributor to morbidity and mortality after LVAD implantation. SGLT2i have been increasingly used in patients who undergo LVAD implantation, however it is unknown whether right heart failure events post-LVAD implantation are meaningfully impacted by SGLT2i use. Objective: The purpose of this study was to evaluate the role of SGLT2i in outcomes after LVAD implantation. The primary endpoint was the onset of a first right heart failure (RHF) event following LVAD implantation. Secondary endpoints included recurrent RHF, first and recurrent hospitalization for RHF, and all-cause mortality. Methods: The study population comprised all consecutive patients who received a HeartMate 3 LVAD implantation at the medical center from 9/25/2015 through 9/1/2023 who are included in the institution’s LVAD Database. Both patients who received and did not receive a SGLT2i were included. A time-dependent model was used to evaluate treatment with SGLT2i as a time-dependent variable. Multivariable propensity score matching was used in the analysis of outcomes. Results: A total of 399 patients were analyzed, which included 175 patients who received SGLT2i and 224 patients who did not receive SGLT2i. Cox proportional hazards regression, employing propensity score stratification, demonstrated SGLT2i use was not associated with a statistical significant effect in the primary endpoint of a first occurrence of RHF event (HR = 1.41, 95% CI = 0.77-2.61, p = 0.268). Similarly, SGLT2i use was not associated with secondary outcomes, including recurrent RHF (HR = 1.28, 95% CI = 0.76-2.16, p = 0.360), first or recurrent hospitalization for RHF (HR = 0.38, 95% CI = 0.11-1.33, p = 0.131 and HR = 0.63, 95% CI = 0.27-1.46, p = 0.285, respectively), and all-cause mortality (HR = 0.90, 95% CI = 0.44-1.83, p = 0.771). Presence or absence of diabetes diagnosis did not significantly impact outcomes. Conclusions: The observational data in this study suggest no incremental benefit of SGLT2i for right heart failure or mortality outcomes after LVAD implantation, however large-scale prospective studies are needed to evaluate the role of SGLT2i in this setting. Further elucidating the role of these medications in LVAD outcomes will be critical in clinical decision-making regarding use of SGLT2i in this population. Presentation: 6/1/2024

12548 Mammary De Novo Lipogenesis During A Hyperinsulinemic-euglycemic Clamp

Abstract Disclosure: T.M. Fordham: None. M. Ramos-Roman: None. E.J. Parks: Consulting Fee; Self; Simply Good Foods. Stock Owner; Self; Sagimet Biosciences. Other; Self; Past President of The Obesity Society. Introduction: The mammary produces large amounts of medium-chain saturated fatty acids. Long-chain saturated fatty acids found in human milk primarily derive from the maternal diet or from the mobilization of stored triglycerides. Previous studies have established the importance of insulin in stimulating mammary differentiation, milk synthesis, and lipogenesis. However, no studies have assessed how changes in insulin concentrations alter human mammary de novo lipogenesis (DNL) nor what effect gestational diabetes may have on insulin’s relationship to lipogenesis during lactation. Through the utilization of stable isotopes and the hyperinsulinemic-euglycemic clamp technique, we tested the differing concentrations of insulin to stimulate mammary DNL. Methods: Eight women (32±4 yrs) with (GDM, n=4) or without (NGT, n=4) recent gestational diabetes and overweight or obesity (28.2±2.9 kg/m2) were recruited to participate in this study at 6 weeks postpartum. The night before the study, participants orally consumed 3 doses of 70% deuterated water to label newly made fatty acids. Participants arrived in the morning for IV placement and immediately pumped milk contralaterally for 20 minutes. Milk was pumped two hours later, again at the end of step 1 of the clamp (10 mU/m2/min) and once more after step 2 (either 20 or 40 mU/m2/min). Milk triglycerides were extracted and prepared for analysis by gas chromatography-mass spectrometry. The incorporation of deuterium into milk triglyceride-fatty acids was the primary outcome. Results: Fasting insulin concentrations were significantly associated with newly-made 16:0 in milk triglycerides (r=0.85, P=0.01). Of all measured triglyceride 16:0, 1.6±1.0% were made de novo. This percentage increased 1.5-fold by the end of step 2 of the clamp (P=0.06). Fasting milk DNL 14:0 was 12.3±4.8% which was significantly greater than DNL 16:0 (P<0.01). DNL 14:0 increased 1.7-fold during step 2 (P=0.04). For both milk triglyceride 12:0 and 14:0 derived from DNL, a significant effect across clamp-stage was observed (P<0.001 for both), but not an effect of group (P=0.12, P=0.11, respectively). Bonferroni posthoc analyses revealed that the insulin effect was significant for both groups for 12:0 (GDM, P=0.02; NGT, P <0.01) and 14:0 (GDM, P<0.01; NGT, P=0.01). Interpretation: The present study is the first to assess the acute effect of a hyperinsulinemic-euglycemic clamp on the synthesis of newly-made triglyceride fatty acids in human milk. These results suggest that the increases in mammary DNL may be fatty acid specific, favoring that of lauric and myristic acids, but not longer chain fatty acids like palmitate. Mammary lipogenesis was stimulated by insulin in all subjects regardless of recent gestational diabetes diagnosis. The role mammary DNL plays in overall milk fat content deserves further investigation. Presentation: 6/3/2024

A-035 Profiling of circulating-microRNAs' signatures in Pre-diabetic versus Diabetic patients

Abstract Background MicroRNAs (miRs) are small non-coding RNAs involved in the process of gene regulation, and hence affect various diseases including metabolic pathways in diabetes. Given their key roles, they are promising candidates as potential biomarkers or better understanding of disease etiology. In this study, our aim is to identify miRs signatures of plasma circulating-miRs related to glycemic control, vitamin D deficiency and platelet activation in diabetic, pre-diabetic versus non-diabetic patients. Methods Plasma samples were collected from 24 patients (both sexes) in total (eight non-diabetic (ND) control, twelve diabetic (DM), and four pre-diabetic (PD)), classified based on their glycemic control (HbA1c levels). miRs were extracted using the miRNeasy Serum/Plasma Advanced kit of Qiagen, run and analyzed on Next Generation Sequencing (NGS). Results Differential expression analysis revealed miRs expression variations between diabetic to pre-diabetic and non-diabetic groups. Expression levels of 131 miRs varied significantly between DM to ND group (92 down- and 39 up- regulated), and 141 miRs in PD compared to ND (97 down- and 39 up- regulated). Although DM and PD had similar differential expression, three miRs (has-miR4776-5p, -6778-3p, and 5002-3p) were over-expressed in PD with very low p-value. Differential expression comparisons accounting sex were performed showing significant differences between males to females that will be presented here. Conclusions Our findings supports the important involvement of circulating miRs in the regulation of glucose homeostasis and pathogenesis of diabetes.Further investigation of candidate miRs could identify promising new biomarkers for the early diagnosis and prevention of Diabetes and related health complications.

Male Gender Expressivity and Diagnosis and Treatment of Cardiovascular Disease Risks in Men

Male gender expressivity (MGE), which reflects prevalent sociocultural pressures to convey masculinity, has been associated with health. Yet, little is known about associations of MGE with the diagnosis and treatment of modifiable cardiovascular disease (CVD) risks. To investigate associations of MGE with modifiable CVD risk diagnoses and treatment in men. This population-based cohort study included data from waves I (1994-1995), IV (2008-2009), and V (2016-2018) of the US National Longitudinal Study of Adolescent to Adult Health (Add Health). Participants were male adolescents (age 12-18 years) followed up longitudinally through younger adulthood (age 24-32 years) and adulthood (age 32-42 years). Data were analyzed from January 5, 2023, to August 28, 2024. Male gender expressivity was quantified in adolescence and younger adulthood using an empirically-derived and validated measurement technique that incorporates participants' responses to existing Add Health survey items to capture how similarly participants behave to same-gendered peers. Outcomes included self-reported diagnoses of CVD risk conditions (hypertension, diabetes, or hyperlipidemia) in adult men with elevated blood pressure, hemoglobin A1c, or non-high-density lipoprotein cholesterol levels, and self-reported treatment with antihypertensive, hypoglycemic, or lipid-lowering medications in adults reporting hypertension, diabetes, or hyperlipidemia. Multivariable regression was used to examine associations of adolescent and younger adult MGE with adult CVD risk diagnoses and treatment, adjusting for sociodemographic covariates. Among 4230 eligible male participants, most were non-Hispanic White (2711 [64%]) and privately insured (3338 [80%]). Their mean (SD) age was 16.14 (1.81) years in adolescence, 29.02 (1.84) years in younger adulthood, and 38.10 (1.95) years in adulthood. Compared with participants whose younger adult MGE was below average, those with higher younger adult MGE were overall less likely to report hypertension (22% vs 26%; P < .001), diabetes (5% vs 8%; P < .001), and hyperlipidemia (19% vs 24%; P < .001) diagnoses and diabetes treatment (3% vs 5%; P = .02) as adults. In multivariable models, every SD increase in adolescent MGE was associated with lower probabilities of adult hypertension treatment (MGE,-0.11; 95% CI, -0.16 to -0.6) and diabetes diagnoses (MGE, -0.15; 95% CI, -0.27 to -0.03). Higher younger adult MGE was associated with lower probabilities of adult hypertension diagnoses (MGE, -0.04; 95% CI, -0.07 to -0.01), hypertension treatment (MGE, -0.07; 95% CI, -0.13 to -0.01), and diabetes treatment (MGE, -0.10; 95% CI, -0.20 to -0.01). Adolescent and younger adult MGE outcomes were not associated with other adult CVD outcomes. In this cohort study of US males, higher adolescent and younger adult MGE was associated with lower adult hypertension and diabetes diagnoses and treatment. These findings suggest that males with high MGE may bear distinctive risks and correspondingly benefit from tailored public health efforts to prevent downstream CVD.

Comparison of the Volumetric Parameters of Platelets in Diabetic Children with and without Diabetic Ketoacidosis: A Case-Control Study in the North of Iran

Background: This study aimed to determine the volumetric parameters of platelets including MPV (Mean Platelet Volume) and PDW (Platelet Distribution Width) in diabetic children with and without diabetic ketoacidosis (DKA) and to evaluate their relationship with the severity of DKA. Materials and Methods: A case-control study was conducted on 112 children with type 1 diabetes mellitus (T1DM), with and without DKA, who referred to Amirkola Children's Hospital, Iran, in 2016-2021. Of them, 43 were boys, and 69 were girls. The diagnosis of diabetes was based on clinical symptoms and diagnostic criteria, and DKA was diagnosed through the analysis of arterial blood gas. The patients’ MPV and PDW were also evaluated, and the P values less than 0.05 were considered significant. Results: Out of 112 children with diabetes (with the mean age of 8.71 ± 3.22 years), 56 persons had DKA. In terms of DKA severity, 17 patients (30.4%) had mild, 29 (51.8%) had moderate, and 10 (17.8%) had severe DKA. The children with DKA had the mean blood glucose of 490.98±46.11mg/dL, MPV of 10.02± 1.19fl), and PDW of 13.07± 1.18flwere significantly higher (P&lt;0.001). It was found that, an increase in the severity of DKA would raise the mean MPV (P = 0.006) and PDW(P&lt;0.001) significantly. Conclusion: Based on the results of this study, as the severity of DKA increases in diabetic children, the mean levels of MPV and PDW increase significantly. Therefore, it is suggested that MPV and PDW be used to predict the severity of DKA in diabetic children.

Heterogeneous Association Between E-Cigarette Use and Diabetes Prevalence Among U.S. Adults

IntroductionE-cigarette use has increased among US adults. While the association between traditional cigarette smoking and the diabetes/prediabetes prevalence is well established, the relationship between e-cigarette use and these conditions remains unclear. This study examines the association between different types of cigarette use (including e-cigarettes alone, combustible cigarettes alone, and dual use) and the prevalence of prediabetes and diabetes among US adults. MethodsWe analyzed 1,285,783 observations from the 2020-2022 Behavioral Risk Factor Surveillance System surveys. Self-reported prediabetes and diabetes diagnoses were outcomes of interest. Propensity score matching with one-to-one nearest-neighbor matching was used to create balanced groups of smokers and non-smokers. Multivariable logistic regressions examined associations between self-reported smoking status and outcomes. We also conducted subgroup analyses to assess potential variations in these associations. Analyses were performed in September-December 2023. ResultsAfter propensity score matching and adjusting for covariates, sole e-cigarette users (adjusted odds ratio [AOR], 1.07; 95% CI, 1.03-1.11) and dual users (AOR, 1.28; 95% CI, 1.23-1.33) had higher odds of prediabetes diagnosis compared with never users. Sole e-cigarette use was not associated with diabetes risk, but dual users showed higher odds for diabetes diagnosis (AOR, 1.09; 95% CI, 1.06-1.11) versus never users. E-cigarette use was associated with varying odds of prediabetes and diabetes across different demographic groups. ConclusionsThis cross-sectional analysis found that e-cigarette use is associated with higher odds of prediabetes, with dual use potentially linked to increased odds of both prediabetes and diabetes. However, due to study limitations, including its cross-sectional design, self-reported data, and unmeasured confounders, these findings should be interpreted cautiously. As causal relationships and temporal sequences cannot be established, large prospective studies are needed to explore the metabolic health implications of emerging tobacco product use.

Protocolo diagnóstico y terapéutico de la diabetes en el embarazo

This clinical protocol addresses the diagnosis and treatment of diabetes during pregnancy, distinguishing between pregestational diabetes and gestational diabetes (GD). GD occurs when pancreatic beta cell function is insufficient to overcome the inherent insulin resistance of pregnancy. Universal screening is recommended between 24–28 weeks of gestation using two strategies: a one-step strategy (75g of glucose) or a two-step strategy (50g of glucose followed by 100g if the first test is abnormal). Management includes capillary glucose monitoring, diet, and exercise as well as insulin treatment if necessary. Patients should be screened for metabolic abnormalities 4–12 weeks after delivery.

Diabetic Retinopathy Diagnosis based on Convolutional Neural Network in the Russian Population: A Multicenter Prospective Study.

Diabetic retinopathy is the most common complication of diabetes mellitus and is one of the leading causes of vision impairment globally, which is also relevant for the Russian Federation. To evaluate the diagnostic efficiency of a convolutional neural network trained for the detection of diabetic retinopathy and estimation of its severity in fundus images of the Russian population. In this cross-sectional multicenter study, the training data set was obtained from an open source and relabeled by a group of independent retina specialists; the sample size was 60,000 eyes. The test sample was recruited prospectively, 1186 fundus photographs of 593 patients were collected. The reference standard was the result of independent grading of the diabetic retinopathy stage by ophthalmologists. Sensitivity and specificity were 95.0% (95% CI; 90.8-96.4) and 96.8% (95% CI; 95.5- 99.0), respectively; positive predictive value - 98.8% (95% CI; 97.6-99.2); negative predictive value - 87.1% (95% CI, 83.4-96.5); accuracy - 95.9% (95% CI; 93.3-97.1); Kappa score - 0.887 (95% CI; 0.839-0.946); F1score - 0.909 (95% CI; 0.870-0.957); area under the ROC-curve - 95.9% (95% CI; 93.3-97.1). There was no statistically significant difference in diagnostic accuracy between the group with isolated diabetic retinopathy and those with hypertensive retinopathy as a concomitant diagnosis. The method for diagnosing DR presented in this article has shown its high accuracy, which is consistent with the existing world analogues, however, this method should prove its clinical efficiency in large multicenter multinational controlled randomized studies, in which the reference diagnostic method would be unified and less subjective than an ophthalmologist.

Telehealth service use and quality of care among US adults with diabetes: A cross-sectional study of the 2022 health information national trends survey.

To characterise telehealth use, reasons for using or not using telehealth and the factors associated with telehealth use among US adults with diabetes. A cross-sectional study. Data were sourced from the 2022 Health Information National Trends Survey. US adults aged 18 years or older with self-reported diagnosis of diabetes (both type 1 and type 2). Past 12-month utilisation of telehealth services, modality (eg, video, voice only), overall perception of quality of care, perceived trust in healthcare system and patient-centred communication score. In an analysis of 1116 US adults with diabetes, representing 33.6 million individuals, 48.1% reported telehealth use in the past year. Telehealth users were likely to be younger, women, with higher income, and urban dwellers. Older adults (≥65 years) were less likely to use telehealth compared with those aged 18-49 years (OR 0.43, 95% CI 0.20 to 0.90). Higher income and more frequent healthcare visits were predictors of telehealth usage, with no significant differences across race, education or location. Across respondents with telehealth usage, 39.3% reported having video-only, 35.0% having phone (voice)-only and 25.7% having both modalities. The main motivations included provider recommendation, convenience, COVID-19 avoidance and guidance on in-person care needs. Non-users cited preferences for in-person visits, privacy concerns and technology challenges. Patient-reported quality-of-care outcomes were comparable between telehealth users and non-users, with no significant differences observed by telehealth modality or area of residence (metro status). Around half of US adults with diabetes used telehealth services in the past year. Patient-reported care quality was similar for telehealth and in-person visits. However, further efforts are needed to address key barriers to telehealth adoption, including privacy concern, technology difficulties, and care coordination issues.

Study on the performance of MoS2/Au composites for non-enzymatic electrochemical glucose detection

Abstract Glucose concentration is considered an indicator for the diagnosis of diabetes, highlighting the importance of accurate glucose detection. Non-enzymatic electrochemical sensors have been extensively studied for glucose detection applications, with nanocomposites composed of molybdenum disulfide (MoS2) and gold nanoparticles (Au NPs) demonstrating high catalytic activity. In this study, a nanocomposite material composed of MoS2 and Au NPs (MoS2/Au) was synthesized and employed to construct a non-enzymatic electrochemical glucose biosensor. The detection limit of this sensor was explored, reaching as low as 1 mM. Additionally, compared to MoS2, the MoS2/Au nanocomposite exhibited a higher linear correlation coefficient and sensitivity, with a linear range of 1–25 mM and a sensitivity of 417.556 μA mM−1 cm−2. The sensor demonstrated excellent performance within the range of human blood glucose concentrations, showing potential for real-time monitoring and precise measurement of glucose levels. Furthermore, it exhibited good stability and reproducibility. These findings indicate the potential applications of MoS2/Au in biosensors and immunoassays.