bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU269 Ethnic Differences In Hepatic Insulin Clearance: A Cross-Sectional Study Comparing South Asians And Non-Hispanic Whites
Authors: Ramanathan Amrita L , Fan Hubert , Muniyappa Ranganath 
Published: October 2023

Abstract
Disclosure: A.L. Ramanathan: None. H. Fan: None. R. Muniyappa: None.
Background: Hepatic insulin clearance homeostaticallyregulates peripheral plasma insulin concentration. Reduced or impaired insulinclearance promotes insulin resistance and hyperinsulinemia, which increase therisk of type 2 diabetes mellitus (T2DM). South Asians (SA) have an elevatedrisk and prevalence of T2DM compared to other ethnic groups, but insulinclearance by ethnicity has not yet been investigated. Our cross-sectional studyexamines insulin clearance in SA compared to non-Hispanic whites (NHW) todetermine ethnic differences in hepatic extraction in both the fasting andpostprandial states. Methods: Thirty healthy SA (age: 39.1 ± 9.4; female: n=12;BMI: 27.7 ± 4.8 kg/m2) and thirty healthy NHW (age: 39.2 ± 11.4;female: n=12; BMI: 26.7 ± 5.3 kg/m2) underwent mixed meal tolerancetests (MMTT) to determine plasma glucose, insulin, and C-peptide levels. Wederived parameters of hepatic clearance using a C-peptide kinetics model, aninsulin secretion model, and an insulin kinetics three-compartmental model. Model parameters included distribution volume of insulin (Vp), control ofplasma glucose on hepatic extraction (aG), basal hepatic extraction levels(HEb), and total hepatic extraction levels (HEtot). Differences by ethnicity werecalculated using an unpaired t-test for parametric variables and a Mann-Whitneytest for nonparametric data. Results: Fasting glucose (93.7 ± 9.77 vs. 89.0 ± 6.96 mg/dL,p=0.06) and fasting insulin (13.30 ± 8.04 vs. 6.58 ± 6.61 mu/mL, p&lt;0.001)were higher in SA. Insulin area under the curve during MMTT was also elevatedin SA (12608 ± 6031 vs. 5892 ± 3533 min*mU/mL, p&lt;0.001). Calculated mean Vp(0.0365 ± 0.0133 vs. 0.0564 ± 0.0130 kg-1, p&lt;0.0001), mean aG(0.2001 ± 0.0409 vs. 0.2285 ± 0.0556 mmol-1, p=0.03), and basalhepatic extraction (54.9 ± 22.6 vs. 65.6 ± 18.8%, p=0.04) were lower in SA.Total hepatic extraction during MMTT was not different between SA and NHW(p=0.33). Conclusions: SA have reduced basal hepatic clearancecompared to NHW, although total extraction remained similar between the twogroups during MMTT. Further investigations are needed to derive accurateinsulin clearance parameters for ethnic groups with elevated T2DM risk.
Presentation: Thursday, June 15, 2023
THU272 Early Time Restricted Feeding As a Weight Neutral Approach To Improved Glycemic Variation
Authors: Nasserifar Shabnam , Bruno Joanne , Vanegas Sally , Popp Collin , Walker Jeanne M , Aleman Diaz Jose Orlando 
Published: October 2023

Abstract
Disclosure: S. Nasserifar: None. J. Bruno: None. S. Vanegas: None. C. Popp: None. J.M. Walker: None. J.O. Aleman Diaz: None.
Abstract: Early time-restricted feeding (eTRF) is a type of intermittent fasting that involves restricting caloric intake to the first 6-8 hours of the day. Various studies suggest that eTRF improves cardiometabolic health and glycemic variation. However, it is unclear whether these effects are a consequence of weight loss that frequently accompanies this dietary intervention or due to the metabolic effects of the feeding strategy itself. To address this, we conducted a randomized 7-day isocaloric crossover supervised feeding study comparing eTRF (80% of calories consumed before 1 pm) to a usual feeding pattern (UFP, 50% of calories consumed after 4 pm) among 10 participants with prediabetes and obesity in a metabolic ward. Participants were randomized 1:1 to eTRF or UFP for days 1-7, and then subsequently crossed over to the alternate arm on days 8-14. In order to determine the weight-independent effects of this intervention, food was provided to meet participants’ calculated caloric needs for weight maintenance. To assess glycemia, continuous glucose monitoring was utilized throughout the study period and OGTTs were performed at baseline, crossover point (day 7), and at the end of the study (day 14). Subjects’ weights were stable across the study duration. Compared to the control (UFP), eTRF resulted in decreased mean amplitude of glycemic excursion (MAGE) of 2.5 mmol/L ± 0.2 vs 2.9 mmol/L ± 0.3 (p&lt;0.05) and decreased time above range of 3.1 % ± 1.3 vs 6.7 % ± 1.7 (p= 0.02). Time in range was similar between the two groups (eTRF 75.4 % ± 4.7 vs UFP 74.9 % ± 4.8 (p=0.88)). There was no significant difference in AUC of OGTT between the study groups (eTRF 16391 ± 1595 vs UFP 1586 ± 1586). In conclusion, our study findings suggest that eTRF can improve glycemic variation and decrease time above range in a weight independent manner. Ongoing studies will elucidate the signaling and metabolomic implications of the observed glycemic improvement.
Presentation: Thursday, June 15, 2023
THU273 Sixteen Years Of Insulin Independence In A Patient With Type 1 Diabetes Mellitus Following Single-Donor Islet Cell Transplantation
Authors: Kachhadia Palak , Khan Shaza , Aldasouqi Saleh , Donley Christina , Abu Limon Ahmad 
Published: October 2023

Abstract
Disclosure: P. Kachhadia: None. S. Khan: None. S. Aldasouqi: None. C. Donley: None. A. Abu Limon: None.
Introduction: Patients with Type 1 Diabetes Mellitus (T1DM) require treatment with long term insulin unless they undergo whole organ pancreatic transplant, or they undergo islet cell transplantation. Due to paucity of donors, there is a trend towards single rather double-donor islet cell transplant. There is about 50% long term viability with single-donor transplants. We are not aware of islet cells viability over 15 years. We present the case of a patient with T1DM who received single-donor islet cell transplant 16 years ago, and she is still insulin independent. Case Presentation: The patient is a 52-year-old female with T1DM who received single-donor islet cell transplantation at the University of Illinois at Chicago Hospital. She was diagnosed with T1DM at age 9 and was using an insulin pump till she received the transplant in May of 2006. She is currently not on insulin therapy and is only taking sitagliptin 100mg once daily (as a beta-cell preservative). To our knowledge, she has the longest islet cell viability from a single-donor transplant (over 16 years). Long term immunosuppressive therapy includes mycophenolate 720mg BID and Tacrolimus 1mg BID. Most recent Hemoglobin A1C is 6.6%. She only has diabetic retinopathy that she developed prior to transplant. Retinopathy has been stable and she has received laser treatments by ophthalmology. Discussion: In this procedure, islets are taken from the pancreas of a deceased organ donor. A patient often receives transplantation of around 500 000 islet cells through the use of a percutaneous catheter into the portal vein of the liver or through mini-laparotomy. Though pancreatic transplantation itself carries a higher rate of insulin independence as compared to islet cell transplantation (75% vs 57%), it is associated with higher risks of infections and hospitalizations. As per the Collaborative Islet Transplant Registry, greater than 90% of those who were experiencing hypoglycemia prior to transplantation were free of such events at follow up of 5 years. In addition, 60% of patients were able to maintain glycemic control at A1C less than 6.5%. Conclusion: In conclusion, physicians should consider islet cell transplant as a viable option for long term treatment of patients who have T1DM with difficulties of achieving glycemic control or with severe or refractory hypoglycemia.
Presentation: Thursday, June 15, 2023
THU284 BCG Clinical Trial Programs In Advanced Type 1 Diabetes - 2023 Update
Authors: Kühtreiber Willem M , Hostetter Emma , Lee Amanda H , Ng Nathan , Wolfe Grace , Aristarkhova Anna , Braley Joan , Zheng Hui , Faustman Denise L 
Published: October 2023

Abstract
Disclosure: W.M. Kühtreiber: None. E. Hostetter: None. A.H. Lee: None. N. Ng: None. G. Wolfe: None. A. Aristarkhova: None. J. Braley: None. H. Zheng: None. D.L. Faustman: None.
The bacillus Calmette-Guerin (BCG) vaccine, first introduced a century ago for tuberculosis prevention, is today being tested in double-blinded, randomized clinical trials for treatment of diverse forms of autoimmunity, including type 1 diabetes (T1D) and multiple sclerosis (MS). There are multiple clinical protocols underway at our institution testing various aspects of BCG’s ability to lower HbA1c, reduce insulin requirements and change day-to-day fluctuations in blood sugars, including: 1) Ten-year follow up of a Phase I study of BCG vaccination in longstanding T1D to study the durability of lowered HbA1c values after BCG treatment; 2) Randomized, double-blinded Phase II clinical trial testing the BCG vaccine in adults with longstanding T1D to demonstrate the reproducibility of BCG’s effects seen in the Phase I trial; 3) Radiologic study to quantify and identify through FDG-CAT scans the organs and organ systems that utilize more sugar after BCG treatment; 4) Study in adults with longstanding T1D to evaluate the effects of two doses of BCG compared to 6 doses of BCG over 5 years of observation; and 5) A multi-center clinical trial of adolescents with &gt; 2 years since T1D diagnosis to evaluate the potential benefits of BCG vaccination. To date, we have enrolled 295 patients as part of a planned enrollment of 500, including 272 BCG-vaccinated patients. Global studies on the effects of BCG on the immune system show that the impact of multi-dose vaccination in MS and T1D is optimized by at least 2 years of follow up and that the effects appear durable without further treatment in both MS and T1D to 5+ years. BCG vaccine therapy may provide a safe and affordable medical intervention in individuals with longstanding autoimmunity.
Presentation: Thursday, June 15, 2023
THU291 Successful Reversal Of Glucose Toxicity After DKA Precipitated By SGLT2 Inhibitor
Authors: Abdelrahman Houda , DeMoranville Beatriz 
Published: October 2023

Abstract
Disclosure: H. Abdelrahman: None. B. DeMoranville: None.
Case: A 40 year old man with history of NAFLD and type 2 diabetes mellitus with HbA1c 12.2% on metformin 750 mg daily, presented with diabetic ketoacidosis (DKA) with blood glucose 275 mg/dL and anion gap 24 (AG 10-12). He had been started on empagliflozin 25 mg daily four days prior as outpatient. He was treated with IV insulin and hydration per DKA protocol. Labs showed C-peptide 3.0 ng/mL (1.1-4.4 ng/mL), Anti-GAD Ab 0.01 nmol/L (&lt;0.02 mol/L), negative anti-insulin cell Ab. He was discharged on glargine 10u qHS, lispro 2u AC plus corrective scale, and metformin 750 mg BID. On outpatient follow-up, pre-meal glucose remained under 130 mg/dL, not requiring corrective insulin. He was started on semaglutide 0.5mg weekly and insulin was discontinued. At 3 months, his HbA1c improved to 5.8%. Self-monitoring glucose levels were at goal.
Discussion: This case illustrates glucotoxicity due to significant hyperglycemia causing beta-cell apoptosis and resulting in insulin deficiency. The initiation of SGLT2 inhibitors (SGLT2i) when insulin deficiency and peripheral resistance are at their peak increases risk of DKA. This patient with type 2 diabetes presented with blood glucose 275 mg/dL in DKA four days after starting empagliflozin, a SGLT2i. SGLT2i increase risk of DKA due to dehydration from glucosuria, inhibiting ketone body excretion by the kidneys, causing a state of carbohydrate deficit and hypovolemia that promotes glucagon release from alpha-cells, an increased glucagon-to-insulin ratio, and thus triggers ketogenesis.1
In glucose toxicity, intra-cellular hyperglycemia-induced molecular dysfunction results in beta-cell apoptosis. Islet cells cultured in a glucotoxic environment (20 mmol/l) had suppressed insulin content, but fully reversed the intra-cellular calcium response after one week of culturing in a euglycemic environment, demonstrating recovery of the molecular steps promoting insulin release. 2
Treatment with insulin close to euglycemic goals promotes the reversal of glucose toxicity. Our patient recovered beta-cell function several weeks after the glucotoxic episode and was able to discontinue insulin therapy.
With the addition of semaglutide, a GLP-1 receptor agonist, which potentiates glucose-dependent insulin release to control post-prandial hyperglycemia, he was able to maintain euglycemia and an HbA1c 5.8%.
Conclusion Patients with type 2 diabetes mellitus may present in diabetic ketoacidosis due to glucose toxicity which can be reversed with short-term insulin therapy.
References
1) Nasa P, et al. Euglycemic diabetic ketoacidosis: A missed diagnosis. World J Diabetes. 2021 May 15;12(5):514-523.
2) Tariq M, et al. Prolonged culture of human pancreatic islets under glucotoxic conditions changes their acute beta cell calcium and insulin secretion glucose response curves from sigmoid to bell-shaped. Diabetologia. 2022 Dec 2. Epub ahead of print. PMID: 36459178.
Presentation: Thursday, June 15, 2023
THU294 Glucagon Like Peptide-1 Analogue Therapy In Obese Patients With Cystic Fibrosis Related Diabetes
Authors: Reddy Ankireddypalli Anvitha , Moheet Amir 
Published: October 2023

Abstract
Disclosure: A.R. Ankireddypalli: None. A. Moheet: None.
Introduction: Cystic fibrosis (CF) has classically been associated with malnutrition and being underweight. Intense emphasis on nutritional augmentation and advancement in medical therapies including recent introduction of CFTR modulators have significantly reduced the prevalence of malnutrition in CF. However, this success has been accompanied by a significant rise in overweight/obesity in CF. Recent studies have reported that one-third of all adult CF patients are overweight or obese. Glucagon like peptide receptor-1 agonists (GLP-1RA) therapy is an effective treatment for type 2 diabetes mellitus (T2DM) and obesity. Current guidelines for CF related diabetes (CFRD), recommend insulin as the mainstay of treatment. However, with increase in prevalence of obesity, there is increased interest in examining the role of incretin-based therapies in CFRD. Gastrointestinal (GI) symptoms like abdominal pain, steatorrhea, gastroparesis are common in CF. Concerns about the potential GI side effects had previously dampened the enthusiasm for these drugs in CF.The objective of this case series is to demonstrate impact on glycemic control and weight, and tolerability of GLP1-RA treatment in obese patients with CFRD and pancreatic insufficiency (PI) after 1 year of therapy. Case 1: A 21-year-old female with CF (delta F508 homozygote) and PI, was diagnosed with CRFD at 15 years. She was initially on lantus 14 units daily with HbA1c of 6.7%. She was started on CFTR modulator therapy and with increase in BMI from 37 to 45 in 1 year with HbA1c of 8.9%. She was started on semaglutide and tolerated the medication well with no GI side effects. 1 year later her BMI reduced to 42 and HbA1c was 8.2%. Case 2: A 62-year-old male with CF (delta F508 heterozygote) and PI, diagnosed with CFRD at age 44 years. He was on lantus 66 units and aspart 1 unit per 5 grams carbohydrate coverage. He was started on CFTR modulator and in 1 year BMI increased from 53 to 57. He was started on semalglutide, which he tolerated well with no GI symptoms. 1 year later his Hba1c improved to 7% with a BMI of 54. Discussion: In this era of CFTR modulator therapy, CF patients are faced with changing metabolic parameters, including weight gain and developing T2DM phenotype with insulin resistance. There is one previous case report of short duration of GLP-1RA use in CFRD. We report &gt; 1 year of clinical experience of GLP-1RA use in 2 patients. GLP-1RA was well tolerated in these patients with improvement in glycemic control and weight loss. GLP-1 RA should be considered in obese, PI patients with CFRD as an add-on therapy to insulin. However, larger studies with long-term follow up are required to study the full impact of GLP-1RA to establish it as a treatment option in CFRD.
Presentation: Thursday, June 15, 2023
THU315 Sleep And Circadian Regulation, And Intrinsically Photosensitive Retinal Ganglion Cells Function In Diabetic Retinopathy
Authors: Reutrakul Sirimon , McAnany J Jason , Park Jason C , Chau Felix Y , Danielson Kirstie K , Bharati Prasad , Pannain Silvana , Van Cauter Eve , Hanlon Erin C 
Published: October 2023

Abstract
Disclosure: S. Reutrakul: None. J.J. McAnany: None. J.C. Park: None. F.Y. Chau: None. K.K. Danielson: None. P. Bharati: None. S. Pannain: None. E. Van Cauter: None. E.C. Hanlon: None.
Background: Diabetic retinopathy (DR) is associated with a dysfunction of intrinsically photosensitive retinal ganglion cells (ipRGCs), a crucial component of the entrainment of the circadian system and of the photic entrainment of melatonin secretion. We explored ipRGC function, sleep, 24-h melatonin and cortisol profiles in patients with and without DR. Methods: Type 2 diabetes patients with DR (n=10) and without DR (n=7,) participated. ipRGC function was inferred from the post illumination pupil response (PIPR). Sleep was assessed by 14-day actigraphy. Serum was sampled at hourly intervals for 24hrs for melatonin and cortisol measurement. Results: Mean (SD) age (53.8 (8.1) vs (54.0 (8.6) yr) and mean A1C (7.5 (1.7) vs. 7.1 (0.9)%) did not differ between DR and no-DR patients. PIPR was significantly smaller in DR than no-DR patients (0.14 (0.16) vs. 0.33 (0.10), p=0.001). Nightly sleep duration and efficiency were similar, but sleep variability (standard deviation of daily sleep duration over 7 nights) tended to be larger in DR than no-DR patients (84.1 (29.8) vs. 59.5 (21.8) minutes), p=0.08. Twenty four-hour serum melatonin output was significantly lower in DR than no-DR patients (103.1 (95.4) pg/ml vs. 231.1 (131.3) pg/ml, p=0.034). All no-DR patients exhibited the classical 24-h profile of melatonin with consistently low levels during the day time and a clear nocturnal rise peaking around the middle of the night. In contrast, a normal melatonin rhythm was observed only in 3 of the 10 patients with DR. Six DR patients had 24-h mean melatonin level under 3 pg/ml, five without any evident day-night pattern. One DR patient had a shift in melatonin timing. There was a significant correlation between PIPR and 24-h melatonin output, r= 0.726, p&lt;0.001, but not with sleep variability. In contrast, mean 24-h cortisol profiles and levels, however, were not significantly different between the two groups (mean levels DR 6.18 (1.23) vs no-DR 6.18 (0.73) μg/dL), Conclusion: DR is associated with ipRCGs dysfunction, irregular sleep, and with major disruptions of the 24-hour melatonin rhythm while cortisol rhythm was maintained, suggesting circadian dysfunction in those with type 2 diabetes and retinopathy. Whether melatonin supplementation is beneficial in type 2 diabetes with DR should be explored.
Presentation: Thursday, June 15, 2023
THU351 Reduced Total Antixoxidant Capacity In Type 1 DM Without Chronic Complications
Authors: Oliveira Sara C , Oliveira Claudia Rafaella S , Stein Carolina S , Lauria Marcio W , Moresco Rafael N , Comim Fabio V , Premaor Melissa O 
Published: October 2023

Abstract
Disclosure: S.C. Oliveira: None. C.S. Oliveira: None. C.S. Stein: None. M.W. Lauria: None. R.N. Moresco: None. F.V. Comim: None. M.O. Premaor: None.
Type 1 diabetes mellitus (T1DM) is a condition associated with chronic inflammation and disturbances in the oxidative stress balance, which may be related to its complications. Our study aimed to investigate some REDOX markers ( TOS=total oxidant status ; TAC= total antioxidant capacity; FRAP =ferric reducing ability of plasma; AOPP=advanced oxidation protein products) in subjects with type 1 diabetes and controls. The local ethics committee approved this study. Overall, 51 subjects with T1DM and 106 controls were evaluated in an outpatient clinic. The age in T1DM group was (mean +− SD) 43.7 +− 17 years versus 43.1 +− 13.5 years in controls (NS).The proportion of smokers (17% vs. 15%) and ethnic composition were comparable between the groups. The mean +− SD HbA1c was 8.15 +− 1.65 % in diabetic patients. Concerning REDOX markers, we could observe a significant reduction in the TAC in T1DM (mean +− SD ) of 1.32 +− 0.17 against 1.47 +− 0.16 mmol Trolox equiv/ L(p&lt;0.001) but not other oxidative stress markers. In the sequence, we proceed with the analysis of four subgroups: group 1: T1DM without any diabetic complication or high blood pressure and BMI &lt;25kg/m2; group 2: T1DM with any diabetic complication, high blood pressure or BMI &gt;= 25 kg/m2; group 3: normal controls without the high blood pressure and BMI &lt;25kg/m2; group 4: controls with metabolic disease(excluding T2DM)and high blood pressure or BMI &gt;= 25 kg/m2. Analyzing the profile of groups 1,(T1DM without complications) against group 3(normal controls), we noted a reduced TAC (mean +− SD) of 1.34 +− 0.2 in G1 versus 1.47 +− 0.16 mmol Trolox equiv/ L in G3 ( p=0.006). No significant differences were perceived in relation to TOS ( mean +− SD) of 102.33 +− 43 in G1 vs. 88.57 +− 48.7 micromol H2O2 equiv/L in G3, FRAP 287 +− 64.5 in G1 vs 306.6 +− 72 micromol/L in G3, or AOPP 252.11 +− 127 in G1 vs 260.38 +− 152 micromol/L in G3. Our results suggest that a reduction in the total antioxidant capacity is present in normal blood pressure T1DM even without chronic complications.
Presentation: Thursday, June 15, 2023