bluuebunny/crossref_metadata_2025 huggingface dataset:
1757-P: Imeglimin Enhances Glucose-Induced Insulin Secretion with Activating Mitochondrial Function
Authors: TAKIGUCHI MAMI , IIDA HITOSHI , UZAWA HIROTSUGU , KANAI AKIKO , UEKI KYOSEI , IKEDA KOKI , KAKEHI SAORI , HARUNA HIDENORI , TAKUBO NORIYUKI , NISHIDA YUYA , SHIMIZU TOSHIAKI , WATADA HIROTAKA
Published: June 2024

The underlying pathology of diabetes mellitus is inadequate insulin secretion and resistance. The resulting hyperglycemia leads to complications, decreased quality of life and shortened life span. New drugs to reduce blood glucose are still required. Imeglimin has a chemical structure derived from the antidiabetic compound metformin, and now is clinically used as an oral hypoglycemic agent with a tetrahydro-triazin structure in Japan. Several studies reported that imeglimin promotes glucose-stimulated insulin secretion (GSIS) in diabetic mouse models and protects pancreatic beta cells from inflammation and ROS-induced apoptosis, however, the underlying mechanism of enhanced GSIS has not been fully elucidated yet. The aim of this study is to investigate the effect of imeglimin on insulin secretion. First, we found that the in vivo administration of imeglimin to C57Bl/6 mice enhanced GSIS with increase of insulin secretion. Next, we investigated the effect of imeglimin on isolated islets from C57Bl/6 mice. Ten µM imeglimin, which is equivalent to the clinically used dose for 24 hours stimulated GSIS from isolated islets, however, 1000 µM imeglimin does not enhance GSIS. Intriguingly, 10 µM but not 1000 µM imeglimin enhanced mitochondrial oxygen consumption rate and membrane potential. While it has been reported that the imeglimin-induced increase in GSIS in streptozotocin-treated mice is attributed to an increase in NAD+ and enhanced calcium influx by activating NAMPT expression, no change in NAD+ levels by imeglimin was observed in C57Bl/6 mice. Our data showed that a clinical relevant dose of imeglimin enhanced GSIS with enhanced mitochondrial function in islets isolated from C57Bl/6 mice.

Disclosure

M. Takiguchi: Research Support; Sumitomo Dainippon Pharma Co., Ltd. H. Iida: Research Support; Sumitomo Dainippon Pharma Co., Ltd. H. Uzawa: Research Support; Sumitomo Dainippon Pharma Co., Ltd. A. Kanai: Research Support; Sumitomo Dainippon Pharma Co., Ltd. K. Ueki: None. K. Ikeda: None. S. Kakehi: Research Support; Sumitomo Dainippon Pharma Co., Ltd. H. Haruna: None. N. Takubo: Research Support; Sumitomo Dainippon Pharma Co., Ltd. Y. Nishida: Research Support; Sumitomo Dainippon Pharma Co., Ltd. T. Shimizu: None. H. Watada: Speaker's Bureau; Bayer Inc., Sanofi, Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Abbott Japan Co., Ltd., Eli Lilly and Company, Boehringer-Ingelheim, Daiichi Sankyo, Taiho Pharmaceutical Co. Ltd., Kowa Company, Ltd., Teijin Pharma Limited, Mitsubishi Tanabe Pharma Corporation. Research Support; Sumitomo Dainippon Pharma Co., Ltd., Boehringer-Ingelheim, Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Abbott Japan Co., Ltd., Teijin Pharma Limited, Takeda Pharmaceutical Company Limited, Taiho Pharmaceutical Co. Ltd., Sanwa Kagaku, Souiken.
1778-LB: Comparing a Somatostatin Receptor 2 Antagonist (SSTR2a) to Exogenous Glucagon (EG) for the Treatment of Severe Insulin-Induced Hypoglycemia
Authors: HOFFMAN EMILY G. , DSOUZA NINOSCHKA , ALEALI NADIA , NOZARIASBMARZ NEWSHA , FATEHI SAMANEH , SHAKERI DORSA , CHAN OWEN , LIGGINS RICHARD , RIDDELL MICHAEL C.
Published: June 2024

Introduction & Objective: Treatment of severe hypoglycemia (SH) with EG causes hyperglucagonemia, resulting in gastrointestinal distress that limits its real-world utility. Prophylactic dosing of SSTR2a augments glucagon counterregulation during insulin-induced hypoglycemia in diabetic rats. Here, we tested the use of SSTR2a as a rescue treatment for SH.

Methods: After 3 episodes of insulin-induced hypoglycemia to impair glucagon counterregulation, healthy male rats received an overdose of regular insulin before a SC injection of vehicle, EG (0.15 mg) or SSTR2a (10 mg/kg ZT-01) at the onset of level 2 hypoglycemia. Blood glucose (BG) and plasma glucagon were monitored for 2 h by saphenous venipuncture.

Results: BG continued to fall gradually with vehicle to a nadir of 1.7±0.6 mM at 110 min. Euglycemia was restored by EG in 6 of 8 rats from t=15-60 min (4.6±1.3 mM, n=8) and maintained in 1 of 8 rats from t=70-120 min (3.0±0.9 mM, n=8). SSTR2a raised BG to level 1 hypoglycemia in 5 of 8 rats (t=15-60 min: 3.4±1.0 mM, n=8) before restoring euglycemia in 4 of 8 rats (t=70-120 min: 5.0±2.3 mM, n=8). Compared to vehicle, BG was higher with SSTR2a from t=15-30 and 90-120 min and glucagon AUC (0-120 min) was 24- & 1.5-fold higher with EG and SSTR2a, respectively.

Conclusion: SSTR2a provided more gradual and sustained recovery from SH than EG without causing systemic hyperglucagonemia.

Disclosure

E.G. Hoffman: None. N. DSouza: None. N. Aleali: None. N. Nozariasbmarz: None. S. Fatehi: None. D. Shakeri: None. O. Chan: None. R. Liggins: Employee; Zucara Therapeutics. Stock/Shareholder; Zucara Therapeutics. M.C. Riddell: Consultant; Eli Lilly and Company. Speaker's Bureau; Novo Nordisk. Advisory Panel; Supersapiens. Consultant; Dexcom, Inc. Speaker's Bureau; Sanofi. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Stock/Shareholder; Zucara Therapeutics.

Funding

Zucara Therapeutics Inc.
1788-LB: Machine Learning–Based Prediction of Diabetic Kidney Disease in Patients with Type 2 Diabetes
Authors: SUN PARK TAE , JI KIM YU , AE LEE KYUNG
Published: June 2024

Background & Objective: Diabetic Kidney Disease (DKD) is leading cause of end-stage renal disease, cardiovascular disease, and mortality in patients with diabetes. This study is aim to develop and validate machine learning (ML)-based DKD prediction model for patients with type 2 diabetes (T2D).

Method: We conducted a retrospective study using common data model based on electronic health records of three tertiary referral hospitals in Korea: Jeonbuk National University Hospital (JNUH) cohort for developing ML model, Wonkwang University Hospital (WKUH) and Kyunghee University Hospital (KHUH) cohorts for external validation. Patients with T2DM who had been followed for more than 3 years were included. Three ML algorithms (Random Forest(RF), XGBoost(XGB), Ensemble(RF+XGB)) were applied, and the optimal model was selected according to the area under a receiver operating characteristic curve (AUROC) and accuracy.

Results: A total of 20,528 patients were included, with a DKD occurrence of 1,361 (26.6%), 269 (26.5%), 5,461 (37.9%) in the JBUH, WKUH, and KHUH cohort, respectively. The RF model yielded the highest AUROC of 0.79 and accuracy of 71% on the JNUH cohort, showing better performance than XGB, Ensemble models. The top five important features included baseline estimated glomerular filtration rate, age, hemoglobin, serum creatinine and hemoglobin A1c. Application of RF model in two external cohorts yielded 57-77% sensitivity, 73-79% specificity, and 0.76-0.85 AUROC.

Conclusion: This study suggested that the RF model could contribute to the prediction of the development of DKD in T2D. Further research is needed on larger samples of participants using different ML models to determine the most effective one.

Disclosure

T. Park: None. K. Lee: None.
179-OR: Assessing the Impact of Hypoglycemia among People with Diabetes in the U.S. and EU
Authors: BELTRAN ALAN , ZENG ALISON , CHANEN SYDNEY , BELL TREVOR , WOOD RICHARD
Published: June 2024

Hypoglycemia, where blood glucose falls below 70 mg/dL, can be an unfortunately common and serious burden for people with diabetes (PWDs) on insulin. Despite this, its prevalence in the daily lives of PWDs is understudied among specific therapy types. This research aimed to comparatively assess patient experiences with hypoglycemia in the US and Europe (EU). From August-October 2023, insulin-using PWD in the US (n=3,355) and EU (n=2,480) took an online survey assessing the impact of hypoglycemia in their lives. Respondents reported how frequently they experience mild (55-70 mg/dL) and moderate (40-54 mg/dL) hypoglycemia. In the study’s analysis, highly impacted individuals were operationalized as PWD experiencing near-daily milds and occasional (weekly) moderates. Hypoglycemia impact was compared across region by type of diabetes and insulin therapy regimen (T1 adults on a pump, T1 adults on multiple daily injections (MDI), T1 kids (<18 years), T2 adults on MDI, and T2 adults on basal insulin only). The prevalence of highly impacted PWD is significantly higher in EU than in the US for all patient segments except PWD on MDI. Compared to in EU, high hypoglycemia impact rates in the US are significantly lower among T1 adults on a pump (15% vs. 21%, p<.001), T1 kids (21% vs. 33%, p<.01), T2 adults on basal insulin only (2% vs. 6%, p<.05). There are no significant differences in the prevalence of high hypoglycemia impact among T1 adults on MDI in the US (20%) and EU (22%), nor among T2 adults on MDI in the US (3%) and EU (4%). It is notable that all patient segments except those on MDI are more impacted by hypoglycemia in EU than in the US, especially given the differences in US and EU health systems. Further research should aim to uncover the origin of this disparity, why it specifically affects pump users and not MDI users, and assess whether it also translates into clinical outcomes and daily lived experiences of PWDs.

Disclosure

A. Beltran: Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Roche Diabetes Care, Tandem Diabetes Care, Inc., Ypsomed AG, Teladoc Health. A. Zeng: Employee; dQ&A. Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Roche Diabetes Care, Tandem Diabetes Care, Inc., Ypsomed AG, Teladoc Health. S. Chanen: Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Roche Diabetes Care, Tandem Diabetes Care, Inc., Ypsomed AG, Teladoc Health. T. Bell: Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Roche Diabetes Care, Tandem Diabetes Care, Inc., Ypsomed AG, Teladoc Health. R. Wood: Research Support; Abbott, Dexcom, Inc., Eli Lilly and Company, diaTribe, Insulet Corporation, Medtronic, Roche Diabetes Care, Tandem Diabetes Care, Inc., Ypsomed AG, Teladoc Health.
1794-LB: Comparison of Metabolic Visceral Fat Score with Other Abdominal Obesity Indicators in Predicting Left Ventricular Hypertrophy in Individuals with Type 2 Diabetes
Authors: WANG LU , WANG DI , WANG YAN , WEI LINGLING , YANG LONGYAN
Published: June 2024

Introduction & Objective: Left ventricular hypertrophy (LVH) is a common complication associated with higher cardiovascular risk in Type 2 diabetes mellitus (T2DM) patients. Although many abdominal obesity indices (AOIs) have been established, studies investigating their associations with LVH in T2DM are limited. This study aimed to investigate the relationship between AOIs and LVH in T2DM.

Methods: A cross-sectional study involving 5,105 T2DM patients without prior cardiovascular disease was conducted in Beijing, China. LVH was assessed using echocardiography. Metabolic Score for Visceral Fat (Mets-VF), Waist Circumference (WC), Hip Circumference (HC), Visceral adipose tissue (VAT), BMI, Waist-to-Hip Ratio (WHR), Waist-to-Height Ratio (WHtR), Body Roundness Index (BRI), Abdominal Volume Index (AVI), Conicity Index (CI), Lipid Accumulation Product (LAP), Cardiometabolic Index (CMI), Visceral Adiposity Index (VAI), and Chinese Visceral Adiposity Index (CVAI) were investigated. Multivariate logistic regression and restricted cubic spline regression models were used to evaluate associations and potential nonlinear relationships between AOIs and LVH risk.

Results: Among 5,105 participants (aged 49.8 ± 12.2 years), 560 (10.9%) had LVH. After adjusting for confounding factors, METS-VF showed the strongest association with LVH (OR 9.78; 95% CI 6.15-15.75, p value <0.001). WC, HC, VAT, BMI, WHR, WHtR, BRI, LAP, CMI, and CVAI also maintained significant associations with LVH (ORs 1.003 to 1.916, p value <0.05). Linear associations were observed for METS-VF, WC, VAT, BMI, and WHtR, while nonlinear associations were found for HC, WHR, BRI, LAP, CMI and CVA. AVI, CI, and VAI showed no independent significant association with LVH.

Conclusions: METS-VF outperforms other well-established AOIs in predicting LVH, highlighting its potential as a valuable tool for assessing cardiovascular risk in T2DM patients.

Disclosure

L. Wang: None. D. Wang: None. Y. Wang: None. L. Wei: None. L. Yang: None.
1802-LB: Magnetic Peripheral Nerve Stimulation (mPNS) for Treatment of Painful Diabetic Neuropathy (PDN)—Sensory, QoL Results
Authors: BROWN LORA
Published: June 2024

Objective: To determine if mPNS improved sensation, QoL in subjects with PDN over 90 days.

Methods: Seventy-one subjects with PDN were treated in 6 site RCT comparing safety, effectiveness of mPNS and Conventional Medical Management (CMM). Subjects were randomized 3:1 to mPNS+CMM or Sham+CMM and were followed through 30 days during double-blind phase. At 30 days, Sham+CMM subjects could crossover (CX) to treatment. mPNS+CMM & CX subjects were then followed to 90 days. Secondary endpoints included group summaries of mean change scores from baseline at Day 90 for Visual Analog Scale (VAS) numbness, QOL-DN, PDI, BPI, and DASS.

Results: Fifty subjects were enrolled mPNS+CMM, 21 were enrolled Sham+CMM. Of the 21 in CMM+Sham, 20 elected to crossover at Day 30. Of all subjects in the full analysis set (FAS), 85% completed through Day 90. One adverse event was reported in AT+CMM unrelated to the study device. After 90 days of treatment, mPNS+CMM subjects improved significantly (p<0.05) on all measures (Table). CX subjects also showed significant improvement in numbness, QoL-DN, PDI, and BPI after 90 days, while DASS scores remained stable in all three areas.

Conclusions: mPNS improves sensation and QoL over a 90-day treatment. Because of the non-invasive nature of mPNS and lack of other effective non-invasive treatments for PDN, mPNS should be considered much earlier in treatment algorithm for PDN.

Disclosure

L. Brown: None.
1809-LB: Hyperglycemia Activated the STING Pathway to Induce Retinal Vascular Endothelial Inflammation and Breakdown of Retinal Tight Junctions
Authors: LIU MINTING , WEN SIYING , CHEN YANMING , SHI GUOJUN
Published: June 2024

Introduction & Objective: Diabetic retinopathy is a common microvascular complications of diabetes mellitus characterized by hyperglycemia and chronic inflammation. Retinal endothelial cells are the primary target cells for diabetes-induced vascular damage causing acellular blood capillary and capillary leakage in clinical observation. This study investigated the role of the stimulator of interferon genes (STING) signaling pathway in human retinal vascular endothelial cells (HRVEC) damage and inflammation under the condition of hyperglycemia.

Methods: HRVEC were treated with Methylglyoxal (MGO), a mimic of hyperglycemia condition. Moreover, we investigated the role of STING in HRVEC by generating a STING-deficient HRVEC using the CRISPR/Cas9 system. The components of the STING signaling pathway and endothelial cell tight junctions at protein levels were determined by Western blotting. Last, RT-qPCR was used for detecting the genes expression of pro-inflammatory cytokines in HRVEC and STING-deficient HRVEC. All those treatment and methods were repeated in the STING siRNA-treated HRVEC.

Results: When treated with MGO, the protein levels of the STING signaling components were increased in a time- and dose-manner, suggesting the activation of the STING pathway, accompany by down-regulation of endothelial cell tight junction protein and increased transcription levels of inflammatory genes. At the same time, the increased transcription levels of inflammation genes and decreased expression levels of tight junction proteins caused by MGO were significantly repressed when the STING gene was deleted or knocked down in HRVEC.

Conclusion: STING deficiency can significantly inhibit the expression of proinflammatory factors in HRVEC, also improving the HRVEC damages induced by MGO.

Disclosure

M. Liu: None. S. Wen: None. Y. Chen: None. G. Shi: None.
1811-LB: Improvement in Diabetic Retinopathy and Achieving Remission of Type 2 Diabetes Mellitus through Digital Twin Technology—A One-Year Intervention Study
Authors: JOSHI SHASHANK , DHARMALINGAM MALA , VADAVI ARUN , KESHAVAMURTHY ASHOK , BHONSLEY SUCHITRA , MOHAMED MALUK , SHAH LISA , THAJUDEEN MOHAMED , PANANDIKAR MAHIKA , SHAMANNA PARAMESH
Published: June 2024

Introduction and Objectives: Digital twin (DT) platform uses Artificial Intelligence (AI) and Internet of Things, to integrate multi-dimensional data to give precision nutrition and health recommendations via the mobile app and by coaches. Remission was defined as A1C levels less than 6.5% without medication for over 3 months. Status of diabetic retinopathy (DR) was assessed in patients on DT platform.

Methods: We monitored 181 T2DM patients, across 4 centers, for remission of T2DM, assessing changes in DR and HbA1c levels, with a focus on participants with initial DR. Validated handheld fundus camera facilitated retinal imaging. Statistical analysis, including the Pearson correlation coefficient, explored the link between HbA1c levels and DR progression or regression.

Results: Mean age, duration of diabetes, were 44 years (±8.6) and 3.7 years (±2.7). Mean HbA1c decrease was 3.03 (8.9% to 5.8), indicating significant glycemic control improvements from baseline to Day 360. 75.69% of the participants (n=137) achieved remission. Among those initially diagnosed with DR (n=16), 43.75% (n=7) showed regression, with no evidence of DR. 55.25% of the participants (n=100), continued, with absence of the evidence of DR. There was a weak negative correlation between remission of T2DM and retinopathy reversal (r=-0.0867) which indicates that remission of T2DM might not be a strong predictor of retinopathy improvement.

Conclusion: DT which leads to remission of T2DM has potential for regressing diabetic retinopathy in a significant subset of patients. The remarkable percentage of individuals moving from DR to absence of DR emphasizes the potential for positive retinopathy outcomes. However, the minimal correlation with remission of T2DM suggests the importance of comprehensive diabetic care strategies, extending beyond glycemic management to include specific retinopathy interventions.

Disclosure

S. Joshi: None. M. Dharmalingam: None. A. Vadavi: None. A. Keshavamurthy: None. S. Bhonsley: None. L. Shah: Employee; Twin Health. M. Panandikar: None. P. Shamanna: None.
1830-LB: Diabetes and Safe Driving—Latvian Medical Doctors Knowledge
Authors: ELINA BERZINA KATRINA , RASA INGVARS
Published: June 2024

Introduction & Objective: Diabetics may experience disorientation and cognitive impairment when their blood glucose levels fall below 4.0 mmol/L a condition known as hypoglycemia. Driving in such a state can be dangerous. MDs must be educated and inform patients to ensure their safety.

Methods: An anonymous questionnaire with 17 questions was sent to MDs from 2022 to February 2024. The survey was completed by 165 MDs. Results were analyzed using IBM SPSS 29.0.

Results: Of the respondents, 8.5% (n=14) were endocrinologists, 91.5% (n=151), internists or GPs. 16% (n=26) did not think diabetes mellitus (DM) is a risk for car accidents. Of those 84% (n=139) who believed that DM is a risk factor 66.9% (n=93) educated their DM patient about safe driving. 97% (n=160) believe that having frequent and severe hypoglycemia episodes makes driving unsafe, but 42% (n=67) of them had advised their DM patients not to drive. 89% (n=147) believed that not recognizing hypoglycemia is a contraindication for driving of whom 38.8% (n=57) recommended DM patients to measure their blood glucose levels before driving.

Conclusion: Less than half of the MDs educate their DM patients about safe driving. MDs must receive education on DM and safe driving to inform their patients properly.

Disclosure

K. Berzina: None. I. Rasa: None.
1834-LB: Different Effects of Occupation and Leisure-Time Physical Activity on Long-Term Glucose Variability in Type 2 Diabetes
Authors: YU HUI-I
Published: June 2024

Introduction: Occupational Physical Activity (OPA) and Leisure Time Physical Activity (LTPA) can both help prevent diabetes. A Finnish study revealed OPA, LTPA reduced total and cardiovascular disease mortality among type 2 diabetes mellitus (DM). Few studies examined the metabolic effect of OPA and LTPA on type 2 DM, but some suggest LTPA can reduce short-term glycemic variability. However, few have assessed the impact of physical activity on long-term glycemic variability.

Method: We recruited patients with type 2 DM, aged 20-75, from our outpatient clinic from August 2014 to July 2021. We evaluated glycemic variability using the HbA1c Variability Score (HVS). We categorized metabolic equivalent of task (MET). min. wk-1 > 3000 as high activity, 600-3000 as moderate activity, and < 600 as low activity. We divided both leisure and occupational activities into thirds based on these activity levels.

Results: We enrolled 758 patients who had at least 3 years of follow-up for final analysis. Younger patients had significantly higher total physical activity (P = 0.019). Their micr- and macro-vascular complications, and oral antidiabetic agents (OAD), insulin use did not differ significantly. High LTPA patients showed significantly lower body mass index (P = 0.004), lower HSV score (P = 0.005), and less statin usage (P = 0.027). A1C was marginally better (P = 0.060). High OPA patients were younger (P < 0.001), predominantly male (P < 0.001), shorter DM duration (P < 0.001) and more biguanide usage (P = 0.026), but HVS did not reduce. Linear regression analysis found that LTPA reduced HVS in crude analysis, but the significance disappeared after adjusting other factors. In high OPA, we found it significantly increased HVS after adjusting other factors.

Conclusion: LTPA and OPA might have different effects in long-term glycemic variability in patients with type 2 diabetes.

Disclosure

H. Yu: None.
1835-LB: Understanding Hypoglycemia Risk in Unstructured Real-World Physical Activities in Adults with Type 1 Diabetes
Authors: DHALIWAL MEHAK P. , TANG KENAN , AIELLO ELEONORA M. , ZAHARIEVA DESSI P. , LAL RAYHAN , SUMMERS CAMERON , ARBITER BRANDON , WATSON KELLY , FIGG LAUREN , BALISTRERI ILENIA , KINGMAN RYAN S. , SUH BAILEY , QIN YAO
Published: June 2024

Introduction & Objective: We analyzed the unstructured real-world physical activity (PA) sessions from the T1DEXI study to evaluate hypoglycemia risk in terms of change in CGM (ΔCGM) readings and percentage of time below range (%TBR) of T1D participants.

Methods: For each session, we calculated the ∆CGM as the difference in glucose readings within 5 mins before and after PA and, %TBR as the percentage of readings <70 mg/dL during PA. ANOVA was used to measure variation in ΔCGM and %TBR associated with activity durations, starting glucose, insulin on board (IOB), and individual factors, i.e. age, sex, and A1c.

Results: We analyzed 9,322 sessions, with 46 activity types, for 404 participants (open and closed loop pump users, age 36.6 ± 14.0 yrs, 75.3% female, BMI 25.5 ± 3.9 kg/m2, A1c 6.6 ± 0.7%, T1D duration 18.5 ± 13.0 yrs, total daily dose 40.1 ± 16.2 U), with an average of 24 sessions in 4 weeks.

Table 1 shows larger ΔCGM and higher %TBR for increasing activity durations, and IOB (all p<0.01), lower %TBR for increasing starting glucose (p<0.01). %TBR differed significantly for age, A1c, and sex groups (all p<0.03), while ΔCGM only for age (p<0.01). Carbohydrate (CHO) intake correlated with a higher %TBR due to a lower starting glucose for sessions with CHO.

Conclusion: Hypoglycemia risk during PA is impacted by population and individual factors, which are important when tailoring glucose management strategies around PA.

Disclosure

M.P. Dhaliwal: Consultant; Tidepool. K. Tang: Consultant; Tidepool. E.M. Aiello: Other Relationship; Tidepool. D.P. Zaharieva: Research Support; Leona M. and Harry B. Helmsley Charitable Trust. Advisory Panel; Dexcom, Inc. Research Support; Insulet Corporation. Speaker's Bureau; Dexcom, Inc. Research Support; International Society for Pediatric and Adolescent Diabetes. Board Member; Juvenile Diabetes Research Foundation (JDRF). R. Lal: Consultant; Abbott, Adaptyx Biosciences, Biolinq, Capillary Biomedical, Inc., Deep Valley Labs, Gluroo, PhysioLogic Devices, Portal Insulin, Tidepool. Advisory Panel; Lilly Diabetes. C. Summers: Consultant; Tidepool. B. Arbiter: Stock/Shareholder; Eli Lilly and Company. Employee; Tidepool. Stock/Shareholder; Dexcom, Inc. K. Watson: Employee; Tidepool. Other Relationship; Luna Diabetes. Stock/Shareholder; Tandem Diabetes Care, Inc. L. Figg: None. I. Balistreri: None. R.S. Kingman: None. B. Suh: None. Y. Qin: None.

Funding

The Leona M. & Harry B. Helmsley Charitable Trust (Grant #2404-06905).
1837-LB: Designer Protein Sweelin, a Novel Hypersweet, Extremophile Protein as a Sugar Substitute
Authors: SAMISH ILAN , LESMES URI , LIFSHITZ YAEL
Published: June 2024

Introduction and Objective: sweelin®, a novel sweet protein, ~3,000 sweeter than sugar enables up to 70% sugar reduction in numerous applications without compromising taste as assessed by professional sensory panels. The protein was designed using Agile-Integrative Computational Protein Design (AI-CPD) to improve stability and sensory profile of the monellin protein found in African fruits. It is produced via precision fermentation resulting with highly purified protein. Unlike small-molecule sweeteners, the protein is not expected to exhibit adverse effects, yet its digestibility required elucidation which was conducted via in vitro digestion models recreating gastric and intestinal proteolysis.

Methods: Digestibility of sweelin® was studied using a computer controlled in vitro semi-dynamic digestion model that mimics the gastrointestinal conditions of a healthy adult via 2 consecutive steps, a dynamic gastric phase and a small intestinal (duodenal) phase that rely on an adjusted version of the INFOGEST in vitro digestion protocol. Digesta samples were collected at different timepoints of gastric and intestinal digestion and subsequently analyzed by SDS PAGE, with Coomassie Blue stain or Western blotting. Bioaccessible peptides were analyzed by LC-MS/MS.

Results: sweelin® was readily digestible under intestinal conditions where bile and pancreatic secretions were added. In fact, the presence of physiological levels of trypsin and chymotrypsin led to the degradation of >95% of sweelin®. LC-MS/MS analysis of bioaccessible peptides reaffirmed that sweelin® is readily digested in the intestine into very short peptides. After 2h of intestinal digestion undigested protein levels were estimated to be <3% of the total ingested dose.

Conclusions: sweelin® is a novel hyper-sweet designer protein shown to be effectively digested in the small intestine, much like commonly consumed proteins. Clinical trials are in progress to demonstrate no effect on diabetes-related biomarkers.

Disclosure

I. Samish: Other Relationship; Amai Proteins. U. Lesmes: None. Y. Lifshitz: Employee; Amai Proteins.
1841-LB: Glycemic Management Patterns of Participants in a Diabetes Integrated Behavioral Health Program
Authors: ESPINOSA DE LOS MONTEROS KARLA , SPIERLING BAGSIC SAMANTHA R. , SORIANO EMILY C. , FORTMANN ADDIE L. , NOUHI NUSHA , PHILIS-TSIMIKAS ATHENA
Published: June 2024

Introduction: In 2016, a large Southern CA health system launched the Diabetes Behavioral Health Integration Program (BeHIP), which co-locates psychological support with clinical diabetes care. Objective: To describe the glycemic management patterns of participants in the BeHIP program. Methods: Patients referred to the BeHIP via warm hand-off or through their EHR undergo an individualized assessment followed by short-term psychotherapy when indicated. Data was collected via EHR extraction. For those with ≥ 1 visit, the change in HbA1c was examined as follows: 1) a linear mixed effects model testing a time by program (i.e., pre vs. post initiation) interaction captured change over time relative to first BeHIP visit; 2) a paired t-test compared individual-level mean change pre- versus post- initiation of BeHIP. Results: BeHIP participants with ≥ 1 visit (N=430) had a mean age of 55.4±17.1; most were female (72.6%), Non-Hispanic White (75.1%), and married (54%). Plots show HbA1c change over time and paired differences (Fig 1A & B); and the difference in average HbA1c between those who engage in multiple BeHIP visits and those who only attend one consultation or are referred but do not engage (Fig 1C). Conclusion: Psychosocial and behavioral support embedded in a real-world clinical program improves glycemic outcomes.

Disclosure

K. Espinosa de los Monteros: None. E.C. Soriano: None. A.L. Fortmann: None. N. Nouhi: None. A. Philis-Tsimikas: Advisory Panel; Dexcom, Inc., Lilly Diabetes, Novo Nordisk, Sanofi, Medtronic, Bayer Inc.
1845-LB: “I’ve Tried Really Hard to Back Off, But…”—The Influence of Type 1 Diabetes on Mothers’ Quality of Life during the Transition to Adulthood
Authors: NESS MICHELLE , SAYLOR JENNIFER
Published: June 2024

Research indicates that continued parental involvement in T1D management is paramount during the transition to adulthood, yet there is a paucity of information about the needs of mothers during this time. To ensure family-centered care throughout the lifespan, this research seeks to gain a better understanding of the influence of T1D on the mother’s quality of life during their adolescent’s transition to adulthood. Participants were recruited from the Parents of Diabetics Facebook page, JDRF, and the Children with Diabetes newsletter. Twelve mothers of adolescents with T1D (average age of adolescent=19.42, SD=1.44, average age at T1D diagnosis=11.14, SD=3.3 years) were interviewed. Interviews were audio and video recorded, transcribed verbatim, and analyzed by two independent researchers using the Family Management Style Framework. Mothers reported continued feelings of anxiousness and uncertainty related to lack of control of their adolescent’s T1D management. Involvement in T1D management ranged from a “hands-off” approach to high levels of involvement, including daily blood glucose monitoring and communication regarding T1D. Management of T1D had a profound influence on mothers' ability to work outside the home, with many mothers reporting that they chose not to work to care for their children full time. Mothers also reported receiving limited support from family and friends as well as strained relationships related to lack of understanding about T1D and its management. Isolation, anxiety, and continued worry about T1D and its ever-present impact on their children led to diminished quality of life for mothers during the adolescents’ transition to adulthood. The needs of mothers of adolescents transitioning to adulthood with T1D are largely ignored. This study highlights the long-term consequences of T1D on mothers as well as the need for continued professional support for mothers during the adolescent's transition to adulthood and beyond.

Disclosure

M. Ness: None. J. Saylor: None.

Funding

Towson University (FDRC funding)
1856-LB: Efficacy and Safety of Mazdutide in Chinese Participants with Overweight or Obesity (GLORY-1)
Authors: JI LINONG , JIANG HONGWEI , LI HUA , TIAN JUNHANG , LIU DEXUE , ZHAO YUZHU , GU JIEYU , LIU ZIHAN , DENG HUAN , WANG YANQI , LI LI , QIAN LEI , GLORY-1 INVESTIGATORS THE
Published: June 2024

Introduction & Objective: To evaluate the efficacy and safety of mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, in Chinese participants with overweight or obesity.

Methods: In this phase 3 randomized, double-blind, placebo-controlled trial (NCT05607680), we assigned 610 Chinese adults with a BMI of 28 kg/m2 or more, or 24 kg/m2 or more and at least one weight-related comorbidity, in a 1:1:1 ratio to receive once-weekly, subcutaneous mazdutide 4 mg, 6 mg or placebo for 48 weeks. Co-primary endpoints were the percentage change in weight from baseline and a weight reduction of 5% or more at week 32.

Results: At baseline, the mean body weight was 87.2 kg, the mean BMI was 31.1 kg/m2, and 83.1% of participants had a BMI of 28 kg/m2 or more. Mazdutide met co-primary endpoints and all key secondary endpoints, demonstrating superiority to placebo on body weight changes, weight-loss targets, and improvements on multiple cardiometabolic risk factors (Table). Mazdutide was well tolerated, with adverse events leading to treatment discontinuation reported in 1.5% of participants with mazdutide 4 mg, 0.5% with mazdutide 6 mg and 1.0% with placebo. The most frequently reported adverse events were gastrointestinal, mostly mild to moderate in severity.

Conclusion: In Chinese adults with overweight or obesity, mazdutide provides significant reductions in body weight and cardiometabolic risk factors.

Disclosure

L. Ji: None. H. Jiang: None. H. Li: None. J. Tian: None. D. Liu: None. Y. Zhao: None. J. Gu: None. Z. Liu: Employee; Innovent Biologics. H. Deng: Employee; Innovent. Y. Wang: Employee; Innoventbio. L. Li: Employee; innovent biologics. Stock/Shareholder; innovent biologics. L. Qian: Employee; Innoventbio.
1866-LB: A Phase 2 Study of Mazdutide 9 mg in Chinese Adults with BMI of 30 kg/m2 or more
Authors: JIANG HONGWEI , JI LINONG , ZHANG YAWEI , CHENG ZHIFENG , PANG SHUGUANG , LI XIAOLI , QIU WEI , MA QINGYANG , LIU ZIHAN , WANG YANQI , DENG HUAN , QIAN LEI
Published: June 2024

Introduction & Objective: To evaluate the efficacy and safety of 9 mg mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, in Chinese participants with obesity.

Methods: In a randomized, double-blind, placebo-controlled phase 2 trial (NCT04904913), 80 Chinese adults with a BMI of 30 kg/m2 or more (mean baseline body weight: 96.9 kg; mean baseline BMI: 34.3 kg/m2) were randomized to receive once-weekly, subcutaneous mazdutide 9 mg (n=60) or placebo (n=20) for 24 weeks. Subsequently, participants voluntarily chose to participate in an extended 24-week double-blind treatment period. The primary endpoint was the percentage change in weight from baseline at week 24.

Results: At week 24, mean percentage change in weight from baseline were −13.3% (SE 0.8) with mazdutide 9 mg and 2.1% (1.5) with placebo (estimated treatment difference: −15.4% [95%CI: −18.8, −12.0], P <0.0001); 81.7%, 65.0% and 31.7% of participants with mazdutide achieved weight reduction of 5% or more, 10% or more, and 15% or more, respectively, while no participant with placebo achieved weight reduction of 5% or more. Furthermore, compared with placebo, greater improvements were observed with mazdutide at week 24 in multiple cardiometabolic risk factors, most notably in triglycerides (−43.5% with mazdutide, −1.7% with placebo), alanine aminotransferase (−32.8%, 12.7%) and serum uric acid (−102.2 µmol/L, −16.1 µmol/L). In participants with baseline liver fat content (as measured by MRI-PDFF) of 5% or more, the liver fat content was reduced by 73.3% after 24-week treatment of mazdutide. Mazdutide 9 mg was well tolerated, with no adverse event leading to treatment discontinuation reported. The most frequently reported adverse events were gastrointestinal, and most were mild to moderate in severity.

Conclusion: In Chinese adults with a BMI of 30 kg/m2 or more, mazdutide 9 mg showed robust body weight reduction and prominent hepatic benefits.

Disclosure

H. Jiang: None. L. Ji: None. Y. Zhang: None. Z. Cheng: None. S. Pang: None. X. Li: None. W. Qiu: None. Q. Ma: Employee; Innovent Biologics (Suzhou) Co., Ltd. Z. Liu: Employee; Innovent Biologics. Y. Wang: Employee; Innoventbio. H. Deng: Employee; Innovent. L. Qian: Employee; Innoventbio.
1902-LB: Evaluating Need for Larger Insulin Reservoir in Patch Pumps—Leveraging Retrospective Dose Data for U.S. Adults with Type 2 Diabetes on MDI
Authors: WRIGHT EUGENE E. , SHAH VIRAL N. , THACH ANDREW V. , JAVADI PASHA , DAVIES SHAWN , SIERADZAN RAY
Published: June 2024

Introduction & Objective: People with T2D may require higher total daily doses (TDD) of insulin with progression to MDI. Study aim was to examine impact of different insulin reservoir sizes for adults with T2D on MDI transitioning to a patch pump.

Methods: Adults (≥18 yr) with T2D on MDI (≥3 daily insulin injections) were included from the US IQVIA ambulatory electronic medical record dataset (01/2017 - 07/2022). Using mean TDD per person, we estimated number (%) of people for whom 200-unit (u) and 300u insulin reservoirs would be sufficient for different wear times and the number of patch pumps needed over time.

Results: Mean ±SD TDD was 96±58u (median 80u) among 41,215 adults with T2D on MDI (52% women; mean age 58±13 yr, mean BMI 34±7 kg/m2). For 72-hr wear, 200u and 300u reservoirs were sufficient capacity for 15,612 (38%) and 26,290 (64%) adults, respectively (Figure). For 48-hr wear, 200u and 300u were sufficient for 64% and 85%, respectively, and for 24-hr wear, 94% and 99%. Number of patches needed with 200/300u reservoirs were estimated at 15/10 per mo, 176/122 per yr at mean TDD of 96u; 12/10 per mo, 147/122 per yr at median TDD of 80u; 23/15 per mo, 274/183 per yr at TDD 150u; 30/20 per mo, 366/244 per yr at TDD 200u.

Conclusions: Findings provide a solid rationale for larger insulin reservoir size, providing longer wear times and fewer patches for adults with T2D on MDI transitioning to a patch pump.

Disclosure

E.E. Wright: Advisory Panel; Abbott. Consultant; Abbott. Speaker's Bureau; Abbott. Consultant; Abbott Diagnostics. Advisory Panel; ADA/ACC Diabetes by Heart Program, Bayer Inc. Consultant; Bayer Inc. Speaker's Bureau; Bayer Inc. Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Lilly Diabetes. Consultant; Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; embecta. Consultant; embecta, GlaxoSmithKline plc. Speaker's Bureau; GlaxoSmithKline plc. Advisory Panel; Medtronic, Renalytix. Consultant; Renalytix. Speaker's Bureau; Renalytix. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Advisory Panel; Stability Health. Consultant; Up-To-Date. V.N. Shah: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi, Medscape. Consultant; embecta, Tandem Diabetes Care, Inc. A.V. Thach: Employee; embecta. Research Support; dQ&A. Employee; AbbVie Inc., Sunovion Pharmaceuticals Inc. P. Javadi: Employee; embecta, Insulet Corporation. S. Davies: None. R. Sieradzan: Employee; embecta. Stock/Shareholder; embecta.
1913-LB: Observed Glycemic and Psychosocial Benefits in the Prospective Bigfoot Unity Real World Study (BURST)—A 6-Month Analysis
Authors: TILLMAN JOHN , BECK ROY , POLONSKY WILLIAM H. , CALHOUN PETER , MOUSE THOMAS J. , BAILEY RYAN , JACOBY JEANNE , NANDAN RAKESH , MALONE JAMES K.
Published: June 2024

Introduction & Objective: The Bigfoot Unity® System is an FDA-cleared smart pen cap system incorporating CGM data (Abbott FreeStyle Libre 2), real-time alerts, and clinician-directed insulin dose recommendations. The objective was to analyze real world, 6-month data for System users.

Methods: We conducted a per-protocol 6-month analysis (N=102) from the prospective, BURST study (NCT05088265). Participants completed baseline, adverse event and patient reported outcome surveys electronically. A1C data were from a home kit or electronic medical record.

Results: Median age was 59 years, 87% had T2D, 42% used CGM previously, 62% were White non-Hispanic and 59% female. Mean A1C decreased from 9.1±1.7% at baseline to 8.0±1.2% at 6 months (mean difference -1.1%, 95%CI -1.4, -0.8; p<0.001). Six severe hypoglycemia events in 4 participants (none System related) and no DKA occurred. Diabetes Distress Scale scores decreased (mean difference -0.7, 95%CI -0.9, -0.5; p<0.001) and Hypoglycemia Confidence Scale scores increased (mean difference 0.4, 95%CI 0.2, 0.5; p<0.001) with System use (Table).

Conclusion: Glycemic improvement along with reduced diabetes distress and increased hypoglycemia confidence occurred using Bigfoot Unity for 6 months. The reduction in A1C occurred while meeting established hypoglycemia targets of <4 and <1% for percent time below 70 and 54 mg/dL, respectively.

Disclosure

J. Tillman: Employee; Abbott. R. Beck: Consultant; Insulet Corporation. Research Support; Insulet Corporation. Consultant; Tandem Diabetes Care, Inc. Research Support; Tandem Diabetes Care, Inc. Consultant; Beta Bionics, Inc. Research Support; Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc. Consultant; Novo Nordisk. Research Support; Novo Nordisk, Eli Lilly and Company. Consultant; embecta, Vertex Pharmaceuticals Incorporated, Hagar, Ypsomed AG, Sanofi, Zucara Therapeutics, Sequel. W.H. Polonsky: Research Support; Abbott Diagnostics, Dexcom, Inc. Consultant; Eli Lilly and Company, Sanofi. Advisory Panel; embecta. Consultant; Vertex Pharmaceuticals Incorporated. Advisory Panel; 9am Health. P. Calhoun: None. T.J. Mouse: Research Support; Bigfoot Biomedical, Inc., MannKind Corporation. R. Bailey: None. J. Jacoby: Employee; Bigfoot Biomedical, Inc., Beta Bionics, Inc., Sequel Med Tech. R. Nandan: Employee; Abbott, Bigfoot Biomedical, Inc. J.K. Malone: Employee; Bigfoot Biomedical, Inc., Abbott.

Funding

Abbott
1921-LB: A Wavelet AI Algorithm to Identify Postprandial Glucose Responses from CGM Profiles
Authors: LIM WANSANG , BARUA SOUPTIK
Published: June 2024

Objective: AI algorithms can potentially identify postprandial glucose responses (PPGR) directly from continuous glucose monitoring (CGM) data, reducing the burden of manual meal logging and PPGR interpretation. However, no standard AI approach for this task currently exists.

Methods: We developed a wavelet AI algorithm to identify PPGRs using a public CGM dataset (Hall'18) from individuals without a prior diagnosis of diabetes (Fig 1). The dataset also included clinic-recorded meal timings on a subset of days. Briefly, the algorithm works by computationally finding the best match for a template shape (the wavelet) in a time series. The algorithm was trained using a 5-fold cross-validation approach, and evaluated using two measures: (i) the time difference between true and predicted PPGR start times, and (ii) the ratio of predicted to true 2-hr area under the PPGR curve (AUC).

Results: We tested our algorithm on 19 participants with 2±1 days of both CGM data and clinic-recorded meal timings. The wavelet algorithm predicted start time of PPGR to within a median 15 [10,26] minutes of true meal time. The median ratio of predicted to true 2-hr AUC PPGR was 1.01 [1.00,1.02], indicating the wavelet algorithm’s ability to faithfully capture the PPGR.

Conclusion: A wavelet AI algorithm accurately identified PPGRs from CGM data, providing a novel automated approach to evaluate the effect of different foods on an individual’s glycemia.

Disclosure

W. Lim: None. S. Barua: None.

Funding

Abramson-Stires award from NYUGSOM Department of Medicine
193-OR: Virtual Diabetes Optimization Program vs. Standard Endocrine Care for Veterans with Uncontrolled Diabetes
Authors: ADEL THOMAS , SHERMAN KATHERINE , HANSEN JILL M. , TAXMAN JILLIAN , REETZ-NORTON MEGHANN E. , JOHNSON CHRISTOPHER , WHITTLE JEFF , MENDEZ CARLOS E.
Published: June 2024

Nearly 25% of veterans have diabetes and 78% are considered overweight or obese. At the Milwaukee VA, a virtual multidisciplinary diabetes optimization program (VDOP) is available to veterans referred to endocrine specialty care. Patients above 18 years-old and with A1c ≥ 8% are offered participation in VDOP, and those who decline, proceed with standard endocrine appointments. VDOP patients are seen by a combination of a pharmacist, dietitian, and occupational therapist in staggered weekly visits under the supervision of a physician diabetologist for 3-6 months. To assess the effectiveness of VDOP, glycemic control, weight, and insulin requirements of 39 program graduates were compared to the 62 veterans that met criteria but declined to join in the same time period. Table 1 shows no significant differences in demographic data between the two groups. VDOP participants had an average of 21 visits versus 6 visits for the comparison group. VDOP participants showed a significant greater decrease in A1c, weight, and total daily insulin dose for measurements taken closest to 6-month mark. Based on these results and when compared to conventional endocrine care, VDOP more effectively helped veterans improve glycemic control, while promoting weight loss and decreased insulin doses. As the program expands, next steps are to examine cost utilization, quality of life, and impact in other clinical outcomes.

Disclosure

T. Adel: None. K. Sherman: None. J.M. Hansen: None. J. Taxman: None. M.E. Reetz-Norton: None. C. Johnson: None. J. Whittle: Research Support; AstraZeneca. C.E. Mendez: Consultant; Siemens Healthcare Diagnostics.
1940-LB: Implementation of an Inpatient Glucose Management Program in a Large U.S. Health System
Authors: CLORE JOHN N. , CALUAG KRISTEN , TEMPLE RICHARD M.
Published: June 2024

Introduction: Translation of inpatient glycemic recommendations has been slow to occur. The recent consolidation of two large healthcare systems provided a unique opportunity to harmonize all ordersets and examine the impact on glycemic control.

Methods: A comprehensive revision of glycemic management was accomplished across the health system. All individuals admitted to any of 48 facilities with glucose > 200 mg/dl were included with metrics of glycemic control designed to assess progress across the health system. An extensive multidisciplinary educational program was developed to provide rationale and guidance for providers. Best practice alerts emphasized the use of weight-based basal insulin when not already in place. The present analysis compares annual metrics for the overall health system before (CY 2019) and after (CY 2023) implementation of the program. Target glucose was established as 140-180 mg/dl and hypoglycemia was defined as < 70 mg/dl. Glucose values after achieving initial target were then analyzed for consistency and significance before and after implementation. Results are shown as mean ± SD.* p<0.001.

Conclusion: Implementation of a comprehensive educational and informatics approach to glycemic control which emphasizes the primacy of basal insulin resulted in an increase in orderset use and a concomitant 18% decrease in hypoglycemia

Disclosure

J.N. Clore: None. K. Caluag: None.