bluuebunny/crossref_metadata_2025 huggingface dataset:
118-OR: The Apelin Receptor Agonist Azelaprag Increases Weight Loss in Diet-Induced Obese Mice on Incretin Agonists and Restores Body Composition and Muscle Function to That of Lean Controls
Authors: WANG YAN , YAN SHIJUN , BANICKI MATTHEW , COCHRAN MARY , PORTILLO CLAUDIA , GUERRERO GABRIEL , PAN YONG , COWDIN SAMANTHA , PATIL CHRISTOPHER , REBO JUSTIN , HUGHES ROBERT , MONTGOMERY RUSTY , MORGEN ERIC , FORTNEY KRISTEN , RUBIN PAUL
Published: June 2024

Introduction & Objective: Incretin receptor agonists have emerged as leading treatments for obesity. Despite the efficacy of these drugs, they can negatively impact body composition, raising interest in complementary mechanisms. In a Phase 1b trial, our oral apelin receptor agonist azelaprag preserved muscle mass, quality, and protein synthesis during bed rest and shifted the plasma proteome into a state associated with endurance exercise, including higher basal metabolic rate and VO2 max. Accordingly, we tested whether azelaprag could improve body composition and muscle function in mice on incretin agonist therapy.

Methods: High fat diet-induced obese (DIO) mice were treated for 20 days with incretin agonists, with or without azelaprag. Food and water intake, serum glucose and protein levels, body composition (via EchoMRI), and grid hang latency were measured.

Results: DIO mice on tirzepatide (10 nmol/kg) lost 16% of body weight, while mice on tirzepatide+azelaprag (1.1 g/L) lost 39%, bringing body weight in range of lean controls. Combined treatment also improved body composition: DIO/tirzepatide mice had lean mass 60% of body weight, vs. 69% for DIO/tirzepatide+azelaprag and 70% for lean controls. Grid hang assays showed that azelaprag fully restored muscle function to that of lean controls (latency, 79 sec): DIO/tirzepatide, 38 sec; DIO/tirzepatide+azelaprag, 86 sec. Similar results were obtained with semaglutide.

Conclusion: Addition of azelaprag to incretin regimens increased weight loss while restoring body composition and muscle function relative to monotherapy. In the clinic, combination therapy has the potential to amplify healthy weight loss, enabling next-generation oral incretin drugs to achieve efficacy comparable to current injectables with improved tolerability.

Disclosure

Y. Wang: None. S. Yan: None. M. Banicki: None. M. Cochran: None. C. Portillo: None. G. Guerrero: None. Y. Pan: None. S. Cowdin: None. C. Patil: None. J. Rebo: None. R. Hughes: None. R. Montgomery: None. E. Morgen: None. K. Fortney: None. P. Rubin: None.
12-PUB: Tirzepatide—Efficacy, Safety, and Satisfaction in Real World Type 2 Diabetes Application in Japan
Authors: KANEKO SHIZUKA , ASAI YUKI , NAKAZAKI AYA , ITO SAYA , HIROBATA TOMONAO
Published: June 2024

To analyze the efficacy and safety of Tirzepatide (Tir) in improving blood glucose control in clinical practice. People with type 2 diabetes who received Tir for 8 months from April 2023, were retrospectively evaluated for changes in HbA1c and given a satisfaction survey. Of the 94 people (49 males, age 63±15 years, BMI 25.3±6.7, starting HbA1c 8.1±1.7 %, 25 people on insulin), 2 were on Tir 10 mg, 3 on 7.5 mg, and the rest on ≤5 mg. HbA1c decreased on average 1.7±1.7 % and 8 were weaned from insulin therapy. Eight had no change in HbA1c or a worsening of around 0.55% on average due to oral medications or insulin dose reductions. Ten ceased Tir therapy, 3 of which achieved effective target HbA1c and were weaned at their request, 1 had large weight loss, 1 experienced hypoglycemia due to combined use with insulin and preferred to discontinue Tir rather than reduce insulin dosage, 5 experienced gastrointestinal symptoms, and 1 changed to a GLP1 formulation due to infrequent hospital visits. In one case, sleep apnea improved, and one person with Alzheimer's disease and uncontrolled food intake achieved a healthy level of food intake. One person with Prader-Willi syndrome could not reach target HbA1c due to dietary restriction limitations caused by possible insufficient Tir dosage. In the survey, 80% were satisfied, 50% would recommend the treatment to others due to superior overall results and weight loss, and 50 % stipulated unwillingness in recommending it to others, although satisfied, due to uncertainty over the effectiveness in others. Two percent were dissatisfied. Eighty percent of respondents indicated continued treatment. In comparison to their previous therapies, 90% felt healthier and more active, that Tir was a better fit and didn't place a burden on their daily lives, and that it was successful in controlling body weight. Further observation is needed.

Disclosure

S. Kaneko: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Eli Lilly and Company. Speaker's Bureau; Novartis AG, Sumitomo Dainippon Pharma Co., Ltd., Otsuka Pharmaceutical, Bayer Inc., Boehringer-Ingelheim. Y. Asai: Speaker's Bureau; Kowa Company, Ltd. A. Nakazaki: None. S. Ito: None. T. Hirobata: Speaker's Bureau; Kowa Company, Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Novartis AG, Otsuka Pharmaceutical, Boehringer-Ingelheim.

Funding

The Cookie Testing Study Group
1204-P: Challenges to Optimal Outcome during Automated Insulin Delivery (AID) Use in High Risk Youth
Authors: MCCONAUGHEY BRANTLEE , CHALEW STUART
Published: June 2024

Introduction: Youth with type 1 diabetes (T1D) often do not achieve A1c target. This is especially problematic among Non-Hispanic Black (NHB) patients who may have less access to advanced technologies. To gain insight into ways to mitigate the disparity in glycemic outcome for high risk patients, we conducted a field trial of AID use among NHB youth with suboptimal A1c.

Methods: Self-identified NHB youth with T1D, aged 10-17, A1c 8-10%, ≥2 clinic visits in past year, no DKA for 6 mon, naive to AID, willing parent, access to video conferencing were invited to participate. Participants (pts) were instructed in use of Medtronic 670G Advanced Hybrid Closed Loop pump, by a CDCES nurse. The same nurse maintained at least once a week contact/support with the family for the first 4 wks. Thereafter, pts could elect to continue AID, plus have 1-on-1 enhanced availability of nurse support as needed/desired via video conference, phone or in person for another 5 mon, in addition to clinic follow up at 3 and 6 mon. The same nurse would initiate contact at least once a month if no contact had been made by the family.

Results: A total of 8 pts initially enrolled. One pt dropped out in the first wk. Remaining pts successfully initiated AID and agreed to continue beyond the first mon. One pt was discontinued after 3 mon due to inability to utilize AID safely. Three pts achieved lower A1c, 2 having A1c<8. While 4 pts had higher A1c compared to pre-AID. Overall group A1c and MBG during AID were similar to baseline. Factors potentially contributing to lack of improvement were reluctance to initiate/seek nurse contact, missing meal boluses, difficulty keeping system in automated mode.

Conclusions: Most pts preferred AID to prior insulin delivery mode and safely used it. However, access to AID and increased availability of staff support were not sufficient to improve overall glycemic control for this group. Innovations to increase pt support and facilitate AID use appear necessary to optimize glycemic outcome for high risk patients.

Disclosure

B. McConaughey: None. S. Chalew: None.
1210-P: Maternal Diets Enriched in Olive Oil Prevent Altered Regulation of mTOR Pathways in the Decidua of the Prepubertal Offspring of Diabetic Rats
Authors: GATTI CINTIA R. , SCHIBERT FLORENCIA J. , LEONARDI MARÍA L. , HIGA ROMINA , JAWERBAUM ALICIA
Published: June 2024

Introduction & Objective: Maternal diabetes can program offspring´s diseases. mTOR pathway is crucial in decidualization, needed for properly early embryo development. In a rat model of pregestational diabetes, the female offspring showed reduced decidual levels of microRNA-21 (miR21), a microRNA involved in decidualization, an alteration prevented by a maternal diet enriched in olive oil. Here, we aim to evaluate targets of miR21 related to mTOR pathway regulation in the decidualized uteri of prepubertal offspring of diabetic rats fed or not with an olive oil-enriched diet.

Methods: A mild pregestational diabetic rat model was induced in F0 females by neonatal administration of streptozotocin (90 mg/kg sc). Control and diabetic females, mated with healthy males, received or not a 6% olive oil-enriched diet from day 1 of pregnancy until parturition. Female offspring (F1) were evaluated on postnatal day 30, after induction of decidualization (PMSG 50 UI- hCG 50 UI). MiR-21 targets PTEN and FOXO1, mTOR pathway negative regulators, were evaluated by RT-qPCR and mTOR pathway activity was evaluated by Western Blot.

Results: The offspring of diabetic rats showed increased PTEN and FOXO1 gene expression in the decidualized uteri (1.54 and 1.68 fold-change respectively, p<0.05 vs. Control Group), alterations prevented by the maternal olive-oil enriched diet. They also showed altered activity of mTOR pathway: reduced phosphorylated-rpS6/total rpS6 ratio (-75%) and phosphorylated-4EBP1/total 4EBP1 ratio (-56%) (p<0.05 vs. Control Group), alterations prevented by the maternal olive-oil enriched diet.

Conclusions: In the decidualized uteri of diabetic rat offspring, increased expression of miR21 target genes that negatively regulate mTOR activity and reduced mTOR activity suggest diabetes-induced programming of dysregulation of a signaling pathway relevant for decidualization, that can be prevented by a maternal olive oil-enriched diet.

Disclosure

C.R. Gatti: None. F.J. Schibert: None. M.L. Leonardi: None. R. Higa: None. A. Jawerbaum: None.

Funding

FONCYT (PICT 2020a -0933)
1218-P: A Critique of Defective Insulin Secretion and Insulin Sensitivity as a Precision Approach to Gestational Diabetes
Authors: JONES DANIELLE , KUSINSKI LAURA C. , MEEK CLAIRE L.
Published: June 2024

Introduction: Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency, both) and demonstrated associations with clinical outcomes. We assessed if this approach is analytically robust, reproducible in a different population and useful diagnostically, prognostically or therapeutically in clinical practice.

Methods: 1308 pregnant women with >1 risk factor having an oral glucose tolerance test were recruited. Specimens were collected for analysis of glucose (standard and enhanced procedures), HbA1c and insulin. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA-2S<25th centile of normal glucose tolerance (NGT) population); insulin-insufficient GDM (HOMA-2B <25th centile); both or neither. We assessed associations with pregnancy outcomes using logistic regression.

Results: Using optimal specimen handling, 1027/1308 (78.5%) women had NGT, 135/1308 (10.3%) had insulin-resistant GDM, 73/1308 (5.6%) had insulin-insufficient GDM and 2/1308 (0.2%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71/1308 (5.4%) had GDM with HOMA-2S and HOMA-2B both >25th centile (GDM-neither). This novel subgroup appeared insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinemia suggesting an isolated postprandial defect in insulin sensitivity, not captured by HOMA-2B or HOMA-2S. Women within most GDM subgroups had comparable pregnancy outcomes to normoglycaemic women. Similar findings were evident using different indices and standard specimen handling techniques.

Conclusions: Precision categorisation of GDM using HOMA-2S and HOMA-2B does not provide useful diagnostic, prognostic or therapeutic information, but distinguished a novel subgroup of GDM, characterised by an isolated postprandial defect in insulin sensitivity.

Disclosure

D. Jones: None. L.C. Kusinski: None. C.L. Meek: Research Support; Dexcom, Inc.

Funding

OPHELIA study was funded by the EFSD- Sanofi innovative outcomes project (2017; OPHELIA pilot study) and the NIHR Cambridge BRC. CLM is supported by Diabetes UK through an intermediate clinical fellowship (17/0005712; ISRCTN number 90795724) and the EFSD-Novo Nordisk Foundation Future Leader’s Award (NNF19SA058974).
1226-P: Inflammation Biomarkers Do Not Mediate Improvement in Markers of Insulin Resistance Seen in Postpartum Obese and Overweight Women Who Are Breastfeeding
Authors: OLIVEIRA JULIA M. , FERRARO ALEXANDRE A. , DUALIB PATRICIA , ALMEIDA-PITITTO BIANCA
Published: June 2024

Introduction: Studies suggest that breastfeeding (BF) decreases the risk of T2DM in Gestational Diabetes Mellitus (GDM) women. The mechanisms by which this improvement occurs are poorly understood. Our objective was to analyze the association of BF with markers of insulin resistance (MIR) and the potential mediation effect of subclinical inflammation (SI) in this association, in women with overweight/obesity and GDM.

Methods: This prospective study enrolled a convenience sample of 99 pregnant women followed from the 1st trimester up until 2-6 months postpartum. Blood was drawn at postpartum. A latent variable of SI was inferred indirectly through a mathematical model from the observable variables: adiponectin, branched chain amino acids, E-selectin, copeptin, zonulin and lipopolysaccharide (LPS). Linear regression models showed the association of BF on MIR, adjusted for covariables identified by the software Daggity. Mediation analyses were performed to determine the total, direct and the indirect effect (via SI) of BF on MIR.

Results: Women who predominantly breastfed (BF group = 44) had lower levels of triglycerides (TG), fasting glucose and insulin, TG/HDL ratio, TyG index, and HOMA-IR. LPS levels were lower in the BF group [6.8 (4.2-10.6) vs 9.2 (6.9-11.5)ng/mL, p=0.048] while other variables were similar among groups. In linear regression models an inverse association was observed between BF and fasting glucose [-6,60(-11.06 to -2.14), p=0.004), HOMA-IR [-0.26(-0.49 to -0.03), p=0.026] and TyG index [-004(-0.06 to -0.01), p=0.003] adjusted for GDM, parity, pre-gestational BMI, scholarity, weight gain during pregnancy and mode of delivery. Mediation analysis showed that SI did not mediate the results seen on the linear regression models.

Conclusion: BF is associated with an improvement in MIR in postpartum obese/overweight women, regardless of GDM. SI did not mediate the association between BF and improvement in MIR.

Disclosure

J.M. Oliveira: None. A.A. Ferraro: None. P. Dualib: None. B. Almeida-Pititto: None.
1234-P: Early Prediction of Gestational Diabetes Based on Novel Biomarkers and Risk Factors in Early and Midpregnancy—A Longitudinal Study
Authors: YANG JIAXI , SACKS DAVID B. , TSAI MICHAEL Y. , CHEN JINBO , ZHANG CUILIN
Published: June 2024

Objectives: We aimed to improve early GDM prediction using a comprehensive biomarker panel in early and mid-pregnancy, considering clinical accessibility.

Methods: In a US study of 2802 multi-racial/ethnic pregnant individuals, we assessed 91 cardiometabolic biomarkers at gestational weeks 10-14 (random blood) and 15-26 (fasting) among 107 GDM cases and 214 controls. Biomarkers significantly associated with GDM were selected for prediction and categorized for clinical accessibility: Group I (routine clinical tests like HbA1c, hs-CRP, lipids), Group II (less routinely assessed biomarkers like IGF axis markers, adipokines), Group III (specialty lab-required targeted metabolomics like amino acids (AAs) and phospholipid fatty acids (FAs)). We developed a comprehensive full model incorporating these biomarkers alongside conventional predictors (age, BMI, plasma glucose) and alternative models based on clinical accessibility. Model performance was evaluated by AUC, proportion of cases followed (PCF, %), and proportion needed to follow (PNF, %).

Results: At 10-14 GW, the full model had the highest discriminative accuracy, AUC of 0.842. Similarly, the full model at 15-26 GW had the highest accuracy, AUC of 0.829. The addition of novel biomarkers improved clinical applications as demonstrated by PCFs and PNFs. For instance, at 10-14 GW, following women with a GDM risk above 80% as estimated by our models would identify 69.5% of GDM cases in the full model vs. 49.1% in the conventional model. To identify 90% of GDM cases, the proportion of women needed to follow based on the estimated risks would be 46.1% in the full model vs. 71.1% in the conventional model.

Conclusion: A selected panel of biomarkers using early-pregnancy random plasma samples can be as predictive as those using mid-pregnancy fasting samples. HbA1c, key IGF axis markers and adipokines, and selected phospholipid FAs and AAs effectively predict GDM risk, offering meaningful clinical utility.

Disclosure

J. Yang: None. D.B. Sacks: Other Relationship; Sebia, Trinity. M.Y. Tsai: None. J. Chen: None. C. Zhang: None.

Funding

Dean's Office, Yong Loo Lin School of Medicine, National University of Singapore; The Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and American Recovery and Reinvestment Act funding: HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C, HHSN275201000001Z
1236-P: Gestational Diabetes Mellitus in Georgia, United States—Factors Associated with Postpartum Glucose Tolerance Testing Completion
Authors: VUNCANNON DANIELLE M. , JOHNSON LESLIE C.M. , LUONG JACKIE , CHANDRASEKARAN SUCHITRA
Published: June 2024

Introduction: National guidelines outline completion of postpartum glucose tolerance testing (GTT) as standard of care for those with gestational diabetes mellitus (GDM). Existing surveillance in Georgia has not evaluated factors associated with GTT completion for the state.

Methods: This retrospective cohort study included all patients with GDM identified on birth certificate data in the state of Georgia from 2017-2020. Georgia Pregnancy Risk Assessment Monitoring System data and birth certificate data were used to evaluate patient factors associated with GTT completion. Associations between patient factors and GTT completion were analyzed using Chi-squared tests. The association between ethnicity and GTT completion was further analyzed using Poisson regression.

Results: The GDM rate was 6.61% within the study timeframe. Patients with GDM had high attendance of postpartum care (88.7%); however, only 47.9% of patients overall or 53.2% who attended postpartum care completed GTT. There was no difference between those who did vs. did not complete GTT for maternal age, race, payor status, or comorbidities. Completion rates were higher among those with higher levels of education (54.0% if >16 vs. 24.1% if <12 years) and lower in rural vs. urban residents (43.3% vs. 48.6%). Hispanic women had lower rates of postpartum care attendance (69.0%) and were less likely to complete GTT (13.8%). Odds of GTT completion were lower for Hispanic women even when controlling for education and insurance status (incidence rate ratio 0.91, 95% CI 0.84-0.99).

Conclusion: In Georgia, attendance of postpartum care was high; however, GTT completion rates were unacceptably low. Hispanic ethnicity, lower levels of maternal education, and rural residence were associated with decreased completion rates. These data demonstrate a significant lack of concordance with recommended GDM care guidelines in Georgia and serve as a call to action to standardize care across the state.

Disclosure

D.M. Vuncannon: None. L.C.M. Johnson: None. J. Luong: None. S. Chandrasekaran: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (P30DK111024)
1257-P: Post-void Residual Urine in Men and Women with Long-Standing Type 1 Diabetes (T1D)—The UroEDIC Study
Authors: BRAFFETT BARBARA H. , IPPOLITO GIULIA M. , AMIGHI ARASH , WESSELLS HUNTER , TRAPANI VICTORIA R. , JACOBSON ALAN M. , BUSUI RODICA , SARMA ARUNA V.
Published: June 2024

Introduction & Objectives: Diabetic cystopathy, characterized by diminished bladder sensation, poor contractility, and increased post-void residual (PVR) urine >100 mL, is understudied in T1D. We describe the distribution of PVR in men and women with T1D enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) UroEDIC ancillary study.

Methods: PVR was measured using BladderScan BVI 3000 (Verathon Inc., Bothell, WA) in 450 men and 413 women. Lower urinary tract symptoms (LUTS) were defined by the American Urological Association Symptom Index (AUASI). Kidney disease was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, neuropathy by symptoms, signs, and abnormal electrophysiology, and cognitive impairment by a decline >1 SD from baseline in psychomotor and mental efficiency.

Results: Mean (SD) age and T1D duration were 63 (7) and 42 (5) years, respectively. Men had significantly higher PVR than women (median [IQR] = 27 [5-94] vs. 5 [1-37] mL, p<0.0001; PVR >100 mL = 23% vs. 9%, p<0.0001). Chronic urinary retention (>300 mL) was present in 4% of men and 1% of women. Older age was associated with higher PVR in men (p=0.01), but not women (p=0.52). Men with vs. without PVR >100 mL had higher median AUASI scores for urgency (p=0.01) and weak stream (p<0.0001). There were no significant differences in AUASI scores for women with and without elevated PVR. Among men, higher PVR volumes were associated with a history of kidney disease (p<0.01), confirmed clinical neuropathy (p<0.001), and cognitive impairment (p=0.03). There were no significant associations between PVR and HbA1c in both men and women.

Conclusion: PVR in long-standing T1D varies by sex. Findings suggest that aging, LUTS, kidney disease, and neuropathy are important factors associated with higher PVR in men only. These findings emphasize the need for sex-specific diagnostic strategies to target optimized interventions for bladder dysfunction at the point of care in men and women with T1D.

Disclosure

B.H. Braffett: None. G.M. Ippolito: None. A. Amighi: None. H. Wessells: None. V.R. Trapani: None. A.M. Jacobson: None. R. Busui: Board Member; American Diabetes Association. Consultant; Procter & Gamble, AstraZeneca, Averitas Pharma, Inc., Bayer Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Ono Pharmaceutical Co., Ltd., Novo Nordisk, Roche Diagnostics. Advisory Panel; ADA/ACC Diabetes by Heart Program. A.V. Sarma: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK116723-01A1)
1284-P: Prevalence of Cardiovascular Risk in Type 1 Diabetes Mellitus in China—Findings from a National Cross-Sectional Study
Authors: WANG WEIHAO , GUO LIXIN , PAN QI
Published: June 2024

Background: The 2019 ESC/EASD recommendations classified cardiovascular risk (CV) in diabetes mellitus (DM). The CV risk assessment and stratification were essential for identifying persons with a very high risk of CVD and active targeted interventions. The purpose of this research is to fill in the lack of epidemiological data on the classification of individuals with a very high cardiovascular risk in patients with type 1 diabetes mellitus (T1DM) from different regions across China.

Methods: This multicenter, cross-sectional, non-interventional study gathered information such as disease duration, body mass index (BMI), traget organ damage including atherosclerotic heart disease, impaired renal function, left ventricular hypertrophy and retinopathy, from outclinic patients by trained doctors. We use the 2019 ESC/EASD standards divided T1DM patients into two categories: with a very high risk and else.

Results: A total of 38260 participants from more than 2,000 hospitals in 30 provinces of China were enrolled from 2020 to 2022, of which 54.81% of T1DM were at very high CV risk. The proportions of very high-risk T1DM were higher in Northeast (72.70%), Southwest (69.99%) and Central (54.41%), while the lowest was Southern China (47.03%). The proportion of very high risk of CV risk in T1DM increased with age and BMI, 33.61% in those among <35 years old subgroups, while in 35-65 years old were 59.57% and among > 65 years old was 70.80%. (P < 0.0001). Male and smoker showed increased prevalence of the very high CV risk in T1DM (P < 0.0001).

Conclusion: This study is the largest observational study of CV risk assessment in T1DM patients in China. The CV risk situation of diabetic patients in China is critical, and comprehensive control and management of CV-related risk factors such as blood pressure, BMI, and lipids in DM patients need to be strengthened so as to reduce the risk of cardiovascular events and death.

Disclosure

W. Wang: None. L. Guo: Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Hengrui (USA) Ltd., Dreisamtech, Dongbao, Gan & Lee, Hansoh. Q. Pan: None.

Funding

This study was supported by Beijing Great Physician Commonwealth Foundation "CV Risk Evaluation" program
1291-P: Early-Onset Type 2 Diabetes in the U.S.—Prevalence from National Health and Nutrition Examination Survey (NHANES) 1999–2020 Data
Authors: LEE CLARE , BOYE KRISTINA , BERGMAN BRANDON , WILLIAMSON SUZANNE E. , NELSON DAVID R.
Published: June 2024

Early-onset T2D, defined as diagnosed before age 40, is increasingly prevalent and may be a more aggressive disease than later-onset T2D, with faster beta cell deterioration, that is less responsive to medications. We estimated the prevalence of diagnosed and undiagnosed early-onset T2D in the US between 1999 and 2020 using the nationally representative NHANES database.

Data from a longitudinal series of cross-sectional surveys of US participants conducted every two years from 1999-2020 were analyzed retrospectively. Participants with early-onset T2D were identified based on a diagnosis of T2D before age 40 (diagnosed T2D), or a fasting glucose ≥126 mg/dL or HbA1c ≥6.5% in those aged <40 years without a T2D diagnosis (undiagnosed T2D).

The estimated number of participants with undiagnosed and diagnosed early-onset T2D in the US increased from 493,000 and 3,869,000 during the 1999-2000 survey cycle to 1,112,000 and 5,560,000 during 2017-2020, respectively (Figure). The prevalence rate for undiagnosed early-onset T2D increased significantly by 46% per 10-year time-period between 1999 and 2020 (OR 1.461, p<0.05), whereas the rate for diagnosed early-onset T2D remained stable.

NHANES data indicate that undiagnosed early-onset T2D is increasing in prevalence over time in the US, suggesting more attention is needed to diagnose and treat younger adults with T2D to improve health outcomes.

Disclosure

C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. K. Boye: Employee; Eli Lilly and Company. B. Bergman: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. S.E. Williamson: Consultant; Eli Lilly and Company, Takeda Pharmaceutical Company Limited, GlaxoSmithKline plc, Novo Nordisk, Lundbeck. D.R. Nelson: Employee; Eli Lilly and Company.

Funding

Eli Lilly and Company
1297-P: Hypergliptinemia —A Compensatory Phenomenon Observed in Asian Population with Newly Diagnosed Type 2 Diabetes Mellitus
Authors: CHIN CHONG SHIAU , SUKOR NORLELA , ROBERT SARAH A. , FONG NG KIM , KAMARUDDIN NOR A.
Published: June 2024

Introduction & Objective: Impaired glucagon-like peptide-1 (GLP-1) secretion in Western patients contributes to the incretin defect in type 2 diabetes mellitus (T2DM). However, several studies from East Asia suggested preserved GLP-1 levels in T2DM. We aimed to resolve these conflicting findings by investigating GLP-1 levels during oral glucose tolerance test (OGTT) among subjects with normal glucose tolerance (NGT) and T2DM.

Methods: A total of 120 subjects consisting of NGT (n=58) and T2DM (n=62) had their plasma total GLP-1 concentrations measured at 0, 30 and 120 min following a 75 g OGTT. Homeostasis model assessment of insulin resistance (HOMA-IR), HOMA of insulin sensitivity (HOMA-IS) and triglyceride glucose (TyG) index were calculated. All the above parameters were subsequently assessed in T2DM subjects of <1 year vs ≥ 1 year of disease duration to elicit if there are any subtle differences in their respective GLP-1 responses.

Results: Total GLP-1 levels at fasting (fGLP-1) and 30 min (GLP-130min) were significantly higher in T2DM than NGT (fGLP-1 27.18±11.56 pmol/L vs. 16.24 ±7.79 pmol/L, p<0.005; GLP-130min 50.22±18.03 pmol/L vs. 31.44 ±22.59 pmol/L, p<0.001; respectively). The GLP-1 levels were positively correlated with HOMA-IR and TyG index but negatively correlated with HOMA-IS. T2DM subjects with disease duration < 1 year had higher GLP-1 response than those with disease duration ≥1 year (GLP-130min 55.33±18.09 pmol/L vs. 46.02±17.12 pmol/L, p<0.05).

Conclusion: The augmented GLP-1 levels in T2DM represents an adaptive compensatory response to increasing insulin resistance, a phenomenon we aptly refer to as “hypergliptinemia”. However, this phenomenon is transient as the incretin response started to diminish after one year of diagnosis in keeping with the progressive nature of T2DM.

Disclosure

S. Chong: None. N. Sukor: None. S.A. Robert: None. K. Ng: None. N.A. Kamaruddin: Speaker's Bureau; Boehringer-Ingelheim, Novo Nordisk, AstraZeneca.

Funding

Universiti Kebangsaan Malaysia (GUP-2017-066); Malaysian Endocrine and Metabolic Society (L12-MEMS6)
1302-P: Long-COVID in Type 1 and Type 2 Diabetes—Prevalence, Clinical Outcomes, and Inflammatory Marker Responses
Authors: O'DOHERTY EMER , ADAM ATIF , SHALIT ALMOG , SHAH HETAL , KING GEORGE L. , MIDDELBEEK ROELAND J.W.
Published: June 2024

Introduction: Diabetes significantly impacts COVID-19 morbidity and mortality, with the long-term sequelae ('long-COVID') in diabetes poorly understood. This study examines the prevalence and clinical outcomes of long-COVID, and the influence of pharmacotherapy, such as metformin use, on COVID-19 symptom persistence. Another objective is to determine inflammatory cytokine concentrations in patients with long-COVID.

Methods: Adult T1D and T2D patients at Joslin Diabetes Center, USA, were surveyed for COVID-19 history with EMRs providing demographic and clinical data. Blood samples were analyzed using Elecsys Anti-SARS-CoV-2 (Roche, Indianapolis) and V-Plex assays (MSD, Rockville) for COVID-19 antibodies and cytokines, respectively.

Results: Among 358 patients (162 T1D, 196 T2D), T2D patients were older (62.8 years, SD 11.9) compared to T1D patients 47.4 years, SD 15.6; p<0.001). The majority were White, with a higher proportion of Asian Americans among T2D (4% vs. 27%, p<0.001). Long-COVID was reported by 30% of T2D and 13% of T1D patients (p=0.002). Comparing T1D and T2D patients with long COVID, T2D patients exhibited higher HbA1c values by 1.1% (SD: 0.48) (p=0.03). No difference in HBA1c was seen in patients with T1D. In T1D, significant increases in IL-1b, IL-6 (p<0.001 each), and TNF-a (p=0.003) were observed, with no change in IL-10 (p=0.62). T2D patients with long-COVID had increased TNF-α (p=0.01) and decreased IL-10 (p=0.04). Additionally, Metformin initiation was linked to a 48% reduced likelihood of long-COVID (p=0.04).

Conclusion: Long-COVID manifests differently in T1D and T2D, with distinct cytokine changes suggesting unique inflammatory responses. In T2D, patients with long-COVID exhibit worse glycemic control and metformin may play a potentially protective role. Ongoing research is needed to determine the relationship between metformin use and inflammatory markers in long-COVID.

Disclosure

E. O'Doherty: None. A. Adam: None. A. Shalit: None. H. Shah: None. G.L. King: None. R.J.W. Middelbeek: Research Support; Novo Nordisk.
1313-P: Association between Changes in Metabolic Syndrome (MetS) Status and Development of Cardiovascular Diseases (CVD)
Authors: TAKIZAWA HIROKI , FUJIHARA KAZUYA , MITSUMA YURIE , GOTO WAKANA , YAMAMOTO MASAHIKO , OSAWA TAEKO , SUZUKI HIROSHI , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: June 2024

We previously determined cut-off values for MetS components to predict CVD and proposed newly optimized criteria for MetS in Japanese. Since MetS status changes over time, we investigated associations between changes in MetS and CVD risk using current and optimized criteria. We divided 201,007 men and 99,579 women without prior CVD into 4 groups according to MetS status at 2 points (beginning and end of baseline) during a 2-year baseline period (MetS-free, MetS-developed, MetS-remission, MetS-persisted). After baseline, incidence of CVD was followed up. Association between changes in MetS and incident CVD was analyzed by a multivariate Cox regression model. During a median follow-up of 5.0 y, 2,831 men and 330 women developed CVD. Compared with the MetS-free group, MetS-developed and MetS-persisted groups had an increased risk of CVD by any criterion (Fig). With optimized criteria, HR was higher in men with MetS-persisted than in women. Compared with MetS-persisted, MetS-remission had decreased CVD risk by any criterion in men but in women it was associated with decreased CVD risk only by optimized criteria. MetS-developed by any criterion was associated with increased CVD risk in both sexes. MetS-remission by newly optimized criteria was associated with reduced CVD risk in both sexes, suggesting changes in MetS status by optimized criteria are strongly related to CVD risk.

Disclosure

H. Takizawa: None. K. Fujihara: None. Y. Mitsuma: None. W. Goto: None. M. Yamamoto: None. T. Osawa: None. H. Suzuki: None. Y. Matsubayashi: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Novo Nordisk, Astellas Pharma Inc., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Eisai Inc., Sumitomo Dainippon Pharma Co., Ltd.
1327-P: Novel Subgroups of the Three-Year Risk of Incident Diabetes and Complications in Chinese Diabetes-Free Adults
Authors: GUO LIXIN , WANG WEIHAO
Published: June 2024

Aims: The aim of this study was to analyze common clinical indicators in diabetes-free cohorts population using innovative clustering methods to derive characteristic clusters and to assess the utility for stratified prediction of diabetes risk and complications.

Methods: We analyzed the data of 13,829 diabetes-free adults from a physical examination cohort of 51,400 people follow-up from 2014 to present in Kunshan, China, and used the Ensemble clustering based on ending indicators and Weighted Naive Bayesian Classification method to select the most important variables from the candidate variables and assessed the 3-year risk of diabetes and the complications.

Result: We screened 13 clinically important variables. In the Kunshan cohort we identified 3 clusters. Cluster 2 (n=4,622) was characterized by the worst control of glucose and lipid metabolism, highest risk of diabetes and complications of FLD. Cluster 3 (n=2,456) was characterized by the oldest age, the highest SBP, BMI, waist circumference, intermediate risk of diabetes and the highest risk of CVD and stroke. Cluster 1 (n=6,751) population had good indicators and a low risk of diabetes and complications such as CVD, FLD and stroke. In the post-correction cox survival analysis for FLD, taking cluster 1 as the reference, HR of cluster 2 was 2.357(95% CI: 2.161-2.571, p<0.001) and HR of cluster 3 was 1.903(95% CI: 1.718-2.108, p<0.001). In the post-correction cox survival analysis of CVD, HR of cluster 2 was 1.193 (95% CI: 0.975-1.459, p=0.087) and HR of cluster 3 was 1.295 (95% CI: 1.041-1.611, p=0.02). The risk of diabetes and CVD predicted by PRS was consistent with that predicted by clinical clustering methods.

Conclusions: Phenotypes derived from the analysis of clinical characteristics using the new clustering method help to identify and stratify the risk of diabetes and related complications.

Disclosure

L. Guo: Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Eli Lilly and Company, Hengrui (USA) Ltd., Dreisamtech, Dongbao, Gan & Lee, Hansoh. W. Wang: None.

Funding

This work was supported by National High Level Hospital Clinical Research Funding, National Natural Science Foundation of China (82170848 and 82370835), Natural Science Foundation of Beijing (7244403), Capital's Funds for Health Improvement and Research (2022-1-4051), Beijing Municipal Science & Technology Commission (No Z221100007422007) and National Key R&D Program of China (2022YFB3203700).
1332-P: Young-Onset Type 2 Diabetes—UK Prospective Diabetes Trial (UKPDS) 30-Year Follow-up
Authors: LIN BERYL , COLEMAN RUTH L. , BRAGG FIONA , MADDALONI ERNESTO , HOLMAN RURY R. , ADLER AMANDA I.
Published: June 2024

Introduction: Young-onset type 2 diabetes (T2D) is associated with premature complications and death.

Aim: To assess whether long-term complications and mortality rates differed with younger age at T2D diagnosis over UKPDS 30-year follow-up.

Methods: Using 1977-2007 data from UKPDS participants with newly-diagnosed T2D without diabetes autoantibodies, we analysed standardised mortality ratios (SMR) using UK general population data and incidence rates of pre-specified aggregate outcomes in young and later onset T2D (<40 years vs >40 years), and by 10-year age intervals at diagnosis.

Results: Of 4550 participants (59% male, HbA1c 9.1%), 429 (9.4%) had young-onset T2D. The SMR was higher in young-onset T2D (3.72, 95% CI 2.98-4.64; median follow-up: 18.0 years) than in later-onset T2D (1.54, 1.47-1.61; 17.4 years). At any given age, the incidence of any diabetes-related endpoint, all-cause mortality, microvascular disease, and myocardial infarction was higher with younger age at diagnosis (Figure). Annual mean HbA1c was higher in the first 20 years of follow-up in those with younger compared with later-onset T2D.

Conclusion: The risk of dying relative to the general population is even greater for people diagnosed with T2D at younger ages. The greater risk of complications and poorer glycaemic control in young-onset T2D suggests a need to develop services to identify and support these individuals over their lifetimes.

Disclosure

B. Lin: None. R.L. Coleman: None. F. Bragg: None. E. Maddaloni: Advisory Panel; Novo Nordisk, Merck Sharp & Dohme Corp. Speaker's Bureau; Abbott, Eli Lilly and Company. Consultant; PikDare. Speaker's Bureau; MTD. R.R. Holman: Advisory Panel; Anji Pharmaceuticals, AstraZeneca, Novartis AG. A.I. Adler: None.
1342-P: A Predictive Model for Five-Year Early Diabetic Kidney Disease
Authors: HOU XUHONG , YE XIAOQI , JIA WEIPING
Published: June 2024

Introduction & Objectives: Early identification of individuals at elevated risk of developing diabetic kidney disease (DKD) could improve clinical care and prognosis through enhanced cost-effective surveillance and better management of underlying health conditions. The aim of this study was to develop an effective and practical model for predicting early DKD risk in a community-based prospective cohort.

Methods: A prospective community-based cohort study was undertaken from 2013 to 2018. We analyzed data from 1545 people with diabetes and normal kidney function at baseline. The least absolute shrinkage and selection operator regression with cross-validation was used to identify potential predictive variables. A less complex DKD prediction model was derived from logistic regression and presented as a nomogram. The performance of the novel DKD prediction model was compared with that of the existing prediction model by assessing model discrimination.

Results: Six predictors of DKD were identified: diabetes duration, family history of diabetes, systolic blood pressure, urine albumin-to-creatinine ratio, estimated glomerular filtration rate, and glycated albumin (GA). The new DKD predictive model demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.797 and was internally validated with a corrected AUC of 0.786. There were no significant deviations between observed probability and predicted probability. The predictive performance of the existing DKD risk prediction model was significantly lower than our new DKD risk prediction model (AUC: 0.681 vs. 0.797, P <0.001). In addition, the predictive value of GA was higher than that of Hemoglobin A1c and fasting plasma glucose.

Conclusions: The 5-year early DKD predictive model, derived from a community-based cohort, demonstrates good performance. Additionally, GA holds more significant importance than other glucose indicators in predicting DKD.

Disclosure

X. Hou: None. X. Ye: None. W. Jia: None.
1345-P: Burden of Injury among People with Type 1 and Type 2 Diabetes
Authors: FELEKE BERHANU E. , AND INJURY DIABETES
Published: June 2024

Introduction & objective: The risk of injury in people with diabetes is not well described. This study was conducted to estimate the risk and excess hospitalisation rate for injury in people with diabetes compared to the general population.

Methods: Data were obtained from the Australian National Diabetes services scheme, Hospitalisation Datasets, the Pharmaceutical Benefits Scheme, the National Death Index, and the national census from 2011-2017. Hospitalisations for injury were coded into the following categories: head, lower extremity, upper extremity, abdominal, vertebral, burns, and other injury. Poisson regression was used to estimate the relative risk (RR) and excess hospitalisation of injury in those with diabetes compared to the general population.

Results: In this study, there were 97,917 admissions among people with diabetes and 3,463,173 among the general population. Compared to the general population, the age, sex, and calendar year adjusted risk of admission for any injury (RR 1.01 [95% CI: 1.01, 1.02]), head injury (1.14 [1.12, 1.15]), burn (1.30, [1.23, 1.39]), and other injury (1.16 [1.13, 1.20]) was higher for people with diabetes. Compared to the general population, a lower risk of hospitalisation was observed for lower extremity injury (0.96 [0.95, 0.98]), abdominal (0.65 [0.64, 0.66]), vertebral (0.88 [0.86, 0.90]), and upper extremity (0.91 [0.90, 0.92]) injury. Compared to the general population, higher risk of injury was observed in people with type 1 diabetes (1.40 [1.37, 1.44]) and type 2 diabetes using insulin (1.27 [1.26, 1.29]), but the risk was lower in those not using insulin (0.92 [0.91, 0.93]). Falls were the primary cause of injury in people with diabetes.

Conclusion: Diabetes, especially those using insulin exhibited higher risk of hospitalisation for injury. Diabetes interventions should consider falls prevention strategies including building muscle strength.

Disclosure

B.E. Feleke: None.
136-OR: Examining New-Onset Type 1 Diabetes Educational Practices among Centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI)
Authors: MCDONOUGH RYAN , OSPELT EMMA L. , EBEKOZIEN OSAGIE , SCHULMEISTER CAROLINE , RIOLES NICOLE , HARDISON HOLLY , PLANTE DEBORAH , MUCCI ANDREA , MATHIOUDAKIS NESTORAS N. , RAMAN VANDANA , CLEMENTS MARK A. , COLLABORATIVE T1DX-QI
Published: June 2024

Background: The diagnosis of Type 1 Diabetes (T1D) requires immediate comprehensive education for people with T1D (PWD) and their caregivers. Educational content, delivery, methodology, location, and duration are not standardized. This study aims to evaluate the current state of new-onset diabetes education among T1DX-QI centers.

Methods: A survey was administered from July to September 2023 to 55 T1DX-QI centers. Descriptive analysis was completed.

Results: 50 of 55 centers (91%) completed the survey. Education consists of 5+ sessions (15%), 4 sessions (42%), 3 sessions (17%), 2 sessions (17%), and 1 session (2%). Communication immediately after diagnosis between PWD/family & care teams occurs daily (33%) or every 2-3 days (25%), and 21% is PWD/family initiated. Common communication modalities included phone calls (77%) and portal messages (19%). Education topics and session processes during new-onset visits were highly varied (Fig 1a). Pediatric centers frequently (85%) have patients consume a meal to aid in skill acquisition related to carb counting and dosing while no adult centers do. Criteria for considering outpatient teaching also varied by pediatric and adult centers. (Fig 1b)

Conclusions: Across T1DX-QI, practices related to new-onset education vary widely. Additional research is necessary to evaluate best-practices as they relate to T1D.

Disclosure

R. McDonough: Speaker's Bureau; Provention Bio, Inc. E.L. Ospelt: None. O. Ebekozien: Advisory Panel; Sanofi, Medtronic. Research Support; Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Vertex Pharmaceuticals Incorporated. Research Support; Medtronic, Lilly Diabetes, Abbott, Dexcom, Inc. C. Schulmeister: None. N. Rioles: None. H. Hardison: None. D. Plante: None. A. Mucci: None. N.N. Mathioudakis: None. V. Raman: None. M.A. Clements: Research Support; Abbott. Consultant; Glooko, Inc. Research Support; Dexcom, Inc.

Funding

Helmsley Charitable Trust
1363-P: Diabetes Control and Complications in West India—Three-Year Results of LANDMARC Trial
Authors: JOSHI SHASHANK R. , SETHI BIPIN , GOPALAKRISHNAN UNNIKRISHNAN AMBIKA , CHAWLA MANOJ S. , PATANGE SONALI A. , SHAH TEJAS , JOSHI AMEYA S. , GOKALANI RUTUL , GANDHI PRAMOD D. , MENON SHALINI K. , GADEKAR ARVIND , CHODANKAR DEEPA
Published: June 2024

Glycemic control, therapy trends, and diabetes complications were evaluated in LANDMARC — a prospective observational 3-year study (CTRI/2017/05/008452) of participants with T2D on ≥2 antihyperglycemic medications. This sub-analysis of 81 sites in West India (Ahmedabad, Mumbai, and Pune) included 1351 participants (mean [SD] baseline [BL] age: 53.2 [9.1] years, T2D duration: 8.9 [5.8] years and A1C: 7.9% [1.5]). At BL, most were insulin-naïve (n=1037; 77.4%), mainly on OADs (n=1013; 76.9%). At 3 years, 68.2% (n=733) were on OADs only, while 29.8% (n=320) were on insulin + OADs. Biguanides was the most prescribed class (BL: 1253 [93.5%] and 3-years: 1007 [93.7%]). Basal insulin usage increased from BL (n=203; 15.2%) to 3 years (n=237; 22.1%). Mean (SD) A1C, FPG, and PPG decreased by 0.4 (1.5) %, 7.2 (48.2) mg/dL, and 16.5 (73.8) mg/dL, respectively; and an increase in proportion of participants with A1C<7% (BL: 257/920 [27.9%]; 3 years: 250/940 [34.4%]), was noted. Myocardial infarction and neuropathy were the most common macro and microvascular complications, respectively (Table). Hypertension and dyslipidemia were most common CV risk factors. West India had the highest proportion of participants with CV risk factors. An understanding of pivotal regional trends in glycemia, therapy, and complications may help strategize future diabetes management practices in India.

Disclosure

S.R. Joshi: Consultant; Twin Health, Marico, Franco Indian, Zydus Cadila, Glenmark Pharmaceuticals. Other Relationship; Novo Nordisk, Sanofi, MSD, Abbott Nutrition, Abbott, Biocon, Alkem, USV Private Limited, Boehringer-Ingelheim. B. Sethi: Other Relationship; Aventis, Novo Nordisk, Eli Lilly and Company, Boehringer-Ingelheim, Merck Sharp & Dohme Corp. A. Unnikrishnan: Speaker's Bureau; Sanofi. Other Relationship; Novo Nordisk. Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Abbott, Intas Pharmaceuticals Ltd. Research Support; Torrent Pharmaceuticals Ltd. M.S. Chawla: Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Biocon. Speaker's Bureau; Biocon. Advisory Panel; Eris Lifesciences Ltd. Speaker's Bureau; Eris Lifesciences Ltd. Advisory Panel; Torrent Pharmaceuticals Ltd. Speaker's Bureau; Torrent Pharmaceuticals Ltd. Advisory Panel; USV Private Limited, Lupin Pharmaceuticals, Inc. S.A. Patange: None. T. Shah: None. A.S. Joshi: None. R. Gokalani: None. P.D. Gandhi: None. S.K. Menon: Employee; Sanofi. A. Gadekar: None. D. Chodankar: Employee; Sanofi.

Funding

Sanofi