bluuebunny/crossref_metadata_2025_split huggingface dataset:
1411-P: Predictive Utility of Single Point Insulin Sensitivity Estimator (SPISE) Index for Metabolic Syndrome (MetS) in U.S. Adults
Authors: CHO WONHEE , ROSENBERG JARED , YOUNG KIM JOON 
Published: June 2024

Although SPISE index was recently introduced as an indicator of insulin resistance (IR), its predictive ability for MetS by race/ethnicity has not been tested. Here, we aimed to: 1) examine racial/ethnic differences in SPISE index among US adults, and 2) compare predictive power of SPISE index for MetS by race/ethnicity and against other well-known IR indices (TG/HDL-C, TyG index, HOMA-IR, and 1/Insulin). A total of 2,168 adults (814 white [W], 690 black [B], and 664 Hispanic [H]) from NHANES 2017-March 2020 was analyzed in this study. MetS was defined by the AHA/NCEP criteria. SPISE index and IR indices were calculated by using physical and cardiometabolic parameters (Image). SPISE index was lowested in H, followed by B and W, with no difference between W vs. B (Image). The area under the curve of receiver operating characteristics of SPISE index for predicting MetS was highested in W (88%), followed by H (86%) and B (82%) (P&lt;0.05 vs. B), with optimal cutoffs of 5.03, 4.84, and 4.89, respectively. In the total cohort, the predictive power of SPISE index for MetS was 85%, higher than the other IR indices (Image; all P&lt;0.05). SPISE index outperforms various IR indices for predicting MetS in US adults, signifying its potential in large-scale observational studies. Race/ethnicity should be stratified when using SPISE index as its predictive power and cutoffs for predicting MetS vary by race/ethnicity.

Disclosure
W. Cho: None. J. Rosenberg: None. J. Kim: None.
1417-P: Youth-Onset Diabetes—Validation of a Large-Scale Surveillance Approach to Identify Incident Cases from Electronic Medical Records
Authors: CRUME TESSA L. , BELLATORRE ANNA , BURGETT SHAWNA , CONWAY REBECCA B. , ANDERSON THERESA , SHIFERAW BETHELHEM A. , DABELEA DANA 
Published: June 2024

Background: Surveillance of incident diabetes among youth is essential to identify health disparities and inform health care planning.
Objective: To evaluate the validity of a large-scale algorithmic approach to ascertaining diabetes incidence in Colorado youth &lt; 20 years of age in 2018, by comparing it against manual chart review.
Methods: The algorithm for identifying incident diabetes status was based on diagnostic codes, medications, and laboratory data. Manual chart review was the gold standard. We calculated the sensitivity, sensitivity, positive predicted value (PPV) and negative predictive value (NPV).
Results:A total of 3779 youth were identified as youth onset diabetes cases by both methodologies between 2002 and 2018. To identify new onset (incident diabetes) the algorithmic approach was 96.4% sensitive, and 99.4% specific compared to chart review while the PPV and NPV were 95.1% and 99.6%, respectively. For incident type 1 diabetes, the algorithmic approach was 94.2% sensitive and 99.3% specific and the PPV and NPV were 93.7% and 99.4%, respectively. For incident type 2, the algorithmic approach was 52.9% sensitive and 99.9% specific and the PPV and NPV were 85.7% and 99.6%, respectively.
Conclusion: The algorithmic approach had high validity in identifying incident cases of type 1 diabetes among youth but performed poorly for type 2.

Disclosure
T.L. Crume: None. A. Bellatorre: None. S. Burgett: None. R.B. Conway: None. T. Anderson: None. B.A. Shiferaw: None. D. Dabelea: None.

Funding
Centers for Disease Control and Prevention (U18DP006517; U18DP006518)
1427-P: Factors Predicting Significant Improvement in Glycemic Control after Endocrinology Referral in Patients with Type 2 Diabetes Mellitus and Hemoglobin A1c ≥ 10%
Authors: WILLIAMS VANESSA , NAIR TRISHA P. , AYEGBUSI OLUBUKOLA , BOTCHWAY ALBERT , BUHNERKEMPE MICHAEL , JAKOBY MICHAEL G. 
Published: June 2024

Endocrinology referral has been shown in several studies to significantly improve glycemic control in patients with uncontrolled type 2 diabetes mellitus (DM2). However, studies identifying factors that predict glycemic improvement are lacking. This is a retrospective study of adults (N =138, age ≥ 18 y) with DM2 who were referred to the Southern Illinois University Division of Endocrinology with initial HbA1c ≥ 10% and attended 6-month follow-up appointments. Patients who achieved HbA1c reduction ≥ 1% at 6-months were defined as the glycemic improvement group, while patients whose HbA1c fell by &lt; 1% or increased were considered controls. There was no difference in mean initial HbA1c for the glycemic improvement (12.0 ± 1.6%) and control groups (12.0 ± 1.2%, P = 0.98). At the 6-month visit, 82% (113/138) of patients achieved glycemic improvement, with mean HbA1c 7.9 ± 1.7% for the improvement group and 12.2 ± 1.7% for the control group (P &lt; 0.0001). There were no differences in demographics, insurance status, or comorbidities between the two groups. In a LASSO regression, factors that predicted glycemic improvement were proportion of endocrinologist appointments attended (OR 4.01, 95% CI 1.33-228.61), initiation of continuous glucose monitoring (OR 2.11, 1.11-45.86), proportion of dietitian and diabetes educator appointments attended (OR 1.91, 1.07-28.41), and initiation of a GLP-1 receptor agonist (OR 1.62, 1.04-11.71). Endocrinology referral significantly improves glycemic control for patient with DM2 and severe hyperglycemia, with compliance with appointments, initiation of CGM, and treatment with GLP-1 receptor agonists appearing to be key predictors of glycemic improvement.

Disclosure
V. Williams: None. T.P. Nair: None. O. Ayegbusi: None. A. Botchway: None. M. Buhnerkempe: None. M.G. Jakoby: None.
1428-P: Impact of Socioeconomic Inequalities on COVID-19 Mortality of People Living with Diabetes during the 2020 Epidemic Waves in France
Authors: GUION MARIE , GORIA SARAH , FOSSE-EDORH SANDRINE , COSSON EMMANUEL 
Published: June 2024

Introduction & Objective: The aim was to describe the impact of socioeconomic inequalities (SEI) on COVID-19 mortality in people living with pharmacologically treated diabetes (TD) during the two 2020 epidemic waves (W1: March-May; W2: September-December) in European France.
Methods: TD were identified using a validated algorithm from the French National Health Data System. COVID-19 mortality in 2020 was obtained from medical causes of death for people alive on January 1, 2020. SEI were measured using the French Deprivation index (FDep, by population quintiles; Q1: corresponding to the least deprived municipalities). Annual average age-standardized (European standard population 2013) mortality rates (aMR) for each wave are presented with their 95% confidence intervals [IC95%] per 100,000 person-years.
Results: During W1, the highest aMR were observed in men with TD living in the least deprived municipalities (Q1: 398 [373-422]). Then, the aMR decreased until Q3 (234 [219-249]) before increasing again until Q5 to 309 [297-321]. The same trends were observed but less pronounced in women with TD (Q1: 257 [240-275]; Q3: 156 [143-169] Q5: 196 [187-206]); and in men and women without TD. During W2, aMR were stable from Q1 to Q4, at around 240/100,000, and significantly higher in Q5: 300 [286-314] in men with TD. In women with TD, no difference was observed according to deprivation level (Q1: 171 [156-186] and Q5: 171 [162-180]), whereas an increasing gradient was observed in men and women without TD (respectively Q1: 45 [42-49]; Q5: 70 [66-74] and Q1: 17 [15-19]; Q5: 28 [25-30]).
Conclusion: These first descriptive results show that the impact of SEI on COVID-19 mortality appeared to change between the two epidemic waves in France in 2020. They raise questions about the impact of barrier measures and non-pharmaceutical interventions in SEI.

Disclosure
M. Guion: None. S. Goria: None. S. Fosse-Edorh: None. E. Cosson: Advisory Panel; Abbott, AstraZeneca, Lilly Diabetes, Novo Nordisk, Sanofi, Roche Diagnostics, Novartis AG, Amgen Inc.
1434-P: Lower Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Proteins Increase Ten-Year Diabetes Risk in Individuals with Obesity
Authors: MAURYA PRIYANSHI , YANEK LISA , YANG JUN , EVERETT ALLEN D. , BECKER LEWIS , VAIDYA DHANANJAY 
Published: June 2024

Introduction: Obesity predisposes to Type 2 Diabetes, thus risk stratification among the nondiabetes people with obesity is important. Insulin-like Growth Factor-1 (IGF1) and Insulin-like Growth Factor Binding Proteins (IGFBPs), which modulate metabolism, may predict diabetes in such high-risk adults.
Methods: In this case cohort analysis nested within the GeneSTAR study, 40 incident diabetes cases and 40 in a random cohort sample with a BMI ≥ 30 kg/m2 at baseline (38% males, 50% African Americans, age range 22-69 years) were followed for incident diabetes during a follow up of ≥10 years. Sampling-weighted logistic regression assessed the relationship between baseline IGF/IGFBP biomarkers measured by ELISA and diabetes risk.
Results: Lower levels of IGF1, IGFBP1, IGFBP2, IGFBP3 and IGFBP6 predicted 10-year diabetes incidence adjusting for demographic factors (Table, Model 1). This association remained statistically significant for IGFBP2, IGFBP3 and IGFBP6 after adjusting for fasting glucose at baseline (Model 2).
Conclusions: IGF/IGFBP complex proteins may serve as early indicators for diabetes risk in people with obesity without current diabetes beyond fasting glucose levels. Future studies should investigate the functional role of the IGF/IGFBP system in glucose metabolism and diabetes prevention.

Disclosure
P. Maurya: None. L. Yanek: None. J. Yang: None. A.D. Everett: Advisory Panel; Merck & Co., Inc. L. Becker: None. D. Vaidya: None.

Funding
National Institutes of Health (HL092165 and HL099747)
1455-P: The Oral Disposition Index (ODI) and Its Components during the Progression of Autoantibody-Positive (Ab+) Individuals to Type 1 Diabetes (T1D)
Authors: ISMAIL HEBA M. , CUTHBERTSON DAVID D. , JACOBSEN LAURA M. , ATKINSON MARK A. , LIBMAN INGRID , REDONDO MARIA J. , SOSENKO JAY 
Published: June 2024

Introduction and Objective: A lower ODI (secretion x sensitivity) has been shown to be predictive of T1D. In a longitudinal analysis, we assessed whether there is differential change during the progression to T1D between the two components of ODI, secretion and sensitivity.
Methods: TrialNet Pathway to Prevention progressors to T1D (n=336) were studied. All had OGTTs at baseline, 0.5 years before diagnosis, and at diagnosis. The mean (±SD) interval from baseline to 0.5 years before diagnosis was 3.6 (2.4) years. AUC C-peptide/AUC glucose (AUC Ratio) and 1/fasting insulin (1/FI) were used as proxies for secretion and sensitivity, respectively. Change/yr was calculated.
Results: Mean (±SD) baseline age and BMI were 13.3 (10.7) years and 23.0 (41.8) kg/m2, respectively. The majority were male (53.3%) and White (91.7%). The change/yr of both ODI and AUC Ratio was not significant from baseline to 0.5 years before diagnosis (table). However, from 0.5 years before to diagnosis, ODI and AUC Ratio declined appreciably (both p&lt;0.001). In contrast, 1/FI did not change significantly in either interval.
Conclusion: In progressors to T1D, insulin secretion (measured by AUC Ratio) has an accelerated decline proximal to diagnosis of T1D, whereas insulin sensitivity (measured by 1/FI) changes minimally. These findings are relevant to the interpretation of the ODI in Ab+ individuals.

Disclosure
H.M. Ismail: Consultant; Sanofi, Rise Therapeutics. D.D. Cuthbertson: None. L.M. Jacobsen: Advisory Panel; Insulet Corporation. M.A. Atkinson: None. I. Libman: None. M.J. Redondo: None. J. Sosenko: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases
1457-P: Challenges in Detecting Immune Checkpoint Inhibitor-Induced Type 1 Diabetes Mellitus by Glucose Monitoring
Authors: SHARP JOHN , PASADYN CASSANDRA , ZHAO SONGZHU , WEI LAI , PRESLEY CAROLYN , OWEN DWIGHT , WYNE KATHLEEN , MEARA ALEXA A. 
Published: June 2024

Introduction: Immune checkpoint inhibitor (ICI) induced type 1 diabetes (T1D) occurs in less than 1% of patients. It is unknown if glucose abnormalities prior to T1D diagnosis occur and in what fashion. We aimed to evaluate whether abnormal glucose trends precede ICI-T1D diagnosis.
Methods: We conducted a single-center retrospective study of patients with ICI-T1D after cancer treatment between 2010 and 2022. Characteristics assessed included serum glucose values at baseline, immediately prior to T1D, and at T1D diagnosis. Linear mixed model with random intercepts for each participant was used to examine glucose trend over time. To test effect modification of sex, age, BMI, autoantibodies, and DKA, interaction terms were added.
Results: Thirty-five patients had ICI-T1D. Median glucose levels were baseline=116 mg/dL (IQR 105-152), prior to T1D=170 mg/dL (IQR 130-298) and at T1D diagnosis=453 mg/dL (IQR 388-544) with median interval between of 16 days. Mixed model demonstrated significant increase in serum glucose of 6.02 mg/dL per day (95% CI 4.18, 7.85, p&lt;0.001). Notably, females had larger increases in serum glucose per day than males (Figure 1).
Conclusion: Patients who develop ICI-T1D have abnormal serum glucose elevations prior to T1D diagnosis though rises were mild. Whether intervention utilizing continuous glucose monitoring could prevent morbidity requires further research.

Disclosure
J. Sharp: None. C. Pasadyn: None. S. Zhao: None. L. Wei: None. C. Presley: Advisory Panel; Regeneron Pharmaceuticals Inc. Other Relationship; Jazz Pharmaceuticals. D. Owen: Research Support; Merck & Co., Inc., Bristol-Myers Squibb Company, Palobiofarma, Genentech, Inc. Other Relationship; Genentech, Inc. Research Support; Pfizer Inc. K. Wyne: None. A.A. Meara: Consultant; AbbVie Inc., Sanofi, Amgen Inc., AstraZeneca.
1458-P: Cardiovascular Risk Is Higher in People with Type 1 Diabetes Living with Overweight or Obesity—Insights from the SFDT1 Cohort
Authors: SALLE LAURENCE , JULLA JEAN-BAPTISTE , AGUAYO GLORIA A. , TATULASHVILI SOPIO , SABLONE LAURA , JOUBERT MICHAEL , RENARD ERIC , LABLANCHE SANDRINE , COSSON EMMANUEL , FAGHERAZZI GUY , RIVELINE JEAN-PIERRE 
Published: June 2024

Introduction and Objectives: Individuals with type 1 diabetes (T1D) are faced with a growing prevalence of obesity, a recognized determinant of cardiovascular (CV) risk. This study aims to evaluate the metabolic profile, CV risk, and diabetes-related complications across body mass index (BMI) classes in individuals with T1D.
Methods: Using data from SFDT1, a multicentric French cohort, individuals with T1D were stratified into four BMI classes: underweight (&lt;18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (OW) (25-29.9 kg/m²), and obesity (OB) (BMI ≥30 kg/m²). Baseline statistical analyses were performed with mean ± SD or frequency (%), with group comparisons through Kruskall-Wallis, variance analysis, and Chi-squared tests. Spearman correlation and logistic regression were applied. CV risk was evaluated using the Steno T1 Risk Engine score (STRS) in people in primary prevention.
Results: Among 1,724 participants (age 38 years, diabetes duration 22 years, BMI 24.9kg/m2, Male 53%), 8% had a CV history and 31% were classified as OW or OB. Age and duration of diabetes (ranging from 17.5 to 25.0 years) increased with BMI class. The mean HbA1c remained comparable (7.5% overall, p=0.5975) but the proportion of participants with HbA1c≥6.9%, as well as those with high blood pressure and dyslipidemia increased with BMI class. BMI was associated with CV history (OR=1.044, CI95% 1.004-1.084), even after adjustments for age, sex, and diabetes duration. In the primary prevention population, compared to normal weight, those with OW and OB had an increase of STRS at 5 years (57% and 74%) and 10 years (50 and 60%) (p&lt;0.001). BMI correlated with 5 and 10-year STRS (p&lt;0.001) and Waist/Height ratio with 10-year risk (p&lt;0.001). OW and OB were associated with retinopathy but not nephropathy.
Conclusion: T1D individuals with OW and OB had more CV history, higher STRS at 5 and 10 years, and more retinopathy. Visceral adiposity was associated with increased STRS.

Disclosure
L. Salle: Advisory Panel; Sanofi, Amarin Corporation. J. Julla: Board Member; Sanofi. Speaker's Bureau; Lilly Diabetes, Novo Nordisk. G.A. Aguayo: None. S. Tatulashvili: None. L. Sablone: None. M. Joubert: Consultant; Abbott, Medtronic, Dexcom, Inc. E. Renard: None. S. Lablanche: None. E. Cosson: Advisory Panel; Abbott, AstraZeneca, Lilly Diabetes, Novo Nordisk, Sanofi, Roche Diagnostics, Novartis AG, Amgen Inc. G. Fagherazzi: Speaker's Bureau; Sanofi. Advisory Panel; Timkl, SAB Biotherapeutics, Inc., Vitalaire, Roche Diabetes Care. J. Riveline: Board Member; Abbott, Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Medtronic, Dexcom, Inc., Insulet Corporation, Air Liquide, AstraZeneca.
1466-P: Screening and Functional Analysis of Mutations and Variations in NEUROD1 Gene in Pedigrees of Maturity-Onset Diabetes of the Young
Authors: LIU LIMEI , ZHANG JUAN , GE XIAOXU , JIANG FUSONG , LI TIANTIAN , LIU CHANWEI , CHEN YATING 
Published: June 2024

Introduction & Objective: To screen the mutations of NEUROD1 gene in maturity-onset diabetes of the young (MODY) families, and to investigate the association of mutations and variants with the onset of MODY6 in Chinese, and its potential pathogenesis.
Methods: PCR-direct sequencing was used for screening NEUROD1 mutations and variations from 96 MODY probands who were negative for mutations in the GCK/MODY2, HNF1A/MODY3, and HNF1B/MODY5 genes. A de novo modeling method was used to predict the three-dimensional (3D) structures of wild type (WT) and mutated NEUROD1 proteins. Transcriptional activities of both WT and mutant of NEUROD1 on insulin gene were detected using dual luciferase reporter gene system. Moreover, the genotypic frequency of NEUROD1 variations were compared between the 96 MODY probands and 100 nondiabetic control subjects.
Results: Glu59Gln (NM_002500.5, c.175G&gt;C), a heterozygous missense mutation in the NEUROD1 gene, was identified in a MODY pedigree. 3D structural analysis showed that the mutation transformed the negatively charged Glu59 of WT into uncharged mutation Gln59, leading to the loss of Glu59-Arg54 and Glu59-Lys88, two salt bridge bonds, and the formation of Gln59-Arg54, one new hydrogen bond. Transcriptional activity of Glu59Gln mutant for insulin gene was reduced 36.3% when compared with that of WT (P&lt;0.01). A common variation Ala45Thr (G-A) was identified, and AA+GA genotypic frequency of the variation was significantly elevated in the 96 MODY probands in comparison to 100 nondiabetic control subjects (P=0.002).
Conclusion: Glu59Gln mutation altered the N-terminal molecular conformation of NEUROD1 protein, resulting in decreased transcriptional activity of insulin gene, which was the cause of the defective insulin secretion in mutation carriers of the MODY6 pedigree. In addition, the Ala45Thr variation was associated with earlier age of onset of diabetes in MODY6 probands.

Disclosure
L. Liu: None. J. Zhang: None. X. Ge: None. F. Jiang: None. T. Li: None. C. Liu: None. Y. Chen: None.

Funding
National Science Foundation of China (81970686,81770791)
147-OR: Obesity Is Associated with Increased Clearance and Reduced Drug Exposure to Metformin in Youth with Type 2 Diabetes
Authors: SRINIVASAN SHYLAJA , YEN KEVIN , FLOREN ALEXANDER , SAVIC RADA 
Published: June 2024

Introduction & Objectives: Youth have higher treatment failure rates on metformin when compared with adults. There is interpatient variability in metformin pharmacokinetics (PK) and the influence of obesity on metformin PK in youth remains unclear. Our objectives were to develop a population PK model for metformin in youth to examine current dosing strategies and to quantify the relationship between metformin PK and obesity in youth with T2D.
Methods: We performed semi-intensive PK sampling in 50 youth &lt; 18 years with T2D on metformin. We measured metformin levels before, 1-2 and 3-6-hours after a supervised 1000 mg dose of immediate-release metformin. We used non-linear mixed effects modeling to develop a population PK model. Simulations were performed to estimate area under the 24-hour metformin concentration-time curve (AUC) values.
Results: Mean participant age was 15.0 (SD 1.6) years, 66% were male, mean body mass index (BMI), 35.9 (SD 6.8) kg/m2, and mean eGFR, 114.7 (SD 22.6) mL/min/1.73m2. A one-compartment model best described the data, with the following parameter estimates: clearance (CL), 110 L/h (7.8% CV); volume of distribution, 461 L (11.0% CV); absorption rate constant, 0.76 /h (9.8% CV). Estimated CL increased by 3% (21.4% CV) for every 1 kg/m2 increase in BMI, and by 6% (53.8% CV) for every 10 mL/min increase in eGFR. When comparing AUC estimates from our model with those from a model developed using data from 236 adults on metformin, median AUC for youth receiving 2000 mg metformin daily was lower than for adults on the same dose (18.47 mg*h/L vs. 27.49 mg*h/L). Simulations showed that in youth, higher doses of at least 2550 mg and up to 3000 mg daily were needed to achieve exposures similar to adults.
Conclusion: Obesity is associated with increased metformin CL and reduced AUC in youth and higher doses are needed to achieve comparable drug exposure to adults. As next steps, we are testing the tolerability and efficacy of higher doses of metformin in a clinical trial.

Disclosure
S. Srinivasan: None. K. Yen: None. A. Floren: None. R. Savic: None.

Funding
National Institutes of Health (K23DK120932)
1472-P: Low CRP Alleles in HNF1A Are Associated with Increased Risk of Cardiovascular Disease—A Meta-analysis
Authors: YANG CHAOCHAO , HAN XUEYAO , JI LINONG 
Published: June 2024

Objective: Rare variants in HNF1A account for Maturity onset diabetes of the young 3 (MODY3). Common variants of HNF1A are associated with serum CRP, and MODY3 patients have greatly low CRP levels distinct from other types of diabetes. Low dose sulfonylureas are recommended for MODY3 patients in ADA guideline. However, available clinical trial showed liraglutide, an anti-diabetic drug protecting from cardiovascular disease (CVD), had similar effect and lower risk of hypoglycemia compared with glimepiride. Since the common variants of HNF1A are associated with higher risk of CVD, we aimed to perform the meta-analysis to investigate the association of the low CRP alleles in HNF1A with CVD and indirectly evaluate the CVD risk of MODY3.
Methods: A comprehensive literature search was conducted using PubMed, Embase and CNKI databases from inception to December 2023. Association studies concerning the association of HNF1A with CRP, CVD, blood lipid and diabetes were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using Review Manager 5.3.
Results: Three common variants in the coding region of HNF1A (rs1169288, rs2464196, rs1169289) were included in our study. The minor alleles of these variants were all associated with low CRP levels (OR 0.89, 95%Cl 0.86-0.91; OR 0.89, 95%Cl 0.88-0.91; OR 0.89, 95%Cl 0.88-0.91, respectively). Their low CRP alleles were associated with increased risk of CVD (OR 1.05, 95%CI 1.04-1.06), elevated LDL cholesterol levels (OR 1.05, 95%Cl 1.03-1.08) and increased risk of type 2 diabetes (OR 1.04, 95%Cl 1.01-1.08).
Conclusion: Our study has revealed an association between low CRP alleles in HNF1A and an elevated risk of CVD, possibly due to dyslipidemia or poor glycemic control. This suggests that for MODY3 patients, it may be more reasonable to prioritize anti-diabetic with cardiovascular protection such as GLP-1 receptor agonist, but not sulfonylureas.

Disclosure
C. Yang: None. X. Han: None. L. Ji: None.