bluuebunny/crossref_metadata_2025_split huggingface dataset:
1281-P: Variants of Unknown Significance (VUS) in Maturity-Onset Diabetes of the Young (MODY)—High Rate of Conundrum Resolution via Reanalysis of VUS
Authors: ALARCON GUIDO , REDONDO MARIA J. , TOSUR MUSTAFA 
Published: June 2023

In the era of next-generation sequencing, clinicians frequently encounter VUS on genetic tests for MODY. Pathogenicity ascertainment of those variants may have substantial impact on optimal diabetes care. We aimed to determine the usefulness of reanalyzing previous VUS results in MODY. We performed a retrospective chart review to identify subjects with a VUS on a MODY genetic test performed &gt; 3 years before the study and requested reanalysis of their genetic data at Athena Diagnostics. We identified 10 subjects with at least one VUS on MODY genetic testing (mean age at diagnosis: 13.4 ± 3.4 years, 60% female, 60% Hispanic, 20% African American and 20% non-Hispanic White). After reanalysis, 50% were recategorized to a different category: 30% “likely pathogenic” and 20% “benign”. All newly reclassified pathogenic variants were in HNF1A, and benign variants were in HNF1B and PDX1. The median time to reclassification since MODY testing was 8 years (range 4-10 years). The mean random C-peptide at diagnosis was 1.17 ± 0.17, 2.24 ± 0.8 and 2.96 ± 1.4 ng/mL for those with variants reclassified as benign, likely pathogenic and those who remained as VUS, respectively. In sum, periodic reanalysis of the genetic data of cases with a VUS on MODY tests may provide high-yield diagnostic information. Further studies are warranted to identify the optimal time and frequency for such analyses.

Disclosure
G.Alarcon: None. M.J.Redondo: None. M.Tosur: Advisory Panel; Provention Bio, Inc.
1282-P: Interactive Tool to Estimate Probability of Partial Clinical Remission in Adult-Onset Type 1 Diabetes
Authors: GRZELKA-WOZNIAK AGATA , JANUSZEWSKI ANDRZEJ S. , FLOTYNSKA JUSTYNA , JENKINS ALICIA , ZOZULINSKA-ZIOLKIEWICZ DOROTA , URUSKA ALEKSANDRA 
Published: June 2023

Introduction: Type 1 diabetes (T1D) diagnosis is often (in adults) followed by a (‘honeymoon’) period of reduced insulin need, also called partial clinical remission (pCR), which is associated with better outcomes. Various definitions of pCR exist.
Aim: To create an online calculator to predict probability of pCR in adult-onset T1D 12-mths post-diagnosis.
Methods: We analysed data from 133 adults at T1D diagnosis (mean±SD age: 27±6, HbA1c: 11.1±2.0%, BMI: 22.5±3.7 kg/m2), 3-mths and 12-mths later. All were enrolled in the prospective observational InLipODiab (NCT02306005) study. We used 4 definitions for pCR 12-mths post-diagnosis: 1) insulin dose-adjusted HbA1c≤9%; 2) insulin dose&lt;0.3U/kg/24h and HbA1c≤6.4%; 3) insulin dose&lt;0.5U/kg/24h and HbA1c&lt;7%; 4) stimulated C-peptide &gt;300pmol/L. Exhaustive search was used to find the best models (based on AIC) based on usually available data at diagnosis and 3-mths. Calculator (Figure 1) available at http://www.bit.ly/T1D-partial-remission.
Results: There was low concordance between pCR definitions (Cohen’s weighted kappa 0.01-0.61.) Combination of age, HbA1c, diastolic BP, triglycerides and smoking at T1D onset predicted pCR (12-mths) with AUC=0.84. HbA1c, triglycerides and insulin dose 3-mths post-diagnosis had an AUC=0.89.
Conclusion: A new online calculator can predict pCR in adult-onset T1D for clinical and research use.

Disclosure
A.Grzelka-wozniak: None. A.S.Januszewski: None. J.Flotynska: None. A.Jenkins: Advisory Panel; Insulet Corporation, Board Member; Insulin for Life, Research Support; Abbott Diabetes, Medtronic, Hemsley Charitable Trust, Juvenile Diabetes Research Foundation (JDRF), National Institutes of Health. D.Zozulinska-ziolkiewicz: Advisory Panel; Abbott, Lilly, Lilly, Novo Nordisk, Medtronic, Speaker's Bureau; Abbott, Ascensia Diabetes Care, Novo Nordisk, Medtronic, Boehringer-Ingelheim, AstraZeneca. A.Uruska: Other Relationship; Lilly, Boehringer-Ingelheim, AstraZeneca, Ascensia Diabetes Care, Sanofi.
1287-P: Identifying When Incident Diabetes Was Diagnosed in Children and Young Adults, Using Natural Language Processing of Clinical Notes
Authors: WONG ANTHONY , ZHONG VICTOR W. , ROSENMAN MARC 
Published: June 2023

Identifying when an incident diabetes (DM) diagnosis was made is complicated using retrospective, structured electronic health record (EHR) data alone. Unstructured clinical notes have been underused but contain valuable information that could complement traditional methods. However, manually reviewing clinical notes is time-consuming. We developed and validated a simple rule-based Natural Language Processing (NLP) method to extract incident DM timing from clinical notes.
In a single center we used structured EHR data to identify a cohort (age &lt;45 as of 12/31/19) with likely type 1 (T1D) or type 2 (T2D) DM based on 2016-2019 records: (≥1 T1D ICD-10 code and insulin and no other DM medication) or ([≥2 T2D and no T1D codes] or [≥1 T2D code and a DM medication besides insulin or metformin]).
This cohort had 2,654 patients (548,316 clinical notes, 2003-present). We randomly selected 58,450 clinical notes (1,465 patients) as a training set to look for relevant text patterns. We handcrafted the rules into our NLP tool. We required 3 distinct concepts at the sentence level to determine an incident DM diagnosis: DM (not, e.g., epilepsy), an onset attribute (e.g., “diagnosed in”), and a temporal component (e.g., 8/2008). We pre-defined all related keywords and date formats for these concepts in our training notes. We then tested the NLP algorithm against manual review in an independent set of 100 randomly selected patients from the cohort. Analysis was at the patient level (true+: ≥1 true+ note per patient).
NLP in the training set found 1,268 patients with at least 1 of the 3 concepts and 826 patients with all 3. In the test set, we excluded 4 patients without substantive notes. NLP correctly detected incident DM timing in 73 of 96 patients. The NLP had recall 88%, specificity 77%, precision (PPV) 96%, and NPV 50%.
NLP was helpful in finding incident DM timing and may complement structured EHR queries for identifying incident DM. Refinement of our NLP algorithm is ongoing.

Disclosure
A.Wong: None. V.W.Zhong: None. M.Rosenman: None.

Funding
Centers for Disease Control and Prevention (1U18DP006693-01-00)
1291-P: Participants in Annual Workplace Health Evaluation Program Had Lower Risk for Developing Diabetes
Authors: TONG CARMEN H. , JALANDONI-BUSTAMANTE MICHELLE , FRAGALA MAREN S. , BIRSE CHARLES E. 
Published: June 2023

Background: We asked whether the risk of developing diabetes would be reduced in individuals who participated in annual employer-sponsored workplace health evaluations compared to those not participating in the program.
Methods: We studied a cohort of all employees with 5 years of administrative claims data (2017-2021) and no diabetes-related pharmacy claims in the baseline year (2017). The health evaluation group was defined as individuals who participated in annual workplace health assessments for 5 consecutive years. The non-health evaluation group did not participate in workplace assessments in any year. The association between health evaluation status and incident diabetes was assessed in Cox regression models that adjusted for variables that differed between the 2 groups at baseline (Table). Incidence of diabetes was defined as any diabetes-related pharmacy claims during follow-up (2018 to 2021).
Results: Of 9,021 participants, 67.8% were female; mean baseline age (standard deviation) was 46.1 (10.4) years. After adjustment (Table footnote), annual workplace health evaluation participants (n=7,957) had a 33% lower in risk of developing diabetes compared to the non-health evaluation group (n=1,064) (Table).
Conclusions: Individuals participating in annual health evaluations in a workplace setting had lower risk of developing diabetes than non-participants.

Disclosure
C.H.Tong: None. M.Jalandoni-bustamante: Employee; Quest Diagnostics. M.S.Fragala: Employee; Quest Diagnostics, Stock/Shareholder; Quest Diagnostics. C.E.Birse: Employee; Quest Diagnostics.
13-LB: Treatment Patterns of Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease in Colombia
Authors: MACHADO MANUEL , GAVIRIA-MENDOZA ANDRÉS , FRANCO JUAN S. , FORERO MARIA D.R. , VIZCAYA DAVID , VALLADALES RESTREPO LUIS F. , MACHADO-ALBA JORGE E. 
Published: June 2023

Aim: Describe treatment patterns of patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in outpatient setting from Colombia.
Methods: We conducted a cross-sectional study characterizing treatment patterns of T2DM and CKD using the Audifarma S.A. drug dispensing database and included all patients with both diagnoses using ICD-10 codes and at least one disease-related prescription from April 1st 2019 to March 31st 2020. Sociodemographic variables, comorbidities, treatment received and combinations were evaluated. Drugs were classified as those for management of T2DM (oral antidiabetic agents, insulins, SGLT2i, GLP-1 analogs (GLP1a), dipeptidyl peptidase-4 inhibitors (DPP4i)), and others including renin angiotensin aldosterone system blockers (angiotensin converting enzyme inhibitors-ACEI, angiotensin receptor antagonists-ARBs) and mineralocorticoid receptor antagonists (MRAs). A descriptive analysis with frequencies and proportions, means and standard deviation was carried out.
Results: Of a total of 194,023 patients with a primary diagnosis of T2DM, it was possible to identify that 14,722 (7.5%) had concomitant CKD, during the observation period. A total of 7513 (51%) were men, and the mean age was 74.7±10.9 years. The main comorbidities were hypertension (n=10665; 72.4%) and hypothyroidism (n=1138; 7.7%). The most used drugs were metformin (n=9901; 67.3%) alone or associated with some other antidiabetic, followed by 52.2% used DPP4i (n=7691), 17.0% an SGLT2i (n=2500), and 5.2% GLP-1a (n=766). Additionally, 67.2% (n=9895) of patients were under treatment with ARBs, 15.8% (n=2325) with ACEIs and 10.9% (n=1598) with MRAs.
Conclusions: This contemporary study from Colombia further highlights the complexity and heterogeneity of treating patients with T2DM and CKD, which could be improved if the beneficial properties of newer agents that have shown positive anti-hyperglycemic and renal outcomes were implemented in the local treatment strategy.

Disclosure
M. Machado: Research Support; Bayer Inc., Pfizer Inc. A. Gaviria-mendoza: Employee; Audifarma S. A, Research Support; Bayer Inc., Pfizer Inc. J. S. Franco: Employee; Bayer Inc. M. D. R. Forero: Employee; Bayer Inc. D. Vizcaya: Employee; Bayer Inc. L. F. Valladales restrepo: Research Support; Bayer Inc., Pfizer Inc. J. E. Machado-alba: None.

Funding
Bayer AG
13-OR: Medication Use among Youth-Onset Diabetes in India—An Analysis of Socioeconomic Factors and Cost of Care
Authors: SAM VARGHESE JITHIN , VARGHESE NAMITHA M. , VENKAT NARAYAN K.M. 
Published: June 2023

Background: Reported prevalence of youth-onset diabetes (15-30y) in India range from 1 to 1.5% with half the cases being diagnosed. National estimates indicate only 2 in 5 diagnosed cases are taking medication. Yet, data are scarce on the socio-economic predictors and financial burden associated with medication use in this population.
Methods: Using data from the National Family Health Survey 2019-21 among youth (n = 4682) with diagnosed diabetes, we estimated the association of socio-economic factors (i.e., household wealth quintile, urbanicity, and household members with diagnosed diabetes) and medication use. We used robust survey-weighted Poisson regression adjusting for sex, age, high school completion and state fixed effects. Using the National Sample Survey 2017-18, we benchmarked the average cost of inpatient and outpatient diabetes medication among youth with diabetes (n = 120) as a proportion of national net per-capita income (Rs. 115,224).
Results: Nationally, 1.2% (1.1 - 1.3) of youth 15-30 years old had diabetes, 75% of these cases were diagnosed and 30.9% (95%CI: 28.8, 33.0) of those diagnosed were talking medications. Urban residence (Prevalence ratio, PR: 1.30 [1.13, 1.51]) and increasing household wealth (highest (ref: lowest) 1.28 [1.02, 1.59]) were associated with higher medication use. A household member with diabetes was associated with lower medication use (0.45 [0.32, 0.63]). Out-of-pocket expenses corresponded to 47.0% (31.7, 62.3) of national per capita income. Medications accounted for 35.9% (22.9, 49.0) and 44.9% (33.1, 56.8) of the annual expenses for in-patient (Rs. 35511 [14935, 56088]) and out-patient (Rs. 18651 [9025, 28275]) care respectively.
Conclusions: Out of pocket expense for persons with youth-onset diabetes in India is, on average, over 40% of per capita income, with medication cost being the biggest driver. These data call for social safety nets to protect family income of those with youth-onset diabetes in India.

Disclosure
J.Varghese: None. N.M.Varghese: None. K.Narayan: None.

Funding
National Institutes of Health (P30DK111024)
130-OR: Tirzepatide Attenuates Hepatic Insulin Resistance and Glucagon Action Independent of Weight Loss and GIP Action in Diet-Induced Obese Mice
Authors: KIM BUKYUNG , TAUER LAUREN A. , HU XIAODI , KIM JASON K. 
Published: June 2023

As a dual GLP-1 receptor and GIP agonist, Tirzepatide (TZP) induces weight loss and improves glycemic control in patients with type 2 diabetes. Here, we performed insulin clamp and glucagon clamp under euglycemic conditions in male C57BL/6J mice fed a high-fat diet (HFD; 12 weeks) after once-daily treatment with TZP (3 nmol/kg) or GIP (25 nmol/kg) for 5 days (n=5). TZP and GIP caused HFD-fed mice to lose 10~15% of weight, but their fat mass remained 7-fold higher than chow-fed controls (C) (Fig. 1). Insulin clamp showed that GIP caused a 37% decrease in hepatic insulin action in chow-fed mice (Fig. 2). In HFD-fed mice, TZP induced significant increases in hepatic insulin action (4-fold) and glucose turnover (25%) compared to GIP, restoring insulin sensitivity to levels comparable to controls (Fig. 2-3). TZP also increased glucose metabolism in brown fat (1,528±155 vs. 798±166 nmol/g/min in GIP). Glucagon clamp showed that TZP significantly reduced hepatic glucose production (HGP) by ~50% compared to controls and GIP (Fig. 4). CONCLUSION: These data indicate that TZP improves insulin action and reduces hepatic glucagon action in obese mice while GIP causes hepatic insulin resistance in lean mice. Our findings suggest that TZP’s glycemic control may involve amelioration of insulin resistance and glucagon resistance, independent of weight loss and GIP action in the liver.

Disclosure
B.Kim: None. L.A.Tauer: None. X.Hu: None. J.K.Kim: None.

Funding
National Institutes of Health (5U2CDK093000)
1303-P: Screening for Metabolic Dysfunction–Associated Fatty Liver Disease (MAFLD) in Asian-Indians with Type 2 Diabetes Using Vibration-Controlled Transient Elastography—A Cross-Sectional Observational Study
Authors: CHANDEL SHIVANI , RAVI TEJA K.V. 
Published: June 2023

Background: Metabolic dysfunction associated fatty liver disease (MAFLD) is a common finding in people with type 2 diabetes (T2D).
Aims: To evaluate the association of liver steatosis and fibrosis in Asian-Indians with T2D using Vibration-Controlled Transient Elastography (VCTE).
Methods: A total of 120 patients underwent NAFLD screening from July 2022 to December 2022 after excluding alcoholics and nondiabetes patients we had 73 people with T2D, recruited from Liver Clinic of Endocrine speciality centre. VCTE (Fibroscan 430 Mini Plus, Echosens, France) was used for Liver Stiffness measurement (LSM) in KiloPascals (KPa) and Controlled Attenuation Parameter (CAP) in Decibels per meter (dB/m). CAP score cut-offs used for steatosis: Grade 0 &lt; 237 dB/m, Grade I is 238 - 259 dB/m Grade II is 260 - 292 dB/m and Grade III &gt; 292 dB/m. LSM cut-off values used: F0 &lt; 7 kPa, F1 is 7 - 10 kPa, F2 is 10 - 13 kPa, F3 is 13 - 16 kPa and F4 &gt; 16 kPa.
Results: The mean age was 53.4 ± 12.5 years and 26% (n=19) were women. Overweight seen in 21.9 % (n=16) and obesity in 67.1 % (n=49). We found liver steatosis in 73.7% (n=56) having Grade I in 16.4 % (n=12), Grade II in 34.2 % (n=25) and Grade III in 26 % (n=19). Liver fibrosis was detected in 30.1 % (n=22) with Mild fibrosis (F1) in 20.5 % (n=15) and clinically significant in 9.5 % (n=7) i.e., Moderate fibrosis (F2) in 6.8 % (n=5) and Cirrhosis grade (F4) in 2.7 % (n=2). We noticed that CAP score had significant positive correlation with BMI (P=0.01) and LSM had significant positive correlation with BMI (p=0.001), SGOT (p=0.01), SGPT (p=0.015) and Platelet count (P=0.04).
Conclusions: Our data demonstrated that people with T2D have a high prevalence of steatosis and fibrosis which can lead to the development and progression of complications with high morbidity and mortality rates. So, we suggest screening for MAFLD should be a universal approach in diabetes co-morbidities management.

Disclosure
S. Chandel: None.K. Ravi Teja: None.
1304-P: Exocrine Pancreatic Insufficiency (EPI) Likely Overlooked in Diabetes as Common Cause of Gastrointestinal-Related Symptoms
Authors: LEWIS DANA M. 
Published: June 2023

Background: Exocrine Pancreatic Insufficiency (EPI/PEI) occurs when the pancreas no longer makes enough enzymes to support digestion. Awareness among diabetes care providers does not match the likely rates of prevalence and contributes to underscreening and underdiagnosis of EPI among people with diabetes.
Methods: A systematic review of EPI was performed. Resulting articles were analyzed for whether the articles were on diabetes or other co-conditions. Articles on EPI and diabetes were analyzed for type of diabetes, prevalence of EPI reported in diabetes, and publication name. A subsequent literature review of prevalence studies of gastrointestinal conditions in people with diabetes was also performed and data was analyzed to estimate prevalence and compare rates of gastroparesis, celiac, and EPI among people with diabetes.
Results: The systematic review of EPI found 644 articles, of which only 40 were focused on EPI and diabetes (12 Type 1, 7 Type 2, 20 both T1/T2 or all types; 1 neonatal). They represent 9.6% of the EPI co-condition literature (n=418) and were published in 29 journals, of which only 9 were diabetes journals. Most were studies on prevalence or diagnosis; whereas one recent article demonstrates a method for evaluating improved glycemic variability following treatment for EPI. The literature review on other GI conditions in people with diabetes found prevalence of 1.3% for gastroparesis, with differing estimates in Type 1 (up to 5% for those who sought care) and Type 2 (1%), and 5% for celiac in Type 1. Prevalence reported for EPI in people with diabetes is higher: estimates vary from 20-50%.
Conclusion: Gastroparesis and celiac are often top of mind for diabetes providers, yet EPI/PEI is ~10 times more common among people with diabetes. Healthcare providers who see people with diabetes should increase the screening of fecal elastase (FEL-1) for people with diabetes who mention gastrointestinal symptoms.

Disclosure
D.M.Lewis: None.
1309-P: Dietary Iron and Kidney Function in Youth and Young Adults with Type 1 Diabetes
Authors: CONWAY REBECCA B. , CRUME TESSA L. , PERNG WEI , MCCLAIN DONALD A. , DABELEA DANA 
Published: June 2023

The association of markers of body iron stores with kidney disease in type 1 diabetes (T1D) is complex, with both positive and inverse relationships observed. Little data are available on the relationship of dietary iron (DI) intake with markers of kidney function, prior to occult disease, in youth and young adults with T1D. We tested the association of DI with albumin-to-creatinine ratio (ACR), both measured at multiple time points over a 14-year period in youth and young adults with T1D. Study participants (n=629) were from the Colorado site of the SEARCH for Diabetes in Youth study who completed research visits at baseline and (&lt;1yr diabetes duration) and at least one follow-up visit over 14 years. We applied linear mixed models (repeated measures analysis) to test the hypothesis that higher DI over time is longitudinally associated with a higher ACR, which was natural log-transformed prior to regression analysis. Results: Mean age and diabetes duration at study baseline were 10.2 (std 4.2) years and 10.4 (std 6.8) months, respectively. Older age at baseline (p=0.009), female sex (vs. male, p=0.002), and Black race (vs Non-Hispanic White, p&lt;0.001) were each associated with higher ACR levels across follow-up. Contrary to our hypothesis, average DI intake was inversely associated with ACR levels in analyses adjusted for age, sex, and race (p&lt;0.05). This inverse relationship persisted after further controlling for average body mass index (BMI) over time. However, controlling for average HbA1c levels over time, which were positively associated with ACR (p=0.001), attenuated the relationship between DI intake and ACR (p=0.12). In conclusion, total DI intake in children and young adults was associated with a lower ACR over 14 years, but the association was confounded by HbA1c, suggesting that DI may be a marker of total glycemic load. Whether this relationship varies by heme/non-heme content needs to be further explored. These data highlight the important role of diet in the early years after T1D onset.

Disclosure
R.B.Conway: None. T.L.Crume: None. W.Perng: None. D.A.Mcclain: None. D.Dabelea: None.
1322-P: Association of Long-Term Blood Pressure Variability and Decrease in GFR on Type 2 Diabetes Mellitus Patients with Hypertension
Authors: SAKAMOTO MASAYA , YUKI MASAHIRO , MIYASHITA KAZUTOSHI , YAMAZAKI TSUTOMU 
Published: June 2023

Introduction: Increased long-term blood pressure variability (BPV), defined as monthly to yearly BPV, has been reported a risk factor of cardiovascular events independent of mean BP level. However, the relationship between long-term BPV and decrease in GFR remains unknown. In this study, we examined the association of Long-Term BPV and decrease in GFR.
Methods: We included 214,443 type 2 diabetes mellitus patients with hypertension, registered in the Japan Diabetes Data Management Study Group, whose BP and HbA1c were simultaneously measured at least 4 times per year for 5 years from 2014-2018. BPV was defined as the 5-year coefficient of variation (CV), and the relationship between BPV and eGFR was examined. We also examined the relationship between BPV and the following background factors: (1) age (2) duration of diabetes (3) HbA1c (4) antihypertensive medications. The Ca-antagonist group was patients who took only Ca-antagonists during the 5-year period, and the ARB group was patients who took only ARBs. This study was a retrospective analysis. Data analyses were performed using the SPSS 28.0 software.
Results: The group with greater 5-year BPV had lower eGFR than the group with smaller BPV, independent of mean BP (P&lt;0.001). Regarding BPV and patient background, (1) BPV tended to increase with increasing age, and was significantly greater in patients over 50 years of age compared to those in their 30s (P&lt;0.001). (2) The longer diabetic duration, the greater the BPV (P&lt;0.001). Especially in patients more than 20 years’ diabetic duration, BPV was significantly larger than that of less than 5 years (P&lt;0.001). (3) There was no association between HbA1c and BPV. (4) BPV was significantly lower in the Ca antagonist group compared with the ARB group over 5 years (0.069 vs. 0.078 P&lt;0.001). Conclusion: Increased long-term BPV was observed older age and long duration of diabetes, but was not related to HbA1c. Interestingly, Patients with greater BPV had lower eGFR at 5 years.

Disclosure
M.Sakamoto: None. M.Yuki: None. K.Miyashita: None. T.Yamazaki: None.