bluuebunny/crossref_metadata_2025_split huggingface dataset:
1367-P: Type 2 Diabetes Mellitus and Obesity Amplifies Nonalcoholic Fatty Liver Disease Risk with Age
Authors: SHARMA ANU , GODINEZ LEIVA EDDISON , LOMONACO ROMINA , VALDEZ SAENZ ENRIQUE , ORTIZ ROCHA ANDREA , GONZALEZ MARIA A. , MARANGI STEPHEN A. , SHRESTHA SULAV , SHETTY SHWETHA S. , BUDD JEFFREY T. , KALAVALAPALLI SRILAXMI , BARB DIANA , CUSI KENNETH 
Published: June 2023

Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent in the general population with multiple known metabolic risk factors. There is limited evidence on the impact of age on the prevalence of hepatic steatosis and fibrosis, and their relationship to cardiometabolic risk factors. To this end, we recruited 761 patients 35-75 years of age, with and without T2DM, who underwent screening for NAFLD with laboratory tests and imaging by elastography (steatosis by controlled attenuation parameter [CAP]; fibrosis by liver stiffness measurement [LSM]). Patients were divided into 3 age groups: &lt;45 years (young), 45-64 years (middle age), and ≥65 years old (older age), with results reported in this order. Of the 761 patients included, 21% (n=161) were young, 52% (n=397) middle age, and 27% (n=203) older. In the older age group, prevalence of obesity was lower (53% vs. 53% vs. 40%, p=0.01) but T2DM was higher (15% vs. 39% vs. 44%; p&lt;0.01). Similarly, hypertension, atherogenic dyslipidemia, and use of antihypertensives and statins were more frequent in the older age group. Despite this, there were no differences in steatosis (CAP ≥274 dB/m: 50% vs. 54% vs. 52%, p=0.7). A marker of NAFLD disease activity (NIS4) worsened with increasing age (p&lt;0.01). There was a trend for fibrosis (LSM≥7.0 kPa) to be higher in middle (11%) and older (8%) vs. younger (5%) age. After multivariable analysis (sex, race, ethnicity, BMI, A1c, cardiometabolic risk factors), BMI was associated with both steatosis and fibrosis in all age groups (p&lt;0.01). There was a significant association between A1c as a continuous variable and steatosis only in the older age group (OR 2.8, 95% CI 1.6-4.9), while its association with fibrosis started at middle age (OR 1.3, 95% CI 1.1-1.7) and was stronger in older age (OR 1.8, 95% CI 1.01-3.2).
Conclusion: Age was not associated with steatosis or fibrosis. BMI was the strongest predictor of hepatic steatosis and synergizes with T2DM for the development of fibrosis with age.

Disclosure
A. Sharma: None. E. Godinez Leiva: None. R. Lomonaco: None. E. Valdez Saenz: None. A. Ortiz Rocha: None. M.A. Gonzalez: None. S.A. Marangi: None. S. Shrestha: None. S.S. Shetty: None. J.T. Budd: None. S. Kalavalapalli: None. D. Barb: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns.
1368-P: Relative Risk of Nonalcoholic Fatty Liver Disease between Women and Men according to Glycemic Status
Authors: KYUNG KIM HAE , LEE SEJEONG , LEE MINYOUNG , LEE YONG-HO , SEOK KANG EUN , CHA BONG-SOO 
Published: June 2023

Background: Nonalcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes (T2D). However, there is no current study for NAFLD risk stratification by sex and glycemic status. We investigated whether different glycemic status may interfere with metabolic effects affecting NAFLD according to sex.
Methods: A total of 552 patients with normal glucose tolerance (NGT), prediabetes, and diabetes, were evaluated for odds ratio (OR) and hazard ratio (HR) for NAFLD (above steatosis stage 1) in cross-sectional and longitudinal study, respectively. Univariate analyses and subgroup analyses were performed to determine the risk factors for developing NAFLD according to sex and glycemic status. Hepatic steatosis and fibrosis were determined using transient elastography and body composition was analyzed by Inbody.
Results: In cross-sectional study, men with prediabetes and diabetes exhibited greater relative differences in metabolic syndrome, triglyceride and HDL cholesterol than women with prediabetes and diabetes when compared with their NGT counterparts. There was no difference in OR for NAFLD observed comparing women and men with prediabetes or diabetes. After 2.6 years of follow up, we found that women with prediabetes showed significantly increased HR (HR 1.81; 95% CI 1.01-3.26; p = 0.049) of NAFLD than men with prediabetes (HR 0.83; 95% CI 0.54-1.30; p =0.42), even after adjusting several confounders. Visceral fat area was significantly higher in women with prediabetes and diabetes compared to men throughout the study. Insulin resistance (HOMA-IR≥2.5) was prediabetes-specific risk factor, contributing for prevalent NAFLD (OR 6.56; 95% CI 1.15-37.31; p=0.034) without interaction between sex and insulin resistance (p=0.99).
Conclusions: Women with prediabetes showed higher risk for developing NAFLD compared to men due to greater burden of metabolic dysregulation between adipose tissue and insulin resistance.

Disclosure
H.Kim: None. S.Lee: None. M.Lee: None. Y.Lee: None. E.Kang: None. B.Cha: None.
1375-P: Child-Reported Food Security in Children with Type 1 Diabetes—Association with Glycemic Control and Mental Health Symptoms Independent of Household Food Security
Authors: JULCEUS EMMANUEL F. , FRONGILLO EDWARD A. , MENDOZA JASON A. , SAUDER KATHERINE A. , MALIK FAISAL , JENSEN ELIZABETH T. , DOLAN LAWRENCE M. , BELLATORRE ANNA , DABELEA DANA , REBOUSSIN BETH A. , REYNOLDS KRISTI , PIHOKER CATHERINE , LIESE ANGELA D. 
Published: June 2023

Introduction: Typically, caregivers report on household food security (FS), but children’s experiences may differ from caregiver reports. We assessed if child-reported food insecurity (FI) was associated with glycemic control, acute complications of diabetes, depressive symptoms, and disordered eating in children with type 1 diabetes (T1D), independently from household FS.
Methods: In a cross-sectional analysis of the multicenter SEARCH for Diabetes in Youth Study (Phase 4, 2016-2019), including 601 children age 10-17 years with T1D, household FS and child-reported FS were assessed using the 18-item Household Food Security Survey Module and the six-item Child Food Security Assessment questionnaire. Age-stratified (10-13, 14-17) regression models were performed to estimate independent associations, adjusting for sociodemographic and clinical factors and household FS.
Results: FI was reported by 13.1% (n=79) of children and 15.6% (n=94) of caregivers. Among child-caregiver dyads, 82.5% (n=496) of reports were concordant and 17.5% (n=105) discordant, Cohen’s kappa = 0.3. Child-reported FI was not independently associated with hemoglobin A1c, diabetic ketoacidosis, and hypoglycemia, including in age-stratified analyses. Child-reported FI was independently associated with elevated odds of depressive symptoms (OR 3.6, 95% CI 1.3-10.3) and disordered eating (OR 2.5, 95% CI 1.4-4.6) compared to FS; these associations remained in both age groups for disordered eating and in the older group for depressive symptoms.
Conclusion: Children with T1D may experience FI differently than caregivers. Child-reported FI was independently associated with depressive symptoms and disordered eating and thus may be an important attribute to assess in addition to household FS in children with T1D.

Disclosure
E.F.Julceus: None. B.A.Reboussin: None. K.Reynolds: Research Support; Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.D.Liese: None. E.A.Frongillo: None. J.A.Mendoza: None. K.A.Sauder: None. F.Malik: None. E.T.Jensen: Consultant; Regeneron. L.M.Dolan: None. A.Bellatorre: None. D.Dabelea: None.

Funding
National Institutes of Health (R01DK117461, 1R01DK127208, 1UC4DK108173, T32GM081740)
1379-P: Adding Salt to Foods and Risk of Severe Nonalcoholic Fatty Liver
Authors: MA HAO , WANG XUAN , LI XIANG , HEIANZA YORIKO , QI LU 
Published: June 2023

Background: High sodium intake is associated with insulin resistance, obesity, and metabolic syndrome, whereas very few studies have assessed the association of sodium intake with risk of nonalcoholic fatty liver disease (NAFLD). We recently found that the frequency of adding salt to foods could reflect a person’s long-term salt taste preference and sodium intake and was significantly related to life expectancy and cardiovascular disease risk. In this study, we aimed to evaluate the association between the frequency of adding salt to foods and liver proton density fat fraction (PDFF, a magnetic resonance imaging-based measure to assess liver fat content) and severe NAFLD risk.
Methods: A total of 494,240 participants from UK biobank, who were free of NAFLD at baseline (2006-2010) were analyzed in this study. Of the above participants, 9816 participants have MRI-PDFF data, measured in 2014. Generalized linear models were used to evaluated association between the frequency of adding salt to foods with liver-PDFF; Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and severe NAFLD risk.
Results: During a median of 11 years of follow-up, 5,294 severe NAFLD cases were documented. Compared with participants who Never/Rarely added salt to foods, the adjusted Hazard Ratios (95% confidence interval) were 1.11 (1.04, 1.18), 1.27 (1.17, 1.37), and 1.45 (1.30, 1.62) across the groups of Sometimes, Usually, and Always, respectively (P-trend&lt;0.001). The liver-PDFF values were 4.7 % (95% CI, 3.9, 5.5), 5.1% (4.3, 5.9), 5.2% (4.4, 6.0) and 5.5% (4.5-6.4) in the groups of Never/Rarely, Sometimes, Usually, and Always added salt to foods, respectively (P-trend&lt;0.001). In sensitivity analyses, we replaced the frequency of adding salt to foods with estimated 24-hour urinary sodium extraction and found similar significant associations.
Conclusions: Our findings indicate that high sodium intake is associated with higher risk of severe NAFLD.

Disclosure
H. Ma: None. X. Wang: None. X. Li: None. Y. Heianza: None. L. Qi: None.
1386-P: Dipeptidyl Peptidase-4 Inhibitors and the Risk of Skin Cancer among Patients with Type 2 Diabetes—Population-Based Cohort Study
Authors: PRADHAN RICHEEK , AZOULAY LAURENT , PLATT ROBERT W. , HOI YUN YU ORIANA 
Published: June 2023

Introduction: The dipeptidyl peptidase-4 (DPP-4) enzyme influences carcinogenic pathways in the skin, although its exact role remains uncertain. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas.
Research Design and Methods: Using the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019. For melanoma, the cohort included 96,739 DPP-4 inhibitor users and 209,341 sulfonylurea users, and 96,411 DPP-4 inhibitor users and 208,626 sulfonylurea users for nonmelanoma skin cancer. Propensity score fine stratification weighted Cox proportional hazards models were to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of melanoma and nonmelanoma skin cancer, separately.
Results: Overall, DPP-4 inhibitors were associated with a 23% decreased risk of melanoma compared with sulfonylureas (49.7 vs. 65.3 per 100,000 person-years, respectively; HR 0.77, 95% CI 0.61-0.96). The HR progressively reduced with increasing cumulative duration of use (0-2 years HR 1.14, 95% CI 0.84-1.54; 2.1-5 years HR 0.44, 95% CI 0.29-0.66; &gt;5 years HR 0.33, 95% CI 0.14-0.74). In contrast, these drugs were not associated with the incidence of nonmelanoma skin cancer, compared with sulfonylureas (448.1 vs. 426.1 per 100,000 person-years, respectively; HR 1.06, 95% CI 0.98-1.15).
Conclusions: In this large, population-based cohort study, DPP-4 inhibitors were associated with a reduced risk of melanoma but not nonmelanoma skin cancer, compared with sulfonylureas.

Disclosure
R.Pradhan: None. L.Azoulay: Advisory Panel; Pfizer Inc., Consultant; Pfizer Inc., Speaker's Bureau; Roche Diagnostics. R.W.Platt: Advisory Panel; Pfizer Inc., Consultant; Boehringer Ingelheim (Canada) Ltd., Biogen, Merck & Co., Inc., Nant Pharma, Other Relationship; Boehringer Ingelheim Inc. O.Yu: Consultant; Novo Nordisk.

Funding
Canadian Institutes of Health Research (FDN143328)
139-OR: An Obesity-centric Approach With and Without Antiobesity Medications Compared with the Usual-Care Approach to Management of Patients with Obesity and Type 2 Diabetes in an Employer Setting—A Pragmatic Randomized Controlled Trial (EMPOWER-T2D)
Authors: PANTALONE KEVIN M. , ROGEN BRUCE , BENA JAMES F. , XIAO HUIJUN , BARNARD GRETCHEN , BORUKH ELENA , PEECHAKARA SEENIA , GRIEBELER MARCIO L. , BURGUERA BARTO 
Published: June 2023

Objective: Among patients with T2D and obesity, determine the effect of combining anti-obesity medications (AOM) with a comprehensive employer-based weight management program [obesity-centric approach (OCA) + AOM] compared with OCA alone, or usual care (UC) on weight and HbA1c.
Methods: A 1-year open-label, randomized, pragmatic clinical trial was conducted at the Cleveland Clinic (CC). Participants were adults with T2D (HbA1c &gt;7.5%) and BMI ≥ 30 kg/m2 enrolled in the CC Employee Health Plan. Participants were randomized 1:1:1 to OCA+ AOM, OCA alone, or UC. Participants in the OCA+AOM group initiated treatment with 1 of 5 US FDA-approved AOMs according to standard practice. Linear mixed effect models were conducted for analysis.
Results: A total of 74 participants were randomized (24 OCA+AOM, 26 OCA, and 24 UC). Participants were predominantly female (59%), median age 53.5 (47, 60) years, 68% Caucasian, with baseline median BMI and HbA1c of 37.4 (34.2, 42.7) and 8.8% (7.9, 10.4), respectively. At 1 year, patients that received UC, OCA alone, and OCA + AOM had their mean % weight change (90% confidence interval, CI) by -4.48% (-6.52 to -2.45), -6.68% (-8.71 to -4.65), and -8.74% (-10.64 to -6.74) and mean HbA1c change (90% CI) by -1.65% (-2.09 to -1.22), -2.22% (-2.65 to -1.79), and -2.18% (-2.61 to -1.74), respectively. Only OCA + AOM treatment was found to be non-inferior (P=0.004) to UC approach in weight loss change. OCA + AOM treatment was also found to be superior to UC approach in weight loss change (P=0.022). OCA+AOM and OCA alone were non-inferior to usual-care in HbA1c change (P &lt;0.05), but neither was superior (P&gt;0.05).
Conclusion: An OCA +AOM approach to T2D treatment was associated with additional weight loss with non-inferior A1C reductions vs. UC. Larger long-term studies evaluating obesity-focused approaches to T2D management are needed.

Disclosure
K.M.Pantalone: Consultant; AstraZeneca, Bayer Inc., Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Sanofi, Research Support; Bayer Inc., Merck & Co., Inc., Novo Nordisk, Twin Health, Speaker's Bureau; AstraZeneca, Corcept Therapeutics, Merck & Co., Inc., Novo Nordisk. B.Rogen: None. J.F.Bena: None. H.Xiao: None. G.Barnard: None. E.Borukh: None. S.Peechakara: None. M.L.Griebeler: None. B.Burguera: Research Support; Novo Nordisk.
1396-P: Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis among Subjects without Type 2 Diabetes (T2D)
Authors: GOLABI PEGAH , PAIK JAMES M. , KUMAR AMEETA , GUNDURAO NAGASHREE , CUSI KENNETH , YOUNOSSI ZOBAIR 
Published: June 2023

Background: NAFLD is highly prevalent in patients with T2D. The prevalence of NAFLD in nondiabetics (ND) is not known.
Aim: Assess the prevalence of NAFLD in ND subjects in the US.
Methods: Data from NHANES 2017-2020 were used. NAFLD was determined by transient elastography with a CAP of ≥285 dB/m without other causes of liver disease. Significant fibrosis (SF) definition was liver stiffness measurement (LSM) &gt;8.0 kPa and advanced fibrosis (AF) definition was LSM&gt;13.1 kPa. Prediabetes (Pre-D) definition was fasting glucose of 100-125 mg/dL or HbA1c of 5.7%-6.5% in T2D absence. ND definition was not having T2D or Pre-D.
Results: Among 5,142 patients (mean age 51.5 years, 19.4% T2D, 35.2% Pre-D and 45.4% ND). The prevalence of NAFLD among T2D, Pre-D and ND was 67.7%, 40.0% and 24.6%. As compared to Pre-D and T2D, ND patients were younger (45.6 years vs 53.4 and 62.2 years), more likely to be female (51.4% vs 43.9% and 45.3%) and less metabolically unhealthy [hypertension: 39.7% vs 56.9% and 83.9%, hyperlipidemia: 63.6%, 73.3%, and 89.0% and HOMA-IR &gt; 2.5: 26.5%, 54.8%, and 84.9% (all p&lt;.001)]. The prevalence of SF and AF among NAFLD with ND, Pre-D and T2D were 17.1% and 4.9%, 16.0% and 6.2%, and 32.4% and 11.8%, respectively. Factors associated with higher risk of AF varied by T2D status (Table).
Conclusions: NAFLD can occur in nondiabetics and associated with insulin resistance and elevated CRP.

Disclosure
P. Golabi: None. J.M. Paik: None. A. Kumar: None. N. Gundurao: None. K. Cusi: Research Support; Echosens, Inventiva. Consultant; Poxel SA. Research Support; LabCorp, Zydus. Consultant; Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns. Z. Younossi: Consultant; AbbVie Inc., BMS, Gilead Sciences, Inc., Novo Nordisk, Merck & Co., Inc., Quest Diagnostics, Siemens, Intercept Pharmaceuticals, Inc., Viking Therapeutics.
1403-P: Agent Orange Exposure and Type 2 Diabetes in Korean Veterans—An Epigenetic Association Study
Authors: HYUN SEO JE , AN KIM YE 
Published: June 2023

Objective: There has been contradictory evidence about the relationship between Agent Orange (AO) exposure and type 2 diabetes. By combining DNA methylation and DNA genotyping analysis, we intended to determine if AO exposure is related with the development of type 2 diabetes and to confirm the causal association between AO exposure and type 2 diabetes.
Research Designs and Methods: An epigenome-wide association analysis and DNA genotyping analyses were done on the blood of AO-exposed and AO-unexposed type 2 diabetes patients and healthy controls. To assess the causal influence of AO-exposure-identified CpGs on type 2 diabetes, methylation quantitative trait locus (meQTL) and Mendelian randomization (MR) studies were used. The risk of type 2 diabetes was compared between subgroups using polygenic risk score (PRS).
Results: Hypermethylated CpG sites (cg20075319, cg21757266, cg05203217, cg20102280, cg26081717, and cg21878650) and one hypomethylated CpG site (cg07553761) were linked to type 2 diabetes in AO-exposed individuals. Methylation levels at some CpG sites (cg20075319, cg20102280, and cg2608171) were considerably different, according to meQTL analyses. CpG sites discovered in AO-exposed patients were causally linked to type 2 diabetes, according to MR analysis; The impact of the reverse causality was insignificant. A PRS analysis revealed no discernible difference in the risk of type 2 diabetes between AO-exposed and AO-unexposed groups.
Conclusions: We validated a causal relationship between AO exposure and type 2 diabetes by identifying distinct epigenetic markers between AO-exposed and AO-unexposed patients with type 2 diabetes. These results highlight the need for more epigenetic research on the link between type 2 diabetes and AO exposure.

Disclosure
J.Seo: None. Y.Kim: None.

Funding
National Research Foundation of Korea (2022R1C1C1002929); Veterans Health Service Medical Center (VHSMC19033); National Institutes of Health; Centers for Disease Control and Prevention (2019-NG-053-02, 2022-NI-067-00)
1418-P: Identification and Follow-up of T2D by Subtypes and Their Cardiovascular Risk in Mexican Population—The Experience of the MIDO State Registry in Guanajuato
Authors: GALLARDO-RINCÓN HECTOR , MONTOYA ALEJANDRA , MORALES-JUAREZ LINDA , RIOS-BLANCAS MARIA J. , ÁLVAREZ-HERNÁNDEZ DIEGO-ABELARDO , ALBERTO MARTINEZ-JUAREZ LUIS , ALBERTO DIAZ-MARTÍNEZ DANIEL , JAVIER MAGOS-VAZQUEZ FRANCISCO , OSWALDO VARGAS EDWIN , TAPIA-CONYER ROBERTO 
Published: June 2023

Type 2 diabetes (T2D) is a complex and heterogeneous disease that has been categorized based on its underlying physiological mechanisms to inform treatment strategies. However, patients with T2D often exhibit a wide range of phenotypic and metabolic profiles, and the subclassification of this disease has only recently been developed, enabling the possibility of personalized management and improved outcomes. The aim of this research was to identify and follow-up T2D subtypes and their cardiovascular risk (CVR) in the Mexican population. In this study, 14,124 patients with incident T2D were assessed to characterize their phenotypic and metabolic profiles and to identify their CVR as part of the MIDO State Registry in Guanajuato, Mexico between April 2014, and April 2022. Of the 14,124 patients with incident T2D, when clustered into subtypes according to their phenotypic and metabolic profile, 3,530 (24.9%) belonged to the mild age-related diabetes (MARD) subtype, 4,304 (30.5%) to the mild obesity-related diabetes (MOD), 3,180 (22.1%) to the severe autoimmune diabetes (SIRD), and 3,111 (11.5%) to the severe insulin-resistant diabetes (SIDD). When the CVR was assessed, 1,767 (50.1%) individuals had a medium CVR and 1,763 (49.9%) had a high CVR in the MARD, 3,313 (76.9%) had a medium CVR and 990 (23.1%) had a high CVR in the MOD, 1,699 (54.6%) had a medium CVR and 1,733 (45.4%) had a high CVR in the SIRD, and 2,290 (72.0%) had a medium CVR and 890 (27.9%) had a high CVR in the SIDD. Of the 13,192 patients that were followed for 6 months, up to 61.0% of the MARD, 61.4% of the MOD, 61.2% of the SIRD, and 40.9% of the SIDD achieved metabolic control (HbA1c &lt;7%). Classifying the subtypes of T2D allows for the design of personalized treatment strategies aiming to delay the progression of the disease and prevent cardiovascular complications. In Mexico, this is a novel approach that seeks to improve the overall outcomes of patients with incident T2D.

Disclosure
H.Gallardo-rincón: None. R.Tapia-conyer: None. A.Montoya: None. L.Morales-juarez: None. M.J.Rios-blancas: None. D.Álvarez-hernández: None. L.Martinez-juarez: None. D.Diaz-martínez: None. F.Magos-vazquez: None. E.Vargas: None.