bluuebunny/crossref_metadata_2025_split huggingface dataset:
1595-P: Evaluating Social Support and T2D Risk Factors among Members of Rural-Dwelling Grandparent-Headed Households
Authors: SMALLS BRITTANY L. , PALMER KELLY N. , CONTRERAS OMAR A. , HATCHER JENNIFER 
Published: June 2020

Objective: The purpose of this paper is to elucidate factors impacting the health, development and management of chronic illnesses, particularly type 2 diabetes of rural grandparent-headed households (GHH).
Research Design and Methods: Prospective data were collected from rural-dwelling members of GHHs living in Appalachia Kentucky with no known diagnosis of T2D. Data collected on family characteristics, T2D clinical risk factors, and social support were assessed using the Medical Outcomes Survey (MOS) Social Support and the Child and Adolescent Social Support Scale (CASSS).
Results: Sixty-six grandparents and 72 grandchildren participated in the study. The average age and HbA1Cs were 59.4 years and 6.2% ± 1.4 for grandparents and 11.8 years and 4.9% ± 0.6 for grandchildren. The majority of grandparents were found to have prediabetes (31%) or undiagnosed diabetes (28%). The number of people living in GHHs were associated with grandparents’ triglycerides, HDL, and BMI whereas custody status was associated with BMI. Average social support scores among grandparents suggested moderately high perceived social support (79 ± 3.4). For grandchildren, social support provided by grandparents had no association with T2D risk factors, whereas support from teachers, classmates, and close friends was associated with HbA1C, BMI, and blood pressure in grandchildren.
Conclusion: This study shows that rural-dwelling grandparent caregivers are at an increased risk for T2D. In addition, increased responsibility may provide a determinant of health due to the potential stress of caregiving for grandchildren. Social support between grandparents and grandchildren has no effect on T2D risk factors. However, social support provided by peers, teachers, and close friends were associated with T2D risk factors in grandchildren. These findings support the use of peer support and school settings as mechanisms for interventions to reduce T2D in adolescents, particularly those of GHHs.

Disclosure
B.L. Smalls: None. K.N. Palmer: None. O.A. Contreras: None. J. Hatcher: None.

Funding
National Institute for Diabetes and Digestive and Kidney Diseases (R03DK101705 to J.H.)
1597-P: Increased Pancreatic Cancer Risk Associated with Dietary Iron in Whites, but Not Blacks with Diabetes
Authors: CONWAY BAQIYYAH , HUDSON ALANA G. , MCCLAIN DONALD A. , BLOT WILLIAM J. 
Published: June 2020

Iron is a risk factor for both diabetes and pancreatic cancer, but whether iron works synergistically with diabetes to increase pancreatic cancer is unknown. Furthermore, risks of both diabetes and pancreatic cancer are increased among African Americans (AA), without clear differences in either iron stores or dietary iron consumption. We therefore tested whether dietary iron consumption increased risk of subsequent pancreatic cancer in a population of AA and Whites with and without diabetes. We conducted a follow up study of pancreatic cancer incidence (2002-2015), using the Southern Community Cohort, a population of mostly low income AA and White participants aged 40-79, with (n=23,489, 40%) and without (n=35,105, 60%) diabetes, recruited from federally qualified health centers. Logistic regression was used to compute ORs (95% CIs) for the risk of incident pancreatic cancer. All models accounted for age, sex, race, BMI, alcohol consumption, and dietary iron consumption. Alcohol and iron consumption were natural log transformed before analyses. There were 262 incident pancreatic cancer cases. Risk of pancreatic cancer and dietary iron consumption were not associated in subjects without diabetes (OR=1.08, 95% CI=0.81-1.45), but trended toward an association in those with diabetes (OR=1.26, 95% CI=0.84-1.90). However, there was a significant three-way interaction among diabetes, race, and total dietary iron consumption (p-interaction=0.04). When stratified by diabetes and race, total dietary iron consumption increased pancreatic cancer risk by over two-fold among Whites with diabetes (OR=2.47, 95% CI=1.14-5.37), but showed no association in any of the other three groups, namely AA with (1.00, 0.97-1.03) and w/o (1.09, 0.78-1.53) diabetes and Whites w/o diabetes (1.03, 0.56-1.89). Our data suggests that increased dietary iron consumption increases risk of pancreatic cancer among Whites with diabetes.

Disclosure
B. Conway: None. A.G. Hudson: None. D.A. McClain: None. W.J. Blot: None.

Funding
5U01CA202979-04
1605-P: Incidence of Hepatocellular Carcinoma in Type 2 Diabetes with Cirrhosis Who Were Treated with Metformin
Authors: TANGJARUSRITARATORN THANIDA , KUNAVISARUT TADA , TANGJITTIPOKIN WATIP 
Published: June 2020

Several studies demonstrated an association between type 2 diabetes (T2D) and a higher risk of hepatocellular carcinoma (HCC). Metformin is widely prescribed for T2D. Metformin has been shown to prevent various cancer developments. The association of metformin use and development of HCC among T2D with cirrhosis is investigated. This study aims to determine if metformin significantly reduces the incidence of HCC in this population. T2D with cirrhosis patients from 2006 to 2014 with age 20 to 80 years were studied as a retrospective cohort. An incidence of HCC in T2D with/without metformin exposure after cirrhosis diagnosis within 5 years was determined by Chi-square test. The exposure was defined as a drug intake at the time of cirrhosis diagnosis, continuing for at least 90 days beyond the diagnosis. The 5-year disease-free survival of HCC in each group was compared using the log-rank test and Kaplan-Meier method. The total of 1,061 T2D with cirrhosis included metformin exposure (N=719) and metformin non-exposure (N=342). The overall HCC incidence was 253 (23.85%). Among patients with metformin exposure, the HCC incidence was 125 (17.39%), compared to 128 (37.42%) in non-exposure group. The development of HCC within 5 years was significantly lower in metformin exposure than in non-exposure group (RR=0.76; 95% CI:0.69-0.83; P&lt;0.001). The 5-year disease-free survival of HCC with metformin exposure is greater than that of non-exposure (0.80 vs. 0.57; HR=0.42; 95% CI:0.33-0.54; p&lt;0.001). Moreover, the result shows that male gender (HR=1.64; 95% CI:1.25-2.14), HbA1C≥7.5% (HR=1.30; 95% CI:1.00-1.68), HBV cirrhosis (HR=1.80; 95% CI:1.13-2.85), HCV cirrhosis (HR=2.31; 95% CI:1.43-3.74), smoking and drinking cessation ≥5 years (HR=1.78; 95% CI:1.31-2.42 and HR=1.74; 95% CI:1.27-2.38 respectively) were linked to a rising 5-year HCC incidence in T2D.
Conclusion: The metformin treatment might reduce the incidence of HCC in T2D with cirrhosis during 5-years and benefit HCC prognosis.

Disclosure
T. Tangjarusritaratorn: None. T. Kunavisarut: None. W. Tangjittipokin: None.
1610-P: Heterogeneity in Diabetes across Socioeconomic Subgroups of Asian-Americans in the U.S.
Authors: SHAH MEGHA K. , GANDRAKOTA NIKHILA , GUJRAL UNJALI , ALI MOHAMMED K. , NARAYAN K.M. VENKAT 
Published: June 2020

Background: In the U.S., some Asian subgroups have disproportionately higher burdens of diabetes which vary by country of origin. Social determinants of health (SDOH)—the conditions in which one grows, lives and works- also influence health disparities. We examined whether diabetes prevalence in Asian subgroups varies by SDOH indices using data from a nationally representative sample.
Methods: We pooled weighted data from National Health Interview Survey 2009-2018 for 6,467 participants who reported their ethnicity as Asian (Chinese, Filipino, Asian Indian, and Other Asian [Korean, Vietnamese, Japanese, and other]). We built multivariate logistic regression models assessing the likelihood of diabetes among Asian subgroups by sociodemographic strata of poverty, marital status, education, health insurance and income, adjusting for age, sex, and overweight/obesity status.
Results: Higher income, compared to poverty status was associated with higher odds of diabetes among Chinese (aOR 2.55, 95%CI 2.51-2.60) and lower odds of diabetes among Filipino, Asian Indian and Other Asian groups (aOR 0.93, 95%CI 0.92-0.94; aOR 0.82, 95%CI 0.81-0.83; aOR 0.60, 95%CI 0.60-0.61, respectively). College education was associated with increased odds of diabetes among Asian Indians, compared to less than high school (aOR 1.55, 95%CI 1.51-1.58) though lower odds of diabetes among Chinese, Filipino, and other Asian groups (aOR .09, 95%CI .09-.09; aOR 0.98, 95%CI 0.96-0.99; aOR 0.51, 95%CI 0.50-0.52, respectively). Health insurance coverage was associated with higher odds of diabetes across all groups. Married status was associated with lower odds of diabetes among Chinese (aOR 0.77, 95%CI 0.76-0.78) but higher for Filipino, Asian Indian, and Other Asian groups.
Discussion: Our data show that SDOHs do not have a uniform influence on diabetes risk in Asian subgroups. Future research should account for this variation and consider subgroup-specific solutions to address diabetes-related health disparities.

Disclosure
M.K. Shah: None. N. Gandrakota: None. U. Gujral: None. M.K. Ali: Research Support; Self; Merck & Co., Inc. K. Narayan: None.

Funding
National Center for Advancing Translational Sciences (UL1TR002378, KL2TR002381)
1618-P: Insulin Secretion Variability According to the Specific Type 1 Diabetes (T1D) Risk Predictor
Authors: JACOBSEN LAURA M. , NATHAN BRANDON M. , ISMAIL HEBA M. , REDONDO MARIA J. , SCHATZ DESMOND , HALLER MICHAEL J. , SIMS EMILY K. , SKYLER JAY S. , PALMER JERRY P. , HEROLD KEVAN C. , SOSENKO JAY 
Published: June 2020

The risk for T1D, a major criterion for entry into disease prevention trials, can be assessed in various ways, but usually includes autoantibody (Ab) and/or metabolic measures. Given inherent variations in these biomarkers, it is possible that informative characteristics differ between populations selected by different risk measures. Thus, we assessed whether indices of insulin secretion [C-pep; first phase insulin response (FPIR)] vary between groups defined by distinctive risk measures. We used data from Diabetes Prevention Trial-Type 1 (DPT-1) participants, all being ICA positive subjects with or without biochemical Ab (bAb) positivity (GADA, IA-2A, mIAA). C-pep and FPIR values from baseline oral and intravenous glucose tolerance tests were compared between those who had 2-3 bAbs (≥2bAb) and those who had 0-1 bAb plus Index60≥0.40 (≤1bAb+Ind60). Index60 is a composite C-pep and glucose measure. These groups were chosen so that T1D risk would be similar (50% 5-year risk for both, log rank p=0.95). Ages (mean±SD) for ≥2bAb (n=289) and ≤1bAb+Ind60 (n=175) were 12.8±8.2 and 13.3±9.6 yrs, respectively (p=0.53). BMI Z-score was greater for ≥2bAb (0.42±1.12 vs. 0.15±1.09, p=0.01). C-pep levels were consistently higher for ≥2bAb than ≤1bAb+Ind60 [30-0 minute C-pep: 2.73±1.58 vs. 2.04±1.12 ng/mL, p&lt;0.0001; area under the curve (AUC) C-pep: 3.70±1.55 vs. 3.27±1.12 ng/ml, p=0.013; AUC C-pep/AUC glucose: 0.030±0.013 vs. 0.025±0.007 (ng/ml)/(mg/dl), p&lt;0.001]. FPIR was also higher for ≥2bAb (122.0±87.3 vs. 96.2±47.1 µU/ml, p&lt;0.01). All comparisons remained significant with adjustments for age and BMI Z-score. Of those with ≤1bAb+Ind60, 0 bAb did not differ from 1 bAb for C-pep indices or FPIR.
In conclusion, C-pep and FPIR values can differ appreciably according to the measure that defines risk. This should be considered in choosing risk measures for prevention trials.

Disclosure
L.M. Jacobsen: None. B.M. Nathan: None. H.M. Ismail: None. M.J. Redondo: None. D. Schatz: None. M.J. Haller: Advisory Panel; Self; SAB Biotherapeutics, Inc. E.K. Sims: None. J.S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Avotres, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings, Inc., Immunomolecular Therapeutics, Intrexon, Oramed Pharmaceuticals, Orgenesis Inc., Sanofi, Tolerion, Inc., Viacyte, Inc. Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Tolerion, Inc. Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. J.P. Palmer: None. K.C. Herold: Consultant; Self; Provention Bio, Inc. J. Sosenko: None.
162-LB: Impact of High-Fat Meal on Circulating microRNA in Youth with T1DM
Authors: TRYGGESTAD JEANIE B. , TEAGUE APRIL M. , SHORT KEVIN R. 
Published: June 2020

MicroRNA (miRNA) are small non-coding RNAs that impact translation via degrading or repressing mRNA. From animal models, circulation abundance of miRNA is impacted by feeding. The goal of this project was to compare levels of specific circulating miRNAs between youth with T1DM and controls and the impact of a high fat meal on miRNA abundance. Fourteen youth (6 females, 8 males) with T1DM and 29 normal weight control youth (14 females, 15 males) ingested a milkshake with 830 kcal; 36% carbohydrate, 54% fat (31 grams of saturated fat), and 10% protein. Circulating miRNAs (miR-122, 126, and 130b) at baseline and 150 minutes post-ingestion were measured by qPCR. The group with T1DM had a median A1c of 8.4% (7.4, 8.9) with an average duration of 7 years. At baseline, miR-126 tended to be higher in the youth with T1DM (47%, p=0.072). In pooled groups, all three miRNAs decreased at 150 min (miR-122: -21%, p=0.036; miR-126: -37%, p=0.001; and miR-130b: -33%, p=0.023). Within the control group, miR-122 and miR-126 decreased 26% and 28% from baseline (p=0.037 and p=0.035, respectively). Within the T1DM group, miR-126 and miR-130b decreased 49% and 50% from baseline (p=0.007 and p=0.011, respectively). The decrease in miR-122 from baseline was correlated with the total energy expenditure for the meal (r=0.-0.379, p=0.017) and insulin under the curve (r=0.350, p=0.029). The decrease in miR-126 and miR-130b were negatively correlated with glucose area under the curve (r=-0.369 and -0.358, p=0.021 and 0.025, respectively), and the decrease in miR-130b was negatively correlated with baseline NEFA (r= -0.328, p=0.042). miR-122 and 130b both target AMPK, which could alter lipid metabolism, thus explaining the associations with NEFA and energy expenditure. miR-126 is known to target both IRS1 and PI3K in the insulin signaling pathway, potentially explaining the association with glucose. It is clear that the circulating abundance of these miRNAs is reduced following a high fat meal, and that response may be modified by the presence of T1DM.

Disclosure
J.B. Tryggestad: None. A.M. Teague: None. K.R. Short: None.

Funding
Harold Hamm Diabetes Center; Ardmore Institute of Health
163-OR: Metabolically Unhealthy Obese Is Transient and Improves with Aerobic Exercise
Authors: HODDY KRISTIN K. , AXELROD CHRISTOPHER L. , MEY JACOB T. , HARI ADITHYA , BEYL ROBBIE A. , KIRWAN JOHN P. 
Published: June 2020

Introduction: A subset of adults with obesity may be classified as having metabolically healthy obesity (MHO). There is a high conversion rate from the MHO condition to a metabolically unhealthy obesity (MUO) condition over time. The insulin sensitizing effects of exercise across these metabolic states has not been established and may inform more precise obesity treatment.
Methods: Sedentary adults (n=43) with obesity, but not diabetes, underwent inpatient testing (anthropometric measurements, blood chemistries, aerobic capacity (VO2MAX), and insulin sensitivity (euglycemic clamp) before and after 12 weeks of aerobic exercise training (5x/week, 60 min/session, ∼85% HRMAX). A metabolic health score (MetScore) was calculated using baseline values (BMI, VO2MAX, HOMA-IR, triglycerides, and cholesterol) to stratify participants with MHO (n= 21; MetScore ≤ 237) or MUO (n=22; MetScore &gt; 237). Linear mixed models determined group differences over time.
Results: MHO and MUO groups differed by MetScore at baseline (202 and 325; P&lt;0.01) and after 12 weeks of exercise (181 and 261; P&lt;0.01), but MHO had lower fasting glucose, insulin, HOMA-IR, and higher HDL-C along with superior M/I, than MUO participants. MetScore improved in the group with MUO (-64; P&lt;0.01) compared to MHO (-20; p=0.06)(P&lt;0.01, between groups). Both groups (MHO v. MUO) experienced similar improvements in VO2MAX (+6.8 and +9.3 ml/kg/min), body weight (-8.8 and -7.5 kg), body fat (-4.2 and -2.9%), triglyceride concentrations (-31.7 and -25.8 mg/dl), and M/I (0.0183 and 0.0166 mg/kg/min/μU/ml) (P&gt;0.20, all between groups). Insulin (-2.62 μU/ml; P=0.0185) and HOMA-IR (-0.71; P=0.022) decreased in the group with MUO with no between group differences (P=0.75 and P=0.52, respectively).
Conclusion: Aerobic exercise enhances individual components of health similarly in persons with MHO and MUO after 12 weeks. However, those with MUO experienced the greatest collective improvement, thus presenting an opportunity for intervention.

Disclosure
K.K. Hoddy: None. C.L. Axelrod: None. J.T. Mey: None. A. Hari: None. R.A. Beyl: None. J.P. Kirwan: None.

Funding
National Institute on Aging (AG012834); National Institute of General Medical Sciences (GM104940); Louisiana Clinical & Translational Science Center (U54-GM104940)
1631-P: Age at Menarche and Its Association with the Metabolic Syndrome in Type 1 Diabetes
Authors: JU JINGHUI , RUBINSTEIN DEBRA , EL KHOUDARY SAMAR R. , ORCHARD TREVOR J. , COSTACOU TINA 
Published: June 2020

Early menarche has been associated with a higher risk of metabolic syndrome (MetS), CVD and its risk factors in the general population. However, limited data exists regarding the association between age at menarche and MetS in women with type 1 diabetes (T1D), a population in which menarche may be delayed. We thus assessed the ability of age at menarche to predict incident MetS in female participants (n=235) of the EDC study, a cohort of childhood onset T1D. MetS was defined using modified AHA NCEP ATP III criteria: waist circumference ≥ 89 cm; triglycerides ≥ 150 mg/dL or treatment for elevated triglycerides; HDL cholesterol &lt; 50 mg/dL; systolic/diastolic blood pressure ≥130/85 mmHg or on antihypertensive medications. Since all participants met the criteria of hyperglycemia, any two of the remaining four criteria were required for diagnosis of MetS. Participants were divided into 3 menarche timing groups: early (≤11 years, n=22), normal (12∼14 years, n=163) and delayed menarche (≥15 years, n=50). At baseline, women with delayed menarche were with longer diabetes duration and more likely to have lower estimated glomerular filtration rate (eGFR) compared with the other groups (all p-values&lt;0.05). However, univariately, the incidence of MetS during the 25-year follow-up did not differ by menarche timing group (63.6% vs. 49.1% vs. 46.0%, respectively, p=0.37). In multivariable Cox models, compared with the normal menarche group, women with early and delayed menarche had non-significantly higher (HR =1.42, p=0.26) and lower (HR =0.89, p=0.64) hazards of developing MetS, respectively. Duration of T1D, HbA1c, BMI and smoking history were significantly associated with a greater risk of MetS, whereas eGFR was significantly associated with a lower hazard of MetS.
In conclusion, unlike findings in the general population where early menarche increased the risk of MetS, in this cohort of women with T1D the incidence of MetS did not differ significantly by menarche timing group.

Disclosure
J. Ju: None. D. Rubinstein: None. S.R. El Khoudary: None. T.J. Orchard: None. T. Costacou: None.

Funding
National Institutes of Health (DK34818)
1638-P: Functional Characterization of HNF1B Variants Can Enhance Diabetes Precision Medicine
Authors: JOHANSSON BENTE B. , PAVITHRAM AISHWARYA , ZHANG HAICHEN , MALONEY KRISTIN A. , RINGDAL MONIKA , KACI ALBA , SAGEN JORN V. , KLEINBERGER JEFFREY , JENG LINDA , NJØLSTAD PÅL RASMUS , POLLIN TONI I. , MOLNES JANNE 
Published: June 2020

Genetic variants in HNF1B encoding the transcription factor hepatocyte nuclear factor-1 beta (HNF-1B) cause Maturity-Onset Diabetes of the Young type 5 (MODY5; HNF1B-MODY) and are the most common known monogenic cause of developmental kidney disease. The aim of this study was to assess pathogenicity of HNF1B variants identified among 312 patients suspected of monogenic diabetes from the Personalized Diabetes Medicine Program (PDMP) at the University of Maryland. Patients suspected of monogenic diabetes underwent next generation sequencing for 40 genes, including HNF1B. Variants were classified according to ACMG/AMP variant interpretation guidelines. To investigate the effect of HNF1B variants on normal HNF-1B transcriptional activity, we used a Dual-Luciferase assay system in transfected HeLa cells. DNA-binding ability was studied by EMSA and protein localization was determined by fractionation and confocal microscopy. Seven HNF1B variants were identified in 7 unrelated individuals. One variant (p.H336Pfs*22) was classified as pathogenic, 5 (p.T88A, p.A167P, p.N394D, p.V458G, p.T544A) as unknown significance (VUS) and 1 variant as benign (p.D82N). Two variants, p.A167P and p.H336Pfs*22, inferred severely reduced transactivation potential (25% and 34% of WT, respectively). In addition, p.A167P demonstrated decreased protein expression (26% of WT) and a significant loss in DNA binding ability (19% of WT). The p.H336Pfs*22 variant carrier has renal agenesis, often associated with HNF1B mutations, while the p.A167P carrier lacks extra-pancreatic features. The functional evidence allowed p.A167P to be reclassified as likely pathogenic when added to existing evidence (computationally predicted deleteriousness and absence from population databases). Obtaining functional data can improve variant interpretation and enable a more precise diagnosis in patients carrying an HNF1B variant.

Disclosure
B.B. Johansson: None. A. Pavithram: None. H. Zhang: None. K.A. Maloney: None. M. Ringdal: None. A. Kaci: None. J.V. Sagen: Other Relationship; Self; Novo Nordisk A/S. J. Kleinberger: None. L. Jeng: None. P. Njølstad: None. T.I. Pollin: None. J. Molnes: None.

Funding
Western Norway Regional Health Authority; University of Bergen; Norwegian Diabetes Foundation