bluuebunny/crossref_metadata_2025_split huggingface dataset:
1155-P: Incidental Findings on Chest CT Are Not Associated with Type 1 Diabetes Status
Authors: KINNEY GREGORY L. , CONWAY REBECCA B. , YOUNG KENDRA , LI YISHA , SNELL-BERGEON JANET K. 
Published: May 2022

Background: Spirometry assessed pulmonary function has been shown to be mildly reduced in type 1 diabetes (t1d) and while this reduction appears to be chronic it doesn’t appear to be progressive. This suggests that functional reduction may not be a microvascular complication of t1d despite the enormous capillary bed in the lungs. CT imaging of the lungs of people with t1d evaluated for pulmonary function is essentially unexplored. We examined CT imaging of participants with and without t1d to explore lung morphology as it relates to t1d.
Methods: The CACTI study conducted CT imaging of the chest as well as pulmonary function testing via spirometry (PFT) . Imaging included the majority of the lungs but does not include the apexes or bases. These lung fields were assessed in a systematic way by a single clinician for incident and these observations were text mined in order to capture the most frequently observed morphologies. PFT results are reported as % predicted values for forced expiratory volume 1 second (FEV1%p) and Forced Vital Capacity (FVC%p) .
Results: 525 CT scans (2t1d, 316 control) were matched to PFT and compared for each of the most common morphologies (nodules (66) , calcified nodes (25) , emphysema (19) , atelectasis (28) , ground glass (13) , airway thickening (34) and granulomatous disease (28) were the most frequently observed) . Participants with t1d had lower FEV1%p (85.9%p vs. 94.4%p, p &lt;0.0001) , lower FVC (87%p vs. 95.5%p, p&lt;0.0001) , were equally likely to be current and former cigarette smokers (28% vs. 27%, p=0,6) , significantly less likely to have calcified nodes (1.6% vs. 4.2%, p=0.03) or granulomatous disease (1.8% vs. 4.6%, p=0.02) but were not different on any of the other incidental findings on CT.
Conclusions: People with t1d have reduced pulmonary function but CT scans of the central lungs do not show morphological changes that may explain this reduction.

Disclosure
G.L.Kinney: None. R.B.Conway: None. K.Young: None. Y.Li: Employee; Vertex Pharmaceuticals Incorporated. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.
116-LB: Interaction between Iron Stores and Metformin Action
Authors: MCCLAIN DONALD A. , USOH CHINENYE O. , LORENZO FELIPE , HARRISON ALEXANDRIA V. 
Published: May 2022

The mechanism of action of MET (MET) remains controversial. MET induces an iron starvation response in yeast, so we hypothesized that tissue iron might influence MET responsiveness in higher organisms. We reviewed electronic health records to correlate MET responsiveness in diabetic humans with serum ferritin, a measure of iron stores. Both higher and subnormal serum ferritin were associated with decreased HbA1c response to MET (N=80, p&lt;0.001) , and MET responsiveness was lost entirely at higher than normal ferritin. Mice were placed on diabetogenic diets with different iron contents, and treated or not with MET. MET responses of fasting glucose values were superior in mice on low-normal and normal iron diets compared to those on high iron: Fasting glucose decreased 60.4 mg/dL on low-normal iron (N=9, p&lt;0.001) , 40.5 mg/dL on normal iron (N=23, p&lt;0.01) and 2.6 mg/dL on high-normal iron (N=27, p=NS) , with significant interaction between iron and MET (p=0.0015, ANOVA) . Other effects of iron (e.g. leptin expression) are known to be mediated by protein modification by O-linked N-acetylglucosamine (O-GlcNAc) . MET increased O-GlcNAc levels 200% in mice on normal iron (p=0.04) but not high-normal iron diets (-8%, p=NS) . In mice with elevated O-GlcNAc resulting from heterozygous deletion of the O-GlcNAcase gene, MET’s ability to decrease fasting glucose levels in mice on high iron was restored, with differences between MET and placebo being 30.3, 61.3, and 56.5 mg/dL on low-normal, normal, and high-normal iron diets (p&lt;0.0001 by ANOVA) ; in contrast to wild type mice, the significant effects of iron and its interaction with MET were lost (p=0.13 and 0.47) . We conclude that tissue iron affects glycemic responses to MET, supporting the hypothesis that MET induces an iron starvation response but that high iron overwhelms that signal. The results on protein O-GlcNAc modification suggest that it mediates the interaction of iron and MET. MET responsiveness in patients with diabetes could be optimized by modulating iron stores.

Disclosure
D. A. Mcclain: None. C. O. Usoh: None. F. Lorenzo: None. A. V. Harrison: None.

Funding
VA Research Service 2I01 BX001140; NIH 1P30DK12472
1176-P: A Population Shift in Meeting Glycemic Targets Following Five Years of a Very-Low-Carbohydrate Intervention (VLCI) and Continuous Remote Care (CRC)
Authors: VOLK BRITTANIE M. , MCKENZIE AMY L. , ATHINARAYANAN SHAMINIE J. , VANTIEGHEM MICHELLE , ADAMS REBECCA N. , ROBERTS CAROLINE G.P. , RATNER ROBERT E. , VOLEK JEFF , PHINNEY STEPHEN , HALLBERG SARAH 
Published: May 2022

Background: We previously reported 1- and 2-year effectiveness of a VLCI via CRC. Here we assess the long term effectiveness of the treatment via achievement of A1c ≤6.5%, &lt;7%, and &lt;8% with and without antidiabetes medications at 5 years.
Research Design and Methods: Patients with T2D who initially enrolled in a 2-year non-randomized, controlled clinical trial and received a VLCI via CRC were offered 3 additional years of prospective follow-up. Of the 200 patients completing 2 years, 169 (84.5%) consented to extend; 122 (72.2%) were retained at 5 years. Among those who extended, McNemar's test was used to assess the change in percent of patients meeting glycemic targets from baseline to 5 years among completers and on an intent-to-treat basis.
Results: At 5 years, the percent of completing patients meeting glycemic goals improved across all defined targets (Table 1) . Of completing patients, 20% achieved diabetes remission, while 32.5% achieved an A1c &lt;6.5% without the use of antidiabetes medications with the exception of metformin.
Conclusions: One fifth of completing patients achieved the international consensus criteria for diabetes remission at 5 years, which is unique among lifestyle interventions. The proportion of people at A1c goal increased, suggesting the VLCI delivered via CRC may be an effective, long-term strategy to improve population health.

Disclosure
B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp. S.Phinney: Employee; Virta Health Corp.
1181-P: Influence of Nutrients Consumed on Associations between the Gut Microbiota Composition and Type 2 Diabetes
Authors: TAMURA AYUMI , DAIMON MAKOTO , KAMBA AYA , MIZUSHIRI SATORU , MURABAYASHI MASAYA , NISHIYA YUKI , ITO RYOMA , ONO SHOMA 
Published: May 2022

Objective: Upon food digestion, the gut microbiota plays a pivotal role in energy metabolism, affecting the development of type 2 diabetes (DM) . We aimed to examine the influence of nutrients consumed on the association between the gut microbiota and DM.
Research Design and Methods: Among participants of the population-based Iwaki study of Japanese held in 2016, those with information of gut microbiota (n=1148) were included. The following individuals were also excluded: over 77 years of age (excluded to minimize age-related diversity in gut microbiota as previously reported) , and were the 55 individuals with an incomplete data set. After these exclusions, 10individuals (403 men, 616 women) aged 52.4 ± 14.1 years were included in the present study.
Results: Compared with non diabetic subjects, diabetic subjects had larger proportions of the genera Bifidobacterium and Streptococcus but smaller proportions of the genera Roseburia and Blautia in their gut microbiotas. The genera Streptococcus and Roseburia were positively correlated with the amounts of energy (β= 0.064, p=0.0297) and of carbohydrate and fiber (β= 0.079, p=0.0069, and β=0.069, p=0.0129, respectively) consumed, respectively. In contrast, the genera Bifidobacterium and Blautia were not correlated with any nutrients consumed. Cluster analyses of these four genera revealed that the Blautia-dominant cluster was most protective against DM, whereas the Bifidobacterium-dominant cluster was a risk for DM, after adjustment for multiple factors including nutrients consumed (vs. the Blautia-dominant cluster; odd ratio 3.97, 95% confidence interval 1.68-9.36) .
Conclusions: Positive correlations of the genera Streptococcus and Roseburia indicate the possible involvement of nutrient factors in the association between the gut microbiota and DM. Furthermore, having a Bifidobacterium-dominant gut microbiota may be a risk for DM whereas having a Blautia-dominant gut microbiota may be protective against DM.

Disclosure
A.Tamura: None. M.Daimon: None. A.Kamba: None. S.Mizushiri: None. M.Murabayashi: None. Y.Nishiya: None. R.Ito: None. S.Ono: None.
1184-P: Adolescent Growth Spurt and Type 2 Diabetes Risk in an American Indian Population
Authors: RAMIREZ-LUZURIAGA MARIA J. , KOBES SAYUKO , SINHA MADHUMITA , KNOWLER WILLIAM C. , HANSON ROBERT L. 
Published: May 2022

Background: Some studies suggest that earlier pubertal development is associated with obesity and metabolic disorders in adulthood, but whether accelerated adolescent linear growth spurt influences type 2 diabetes (T2D) in populations at high risk of diabetes is unclear.
Aim: To examine associations of age at initiation of the adolescent growth spurt (i.e., take-off) (ATO) , velocity at take-off (VTO) , and age at peak velocity (APV) with T2D incidence.
Methods: Height measurements obtained from a longitudinal study of diabetes in American Indians were used to estimate biological growth parameters using the Preece-Baines growth model I, a parametric model of the human growth curve. Diabetes incidence was analyzed among individuals who had ≥ 4 height examinations at ages 5-17 years and who remained nondiabetic at first examination after age 18. Participants were followed until diabetes developed or last examination. Associations of growth parameters with diabetes incidence were analyzed by Poisson regression.
Results: Among 649 originally nondiabetic participants, 135 females and 82 males developed diabetes in a median follow-up of years. With adjustment for age, birth date and maternal diabetes, younger ATO and APV were associated with T2D incidence in males (incidence rate ratio (IRR) =1.75 per year, 95% CI, 1.23, 2.50; and IRR=1.33, 95% CI, 1.01, 1.75, respectively) but not in females (IRR=0.93, 95% CI, 0.75, 1.16; and IRR=1.04, 95% CI, 0.86, 1.26, respectively) . Higher VTO was associated with T2D incidence in males (IRR=1.80 per cm/y, 95% CI, 1.15, 2.81) but not in females (IRR=1.15, 95% CI, 0.88, 1.50) . With further adjustment for adult and childhood BMI and fasting insulin, the associations were attenuated for APV and VTO but remained significant for ATO in males.
Conclusion: Our findings suggest that an early and accelerated adolescent growth spurt is a risk factor for T2D, at least in males. These associations are only partially explained by measures of adiposity and insulinemia.

Disclosure
M.J.Ramirez-luzuriaga: n/a. S.Kobes: None. M.Sinha: None. W.C.Knowler: None. R.L.Hanson: None.
1186-P: The Effect of Age on the Risk Relationship between Prediabetes and Mortality and Major Adverse Clinical Events
Authors: ZHANG XINGE , WU HONGJIANG , LAU ERIC S.H. , SHI MAI , FAN BAOQI , YANG AIMIN , CHOW ELAINE , KONG ALICE P. , CHAN JULIANA C. , MA RONALD C. , LUK ANDREA 
Published: May 2022

Background: Prediabetes is associated with increased risk of cardiovascular disease (CVD) , kidney disease and death but the extent to which the risk associations between prediabetes and clinical events are modified by age is not known.
Methods: We conducted a retrospective analysis of a territory-wide diabetes surveillance dataset from the Hong Kong Hospital Authority including 2,692,880 individuals with at least one glycaemic measurement between 2000 and 2019. Prediabetes was defined according to the American Diabetes Association criteria. Proportional Cox regression was used to derive hazard ratios (HR) and 95% CI of prediabetes vs. normoglycaemic for incident CVD, end-stage kidney disease (ESKD) , all-site infection and all-cause death, stratified by baseline age categories (20-39, 40-59, 60-79 and ≥80 years) .
Results: Compared with people with normoglycaemia, people with prediabetes had greater hazards for clinical events in all age groups but the effect size attenuated with ascending age. In the youngest and in the oldest age categories, the respective HRs (95% CI) of prediabetes vs. normoglycaemia were 1.93 (1.71-2.17) and 1. (1.01-1.12) for CVD, 1.72 (1.42-2.08) and 1. (1.03-1.17) for ESKD, 1.48 (1.36-1.62) and 1. (1.00-1.08) for all-site infection, and, 1.52 (1.33-1.73) and 1. (1.04-1.10) for all-cause death. The associations remained after excluding people who later developed diabetes and after adjusting for metabolic factors.
Conclusion: Prediabetes increases the risk of major clinical events and death independent of subsequent development of diabetes and metabolic factors. The risk relationships between prediabetes and clinical events are stronger in young than older people.

Disclosure
X.Zhang: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. A.Luk: None. H.Wu: None. E.S.H.Lau: None. M.Shi: None. B.Fan: None. A.Yang: None. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd.
119-LB: Targeted IL-22 Improves Glucose Tolerance and Reduces Hepatic Steatosis and Hepatic Fibrosis in Murine Models of Diabetes and Liver Disease
Authors: PRINS JOHN B. , SAJIIR HARESSH , KESHVARI SAHAR , WONG KUAN YAU , LOCKETT JACK , MCGUCKIN MICHAEL , HASNAIN SUMAIRA Z. 
Published: May 2022

The cytokine interleukin-22 (IL-22) is an inhibitor of cellular stress. In HFD murine models, systemic IL-22 is efficacious to restore glucose tolerance, reduce circulating triglycerides and hepatic steatosis, and improve AST:ALT ratio, but is also associated with gut and skin toxicity. As an approach to maintain efficacy without skin/gut adverse effects we have developed a prototype IL-22-based bispecific biologic drug candidate (IL-22-ScFv) which is targeted towards the pancreas and liver. In mouse models of T2D and NAFLD/NASH twice-weekly subcutaneous administration of IL-22-ScFv provides numerous therapeutic and metabolic benefits. After IL-22-ScFv administration for four weeks in HFD mice random glucose, glucose tolerance and insulin tolerance were normalised (c.f. chow fed controls) . Significant reduction in hepatic steatosis was also seen, evidenced by liver weight, histology, oil-red-O, and (normalisation of) key lipogenic gene expression patterns. In both Thioacetamide/HFD and Choline Deficient L-Amino acid defined/HFD mice IL-22-ScFv administration significantly reduced hepatic fibrosis (Masson’s trichrome, picrosirius red, and normalisation of hepatic expression of Col1a1&2, Col3a1, Timp2, Mmp2 and Cd68) . Effective targeting of IL-22 to liver and pancreas was observed with minimal IL-22 exposure to gut and skin. Following four weeks administration of a range of doses of IL-22-ScFv no adverse effects were observed. Histological analysis of gut and skin showed no features of hyperproliferation, consistent with effective targeting of IL-22 to liver and pancreas. Mechanism of action of IL-22-ScFv was again shown to be reduction in cellular stress via IL-22 receptor mediated STAT3 phosphorylation.
In conclusion, liver/pancreas targeted IL-22 shows promise as a therapeutic approach to metabolic liver disease, with concomitant improvement in disorders of glucose homeostasis.

Disclosure
J. B. Prins: None. H. Sajiir: None. S. Keshvari: None. K. Wong: None. J. Lockett: Advisory Panel; Lilly Diabetes. M. Mcguckin: None. S. Z. Hasnain: None.
119-OR: Metabolic Abnormalities across the Liver Fat Continuum: How Much Liver Fat Is “Normal”?
Authors: LE MINHDA , WU ELAINE (YILING) , BERRY JARETT , BROWNING JEFFREY , DELEMOS JAMES , NEELAND IAN , LINGVAY ILDIKO 
Published: May 2022

Proton magnetic resonance spectroscopy (MRS) provides an accurate quantification of liver fat, but the threshold of 5.5% for “normal” is challenged. We evaluated the relationship between liver fat content and metabolic parameters to explore what might be a metabolically healthy liver fat content. We analyzed data from adult participants in the Dallas Heart Study who underwent clinical evaluation and liver fat quantification by MRS. We compared metabolic characteristics across groups stratified by liver fat quintiles using ANOVA for normal continuous variables, Kruskal-Wallis test for non-normal continuous variables, and Chi-square test for categorical variables. Mean age of the entire cohort was 44 years and 47% were men. Metabolic abnormalities were more prevalent across liver fat quintiles (p&lt;0.0001) : BMI, weight, waist circumference, HTN, diabetes, cholesterol, triglycerides, CRP, leptin, fasting glucose, HOMA-IR, coronary artery calcium score, visceral fat, abdominal subcutaneous adipose tissue, and lower body subcutaneous adipose tissue (table) . Increase in these metabolic abnormalities was noticeable even between the lowest two quintiles. Clinically relevant metabolic abnormalities increased across all quintiles of liver fat, with increment occurring at well below what is currently considered “normal.” Our findings suggest that the presence of any liver fat may be abnormal.

Disclosure
M.Le: None. E.Wu: None. J.Berry: Consultant; Cooper Institute, Roche Diagnostics, Research Support; Abbott Diagnostics. J.Browning: None. J.Delemos: Advisory Panel; Eli Lilly and Company, Novo Nordisk. I.Neeland: Advisory Panel; Boehringer Ingelheim International GmbH, Merck & Co., Inc., Consultant; Nestlé Health Science. I.Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; NovoNordisk; Mylan; Merck, Sanofi.
1191-P: Predictors of Hemoglobin A1c Testing in Adults with Type 2 Diabetes Covered by Alabama Medicaid
Authors: PRESLEY CAROLINE A. , HOWELL CARRIE R. , KHODNEVA YULIA , RIGGS KEVIN R. , HUANG LEI , LEVITAN EMILY B. , CHERRINGTON ANDREA 
Published: May 2022

Background: ADA Standards of Care recommend A1C tests at least twice per year for patients with diabetes. We evaluated predictors of A1C testing among adults with type 2 diabetes covered by Alabama Medicaid.
Methods: We conducted a retrospective analysis of Medicaid claims data between 2011-2020 using person-year observations as the unit of analysis. Inclusion criteria were ages 19-64 years, type 2 diabetes diagnosis, continuous Medicaid enrollment for the full calendar year and the year prior. The primary outcomes were receiving ≥1 and ≥2 A1C test (s) during a calendar year. We conducted multivariable Poisson regression stratified by eligibility (i.e. disability, poverty) to evaluate the relationships of study year, demographics, clinical factors, and healthcare utilization with A1C tests using generalized estimating equations to account for individuals contributing &gt;1 observations.
Results: We analyzed 288,379 person-year observations; 69% were female; 49% were Black; 47% were 35-54 years old, 44% 55-64 years old; 51% were eligible based on disability, 49% based on poverty. Overall, 57% observations had ≥1 A1C test per year, 35% had ≥2 A1C tests. More observations eligible by disability had ≥1 A1C test (76% vs. 38%) and ≥2 A1C tests (49% vs. 20%) than those eligible by poverty. For observations eligible by disability, Black race and older age were associated with higher likelihood of having ≥1 A1C test. For observations eligible by poverty, year after 2011, female sex, and younger age were associated with higher likelihood of having ≥1 A1C test. For both groups, rurality, insulin use, endocrinology care, diabetes complications, and ambulatory care visits were associated with higher likelihood of having ≥1 A1C test.
Conclusions: Just over one-third of adults with diabetes covered by Alabama Medicaid had at least 2 A1C tests per year. A1C testing frequency differed by Medicaid eligibility; poverty-based eligibility was associated with lower likelihood of having recommended A1C testing.

Disclosure
C.A.Presley: None. C.R.Howell: None. Y.Khodneva: None. K.R.Riggs: n/a. L.Huang: None. E.B.Levitan: Research Support; Amgen Inc. A.Cherrington: Consultant; Bayer AG, Other Relationship; Novo Nordisk.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases R18DK109501PI: CherringtonUAB Diabetes Research Center P30 DK079626PI: Cherrington