bluuebunny/crossref_metadata_2025_split huggingface dataset:
1139-P: The Association between Age of Onset of Type 2 Diabetes and the Long-Term Risk for Major Diabetes-Related Complications
Authors: MORTON JEDIDIAH I. , LAZZARINI PETER , POLKINGHORNE KEVAN , MAGLIANO DIANNA J. , SHAW JONATHAN E. 
Published: May 2022

We evaluated the association between age of onset of type 2 diabetes and the risk for major diabetes complications. We included 1.1 million people with type 2 diabetes from the Australian diabetes registry, followed from 2010-2019. We evaluated the incidence of hospitalization for, or death from, myocardial infarction (MI) , stroke, and heart failure (HF) , and hospitalization for lower extremity amputation (LEA) ; the incidence of end-stage kidney disease (ESKD; including kidney replacement therapy or death from ESKD) ; and all-cause mortality (ACM) . Poisson regression was used to model rates by age of diabetes onset, current age, and diabetes duration. During 6.9 million person-years of follow-up, 72338, 46533, 101023, 20024, 13331, and 203542 MI, stroke, HF, LEA, ESKD, and ACM events occurred, respectively. The risk for all outcomes increased exponentially with diabetes duration (Figure) . The effects of age and duration differed for each: age was the stronger risk factor for MI, stroke, HF, and ACM, while duration was the predominant determinant of ESKD and LEA risk. At a given age, a 10-year younger age of onset was associated with a 1.1-1.5-fold increased risk of stroke and ACM, a 1.5-2-fold increased risk of MI and HF, and a 2-4-fold increased risk of LEA and ESKD. Thus, the increase in prevalence of young-onset type 2 diabetes may shift the burden of diabetes complications in coming decades.

Disclosure
J.I.Morton: None. P.Lazzarini: None. K.Polkinghorne: None. D.J.Magliano: None. J.E.Shaw: Advisory Panel; Abbott Diagnostics, AstraZeneca, Eli Lilly and Company, Pfizer Inc., Roche Diagnostics, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi.

Funding
JIM is supported by an Australian Government Research Training Program (RTP) Scholarship and Monash Graduate Excellence Scholarship. PAL is supported by a National Health and Medical Research Council Early Career Fellowship. DJM is supported by a National Health and Medical Research Council Senior Research Fellowship. JES is supported by a National Health and Medical Research Council Investigator Grant. This work is partially supported by the Victorian Government’s Operational Infrastructure Support Program.
114-OR: A Randomized Clinical Trial of Etanercept and Alpha-1 Antitrypsin in TPIAT
Authors: ABDEL-KARIM TASNEEM R. , HODGES JAMES S. , PRUETT TIMOTHY L. , RAMANATHAN KARTHIK , BEILMAN GREG , BELLIN MELENA 
Published: May 2022

Total pancreatectomy with islet auto-transplant (TPIAT) can relieve pain for patients with intractable pancreatitis. However, inflammatory damage to transplanted islets from the instant blood mediated inflammatory response (IBMIR) limits the IAT's success. We hypothesized blockade of IBMIR would improve islet engraftment, resulting in improved islet function.
We randomized 43 participants to A1AT (90 mg/kg IV x6 doses) , or etanercept (50 mg then 25 mg SQ x 5 doses) , or standard care in a 1:1:1 ratio. Islet graft function was assessed with mixed meal tolerance test (MMTT) , intravenous glucose tolerance test (IVGTT) , glucose-potentiated arginine-induced insulin secretion (GPAIS) , HbA1c, and insulin use 3 months and 1 year after TPIAT. Acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) 3 months after TPIAT were higher in the etanercept-treated group (p&lt;0.025, Fig 1) , but neither treatment differed significantly from controls at 1 year (Fig 1) . MMTT, GPAIS, HbA1c, and insulin use did not differ between groups. Multivariate modelling suggested a sex-specific response, with females on A1AT showing the most robust insulin secretion from GPAIS at 1 year (p≤0.033) .
In conclusion, this randomized pilot study suggests etanercept may improve early islet engraftment. The long-term effect of etanercept or A1AT on islet engraftment is less clear, though speculatively females may have a sex-specific benefit.

Disclosure
T.R.Abdel-karim: None. J.S.Hodges: None. T.L.Pruett: None. K.Ramanathan: None. G.Beilman: None. M.Bellin: Advisory Panel; Insulet Corporation, Research Support; Dexcom, Inc., Viacyte.

Funding
National Institute of Health (R01DK109914)
115-LB: Dorzagliatin Showed Sustained Remission in an Observational Study after Discontinuation of Treatment in T2D Patients Who Achieved Good Glycemic Control with Dorzagliatin Monotherapy
Authors: ZENG JIAOE , GAN SHENGLIAN , DONG XIAOLIN , LIU YUNFENG , SU XIAOFEI , LUO JIANFENG , MA JIANHUA 
Published: May 2022

Diabetes remission is the optimal goal for treating T2D. While most remission studies focused on metabolic surgery, lifestyle interventions, and intensive insulin therapy, little evidence was found with oral antidiabetic drugs. Dorzagliatin is an oral dual-acting glucokinase activator which has shown effective glycemic control with significant improvements in early-phase insulin secretion and β-cell function. DREAM was an observational, non-pharmacological, non-interventional diabetes remission study, an extension study of a phase 3 monotherapy trial (SEED) with dorzagliatin. Initiated by investigators from 5 in 40 study sites in SEED, DREAM aimed to observe whether patients who had completed SEED and achieved good glycemic control were able to achieve diabetes remission without any antidiabetic medication. In total, 69 subjects previously with drug-naïve T2D and treated with dorzagliatin for 28 or 52 weeks in SEED were enrolled. The primary endpoint was the diabetes remission rate after 52 weeks of dorzagliatin withdrawal, estimated by the Kaplan-Meier method. At week 52, 36 subjects maintained stable glycemic control and the remission rate was 65.2% (95% CI, 53.4 to 77.0) . These 36 patients had shown improvement of early-phase insulin secretion (C30/G30) after dorzagliatin treatment in SEED. Improvements of β-cell function and insulin resistance were sustained during DREAM (indicated by HOMA2-β of 43.8 at baseline and 56.6 at week 52, HOMA2-IR of 1.58 at baseline and 1.46 at week 52) . According to a consensus released in Aug 2021 by ADA, diabetes remission was defined as HbA1c&lt;6.5% measured at least 3 months after cessation of glucose-lowering pharmacotherapy. Based on this definition, the remission rate was 52.0% (95% CI, 31.2 to 69.2) . DREAM observed sustained glycemic control in a high proportion of subjects after withdrawal of dorzagliatin monotherapy, indicating that improvements of early-phase insulin secretion and β-cell function may be a potential mechanism for diabetes remission.

Disclosure
J. Zeng: None. S. Gan: None. X. Dong: None. Y. Liu: None. X. Su: None. J. Luo: None. J. Ma: None.
1156-P: Ischaemic Heart Disease in Type 2 Diabetes Before and After Diagnosis: Impact on Expected Lifetime and Trends 1996–2020
Authors: CARSTENSEN BENDIX , CLEMMENSEN KIM K. , AMADID HANAN 
Published: May 2022

Background: Complications can be present at type 2 diabetes (T2D) diagnosis or develop later. We describe trends in burden of ischaemic heart disease (IHD) in T2D.
Methods: T2D cases in Denmark 1996-2020 in a national diabetes register were used. Events of IHD 1994-2020 were from the National Patient Register. Prevalence of IHD at time of T2D was described by a binomial model. New IHD and death during follow-up were analysed by rate models and used to estimate the time in the states (no IHD / IHD at T2D / IHD after T2D) .
Results: 410,4 persons with T2D 1996-2020 were included; 61,378 with pre-existing IHD. Prevalence of IHD at T2D diagnosis was increasing 1.7%/year. Incidence rates of IHD after diagnosis was decreasing 5.7%/year. Mortality among T2D persons without IHD decreased 5.7%/year; for those with IHD it decreased 3.5%/year. During the first years, expected lifetime was 8.1 and 8.8 years for men diagnosed at age 65 in 1998 and 2018, respectively. Time without IHD was 6.2 and 6.9 years, with new IHD 0.9 and 0.5 years and with preexisting IHD 1.0 and 1.5 years in 1998 and 2018. We saw an increase in expected lifetime, partly as increase in lifetime with preexisting IHD. Similar patterns were seen for women and for persons diagnosed in other ages.
Conclusions: We saw an increase in expected lifetime, as well as decreasing mortality rates regardless of IHD status. Prevalence of IHD at the time of diagnosis was increasing, possibly due to more detailed diagnoses of IHD; in our data only IHD complications after 1994 are included which may be a partial explanation of the increase in prevalent IHD at the date of T2D diagnosis. In general the IHD burden in T2D in Denmark is decreasing.

Disclosure
B.Carstensen: Stock/Shareholder; Novo Nordisk A/S. K.K.Clemmensen: Employee; Novo Nordisk A/S, Research Support; AstraZeneca, Novo Nordisk Foundation, Stock/Shareholder; Lundbeck, Novo Nordisk A/S. H.Amadid: Stock/Shareholder; Novo Nordisk.
1165-P: Combined Severe Diabetic Complications: The New Life-Altering Outcome
Authors: YAGUCHI YUTA , FUJIHARA KAZUYA , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , IWANAGA MIDORI , KITAZAWA MASARU , YAMAMOTO MASAHIKO , KODAMA SATORU , SONE HIROHITO 
Published: May 2022

Since advanced microangiopathy of diabetes severely impairs activities of daily living (ADL) and quality of life (QoL) and macroangiopathy is life-threatening regardless of severity, treatment of diabetes requires appropriate risk management to avoid all such complications. However, current studies have analyzed and reported diabetes complications separately, despite varying incident rates and impacts on ADL/QoL and severity of illness. It is difficult to determine which predictors should be prioritized when extrapolating the results of these studies to the comprehensive care of individual patients. We defined the combined severe diabetic complications as a new life-altering outcome and determined the association of established risk factors with combined severe diabetic complications. We analyzed data from a nationwide database involving 36,994 participants with diabetes mellitus without any prior life-altering complication of diabetes during 2008-19. Combined severe diabetic complications included severe diabetic eye disease, initiating dialysis, coronary artery disease (CAD) , cerebrovascular disease (CVD) , heart failure (HF) , or amputation which were determined according to ICD-codes, medication and medical procedures. During a median follow-up period of 5.0 years, the following events occurred: severe diabetic eye disease, 774; dialysis initiated, 134: CAD, 703; CVD, 535; HF, 161; and amputations, 31. Multivariate Cox regression model showed the HRs per 1SD for combined severe diabetic complications of HbA1c, SBP, current smoking, HDL-C, BMI and LDL- C were 1.54 (1.49-1.59) , 1.37 (1.31-1.42) , 1.35 (1.23-1.48) , 0.83 (0.79-0.88) , 0.85 (0.81-0.90) and 1. (1.06-1.16) , respectively. We found that HbA1c was the most strongly associated with combined severe diabetic complications among established risk factors. Also, our results implied the necessity of revisiting the value of BMI in risk management for combined severe diabetic complications.

Disclosure
Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.
1169-P: Circulating MicroRNA-378a-5p and Improvement in Glucose Homeostasis in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) Trial
Authors: XUE QIAOCHU , HEIANZA YORIKO , LI XIANG , DENG HONG-WEN , ROOD JENNIFER , BRAY GEORGE , SACKS FRANK , QI LU 
Published: May 2022

Background: MicroRNA-378a (MiR-378a) has been identified as a key regulator of glucose homeostasis and emerging as a promising target for the improvement of glycemic dysregulation including type 2 diabetes. Hypothesis: We assessed associations of circulating miR-378a-5p with improvements in insulin sensitivity and glucose metabolism in a 2-year dietary intervention trial.
Methods: Circulating miR-378a-5p levels were measured at baseline and 6 months among 5participants with overweight or obesity. Outcome measurements including fasting glucose, hemoglobin A1c (HbA1c) , fasting insulin, and homeostasis model assessment-of-insulin resistance (HOMA-IR) were assessed at baseline, 6 and 24 months.
Results: Higher level of miR-378a-5p was associated with greater fasting glucose (p =0.031) at baseline. Greater decrease in miR-378a-5p was significantly associated with greater improvements in fasting insulin (p =0.012) and HOMA-IR (p =0.017) over 6 months. The initial (6-months) decrease of miR-378a-5p was also significantly related to long-term (24-months) improvements in glucose, insulin, and HOMA-IR (p &lt;0.for all) . Individuals in the lowest tertile group of the baseline miR-378a-5p showed consistently improved fasting insulin and HOMA-IR over 2 years, as compared to those with higher levels of miR-378a-5p (p time*miR-378a-5p =0.015 and 0.007, respectively) . We also found significant interactions between baseline miR-378a-5p and dietary fat in the 6-months change in HbA1c (p = 0.003) ; a lower level of baseline miR-378a-5p showed a greater reduction of HbA1c at 6 months among participants who consumed a low-fat diet.
Conclusions: In conclusion, decreased circulating miR-378a-5p levels were related to significant improvements in insulin sensitivity and glucose metabolism in response to dietary weight-loss interventions; and dietary fat intake modified such associations.

Disclosure
Q.Xue: None. Y.Heianza: None. X.Li: None. H.Deng: None. J.Rood: None. G.Bray: None. F.Sacks: None. L.Qi: None.

Funding
National Heart, Lung, and Blood Institute (HL071981, HL034594, and HL126024) ;National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, and DK100383) ;Fogarty International Center (TW010790)
1171-P: Food Insecurity and Glycemic Goals among Medicare Beneficiaries with Type 2 Diabetes
Authors: NG BOON PENG , STEWART MORGAN P. , LAMANNA JACQUELINE B. , PARK CHANHYUN 
Published: May 2022

Food insecurity, a modifiable risk factor, has a significant impact on individuals' health and well-being. This study examined the association between food insecurity and glycemic goals among Medicare beneficiaries aged ≥65 years with type 2 diabetes (T2D) , using the 20Medicare Current Beneficiary Survey (n=1,340) . The binary dependent variable was whether beneficiaries' blood glucose (BG) was at target (i.e., having A1C ≤7.5% or average fasting BG of ≤140 mg/dL, all/most of the time) . Food insecurity, a binary variable, was defined as having ≥2 affirmative responses on 4 selected questions of the USDA's food security questionnaire. A survey-weighted multivariable logistic model, adjusted for socio-demographics and comorbidities, was conducted to estimate predictive margins for comparing prevalence of having higher than target BG levels across groups. Of study beneficiaries with T2D, 20.9% reported not achieving glycemic targets. Beneficiaries not meeting BG goals were more likely to be: female (60.5% vs. 49.1%, p=0.002) , less educated (&lt;high school, 21.9% vs. 13.4%, p=0.013) , and experiencing food insecurity (20.4% vs. 8.9%, p&lt;0.001) . In the adjusted analysis, the predictive marginal prevalence of having higher than target BG levels was significantly greater in females over males (23.8% [95% CI, 20.0-27.5] vs. 16.6% [13.4-19.8]) ; those with less than high school education over those with greater education (30.9% [23.6-38.3] vs. 18.5% [14.7-22.3]) ; and those reporting food insecurity over their counterparts (33.4% [24.5-42.3] vs. 19.1% [16.5-21.6]) . This study identified that females, those with low education levels, and those experiencing food insecurity may be less likely to achieve BG goals, placing them at-risk of developing potentially preventable complications and incurring higher overall healthcare costs. Routine screening and interventions to reduce these disparities should be considered by all healthcare team members caring for Medicare beneficiaries with T2D.

Disclosure
B.Ng: None. M.P.Stewart: None. J.B.Lamanna: None. C.Park: None.
1172-P: Higher Dairy Consumption Is Associated with Lower Risk of Type 2 Diabetes among U.S. Adults: A Nationally Representative Study
Authors: TOMAH SHAHEEN , HAMDY OSAMA 
Published: May 2022

Dairy consumption has been associated with a modestly lower risk of type 2 diabetes and other components of the metabolic syndrome in few cohort studies. However, confounding by overall diet quality and physical activity levels remains present. We evaluated 4,934 adults who participated in the 2017-2018 National Health and Nutrition Examination Surveys (NHANES) and underwent two 24-hr dietary recalls in addition to general health questionnaires, examinations, and laboratory assessments. Dairy intake data (milk, yogurt, and cheese but not dairy-based desserts) were extracted and transformed into USDA-defined serving sizes then categorized based on number of servings: non-consumers, &lt;1 serving, 1 to &lt;2 servings, and ≥2 servings. We defined diabetes mellites (DM) as physician-diagnosed DM, A1c ≥6.5%, or fasting plasma glucose ≥126 mg/dL. We calculated the Healthy Eating Index-2015 (HEI-2015) , an indicator of overall diet quality. The average age of this cohort was 49.6±18.5 yrs, 51% were female, 73.5% were overweight or obese, and 17% had DM. After multivariate adjustment for age, gender, BMI, smoking, vigorous physical activity, and HEI-2015, intake of ≥2 servings of dairy was associated with lower risk of DM (OR: 0.9, 95% CI 0.81-0.99, p=0.049) compared with non-consumers. In sensitivity analysis, the association between intake of ≥2 servings of dairy and prevalent DM showed directionally dissimilar results when adding dairy type-specific servings to the model (Milk, OR: 0.9, 95% CI 0.77-1.05, p=0.vs. combined cheese and yogurt, OR: 0.87, 95% CI 0.76-0.99, p=0.036) . In conclusion, higher dairy intake is associated with lower risk of DM among US adults while adjusting for diet quality. This association seems to be driven by cheese and yogurt intake rather than by milk. These findings need to be evaluated in randomized prospective intervention trials.

Disclosure
S.Tomah: None. O.Hamdy: Advisory Panel; L-Nutra Inc., Nestlé, Consultant; Abbott, Sanofi, Research Support; Eli Lilly and Company, Gilead Sciences, Inc., National Dairy Council, Novo Nordisk, Stock/Shareholder; Healthimation.

Funding
The authors received specific funding for this research
1173-P: Metabolomic Signatures of Refined Grains Intake and Risk of Gestational Diabetes
Authors: ZHU YEYI , ZHENG SIWEN , NGO AMANDA , CHEHAB RANA F. , WANG EMILY Z. , FIEHN OLIVER , FERRARA ASSIAMIRA 
Published: May 2022

Previous studies linked refined grains intake to risk of gestational diabetes (GDM) ; however, the underlying mechanisms remain understudied. We aimed to identify and validate refined grains-related metabolites as biomarkers for GDM. In a nested case-control study of 91 women with GDM and 180 non-GDM controls (discovery set) in the Pregnancy Environment and Lifestyle Study (PETALS) cohort, we assessed dietary intake of refined grains by a validated food frequency questionnaire and measured fasting serum untargeted metabolomics at gestational weeks (GW) 10-13. We identified metabolites associated with refined grains intake using multivariable linear regression and examined prospective associations of refined grains-related metabolites at GW 10-13 with risk of GDM in later pregnancy using conditional logistic regression. We further examined incremental predictivity of refined grains-related metabolites selected by 10-fold cross-validated LASSO regression beyond conventional risk factors in the discovery set and a random PETALS subsample (38 GDM, 336 non-GDM) as the validation set. Among 821 known metabolites, 42 (mostly lipids/lipid-like molecules and organic oxygen/acids compounds) were associated with refined grains intake in early pregnancy, of which 17 were significantly associated with GDM risk (all FDR &lt; 0.05) . Adding seven out of 17 metabolites selected by LASSO regression to a conventional risk factor-based prediction model increased the C-statistic from 0.71 (95% CI 0.64-0.77) to 0.77 (0.71-0.83) ; P-for-difference &lt; 0.05. Similar improvement was observed in the validation set [0.77 (0.69-0.86) to 0.81 (0.74-0.89) ; P-for-difference &lt; 0.05]. Refined grains intake may be associated with risk of GDM via perturbed metabolic pathways of glycerolipids, glycerophospholipids, and sphingolipids. Refined grains-related metabolites might help improve prediction of GDM risk and inform diet-related preventive strategies. Further validation studies are warranted.

Disclosure
Y.Zhu: None. S.Zheng: None. A.Ngo: None. R.F.Chehab: None. E.Z.Wang: None. O.Fiehn: None. A.Ferrara: n/a.

Funding
National Institutes of Health Building Interdisciplinary Research Careers in Women's Health (BIRCWH) Program (K12HD052163) ; National Institute of Diabetes and Digestive and Kidney Diseases (K01DK120807)
1177-P: Mediterranean Diet Is Associated with a Better Estimated Renal Function in Overweight, but Not in Obese, Adults with Impaired Fasting Glucose
Authors: LEONE ALESSANDRO , DE AMICIS RAMONA , FOPPIANI ANDREA , BERTOLI SIMONA , BATTEZZATI ALBERTO 
Published: May 2022

Background: Impaired fasting glucose (IFG) is a risk factor for renal function, whereas adherence to the Mediterranean diet may be protective.
Methods: Cross-sectional study on 1016 overweight (OW) and 1297 obese (OB) adults (52 ± 12 yrs, 55% women) with IFG (s-glucose: 100-125 mg/dl) . Anthropometry, fat-free mass by BIA, s-creatinine, blood pressure, marital status, education, familiarity for diabetes and CVD, smoking and physical activity were evaluated. The 14-item MEDiterranean Diet Adherence Screener (MEDAS, score: 0-14 points) was used to assess Mediterranean diet. Glomerular filtration rate (eGFR) was estimated by CKD-EPI formula. Normal renal function was defined as eGFR ranged 90-140 ml/min/1.73m2, so that both cases of loss of renal function and cases of glomerular hyperfiltration were considered at risk of renal damage. Logistic regression stratified for BMI class and adjusted for above confounders was fitted to assess association of Mediterranean diet with normal renal function.
Results: The prevalence of normal renal function was 55% (60% in OW, 52% in OB) . Compared to the first tertile, the highest tertile of MEDAS score was associated to higher odds being normal renal function in OW (OR 1.48, 95%CI 1.07, 2.04, Ptrend=0.014) but not in OB patients.
Conclusion: Mediterranean diet is associated with a better renal function in OW patients with IFG.

Disclosure
A.Leone: None. R.De amicis: None. A.Foppiani: None. S.Bertoli: None. A.Battezzati: None.