bluuebunny/crossref_metadata_2025 huggingface dataset:
105-OR: Microbiome-Derived Metabolite Signatures in Early- to Midpregnancy for Risk of Gestational Diabetes (GDM)
Authors: ZHU YEYI , SUSARLA SITA MANASA , BARUPAL DINESH , NGO AMANDA , CHEHAB RANA F. , FIEHN OLIVER , FERRARA ASSIAMIRA
Published: May 2022

Pre-diagnostic disturbances in gut microbiome and metabolome have been associated with an increased risk of diabetes in non-pregnant populations. However, such prospective studies in pregnant women are scant. We aimed to develop and validate microbiome-derived metabolite predictive markers in early to mid-pregnancy for GDM. We designed a nested case-control study (91 GDM, 180 non-GDM; discovery set) and a random subsample (42 GDM, 372 non-GDM; validation set 1) from the PETALS cohort, and a case-control study from the GLOW trial (35 GDM, 70 non-GDM; validation set 2) . We collected fasting serum untargeted metabolomics data at gestational weeks (GW) 10-13 and 16-by gas chromatography/time-of-flight mass spectrometry (TOF-MS) , liquid chromatography (LC) /quadrupole TOF-MS, and hydrophilic interaction LC/quadrupole TOF-MS. Among 1167 annotated metabolites, 193 microbiome-derived metabolites were identified from the Virtual Metabolic Human Database. Multivariate enrichment analysis examined metabolite-GDM associations. Ten-fold cross-validated LASSO prediction models identified metabolite signatures for GDM. At GW 10-13, the branched-chain amino acids cluster was marginally, positively associated with GDM risk (FDR = 0.073) . At GW 16-19, the ceramides, pyridines, pyrimidine nucleosides, and unsaturated fatty acids clusters were significantly, positively associated with GDM risk (all FDR <0.05) . A 38-metabolite panel at GW 10-13 outperformed the model using conventional risk factors including fasting glucose (discovery AUC: 0.915 vs. 0.743; validation 1: 0.865 vs. 0.731; validation 2: 0.970 vs. 0.742; P <0.01) . Similar results were observed for a 21-metabolite panel at GW 16- (discovery AUC: 0.842 vs. 0.760; validation 1: 0.840 vs. 0.774; P <0.01) . Panels of microbiome-derived metabolites in early to mid-pregnancy can predict GDM risk beyond conventional risk factors, suggesting the role of microbiome-metabolome-host interactions in GDM.

Disclosure

Y.Zhu: None. S.Susarla: None. D.Barupal: None. A.Ngo: None. R.F.Chehab: 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)
1050-P: COVID-Severity and Diabetes in Pregnancy
Authors: RIVERA ADRIANA NIGAGLIONI , PAUL RACHEL , FROLOVA ANTONINA I. , RAGHURAMAN NANDINI , KELLY JEANNIE , ODIBO ANTHONY O. , CARTER EBONY B.
Published: May 2022

Diabetes and pregnancy are independently associated with increased risk of severe COVID-infection. However, little is known about the relationship between severe COVID-and diabetes in pregnancy. We sought to determine whether diabetes in pregnancy was associated with increased risk of COVID-infection and severity. We conducted a case-control study of all delivering patients at a tertiary hospital from June 2020-September 2021 and accepted universal COVID-testing. Patients with no COVID-test results were excluded. The proportion of patients with any COVID-infection and severe COVID-infection during pregnancy were compared between patients with and without diabetes using chi-square. Severe COVID-was defined as meeting any WHOOSCI or NCPERET criteria (dyspnea, respiratory rate ≥30 breaths per minute, blood oxygen saturation of ≤93%, PaO2/FiO2 <300, lung infiltrates involving >50% on imaging, non-invasive ventilation or high flow oxygen use, intubation and mechanical ventilation, or ventilation with additional organ support) . Of 4,253 patients in our analysis, 292 (6.9%) had COVID-during pregnancy. Demographic characteristics were similar between patients with a COVID-infection in pregnancy and those that were negative; 71 (24.3%) had a severe infection, and 451 (10.6%) had diabetes. There was no difference between patients with and without diabetes in incidence of COVID-infection (9.6% vs. 10.7%, p=0.56) or severe COVID-infection (11.3% vs. 9%, p=0.58) . Diabetes in pregnancy was not associated with increased risk of COVID-infection or severe infection. Future research in larger samples may further elucidate the association between diabetes and COVID-infection in pregnancy.

Disclosure

A.Nigaglioni rivera: None. R.Paul: None. A.I.Frolova: None. N.Raghuraman: None. J.Kelly: None. A.O.Odibo: None. E.B.Carter: None.
1058-P: Diabetic Ketoacidosis during Pregnancy: Maternal Characteristics and Pregnancy Outcomes
Authors: DHANASEKARAN MAHESWARAN , MOHAN SNEHA , ERICKSON DANA , SHAH PANKAJ , SZYMANSKI LINDA M. , VELLA ADRIAN , EGAN AOIFE M.
Published: May 2022

Diabetic ketoacidosis (DKA) during pregnancy is an obstetric emergency associated with morbidity and mortality. As this condition is rare (affecting 1-3% pregnant women with preexisting diabetes) , available data are limited. The aim of this retrospective cohort study is to present comprehensive data on maternal characteristics and pregnancy outcomes for women with DKA who attended our center for prenatal care from 2001-21. In total 71 DKA episodes were identified in 58 women, of whom 86% (n=50) had type 1 diabetes mellitus and 83% (n=48) were White. The mean (±SD) maternal age was 28 (±7) years and diabetes duration was (±7) years. Pregnancy loss during or within 1 week of the DKA episode occurred in 17% (6 miscarriages and 4 stillbirths) . There were no maternal deaths. Women were poorly prepared for pregnancy [mean 1st trimester HbA1c 9.3 (±2.5) %]. Social stressors were present in 52% (n=30) and 24% (n=14) reported smoking. The mean gestational age at DKA was 25.4 weeks (16.3 weeks for pregnancies with fetal demise vs. 27.5 weeks for livebirths, p<0.001) . Insulin non-adherence was the most common precipitating factor (40%) , followed by infection (23%) , and a new diagnosis of type 1 diabetes (10%) . Pre-existing hyperemesis was associated with fetal demise (31%, n=4 vs. 3%, n=2 among livebirths; p=0.004) . The mean plasma glucose at presentation was 362 mg/dL and the β-hydroxybutyrate was 4.2 mmol/L, with 28 (39%) women requiring intensive care unit (ICU) admission. Among livebirths, the mean gestational age at delivery was 32.7 weeks with 41% (n=21) requiring emergency cesarean. Large for gestational age occurred in 29% (n=17) and 8% (n=4) had shoulder dystocia. Congenital anomaly was present in 10% (n=5) . Neonatal hypoglycemia occurred in 60% (n=29) and neonatal ICU admission was required in 52% (n=25) .

In summary, pregnancies affected by DKA continue to be associated with numerous adverse pregnancy outcomes. Future work should focus on optimizing prevention strategies in high-risk women.

Disclosure

M.Dhanasekaran: None. S.Mohan: None. D.Erickson: None. P.Shah: None. L.M.Szymanski: None. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk. A.M.Egan: None.

Funding

National Institutes of Health (K12 HD065987/HD/NICHD)
106-LB: Comparable Total Exposure of Once-Weekly Insulin Icodec between Different Subcutaneous Injection Regions
Authors: PLUM-MOERSCHEL LEONA , ANDERSEN LIZETTE R. , HANSEN SOLVEJG , HÖVELMANN ULRIKE , KRAWIETZ PATRICIA , KRISTENSEN NIELS R. , LANG LEHRSKOV LARS , HAAHR HANNE
Published: May 2022

People with diabetes may inject s.c. insulin in different body regions. To address if choice of injection region affects insulin icodec exposure and glucose-lowering effect, this study compared icodec administration in different s.c. injection regions. In a randomized, open-label, three-period crossover trial, 25 individuals with T2D on basal insulin (22 males; mean±SD age 60±7 yrs, BMI 30.7±4.6 kg/m2) received single s.c. icodec doses (5.6 U/kg) in the thigh, abdomen and upper arm (9-13 weeks washout) . Blood was sampled for pharmacokinetics (PK) until 840 h (35 days) post-dose. Glucose-lowering effect was assessed at 36-60 h post-dose in an automated glucose clamp (target 135 mg/dL) . Total icodec exposure (AUC0-∞,SD) was similar after single-dose s.c. injection in the thigh, abdomen and upper arm (Table) . Maximum concentration (Cmax,SD) was higher for abdomen/upper arm vs. thigh. Extrapolation of PK profiles to steady state using a PK model showed smaller differences in Cmax,SS for abdomen/upper arm vs. thigh than after single dose. Partial glucose-lowering effect 36-60 h after single dose (AUCGIR,36-60h,SD) was comparable across injection regions (geom. mean [CV%] of 1961 [51], 2130 [52] and 2391 [40] mg/kg for thigh, abdomen and upper arm) .

In conclusion, insulin icodec can be administered s.c. in the thigh, abdomen or upper arm with essentially similar exposure and glucose-lowering effect.

Disclosure

L. Plum-moerschel: Other Relationship; Eli Lilly and Company, Gan & Lee Pharmaceuticals, Novo Nordisk A/S. L. R. Andersen: None. S. Hansen: None. U. Hövelmann: None. P. Krawietz: None. N. R. Kristensen: Employee; Novo Nordisk. L. Lang lehrskov: Employee; Novo Nordisk A/S. H. Haahr: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S.

Funding

Novo Nordisk
106-OR: Fetal Sex Influences Maternal Insulin and Glucose Metabolism in Pregnancy
Authors: MULLINS THOMAS P. , GIBBONS KRISTEN S. , MADSEN LENE R. , MA RONALD C. , TAM WING H. , CATALANO PATRICK , SACKS DAVID A. , BARRETT HELEN L. , MCINTYRE DAVID
Published: May 2022

Aims and Hypothesis: Women carrying a male fetus are suggested to have altered maternal glucose and insulin dynamics and increased rates of GDM, but current literature remains inconclusive. We aimed to determine the relationship between fetal sex and maternal glucose and insulin metabolism and assess whether inclusion of fetal sex improves prediction of IADPSG GDM.

Methods: Using blinded data from five Hyperglycaemia and Adverse Pregnancy Outcome study centres, we examined maternal metabolic data at mean gestational week 28 in 6337 untreated women. Stratifying women by either male (n = 3273) or female fetus (n = 3064) we analysed data from the 75g OGTT, estimates of insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral Disposition index) using multiple linear regression analysis. To assess the relationship and predictive ability of fetal sex and GDM we utilised multiple logistic regression and receiver operating characteristic curve analysis.

Results: Women carrying a male fetus were found to have a modest increase in fasting plasma glucose (4.52 vs. 4.44 mmol/L; P=0.008) and 1 h glucose (7.57 vs. 7.46 mmol/L; P=0.015) during OGTT which translated into an overall increase in the OGTT z score (0.vs. 0.02; P=0.005) . The Matsuda (β: -0.06; 95% CI [-0.10, -0.02]; P=0.008) and oral Disposition index (β: -0.07; 95% CI [-0.11, -0.02]; P=0.005) were significantly reduced in women carrying a male fetus after correction for established maternal clinical risk factors. Women carrying a male fetus were not at higher odds of developing GDM in adjusted (aOR: 1.04; 95% CI [0.9, 1.19]; P=0.6) or unadjusted (OR: 1.09; 95% CI [0.96, 1.25]; P=0.16) models.

Conclusion/interpretation: The male fetus is associated with increased maternal fasting and postprandial glucose with concomitant decreased insulin sensitivity and β-cell compensation. The alterations in maternal glucose and insulin dynamics associated with having a male fetus does not translate into a clinical diagnosis of GDM.

Disclosure

T.P.Mullins: None. K.S.Gibbons: None. L.R.Madsen: 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. W.H.Tam: None. P.Catalano: None. D.A.Sacks: None. H.L.Barrett: None. D.Mcintyre: None.
1060-P: Exploring Differences in the 24-Hour Glucose Cycle by Physical Activity Level in Women with Pregnancy Hyperglycemia
Authors: EHRLICH SAMANTHA F. , RAND BETHANY G. , ZITE NIKKI , FORTNER KIMBERLY B. , PAUDEL ALISSA M. , PETERSON CHRISTINA , MAPLES JILL M.
Published: May 2022

Physical activity (PA) improves glucose levels. PA’s impact on the 24-hour glucose cycle in pregnancy hyperglycemia is unknown. This study examined baseline data from women participating in a small pilot feasibility randomized controlled trial. At baseline, they completed a survey which included the Stanford Leisure-Time Activity Categorical Item (L-Cat) for comparison to national PA recommendations. PA over the past month was assessed. Dexcom G6 CGMs linked to blinded receivers were worn for 7 days. Typical 24-hour glucose functions were estimated with B-splines and generalized regression analyses controlling for gestational diabetes (GDM) conducted in JMP. CGM was available for 14 participants; 4 (29%) had GDM and 3 (21%) reported meeting PA recommendations. Mean glucose was 91.5 mg/dl (SD 17) for sufficient PA and 93.6 mg/dl (SD 20) for insufficient PA. Figure 1 displays the 24-hour glucose functions (3rd degree polynomials with 17 knots) for sufficient PA (red) versus insufficient PA (blue) . Lower glucose was observed in the early morning, i.e., from midnight through approximately 6am and likely fasted, in sufficient versus insufficient PA, but the difference did not attain statistical significance. Glucose was higher in those with GDM, controlling for PA (P < .05) . Findings in a small sample of women with pregnancy hyperglycemia suggest that PA may improve early morning glucose.

Disclosure

S.F.Ehrlich: None. B.G.Rand: None. N.Zite: None. K.B.Fortner: Other Relationship; Pfizer Inc. A.M.Paudel: None. C.Peterson: None. J.M.Maples: None.

Funding

K01DK105106
1062-P: Outcomes in Pregnancies with Preexisting Type 1 Diabetes vs. Healthy Controls over a 14-Year Period
Authors: KAUR RAVINDER JEET , RIZVI SHAFAQ RAZA , DESJARDINS DONNA , ZANILETTI ISABELLA , REID COREY , MCCRADY-SPITZER SHELLY K. , TRINIDAD MARI CHARISSE , KUDVA YOGISH C.
Published: May 2022

Background: We studied maternal and neonatal outcomes in pregnancies with preexisting T1D and matched controls (age, gravida, BMI) to address limited data in this field in the US.

Methods: Pregnancies (n=165) in preexisting T1D and matched healthy controls (n=165) were retrospectively studied (01/01/20to 12/1/2020) at a single center. Conditional logistic regression, Wilcoxon signed rank and Wilcoxon rank sum tests were used for analyses.

Results: Pregnancies with T1D had significant hypertension [32% (19% pre-existing) vs. 10% (2% pre-existing) , p<0.01], preeclampsia (28% vs. 7%, p<0.01) , thyroid dysfunction (24% vs. 7%, p<0.01) and were affected by polyhydramnios (14% vs. 4%, p<0.01) , macrosomia affecting labor (16% vs. 2%, p<0.01) , increased C-section’s rate (16% vs. 7%, p=0.02) and complicated C- sections (6% vs. 1%, p=0.04) . In T1D, four neonates had cardiac complications and 14 (8.5%) were large for gestational age compared to 2 (1%) controls. More neonates in T1D were preterm (34.5% vs. 14.5%, p<0.01) , with fetal anomalies (15.8% vs. 4%, p<0.01) , Respiratory Distress Syndrome (25.5% vs. 7%, p<0.01) , apnea (14% vs 5.5%, p=0.01) , other pulmonary complications (13% vs. 5%, p<0.01) and respiratory failure (11% vs. 3%, p=0.01) . Significant hypoglycemia (16% vs. 7%) , sepsis (7% vs. 1%) , jaundice (70% vs. 36%) and upper GI complications (39% vs. 16%) were observed in neonates born to mothers with T1D. T1D neonates had higher birth weight (p =0.01) and were born early (37.2 vs. 39 wks, p<0.01) . HbA1c >7% was associated with above neonatal complications compared to those who with HbA1c <6.7%.

Conclusion: Pregnancies with type 1 diabetes continue to be associated with high maternal and neonatal morbidity and need urgent development of interventions to improve outcomes.

Disclosure

R.Kaur: None. S.Rizvi: None. D.Desjardins: None. I.Zaniletti: None. C.Reid: None. S.K.Mccrady-spitzer: None. M.Trinidad: None. Y.C.Kudva: Advisory Panel; Novo Nordisk, Research Support; Dexcom, Inc., Hemsley Charitable Trust, JDRF, National Institutes of Health, Roche Diabetes Care, Tandem Diabetes Care, Inc.
1072-P: Diabetes Mellitus and Risk of Breast Cancer: A Large-Scale, Prospective, Population-Based Cohort Study
Authors: XIONG FANXIU , WANG JINGXUAN , NIERENBERG JOVIA L. , SCHMAJUK GABRIELA , GRAFF REBECCA E.
Published: May 2022

Background: A previous meta-analysis identified a weak association between diabetes and breast cancer (BCa) risk among postmenopausal women. The heterogeneity among studies, however, was substantial, and many of the included studies were susceptible to residual confounding by body mass index (BMI) and other BCa risk factors. The objective of this study was to evaluate associations of diabetes overall, type 1 diabetes (T1D) , and type 2 diabetes (T2D) with BCa risk within the UK Biobank cohort.

Methods: We included 250,312 women aged 40-69 years between 20 and 2010, who were free of cancer at enrollment. Multivariable Cox regression models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of diabetes and its two major types with the time from enrollment to incident BCa.

Results: We identified 8182 BCa diagnoses during a median follow-up of 11.1 years. We found no overall association between diabetes and BCa risk (adjusted HR [aHR] = 1.03, 95% CI = 0.93- 1.15) . When further accounting for diabetes subtype, T2D did not demonstrate a significant association with BCa (aHR = 1.01, 95% CI = 0.90- 1.12) . Women with T1D, however, had a higher risk of BCa than women without diabetes (aHR = 1.51, 95% CI = 1.03 - 2.22) . The associations of diabetes, T1D, and T2D with BCa did not vary by age, menopausal status, BMI, or other BCa risk factors.

Conclusions: We did not observe associations between diabetes or T2D and BCa among women within the UK Biobank. However, our data suggested that women with T1D may have an increased risk of BCa. Larger studies are warranted to investigate the relationship of T1D with BCa and its subtypes.

Disclosure

F. Xiong: None. J. Wang: None. J.L. Nierenberg: None. G. Schmajuk: None. R.E. Graff: None.
1074-P: Variation in Predicted Fracture Risk by Diabetes and Obesity Status in Older U.S. Asian and White Women
Authors: LO JOAN C. , CHANDRA MALINI , GORDON NANCY P. , LEE CATHERINE
Published: May 2022

Introduction: Diabetes (DM) is a risk factor for fracture but women with DM have less osteoporosis by bone density (BMD) , due in part to higher body mass index (BMI) . The FRAX fracture risk calculator incorporates age, race/ethnicity, BMD, BMI, and other risk factors but not DM. Few studies have examined FRAX by DM and obesity status in different race groups. We compared predicted fracture risk in US Asian and White women by DM and obesity status.

Methods: We studied 3,640 Asian (26% DM, 24% osteoporosis, 15% obese) and 11,7White (11% DM, 12% osteoporosis, 40% obese) women aged 65-75y with BMD, excluding those with recent fracture, osteoporosis therapy, dialysis/transplant, metabolic bone disease or advanced cancer. DM (≥2 visit diagnoses + DM treatment) , obesity (BMI ≥30 kg/m2) and osteoporosis (BMD T score ≤-2.5) were obtained from electronic health data. Using the US FRAX with BMD, 10-year predicted hip fracture risk ≥3% was considered high (above treatment threshold) .

Results: The overall proportions with FRAX-Hip ≥3% were higher for those with No DM vs. DM (White 18% vs. 11%; Asian 9% vs. 7%) . However, within both DM and no DM groups, FRAX-Hip ≥3% was much higher in non-obese vs. obese women of both races (FIGURE) .

Conclusion: Predicted hip fracture risk varies by DM and especially by obesity status in White and Asian women. Future studies should examine the accuracy of FRAX for actual hip fracture risk in these subgroups.

Disclosure

J.C.Lo: None. M.Chandra: None. N.P.Gordon: None. C.Lee: None.

Funding

National Institute on Aging, National Institutes of Health (AG069992)
1078-P: Elderly Patient with DM2 during the COVID-Pandemia: Forgotten but Good Glycemic Control
Authors: TRESCOLI CARLOS , QUINTANA JAVIER , PLA ZULEMA , VERCHER MANUEL , GARCIA GABRIEL , GALIPIENSO NADIA , SANCHO PABLO
Published: May 2022

COVIDpandemic has changed clinical practice in Primary and Hospital Care. Chronic Diseases Care have been relegated after COVID19, emergencies and severe pathologies (cancer) Elderly patients with DM2 had less access to medical services due to COVIDprotocols. HbA1c is important to manage patients with DM2. Between COVIDwaves and specially in 2021 there was a program to recover Diabetic Care in our 250000 inhabitants Health Department, specially most frail elderly patients with DM2

Aim: Find out if Elderly patients with DM2 chronic care was reduced during the COVIDpandemic period and if that affected their diabetic control.

Methodology: HbA1c tests taken to patients with DM2 and > 70 year between January 20 and November 2021 were obtained as they are all done in our hospital either from Primary or Hospital Care. Data was calculated by Mean Monthly Number HbA1c tests (MMNHT) during prepandemic: March 20to February 2020, pandemic: March 2020 to February 2021 and postpandemic: March 2021 to November 2021. Diabetic control was calculated in three groups: % HbA1c <7%; 7-8% and > 8% of all tests done in those three periods.

Results: MMNHT had increased by 5% annually and a trend to better diabetic control was seen since 20until 2019. MMNHT were prepandemic vs. pandemic: 1313 vs. 10 (- 22.5%) and pandemic vs. postpandemic: 10vs. 1334 (+ 31%) % . Those changes were similar in Primary and Hospital Care.%HbA1c 7; 7-8 and > 8% was in prepandemic: 50, 31 and 19%; pandemic: 50, 30 and 20% and postpandemic: 67, 28 and 11%.

Summary: During COVIDpandemic, Elderly patients with DM2 had less chronic medical care as had a 23% reduction of MMNHT although it did recover posteriorly. Protocols to identify and recover diabetic chronic care in patients > 70 year might be helpful in our experience. Diabetic control was similar before, during and after the COVIDpandemic period: March 2020 to February 2021.

Disclosure

C.Trescoli: None. J.Quintana: None. Z.Pla: None. M.Vercher: None. G.Garcia: None. N.Galipienso: None. P.Sancho: None.
1092-P: Lipoprotein Insulin Resistance Index and Mortality in Heart Failure: A Population Study
Authors: TURECAMO SARAH , WOLSKA ANNA , OTVOS JAMES D. , REMALEY ALAN , CONNERS KATIE , JOO JUNGNAM , PARK HO YOUNG , SAMPSON MAUREEN , BIELINSKI SUZETTE J. , SAUVER JENNIFER ST , ROGER VERONIQUE L.
Published: May 2022

Heart failure (HF) is associated with metabolic alterations, including insulin resistance (IR) . Perturbations in lipid metabolism and insulin signaling may impact outcomes, but the relationship between IR and mortality is not well characterized. The Lipoprotein Insulin Resistance Index (LPIR) is a score (0-100; higher values signify greater IR) calculated from 6 lipoprotein subclass/size parameters measured by nuclear magnetic resonance (NMR) . We examined the association between LPIR and death in a HF community cohort. LPIR was measured by NMR LipoProfile®. Meta-Analysis Global Group in Chronic HF (MAGGIC) scores were calculated from clinical data. Kaplan-Meier curves were used to evaluate survival; Cox regression was used to estimate risk of death by LPIR quartile. Among 1,381 community-dwelling persons with HF, the median LPIR score was 38 (IQR 21-56) . Higher LPIR was associated with younger age, diabetes, smoking, obesity, and lower MAGGIC scores, but not ejection fraction. Survival increased by LPIR quartile (p<0.001) and at 5 years was 36% [95% CI 31-42], 42% [95% CI 38-48], 51% [95% CI 46-56], and 65% [95% CI 60-70] for quartile 1-4, respectively. The association between LPIR and death was independent of MAGGIC score (Figure) . Higher LPIR was associated with better survival in HF, independently of a validated clinical risk score. More research is needed to examine this paradoxically protective association.

Disclosure

S. Turecamo: None. A. Wolska: None. J.D. Otvos: Employee; LabCorp. K. Conners: None. S.J. Bielinski: Consultant; Novartis Pharmaceuticals Corporation. J. St Sauver: Research Support; Exact Sciences. V.L. Roger: None.

Funding

Research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute (NHLBI) at National Institutes of Health and by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, and the Colgate-Palmolive Company.
1095-P: Clusters of Prediabetes and Type 2 Diabetes Stratify All-Cause Mortality in a Cohort of Participants Undergoing Invasive Coronary Diagnostics
Authors: PRYSTUPA KATSIARYNA , DELGADO GRACIELA , MOISSL ANGELA P. , KLEBER MARCUS E. , HENI MARTIN , BIRKENFELD ANDREAS L. , FRITSCHE ANDREAS , MAERZ WINFRIED , WAGNER ROBERT
Published: May 2022

Risk for complications and mortality among patients with type 2 diabetes (T2D) is heterogenous. Different trajectories can be identified in the prediabetic state, which comprises heterogenous metabolic clusters. It is not known whether such pathophysiologic clusters of prediabetes and diabetes affect survival in at-risk persons being evaluated for coronary heart disease. The LURIC Study recruited patients referred for coronary angiography at a median age of 63 (IQR 56-70) who have since been followed-up for a median of 14.5 (IQR 9.6-17.7) years. Clustering of 1269 subjects without diabetes was performed with oGTT-derived glucose and insulin; fasting triglyceride, high-density lipoprotein, BMI, waist and hip circumference. Patients with T2D (n=794) were clustered using age, BMI, glycemia, homeostasis model assessment, and islet autoantibodies. Associations of clusters with mortality were analyzed using Cox regression. Individuals without diabetes were classified into six subphenotypes, with 884 assigned to subjects at low-risk (cluster 1,2,4) and 385 at high-risk (cluster 3,5,6) for diabetes. We found significantly increased mortality in clusters 3 (hazard ratio (HR) 1.42) , 5 (HR 1.43) and 6 (HR 1.46) age-, BMI-, HbA1c- and sex-adjusted. In the T2D group, 5were assigned to mild age-related diabetes (MARD) , 183 to severe insulin-resistant diabetes (SIRD) , 84 to mild obesity-related diabetes (MOD) , to severe insulin-deficient diabetes (SIDD) . Compared to the low-risk nondiabetes group, crude mortality was not different in MOD. An increased mortality was found for MARD (HR 2.2) , SIRD (HR 2.2) and SIDD (HR 2.5) . Metabolic clustering successfully stratifies survival even among persons already undergoing invasive coronary diagnostics. Novel clustering approaches based on glucose metabolism can identify persons who require special attention as they are in danger of increased mortality

Disclosure

K.Prystupa: None. G.Delgado: None. A.P.Moissl: None. M.E.Kleber: Employee; SYNLAB Holding Deutschland GmbH. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. A.L.Birkenfeld: None. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. W.Maerz: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH.

Funding

German Federal Ministry of Education and Research (BMBF) (01GI0925)
1114-P: Diabetes Screening among Asian Americans after the 2015 American Diabetes Association Guideline Update
Authors: DEMARSILIS ANTEA , USISKIN ILANA , MUKAMAL KENNETH J.
Published: May 2022

In 2015, the American Diabetes Association (ADA) lowered the BMI cut-off for diabetes screening for Asian-Americans (AA) from BMI ≥ 25 to ≥ 23 kg/m2. We asked whether this led to increased screening among AA with BMI 23-25. We analyzed pooled, weighted data from the 2013, 2014, 2018, and 20Behavioral Risk Factor Surveillance System (BRFSS) , a nationally-representative phone survey. A question on self-reported incidence of diabetes screening in the past three years was included by 20 states in all 4 study years. We included AA ages 18-80 with BMI 23-24.9 and 25-29.9 without prediabetes or diabetes. We calculated screening rates before (2013, 2014) and at least three years after (2018, 2019) the update. By a difference-in-differences approach, we compared change in diabetes screening by BMI group, using generalized linear models with an identity link adjusted for age and sex. A total of 6,672 respondents were included. The weighted screening rate among AA with BMI 23-25 was similar before and after the guideline update (Table) . The change in likelihood of diabetes screening among AA with BMI 23-25 did not differ from those with BMI 25-30 (difference in differences -3.5%, 95% CI: -13.3% to 6.4%, p=0.49) . We found no increase in diabetes screening among AA with lower BMI despite updated ADA guidelines. Increased attention to screening in this at-risk group is needed. Note: Two first authors contributed equally.

Disclosure

A.Demarsilis: None. I.Usiskin: None. K.J.Mukamal: Other Relationship; US Highbush Blueberry Council.
1127-P: Diabetes Risk in Marginalized Urban Settings in Mexico City
Authors: SILVA-TINOCO RUBÉN , BOUCHAN-DELINO SAMUEL , REVUELTA-LARA LUIS , TREJO DANIEL , ARISTA GILBERTO , MARTINEZ-SANTANA NANCY , NÚÑEZ-RODRÍGUEZ ADRIÁN , GUTIERREZ TERESA , LEÓN-GARCÍA ENRIQUE , OCHOA-MORENO JORGE , SERNA JAVIER , LOPEZ-ARELLANO OLIVA
Published: May 2022

Type 2 diabetes (T2D) is a leading cause of morbidity and mortality in Mexico. Routine identification of persons with high risk for developing T2D is poorly executed in low- and middle-income countries. Thus, we aimed to analyze the characteristics of participants of a public health initiative to identify diabetes risk (SaludEnTuVida/Health In Your Life) in habitants of the mayoralty of Iztapalapa in Mexico City. The mayoralty of Iztapalapa is characterized by being a densely populated area, with a high index of marginalization, and adverse determinants of health. FINDRISC score (FDS) was used to assess the risk of T2D in adults over 20 years of age from September to December 2021. Data from 15,271 participants was analyzed. The mean age of participants was 46.3±15.4 years, most participants were woman (67%) , and with secondary or less education (59.8%) . The following proportions of risk factors were reported: first degree familiar history of T2D in 52.6%, overweight in 41.3%, obesity in 32%, and hypertension in 14.4%. Low risk with FDS <7 was observed in 22.1% of the sample (BMI 24.5±3.2 kg/m2, female 55.7%) compared to 77.9% in the greater risk (GR) group with FDS ≥7 (BMI 29.1± kg/m2, female 70.3%, p<0.0001, p<0.00 respectively) . Among GR group, there were variable T2D risk levels; slightly elevated 31.9%, moderately elevated 32.6%, and highly elevated 13.3%. GR risk for T2D were observed in women (OR 1.88 95%IC 1.7-2.1) and in participants with secondary or less education (OR 1.91 95%IC 1.72-2.12) . The prevalence of overweight and obesity in young adults (<40 years old) was 66.6%, and 62% were found with increased risk for T2D. These results show a higher risk of T2D in the population evaluated compared to the reported in national health surveys. Our findings enhances the need for the implementation of preventive public health care policies in high risk populations, including binding actions to diagnosis and to prevention care programs, particularly in women, people with low education, and young adults of marginalized urban settings.

Disclosure

R.Silva-tinoco: n/a. J.Ochoa-moreno: n/a. J.Serna: None. O.Lopez-arellano: None. S.Bouchan-delino: None. L.Revuelta-lara: None. D.Trejo: None. G.Arista: None. N.Martinez-santana: None. A.Núñez-rodríguez: n/a. T.Gutierrez: None. E.León-garcía: None.
1136-P: A Population-Based Assessment of the Risk of Severe Hypoglycemia with Concomitant Use of Sulfonylureas and Peptidomimetic Dipeptidyl Peptidase-4 Inhibitors
Authors: DIMAKOS JENNY , CUI YING , PLATT ROBERT W. , RENOUX CHRISTEL , FILION KRISTIAN B. , DOUROS ANTONIOS
Published: May 2022

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas (SU) to increase their risk of hypoglycemia. However, it is unclear whether this risk varies with the pharmacologic properties of DPP-4i. Thus, we compared the risk of severe hypoglycemia between concomitant use of SU and peptidomimetic DPP-4i (vildagliptin, saxagliptin) vs. non-peptidomimetic DPP-4i (sitagliptin, linagliptin, alogliptin) in patients with type 2 diabetes.

Methods: We conducted a retrospective cohort study using the UK's Clinical Practice Research Datalink linked to hospitalization and vital statistics data of patients with type 2 diabetes initiating SU between 20 and 2020. Time-dependent Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI) of severe hypoglycemia associated with current concomitant use of SU and peptidomimetic DPP-4i compared to current concomitant use of SU and non-peptidomimetic DPP-4i, adjusted for baseline confounders. Secondary analyses stratified by age (<65 vs. ≥65 years) and sex.

Results: Our cohort included 196,138 SU initiators. The crude incidence rate of severe hypoglycemia was 7.2 per 1000/year. Compared to concomitant use of SU and non-peptidomimetic DPP-4i, concomitant use of SU and peptidomimetic DPP-4i was not associated with the risk of severe hypoglycemia (HR, 0.96; 95% CI, 0.76-1.22) . In female patients, concomitant use of SU and peptidomimetic DPP-4i was associated with a trend towards an increased risk (HR, 1.32; 95% CI, 0.97-1.81) ; in male patients, there was an association with a decreased risk (HR, 0.69; 95% CI, 0.48-0.99) . Age did not modify the association.

Conclusion: Our population-based study showed no increased risk of severe hypoglycemia with concomitant use of SU and peptidomimetic DPP-4i compared to concomitant use of SU and non-peptidomimetic DPP-4i. Further research is needed to corroborate the observed effect modification by sex.

Disclosure

J.Dimakos: None. Y.Cui: None. R.W.Platt: Consultant; Amgen Inc., Biogen, Merck & Co., Inc., Nant Pharma, Pfizer Inc. C.Renoux: None. K.B.Filion: None. A.Douros: None.

Funding

Canadian Institutes of Health Research (PJT-165882)
1137-P: Continuous Glucose Monitoring (CGM) Use and Its Impact on Glycemic Control and Acute Complications among Older-Onset Type 1 Diabetes Patients within the Veterans Health Administration (VHA)
Authors: ZHOU JIN , NEWELL MICHELLE , RIVAS SALVADOR , ZHOU XINKAI , NORMAN GREGORY J. , REAVEN PETER
Published: May 2022

There is increasing recognition that older onset type 1 diabetes (T1D) is not uncommon. Although CGM use is rising dramatically among those with T1D, little is known regarding its use and benefits within this older T1D population. To address these questions, we identified new CGM users (new CGM sensor prescriptions for T1D developing after military enrollment) and non-users (T1D receiving care and glucose strips from the VHA) during the years 2015-2020 and used national VHA healthcare data and ICD-9/ICD-diagnostic codes from visit encounters to compare baseline characteristics, change in glucose control and new emergency (ER) or hospital admissions. Linear mixed models and Cox proportional models (with propensity score overlap weighting) , were used to compare pre/post changes in HbA1c, and time to acute admissions, respectively. Compared with 4732 nonCGM users, CGM users (n=5,143) had similar HbA1c levels but differed in many ways at initiation of CGM, including: being significantly younger (59 vs. 65 years) , higher proportion White (83 vs. 75%) , and more frequently using glucagon (36 vs. 12 %) , short-acting insulin (99 vs. 86%) and insulin pumps (54 vs.7%) . After propensity overlap weighting, all characteristics were nearly identical between groups. Initiation of CGM was associated with reduced HbA1c levels (- 0.2 and -0.26% at 6 and 12 months (p’s< 0.001) compared with nonCGM users. Similarly, CGM users also had greater declines in risk for total hospitalizations (HR = .88; CI 0.79-0.98) and hypoglycemic (HR = .69; CI 0.53-0.90) and hyperglycemic (HR = .77; CI 0.64-0.94) related ER visits/hospitalizations (all p’s < 0.02) . In this large national study of CGM initiation in older T1D patients, CGM use was linked with improved glucose control as well as reduced ER and/or hospital admissions for hypoglycemia, hyperglycemia or any cause.

Disclosure

J.Zhou: Research Support; Dexcom, Inc. M.Newell: Research Support; Dexcom, Inc. S.Rivas: None. X.Zhou: None. G.J.Norman: Employee; Dexcom, Inc. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc.

Funding

DexCom, Inc
1142-P: In-Hospital Hyperglycemia: An Independent Marker for In-Hospital Health Care-Associated Infection and Acute Kidney Injury in Patients with and without Known Diabetes: The DINGO Study
Authors: BARMANRAY RAHUL , KYI MERVYN , WORTH LEON J. , COLMAN PETER G. , FAZIO TIMOTHY N. , RAYMAN GERRY , FOURLANOS SPIROS
Published: May 2022

Objective: To investigate the relationship between hyperglycemia and adverse in-hospital outcomes in patients with and without known diabetes

Research Design and Methods: The Diabetes IN-hospital: Glucose and Outcomes (DINGO) prospective cohort study was conducted over 26 weeks between Oct-20 and Mar-2020 at The Royal Melbourne Hospital. Admissions with ≥2 capillary glucose values and length of stay >24 hours were eligible. Stratification was by in-hospital hyperglycemia (IHH) , defined as ≥2 capillary glucose values of ≥11.1 mmol/L [≥200 mg/dL].

Results: We included 2,6admissions, of which 1,189 (46%) experienced in-hospital hyperglycemia. Following adjustment (covariates) , IHH was independently associated with in-hospital healthcare-associated infection (HAI) , acute kidney injury (AKI) , stroke, and mortality (see figure for incidence rate ratios [IRR]) . For each outcome the association was independent of diabetes status, except for mortality where the association was stronger in those without known diabetes. Patient-day mean glucose was elevated in those with HAI and AKI, on both whole-of-admission and prior-to-event calculations.

Conclusions: In-hospital hyperglycemia is independently associated with in-hospital HAI and AKI in patients with and without known diabetes.

Disclosure

R.Barmanray: None. M.Kyi: None. L.J.Worth: None. P.G.Colman: None. T.N.Fazio: None. G.Rayman: None. S.Fourlanos: Advisory Panel; Pfizer Inc., Viatris Inc., Speaker's Bureau; AstraZeneca, Novo Nordisk.

Funding

Rowe Family Foundation Perpetual GrantAustralian Government Research Training Program Scholarship
1144-P: Risk of Diabetic Retinopathy in Early-Onset Type 2 Diabetes in Mexico
Authors: SILVA-TINOCO RUBÉN , CUATECONTZI-XOCHITIOTZI TERESA , CABRERA-GERARDO DOLORES , DELATORRE-SALDAÑA VIRIDIANA , CASTILLO-MARTINEZ LILIA , BERNAL-CEBALLOS FERNANDA , GUZMAN EILEEN B. , BOUCHAN-DELINO SAMUEL , RAMIREZ ANGELICA , LEÓN-GARCÍA ENRIQUE , OCHOA-MORENO JORGE , LOPEZ-ARELLANO OLIVA
Published: May 2022

Early onset type 2 diabetes (EOD) seems to have an aggressive disease progression with a higher risk for diabetes complications at an early age. Screening for Diabetic Retinopathy (DR) is poorly executed in primary care of low-and-middle income countries. Thus, we aimed to analyze the characteristics of EOD in comparison with later-onset group. Data were obtained from the largest cohort of patients evaluated for DR within the primary care in Mexico (DIABEMPIC program) . Early and later-onset groups were defined as age of diagnosis <40 and ≥40 years, respectively. DR assessment by an ophthalmologist included fundoscopy with a mydriatic camera. Proliferative DR and severe non-proliferative DR were considered as severe DR. A total of 3063 patients with T2D were included of which 9had EOD. Prevalence of DR and severe DR was significantly higher in the EOD group than in the later-onset group (p<0.0001) ; however, an increase in the prevalence of DR and severe DR was observed after years of diagnosis (p<0.0001) . Burden of DR at different diabetes durations are shown in Table 1. EOD was associated with increased risk of DR compared with late onset T2D (OR 2.18, 95%CI 1.85-2.57) .

In conclusion, EOD patients with regular primary care presented a higher risk of DR and of severe DR not only explained for longer disease duration. Our study enhances the need for the management of DR risk factors and proper screening of DR in patients with T2D, especially in EOD.

Disclosure

R.Silva-tinoco: n/a. E.León-garcía: None. J.Ochoa-moreno: n/a. O.Lopez-arellano: None. T.Cuatecontzi-xochitiotzi: None. D.Cabrera-gerardo: n/a. V.Delatorre-saldaña: None. L.Castillo-martinez: None. F.Bernal-ceballos: None. E.B.Guzman: None. S.Bouchan-delino: None. A.Ramirez: None.
1148-P: Risk Factor Control and Risk of Hospitalization for Heart Failure in Diabetic Patients
Authors: MA HAO , WANG XUAN , HEIANZA YORIKO , QI LU
Published: May 2022

Both diabetes and ischemic heart disease (IHD) are important risk factors for heart failure hospitalization. We investigated the association between the degree of risk-factor control and risk of heart failure in diabetic patients with and without IHD. A total of 20,9diabetic patients from UK Biobank were included, and matched with 82,582 controls based on age, sex, the presence of IHD, and assessment center. Risk-factor control was evaluated by 3 factors: glycated hemoglobin <53 mol/mol, blood pressure <140/90 mm/Hg and non-HDL-cholesterol <130 mg/dl. The Cox regression model was used to assess the association between the number of risk-factor control and the risk of heart failure. During a mean follow-up of 8.7 years, 1,139 incident heart failure hospitalization were documented. Higher degree of risk-factor control was significantly associated with a lower risk of heart failure in diabetic patients without IHD, but not in diabetic patients with IHD (P-interaction=0.008) . Moreover, as compared with non-diabetic controls, the diabetes-related excess risk of heart failure became diminished when all the three risk factors were under control in diabetic patients without IHD; the hazard ratio for heart failure was 1. (95%, CI, 0.85-1.49) . Our findings highlight the importance of early intervention for controlling cardiovascular risk factors in preventing heart failure, especially before the onset of IHD.

Disclosure

H.Ma: None. X.Wang: None. Y.Heianza: None. L.Qi: None.
1163-P: Prognostic Factors in Type 2 Diabetic Patients Diagnosed with COVID-in a Latin American Hospital
Authors: DULCEY SARMIENTO LUIS A. , CALTAGIRONE RAIMONDO A. , THERAN LEON JUAN S. , PARRA HECTOR MORENO , PARADA JONATHAN PINEDA , STRAUCH RAFAEL PARALES
Published: May 2022

Background: To determine the factors associated with mortality in adult patients diagnosed with type 2 diabetes hospitalized for COVID-in a hospital of Latin America.

Methods: Prospective cohort study from June 2020-june 2021. Patients with a diagnosis of type 2 diabetes older than 18 years with a confirmed diagnosis of COVID-infection were included.

Results: A total of 813 adults were included. The mean age was 61.2 years, 575 (70.5%) were male. The most frequent comorbidities were hypertension (34.1%) and obesity (25.9%) . A total of 114 (14.0%) patients received mechanical ventilation, 38 (4.7%) were admitted to the Intensive Care Unit and 377 (46.4%) died. The requirement for ventilatory support, increased lung involvement, comorbidities and inflammatory markers were associated with mortality. Admission to the intensive care unit and the need for mechanical ventilation increased 1.39 (95% CI: 1.13 to 1.69) and 1.97 (95% CI: 1.69 to 2.29) the mortality. Those patients whose glycosylated hemoglobin on admission was greater than 10%, for every 1% increase above 10%, this increased the risk of death by 32% (RR: 1.32 95% CI: 1.25 to 1.38) .

Conclusion: The mortality found in our study was associated with age, poor control of type 2 diabetes and respiratory compromise. Ensuring a satisfactory metabolic control of the patient with type 2 diabetes would decrease complications related to COVID-infection.

Disclosure

H. Moreno Parra: None.
1175-P: Association between Equol-Producer and Type 2 Diabetes Mellitus in a Japanese Elderly Population
Authors: HAMAURA KIHO , MURAKAMI HIROSHI , TAMURA AYUMI , NISHIYA YUKI , MIZUSHIRI SATORU , DAIMON MAKOTO
Published: May 2022

Objective: Equol (Eq) , a metabolite produced from soy isoflavone daidzein by intestinal bacteria, exhibits estrogen activity and may exert effects on glucose metabolism. Eq levels vary extensively depending on the capability for Eq production and amounts of daidzein consumed. We examined the relationship between Eq levels and type 2 diabetes mellitus.

Research Design and Methods: Among 1,395 outpatients with diabetes at our hospital, 147 subjects (age: 70-89 years) were recruited (DM group) . Also, 147 age-/sex-matched non-DM subjects were recruited from 1,113 individuals who underwent routine health examinations (non-DM group) . As the estrogenic effect of Eq becomes apparent after menopause, the subjects were age restricted. Eq producers (EqPr) were determined based on the logarithm of the ratio of urinary Eq to the concentration of daidzein with a cut-off value of −1.75.

Results: Urinary daidzein (p=0.03) and Eq concentrations (p=0.01) were significantly lower in the DM group versus the non-DM group. The proportion of EqPr differed significantly between the groups (38.8% and 53.1%, respectively; p=0.01) . However, analyses with sex-based stratification showed such difference only in women; the proportion of EqPr was 31.4% and 52.8%, respectively (p<0.01) . Reversely, there were significantly fewer DM subjects among EqPr versus non-EqPr (p=0.01) . Among women, EqPr had significantly less DM than non-EqPr (p<0.01) . However, such differences were not observed in men. Correlation analyses showed a significant positive correlation between urinary Eq and daidzein concentrations only in EqPr (r=0.55, p<0.01) .

Conclusion: In postmenopausal women, EqPr were less diabetic; this status appears to be protective against DM. Eq levels increased in parallel with the amount of daidzein consumed in EqPr, but not in non-EqPr. Therefore, Eq supplements and/or enteric bacteria transplantation, rather than dietary intervention, may be effective in preventing DM in non-EqPr.

Disclosure

K.Hamaura: None. H.Murakami: None. A.Tamura: None. Y.Nishiya: None. S.Mizushiri: None. M.Daimon: None.