bluuebunny/crossref_metadata_2025_split huggingface dataset:
1194-P: Gender Differences in Incidence of Prediabetes and Diabetes in South Asians
Authors: NARAYAN K.M. VENKAT , KONDAL DIMPLE , STAIMEZ LISA R. , ANJANA RANJIT MOHAN , GUJRAL UNJALI , DEEPA MOHAN , PATEL SHIVANI A. , ALI MOHAMMED K. , PRABHAKARAN DORAIRAJ , CHANG HOWARD H. , TANDON NIKHIL , MOHAN VISWANATHAN 
Published: May 2022

Background: Among South Asians, women have higher prevalence of diabetes than men, but few studies have examined gender differences in incidence.
Methods: We analyzed data from 2714 adults aged ≥20 years, enrolled in the Chennai site of prospective Cardiometabolic risk reduction in South Asia (CARRS) study. We defined normal glucose tolerance (NGT) , isolated impaired fasting glucose (iIFG) , impaired glucose tolerance (IGT) , and diabetes based on ADA criteria. We estimated incidence densities for: NGT (n=2205) to iIFG and iIFG (n=641) to diabetes; NGT (n=2205) to IGT; and IGT (n=341) to diabetes.
Results: Prevalence of iIFG was higher in women (20.5% vs. 11.8%) , while prevalence of IGT was lower (6.6% vs. 8.5%) than in men. During median 2.6 y (IQR: 0.7, 5.8) of follow-up, 316 individuals progressed from NGT to iIFG, 239 from NGT to IGT, 155 from iIFG to diabetes, and 135 from IGT to diabetes. Overall, incidence (95% CI) of NGT to iIFG was higher than incidence of NGT to IGT (36.3 [32.5, 40.5] vs. 27.4 [24.1, 31.1] per 1,000 person-years [PYR], respectively) . However, the incidence of iIFG to diabetes was lower than incidence of IGT to diabetes (47.3 [40.4, 55.4] vs. 77.1 [65.1, 91.3] per 1,000 PYR, respectively) . Compared with men, women had higher conversion from NGT to iIFG (42.1 [36.9, 48] vs. 27.7 [22.7, 33.8]) , but lower incidence of NGT to IGT, 22.9 (19.2, 27.4) vs. 34.2 (28.5, 40.9) . Women had higher conversation both from iIFG to diabetes [49.0 (40.8,58.8) vs. 43.1 (31.6,58.7) ] and IGT to diabetes (87.7 [70.5,109.0] vs. 65.3 [50.0,85.2]) . In Cox models adjusting for age, BMI and family history of diabetes, women were 1.41 times (95% CI: 1.07,1.84) likely to convert from NGT to iIFG compared to men, but, men are 1.76 (1.33, 2.34) times at risk from NGT to IGT. There was no gender difference for conversion from iIFG or IGT to diabetes.
Conclusion: Prevalence and incidence of iIFG is higher in South Asian women than men, while prevalence and incidence of IGT is higher in men. Conversion from iIFG or IGT to diabetes is similar among genders.

Disclosure
K.Narayan: n/a. H.H.Chang: None. N.Tandon: None. V.Mohan: None. D.Kondal: None. L.R.Staimez: None. R.Anjana: None. U.Gujral: None. M.Deepa: None. S.A.Patel: Research Support; Johnson & Johnson. M.K.Ali: Advisory Panel; Bayer AG, Research Support; Merck & Co., Inc. D.Prabhakaran: None.

Funding
The National Heart, Lung, and Blood Institute (NHLBI) , National Institutes of Health (HHSN268200900026C)
1195-P: Investigating the Data Sufficiency, Prevalence, and Population Characteristics of Type 2 Diabetes Remission Using Laboratory Value-Enriched Claims Data
Authors: SHEILS NATALIE , JARVIS MEGAN , BANGERTER LAUREN , ASCH DAVID , CLARK CALLAHAN 
Published: May 2022

The application of the 2021 international consensus statement, defining type 2 diabetes remission as A1c less than 6.5% at least 3 months after stopping glucose-lowering therapy, remains unexplored in retrospective claims-based studies. We used de-identified administrative claims enriched with laboratory values from commercial and Medicare Advantage plans to identify the (1) proportion of individuals with insufficient data to be assessed for remission (2) prevalence of diabetes remission and (3) sensitivity of remission definitions to changes in claims-based logic. We designed three alternative definitions adapted to claims by varying the glycemic, temporal, and pharmacologic components. Among 524,076 adults with a type 2 diabetes claim and an available A1c value of at least 6.5%, 185,285 (35.4%) had insufficient additional laboratory values and/or enrollment data to assess for remission. Of the 338,791 who were assessable for remission, 10,694 (3.2%) met the consensus statement definition. The proportion meeting the three alternative definitions ranged from 0.8% to 2.3%, demonstrating the feasibility of a laboratory-value enriched claims-based assessment of remission. Establishing stable claims-based markers of remission can enable population assessments and evaluate the association between remission and clinical outcomes.

Disclosure
N.Sheils: Employee; UnitedHealth Group, Stock/Shareholder; UnitedHealth Group. M.Jarvis: Employee; UnitedHealth Group, Stock/Shareholder; UnitedHealth Group. L.Bangerter: Employee; UnitedHealth Group. D.Asch: Other Relationship; UnitedHealth Group, VAL Health. C.Clark: Employee; UnitedHealth Group, Stock/Shareholder; UnitedHealth Group.
1199-P: Racial/Ethnic and Socioeconomic Disparities in the Look AHEAD Trial
Authors: CROMER SARA JANE , MEIGS JAMES B. , WEXLER DEBORAH J. 
Published: May 2022

Background: It is unknown whether the benefits of intensive lifestyle interventions (ILI) are equally distributed among participants with type 2 diabetes of different races/ethnicities or educational attainment. We hypothesized that individuals of White race/ethnicity and greater educational attainment (EA) would receive greater benefit from ILI within a clinical trial.
Methods: Using data from the Look AHEAD trial which assigned adults with T2D to an ILI or diabetes support and education (DSE) , we examined weight outcomes (achievement of the 7% weight loss goal, percent weight change) , stratified by race/ethnicity and EA. Differences between groups are described using univariate analyses and multivariable linear and logistic regression adjusted for age, sex, treatment arm, and baseline insulin use.
Results: Among 4,640 participants (mean age 59 years, 58% women) , 17% were non-Hispanic Black, 14% were Hispanic, and 13% did not have a high school degree. Black and Hispanic participants were less likely to achieve the weight loss goal in both the ILI (45.8% vs. 60.7%, p&lt;0.0 and 53.0% vs. 60.7%, p=0.01, respectively) and DSE arms of the trial and achieved lesser percent weight loss in the ILI arm. By contrast, participants with lower EA (less than a high school degree) were more likely to achieve the weight loss goal in the ILI but numerically less likely to achieve it in the DSE arm, with evidence of an arm by education interaction (p for interaction 0.015) , suggesting greater benefit from the ILI in this subgroup. Participants with lower EA also achieved greater percent weight change than peers in the ILI at both 1 year and 4 years after randomization, with ongoing evidence of an arm by education interaction at 4 years.
Conclusions: Black and Hispanic participants experienced less weight loss in both arms of the Look AHEAD trial, whereas those with lower EA experienced superior benefits in the ILI compared to other groups. Individuals with low EA may receive relatively greater benefits from ILIs, compared to those with higher EA.

Disclosure
S.Cromer: Other Relationship; Johnson & Johnson Medical Devices Companies, Research Support; National Institute of Diabetes and Digestive and Kidney Diseases. J.B.Meigs: Consultant; Quest Diagnostics. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate.

Funding
NIDDK F32DK127545
1206-P: Association of Hepatic Steatosis Index (HSI) and Fibrosis (Fib) -4 Score with Prediabetes Risk in the POP-ABC Study: Potential Mechanisms
Authors: BARRETO BRIGIDA COLON , EBENIBO SOTONTE , DAGOGO-JACK SAMUEL 
Published: May 2022

Nonalcoholic fatty liver disease (NAFLD) is prevalent in people with type 2 diabetes (T2D) . Here, we evaluated the association of NAFLD (assessed by HSI and Fib-4 score) with prediabetes risk and related mechanisms in healthy, normoglycemic (NGT) White and Black offspring of parents with T2D enrolled in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The primary outcome of POP-ABC was progression from NGT to prediabetes during ∼5-yr followup. Baseline assessments included clinical exam, OGTT, LFTs, hsCRP and adiponectin levels. Assessments during year 1 included insulin sensitivity (ISI, euglycemic clamp) and insulin secretion (AIR) . Baseline HSI ([8 × ALT/AST] + BMI + [2 if female]) and FIB-4 score ([age × AST]/[platelets count × √ALT]) values were used to stratify the cohort by quartiles (Q1 to Q4) .
The cohort (N 376; 159 White, 217 Black) mean age at baseline was 44.2 ± 10.6 yr, BMI 30.2 ± 7.23 kg/m2, with 343 (91%) evaluable subjects. The baseline fasting glucose was 90.9 ± 7.70 mg/dl and 2-hr glucose was 125 ± 26.5 mg/dl. During 5 years of followup, prediabetes occurred in 16.2, 21.6, 31.5 and 30.6% among participants in Q1 to Q4 of baseline HSI, respectively. Kaplan-Meier analysis showed higher probability of prediabetes with increasing baseline HSI (P=0.02) . Fib-4 scores were uncoupled from prediabetes rates. HSI correlated robustly with ISI (r=−0.438, P &lt;0.0001) ; FIB-4 correlated weakly with ISI (r=0.14, P= 0.0459) , and both showed weak correlation with AIR that was insignificant after controlling for ISI. HSI (r=0.456, P &lt;0.0001) and Fib-4 (r=0.164, P=0.0032) associated directly with hsCRP and inversely with adiponectin (HSI: r=−0.235, P &lt;0.0001; Fib-4: r=−0.156, P=0.0051) . Hepatic steatosis increases incident prediabetes risk via mechanisms that involve insulin resistance and inflammation.

Disclosure
B.Colon barreto: None. S.Ebenibo: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi.

Funding
American Diabetes Association (7-07-MN-13) ; National Institutes of Health (R01 DK067269)
123-LB: Extended Fasting Reveals Effect of Canagliflozin to Mobilize Ketones in Canines
Authors: ADER MARILYN , SEDIGHI RASHIN , KABIR MORVARID , BERGMAN RICHARD N. 
Published: May 2022

SGLT2 inhibitors (SGLT2i) improve glycemic control by inhibiting renal proximal tubular glucose reabsorption. SGLT2i may also elevate ketones. Fasting is expected to increase endogenous ketones, and SGLT2i may enhance ketosis. We asked if SGLT2i alters circulating ketones (β-hydroxybutyrate; BOHB) and disrupts glycemia during prolonged fasting. Dogs (n=7) were studied with a crossover design. Dogs received either canagliflozin (CANA; 300 mg) or placebo (PL) once/day for 7 d, after which a 48 h fast was performed while treatment was continued. To begin the fast, after morning feeding (9 am to noon) , remaining food was removed (“t=0”) . Blood was sampled at regular intervals over a 48 h period of total fasting (urine collected over final 3 h) . After the fast, dogs were fed over 3 h. Treatment was then discontinued for 2 wk washout, and dogs were then assigned to the alternate treatment (CANA or PL) for 7 d, after which fasting experiment was repeated. Glycemia was sustained in both treatment groups during initial 22 h of fasting, presumably due to reduction of insulin (↓50.7±13.1% and ↓49.5±21.5% for CANA and PL, respectively; p&lt;0.035 for both) . But marked effects of CANA alone were revealed after 22 h of fasting, when glucose declined markedly in CANA (52.9±3.4 mg/dl at t=48 h) , but not PL (86.6±2.5 mg/dl at 48 h; p=0.0002 vs. CANA) , due to drug-induced glycosuria (13948±543 vs. 19.6±1.5 mg/dl; p&lt;0.0001) . After 22 h of fasting, CANA induced ∼5-fold increase in FFA (p&lt;0.03) and marked increase in plasma BOHB that persisted for duration of fast (CANA: 0.560±0.065 mM, PL: 0.048±0.006 mM; p&lt;0.0001) . After refeeding, glucose and BOHB normalized, although BOHB remained higher in CANA (p&lt;0.0007) .
In conclusion, effect of SGLT2i on ketones is manifest after 24 h of total food restriction. CANA treatment induces glycosuria, after which reduction in carbohydrate stores switches animals to fat-based metabolism, characterized by increased FFA and ketosis. CANA appears to induce ketosis when carbohydrate stores are depleted.

Disclosure
M. Ader: None. R. Sedighi: None. M. Kabir: None. R. N. Bergman: Consultant; Fractyl Health, Inc., Novo Nordisk, Research Support; AstraZeneca, Janssen Research & Development, LLC.

Funding
Janssen Pharmaceutica, Inc.; NIH (DK29867, DK27619)
1239-P: Predictors for COVID-Severity among Hospitalized Patients with Diabetes in Japan
Authors: SHOJI MAYUMI , TERAMOTO NAOYA , HAYASHI AIKO , MAEDA YUKARI , OCHIAI HIDETOSHI , TSUKAGOSHI AYANO , MAEZAWA YOSHIRO , KOSHIZAKA MASAYA , YOKOTE KOUTARO 
Published: May 2022

Background: COVID-is a pandemic disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . Diabetes is a major risk factor for the severe progression and outcome of COVID-infection. Although some risk factors have been revealed, determining undetected risk factors for severe infection would enable identifying patients who may benefit from aggressive supportive care and early intervention.
Methods: A retrospective observational study of 100 diabetes patients who were admitted with confirmed COVID-infection was conducted. The patients were divided into two groups - severe and moderate - based on intensive care unit (ICU) admission. The differences between the groups were analyzed with multivariable logistic regression to reveal the risk factors.
Results: Of 100 patients, the mean (SD) age was 62.1 (13.0) years, 70 (70.0%) were male, and 48 (48.0%) were ≥ 65 years. Among patients with severe COVID-infection, 25 (25%) were admitted to ICU, and one patient died. Patients with severe infection had a significantly lower albumin level (severe 2.81 ± 0.37 g/dL vs. moderate 3.39 ± 0.50, p&lt;0.01) , and a higher blood glucose (221.5 ± 91.3 mg/dL vs. 178.9 ± 73.4, p=0.02) , white blood cell count (8969 ± 5002 /μL vs. 6227 ± 2644, p=0.01) , C-reactive protein (CRP) (12.5 ± 9.2 mg/dL vs. 6.4 ± 5.5, p&lt;0.01) , and lactate dehydrogenase (572.5 ± 165.9 U/L vs. 353.5 ± 150.9, p&lt;0.01) level than did patients without severe infection. There was no significant difference with hypertension, dyslipidemia, smoking, obesity, and HbA1c. Patients with severe infection had significantly lower total protein and albumin levels. On multivariable logistic regression analysis, risk factors for severe infection included CRP on admission (odds ratio [OR], 1.090; 95% CI, 1.005-1.183) , age (OR, 0.944; 95% CI, 0.899-0.991) , and albumin (OR, 0.036; 95% CI, 0.007-0.191) .
Conclusions: In patients with diabetes, albumin was an independent predictor for the development of severe COVID-19.

Disclosure
M.Shoji: None. N.Teramoto: None. A.Hayashi: None. Y.Maeda: None. H.Ochiai: None. A.Tsukagoshi: None. Y.Maezawa: None. M.Koshizaka: None. K.Yokote: None.
1266-P: Random C-Peptide Testing Identified One-Tenth of Thai Adult Patients Misdiagnosed with Type 1 Diabetes Mellitus
Authors: THEWJITCHAROEN YOTSAPON , NAKASATIEN SOONTAREE , BUTADEJ SIRIWAN , WANOTHAYAROJ EKGALUCK , KRITTIYAWONG SIRINATE , HIMATHONGKAM THEP 
Published: May 2022

Background: A C-peptide testing carried out several years after a clinical diagnosis of T1DM could uncover a misdiagnosis in some cases. T1DM in Asian population are extremely low in prevalence and display some unique features. This study aims to determine the prevalence and characteristics of Thai adult patients with clinically misdiagnosis with T1DM.
Materials and Methods: A cross-sectional study of Thai patients diagnosed with T1DM registered at the Theptarin Hospital, Thailand was performed. Random plasma C-peptide were measured in all cases and mixed meal tolerance test (MMTT) were performed if random plasma C-peptide was in between 0.1-0.5 ng/mL. Clinically misdiagnosis with T1DM defined by preserved endogenous insulin secretion (random C-peptide ≥ 0.6 ng/mL or stimulated C-peptide after MMTT ≥ 0.6 ng/mL) after at least 3 years after onset of DM.
Results: A total of 73 patients (females 52.1%, mean age 42.2±12.5 years, BMI 23.2±3.3 kg/m2, A1C 7.8±1.3%) with duration of diabetes 20.3±11.3 years were studied. Only 42.5% of patients had measurement of pancreatic auto-antibodies. The prevalence of anti-GAD and anti-IA2 were 53.3% and 20.8%, respectively. Preserved endogenous insulin secretion (random C-peptide ≥ 0.6 ng/mL) were found in 8 patients. The overall prevalence of clinically misdiagnosis with T1DM was 11.0%. When compared with truly T1DM, misdiagnosed patients had higher prevalence of hypertension and diabetic complications. Five were reclassified as having T2DM and 3 patients were suspected to have monogenic diabetes.
Conclusions: Our results were consistent with previous studies from Caucasian patients that about 10-15% of clinically diagnosed T1DM had been wrongly diagnosed. In clinical practice, positivity for pancreatic auto-antibodies was less helpful than a simple random C-peptide measurement. C-peptide testing a few years after a diagnosis of T1DM should be a routine procedure to identify some patients who might have been misdiagnosed.

Disclosure
Y. Thewjitcharoen: None. S. Krittiyawong: None.
1279-P: Caveolin 1 rs1997623 Is Associated with Metabolic Syndrome in Arab Adult Individuals from Kuwait
Authors: MADHOUN ASHRAF AL , HEBBAR PRASHANTHA , NIZAM RASHEEBA , HADDAD DANIA , DASHTI MOHAMMED H. , ABU-FARHA MOHAMED , AHMAD RASHEED , THANGAVEL ALPHONSE T. , ALMULLA FAHD 
Published: May 2022

Studies have implicated CAV1 in the pathophysiology of diabetes and obesity. Previously, we demonstrated a potential association between the CAV1 rs1997623 C/A variant and metabolic syndrome (MetS) in Kuwaiti children. In the present study, we substantiate the association of CAV1 with MetS in adult Arab individuals. Method: The CAV1 rs1997623 was genotyped in three cohorts of Arabs (n=479) , South Asians (n=660) and South East Asians (n=362) . MetS status of the individuals was diagnosed using the IDF criteria (i.e., presence of central obesity and of at least two abnormalities of high TG, low HDL, hypertension, or type 2 diabetes) . The quantitative measure of MetS was calculated as siMS=2*WC/Height + FBG/5.6 + TG/1.7 + SBP/130 - HDL/1.02 for males or HDL/1.28 for females. Allelic associations with quantitative and dichotomous traits were assessed using linear and logistic regression, respectively, with and adjustment for age and sex. CAV1 transcripts were quantified in adipose tissues from a cohort of 50 Arab individuals differing in siMS score. Results: The CAV1 variant was significantly associated with MetS status (OR=1.8[1.25-2.61]; P-value=0.0015; Pemp=0.0013) and with siMS (Effect size = 0.206; P-value=0.0035; Pemp=0.0028) in the cohort of Arab individuals. The variant was weakly and insignificantly associated in the cohorts of South Asian and South East Asian individuals (OR= 1.and 1.11; P-values= 0.25 and 0.67, respectively) . siMS scores correlated positively with mRNA levels of CAV1 in adipose tissue. Conclusion: The association of CAV1 rs1997623 C/A with MetS in Arab pediatric is now demonstrated in adults as well. Higher expression levels were seen in individuals poses increasing MetS rates further validates the implication of CAV1 rs1997623 C/A variant in MetS phenotype. Only a weak association signal was seen in the South Asian and South East Asian populations leading us to propose that the CAV1 rs1997623 association with MetS is probably specific to Arab ethnicity.

Disclosure
A.Al madhoun: None. P.Hebbar: None. R.Nizam: None. D.Haddad: None. M.H.Dashti: None. M.Abu-farha: None. R.Ahmad: None. A.T.Thangavel: None. F.Almulla: None.

Funding
Kuwait Foundation for the Advancement of Sciences (KFAS) and Dasman Diabetes Institute, Project RA CB-2021-007
1280-P: Use of Machine Learning to Determine the Relative Influence (RI) of Genetic Risk Scores of Glycemic Traits on Myocardial Infarction and Stroke in 409,633 Participants in the UK Biobank
Authors: DESHMUKH HARSHAL , MILES MARIA , BHAIJI AMIRA , SHAH NAJEEB , AKBAR SHAHZAD , PAPAGEORGIOU MARIA , SATHYAPALAN THOZHUKAT 
Published: May 2022

Introduction: Genome-wide association studies have identified numerous glycemic traits-associated SNPs with myocardial infarction (MI) and stroke. However, conventional regression methods combining these large numbers of highly significant SNPs in a weighted genetic risk score (wGRS) have only explained a small proportion of variance in MI and stroke. Therefore, we used a machine-learning algorithm (gradient boosting) to test the association of genetic risk for glycemic traits with MI and stroke in the UK Biobank population.
Methods: We identified 4626 SNPs associated with glycemic traits from the NGHRI catalogue for GWAS studies. wGRS were calculated using the effect estimates from the GWAS studies. We used a gradient-boosting machine-learning (GBM) model to identify the relative influence (RI) of baseline variables and wGRS of the glycemic traits on prevalent stroke and MI in the UK Biobank population.
Results: The study consisted of 409,633 individuals (53% females) with a median age of 58 (51-63) years and a median BMI of 26.7 (24.1-29.8) kg/m2. The prevalence rates of MI and stroke were 3.6% and 2.3%. In the GBM model, top wGRS associated with MI were type 2 diabetes (RI=14.6) , blood glucose levels adjusted for fasting time (RI=12.2) and beta-cell glucose sensitivity (RI=10.06) . In contrast, the top wGRS associated with stroke were HbA1c (RI=12.13) and fasting insulin levels (RI=10.31) . The addition of wGRS’s to the model comprising the baseline characteristics slightly improved the AUC for predicting stroke and MI.
Conclusion: We showed a differential effect of wGRS for various glycemic traits on the risk of MI and stroke in the UK Biobank population. However, even in machine learning models, these wGRS for various glycemic traits had a limited utility in predicting stroke and MI in the general population.

Disclosure
H.Deshmukh: None. M.Miles: None. A.Bhaiji: None. N.Shah: None. S.Akbar: None. M.Papageorgiou: None. T.Sathyapalan: n/a.

Funding
NIHR Clinical Lectureship