bluuebunny/crossref_metadata_2025_split huggingface dataset:
1065-P: The Use of OGTT and Phenotypic Characteristics to Identify GDM Subtypes in Mexican Women, an Approach towards Precision Medicine
Authors: GALLARDO-RINCÓN HECTOR , ORTEGA-MONTIEL JANINNE , MARTINEZ-JUAREZ LUIS ALBERTO , LOMELIN-GASCON JULIETA , MONTOYA ALEJANDRA , REYES-MUÑOZ ENRIQUE , GALICIA-HERNANDEZ VICTORIA , AVILA-DOMINGUEZ ROSANGELA , PEREZ-TORRES LUCIA V. , GARCIA-GONZALEZ NATALI , PEREZ-HERNANDEZ AZUCENA H. , PEREZ-ROMERO BRENDA , GRANILLO-RAMIREZ CYNDY G. , TAPIA-CONYER ROBERTO 
Published: May 2022

GDM is a heterogeneous disease. Three subtypes of GDM have been identified, insulin sensitivity defect, insulin secretion defect, and both. Insulin sensitivity defect is associated with higher risk for fetal overgrowth and GDM associated adverse outcomes. Based on the 2hr-OGTT-75g values, the phenotype of GDM-sensitivity is associated with elevated fasting glucose and GDM-secretion by elevated one and/or two hours post-load glucose values. We evaluated the 2hr-OGTT-75g values of 1713 in Mexican pregnant women without previous diagnosis of T2D from the cohort study Cuido mi Embarazo between April 20 and December 2021. We identified 251 cases of GDM (14.6%) . Based on the distribution of 2hr-OGTT-75g values related to known GDM subtypes, 132 (52.6%) had elevated fasting glucose but normal post-load glucose values (GDM-sensitivity) , 90 (35.8%) had elevated post-load glucose but normal fasting glucose values (GDM-secretion) , and 29 (11.6%) patients with elevated fasting and post-load glucose values (GDM-mixed) . Women in the GDM-sensitivity group were younger (27.3 ± 6.5 yr) , nulliparous (56.1%) and more often had a family history of T2D (50.0%) compared to the women in the GDM-secretion and GDM-mixed groups. However, there was no statistical difference between the principal groups regarding pregestational BMI (GDM-sensitivity: 27.7 ± 5.5; GDM-secretion: 27.4 ± 4.4; GDM-mixed: 28.4 ± 6.2 kg/m2, p=0.90) ; although this last group showed the higher prevalence of obesity (29.4% - 23.3% - 38.0% respectively for each group) . To our knowledge, this is the first analysis of GDM subtypes in Mexican pregnant women. The high proportion of GDM diagnoses with normal fasting glucose supports the importance of unavoidably offering a complete OGTT. This strategic approach by classifying GDM subtypes according to OGTT values takes clinical importance in the offering of personalized and timely management care to minimize perinatal and newborn adverse outcomes.

Disclosure
H.Gallardo-rincón: None. N.Garcia-gonzalez: None. A.H.Perez-hernandez: None. B.Perez-romero: None. C.G.Granillo-ramirez: None. R.Tapia-conyer: None. J.Ortega-montiel: None. L.Martinez-juarez: None. J.Lomelin-gascon: None. A.Montoya: None. E.Reyes-muñoz: None. V.Galicia-hernandez: None. R.Avila-dominguez: None. L.V.Perez-torres: None.

Funding
Eli Lilly and Company
1105-P: Moderate-to-Advanced Liver Fibrosis Is Common in Patients with Type 1 Diabetes (T1D) and Nonalcoholic Fatty Liver Disease (NAFLD)
Authors: TOMAH SHAHEEN , SALAH TAREQ , AL-BADRI MARWA , DHAVER SHILTON E. , CURRY MICHAEL P. , JIANG ZHENGHUI , LAI MICHELLE , ELENANI OMNIA A. , KIBAA KARIM , GARDNER HANNAH , MCCARRAGHER RYAN , KAUSHIK AARYA A. , ZIEMNIAK NOLAN A. , HAMDY OSAMA 
Published: May 2022

ADA guidelines recommend screening for significant fibrosis in patients with type 2 diabetes and steatosis or elevated ALT. In contrast, there are limited or inconsistent data about the prevalence of NAFLD and liver fibrosis in patients with type 1 diabetes (T1D) . We screened patients with T1D unaware of having NAFLD at a tertiary diabetes center and excluded those with secondary causes of fatty liver or heavy alcohol consumption. We utilized liver stiffness measurement (LSM) by transient elastography for fibrosis screening and controlled attenuation parameter (CAP) for steatosis screening. Referral to hepatology unit was done based on a priori criteria suggestive of clinically significant fibrosis (≥F2) .
We screened 285 patients with T1D (age 48±16 yrs; 55% females; 93% non-Hispanic whites; BMI 27±4.9 kg/m2; diabetes duration 28±15 yrs; A1c 7.1±1.1%; total insulin dose 48±27 units/day; AST 23±9 IU/L; ALT 20±12 IU/L) . The prevalence of NAFLD (CAP≥274 dB/m) was 29.3% (95%CI 24-35) and fibrosis (LSM≥7 kPa) 11% (95%CI 7-15) . Among those with NAFLD (n=76) , 13% (95%CI 5-20) had ≥F2 fibrosis (LSM ≥ 8.2 kPa) suggesting nonalcoholic steatohepatitis. Among patients with NAFLD and those with fibrosis respectively, 72% and 59% had ALT≤30 IU/L (men) or ≤IU/L (women) . After multivariate adjustment, larger waist circumference (&gt;102 cm [men]; &gt;88 cm [women]) and BMI &gt;30 kg/m2 were associated with increased risk of steatosis (OR 4.13, 95%CI 1.61-10.6, p=0.014; 2.4, 1.3-4.5, p=0.007, respectively) . Continuous glucose monitoring parameters (e.g., %TIR) were not associated with steatosis or fibrosis.
In conclusion, NAFLD and liver fibrosis are common in patients with T1D. ALT alone is inadequate for screening. Central obesity, consistent with insulin resistance, independently predicts NAFLD. Future guidelines should consider screening for steatosis and significant fibrosis in patients with T1D and high BMI or large waistline even without elevated ALT.

Disclosure
S.Tomah: None. H.Gardner: None. R.Mccarragher: None. A.A.Kaushik: None. N.A.Ziemniak: 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. T.Salah: None. M.Al-badri: None. S.E.Dhaver: None. M.P.Curry: Consultant; Gilead Sciences, Inc., Mallinckrodt, Sonic Incytes, Research Support; Gilead Sciences, Inc., Mallinckrodt, Sonic Incytes. Z.Jiang: Advisory Panel; Olix Pharmaceutical, Research Support; Gilead Sciences, Inc., Pfizer Inc. M.Lai: None. O.A.Elenani: None. K.Kibaa: None.

Funding
Investigator-initiated grant from Gilead Sciences (IN-US-989-5675)
1145-P: Individual SGLT2 Inhibitors and the Risk of Diabetic Ketoacidosis
Authors: ABRAHAMI DEVIN , D'ANDREA ELVIRA , KIM SEOYOUNG C. , WEXLER DEBORAH J. , PAIK JULIE M. , PATORNO ELISABETTA 
Published: May 2022

SGLT2 inhibitors (SGLT2i) are increasingly prescribed to treat type 2 diabetes (T2D) given their cardiovascular benefits. However, SGLT2i are known to increase the risk of diabetic ketoacidosis (DKA) , a rare yet serious outcome. It remains unclear whether individual SGLT2i are associated with a differential risk of DKA. Using 3 US healthcare claims databases (1/2014 - 12/2020) we assembled 2 cohorts of adults with T2D initiating (1) individual SGLT2i, i.e., canagliflozin, dapagliflozin, or empagliflozin, for a within-class comparison between SGLT2i (cohort #1, median age=62 years, 55% male) , and (2) individual SGLT2i or dulaglutide, for comparisons between SGLT2i and an out-of-class comparison (cohort #2, median age=63 years, 54% male) . Cohorts were reweighed using inverse probability of treatment weights, accounting for &gt;130 baseline patient characteristics. Hazard ratios (HRs) and 95% CIs were estimated for hospitalization for DKA in each database and pooled using random-effects models. Over a median follow-up of 6 months, neither empagliflozin [HR (95% CI) = 0.96 (0.78-1.19) ], or dapagliflozin [HR (95% CI) = 0.76 (0.58-1.01) ] had a differential DKA risk vs. canagliflozin. All 3 SGLT2i were associated with a similar increase in DKA risk vs. dulaglutide (Table) . In this large cohort study, we found no difference in the risk of DKA across individual SGLT2i, but all SGLT2i types were associated with an increased risk of DKA vs. dulaglutide.

Disclosure
D.Abrahami: None. E.D'andrea: None. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. J.M.Paik: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

Funding
Patient-Centered Outcomes Research Institute (DB-2020C2-20326)
1213-P: REVEAL-CKD: Undiagnosed Chronic Kidney Disease in Patients with Type 2 Diabetes in Germany and France
Authors: SCHNEIDER MARKUS P. , VIRGITTI JEAN B. , PEACH EMILY , BARONE SALVATORE , ARNOLD MATTHEW , TANGRI NAVDEEP 
Published: May 2022

Background: Early recognition of chronic kidney disease (CKD) is crucial to slow its progression, yet underdiagnosis remains high. This study assesses prevalence of and factors associated with undiagnosed stage 3 CKD in patients with pre-existing type 2 diabetes (T2D) .
Methods: REVEAL-CKD is a multi-national secondary data study. Data were extracted from THIN (Cegedim Health Data, France) and Disease Analyzer (IQVIA, Germany) . Patients were aged ≥18 years with 2 consecutive estimated glomerular filtration rate (eGFR) results 30-59 mL/min/1.73 m2 recorded 90-730 days apart in 2015-2021. T2D was identified by a diagnosis code before 2nd eGFR. Patients with no CKD code before 1st eGFR and ≤6 months after 2nd eGFR were considered undiagnosed.
Results: The cohorts included 3,532 patients with T2D and stage 3 CKD in France and 6,935 in Germany. In both cohorts, undiagnosed CKD was high (94% and 74%, respectively) , and was greater in those aged ≥65 years and in females. In patients with additional pre-existing comorbidities undiagnosed CKD remained high, ranging between 65% - 96% (Table 1) .
Conclusion: A high prevalence of undiagnosed CKD in patients with T2D was observed for France and Germany. Older patients and females were particularly vulnerable to undiagnosed CKD. Considerable opportunities exist to increase early identification and proactive management of CKD to slow progression and improve outcomes.

Disclosure
M.P. Schneider: Consultant; AstraZeneca. J.B. Virgitti: Advisory Panel; AstraZeneca, Lilly, Novo Nordisk. E. Peach: Employee; AstraZeneca. Stock/Shareholder; AstraZeneca. S. Barone: Employee; AstraZeneca. M. Arnold: Employee; AstraZeneca. N. Tangri: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc., Pulsedata, Renibus, Tricida, Inc. Stock/Shareholder; Clinpredict, Klinrisk.
1250-P: Identifying Pediatric A-ß+ Ketosis-Prone Diabetes (KPD)
Authors: KUBOTA-MISHRA ELIZABETH A. , HUANG XIAOFAN C. , MINARD CHARLES G. , ASTUDILLO MARCELA , REFAEY AHMAD K. , MONTES GRACIELA , SISLEY STEPHANIE , BALASUBRAMANYAM ASHOK , REDONDO MARIA J. , TOSUR MUSTAFA ,   RADIANT STUDY GROUP
Published: May 2022

KPD is characterized by diabetic ketoacidosis (DKA) in persons lacking the phenotype of autoimmune type 1 diabetes. The validated "Aβ" system classifies 4 KPD subgroups in adults, one of which (A-β+ KPD) is an atypical form that otherwise resembles type 2 diabetes (T2D) . Although recognized in children, better understanding of the prevalence and characteristics of pediatric A-β+ KPD is needed. The Rare and Atypical Diabetes Network (RADIANT) has modified the criteria for A-β+ KPD to: DKA within 6 months of diagnosis (dx) , not on SGLT2i, off insulin within 6 months of DKA with HbA1c &lt;7% on oral agents alone, and negative islet autoantibodies. We compared clinical characteristics of pediatric T2D with and without DKA at dx, and in the former group estimated the prevalence of A-β+ KPD. A retrospective chart review identified 716 children with T2D over 3 years at Texas Children’s Hospital. Mean age at dx was 13.7 ± 2.4 yr; 63% females; 59% Hispanic, 29% African American (AA) , 9% non-Hispanic white, 3% others. Of them, 57 (8%) presented with DKA with negative antibodies. Children with DKA at dx, vs. those without it, were more often AA (45% vs. 28%, p=0.008) , male (60% vs. 35%, p=&lt;0.001) and older (14.4 vs. 13.6 y/o, p=0.02) ; had lower random C-peptide (1.4 vs. 4.23 ng/mL, p&lt;0.001) , higher glucose (375 vs. 240 mg/dL, p&lt;0.001) , higher BMI-z score (2.38 vs. 2.25, p=0.02) and higher HbA1c (12.1 vs. 9.4%, p&lt;0.001) at dx. In a multivariable model with age, sex, race, C-peptide, glucose, HbA1c and BMI z-score at dx, older age (p=0.004) , lower C-peptide (p&lt;0.0001) , higher glucose (p=0.003) and BMI z-score (p=0.004) remained significantly associated with DKA. Eight children with DKA (14%) met all RADIANT criteria for A-β+ KPD. Most of the other children with DKA failed KPD criteria because they remained on insulin treatment for &gt;6 months. Children with T2D and DKA at dx were more likely to be older, had lower C-peptide and higher glucose and BMI-z score at dx. Of them, 14% met all RADIANT A-β+ KPD criteria and are eligible for enrollment in RADIANT.

Disclosure
E.A.Kubota-mishra: None. M.Tosur: Advisory Panel; Provention Bio, Inc. Radiant study group: n/a. X.C.Huang: None. C.G.Minard: None. M.Astudillo: None. A.K.Refaey: None. G.Montes: None. S.Sisley: Speaker's Bureau; Rhythm Pharmaceuticals, Inc. A.Balasubramanyam: None. M.J.Redondo: Advisory Panel; Provention Bio, Inc.
126-OR: Long-Term Consequences of Diabetic Foot Infection: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: FANG MICHAEL , HU JIAQI , MATSUSHITA KUNIHIRO , SELVIN ELIZABETH , HICKS CAITLIN W. 
Published: May 2022

Introduction: Foot infections are a common complication of type 2 diabetes. However, the clinical sequelae of diabetic foot infection (DFI) in the general population remain poorly characterized.
Methods: We conducted a prospective cohort analysis of 1,451 participants with diabetes (mean age, 63 years [SD: 5.6]; 33% black; 47% female) in the ARIC study (visit 4: 1996-1998) . DFI was ascertained using ICD-9/codes from Medicare claims and hospital discharge records. We used Kaplan-Meier analyses to estimate the 5-year cumulative incidence of nontraumatic lower-extremity amputation (NLEA) , major fall, cardiovascular disease (CVD) [coronary heart disease, stroke, or heart failure], and death following incident DFI. We evaluated the association between incident DFI (modeled as a time-varying exposure) and the subsequent risk of clinical outcomes with Cox models.
Results: During over two decades of follow-up (1996-1998 to 2017) , there were 328 incident DFIs, 72 NLEAs, 502 major falls, 748 CVD events, and 915 deaths. Following incident DFI, the five-year cumulative incidence of major clinical outcomes ranged from 14.7% (NLEA) to 38.6% (death) (Fig 1a) . Incident DFI was significantly associated with all clinical outcomes after multivariable adjustment (Fig 1b) .
Conclusion: DFI is a high-risk marker for major morbidity and mortality in the general population of adults with diabetes.

Disclosure
M.Fang: n/a. J.Hu: None. K.Matsushita: Consultant; Akebia Therapeutics, Inc., Mitsubishi Tanabe Pharma Corporation, Other Relationship; Fukuda Denshi, Research Support; Kyowa Kirin Co., Ltd. E.Selvin: Other Relationship; Wolters Kluwer. C.W.Hicks: None.

Funding
HHS (N268201700001I) , HHS (N268201700002I) , HHS (N268201700003I) , HHS (N268201700005I) , HHS (N268201700004I) , NHLBI (K24HL152440)
1262-P: Developing a Computable Phenotype Algorithm for Identification of Children and Adolescents with Diabetes Using Electronic Health Records
Authors: LI PIAOPIAO , SPECTOR ELIOT , ALKHUZAM KHALID , PATEL RAHUL S. , DONAHOO WILLIAM T. , BOST SARAH , LYU TIANCHEN , WU YONGHUI , HOGAN WILLIAM , PROSPERI MATTIA , DIXON BRIAN E. , DABELEA DANA , UTIDJIAN LEVON H. , CRUME TESSA L. , THORPE LORNA , LIESE ANGELA D. , SCHATZ DESMOND , ATKINSON MARK A. , HALLER MICHAEL J. , SHENKMAN ELIZABETH , BIAN JIANG , GUO YI , SHAO HUI , ATKINSON MARK A. 
Published: May 2022

The Assessing the Burden of Diabetes by Type in Children, Adolescents, and Young Adults (DiCAYA) Network, a CDC/NIDDK-funded collaborative, aims to create a multi-site electronic health record (EHR) -based diabetes surveillance system. Foundational to the network's efforts is the development of a computable phenotype (CP) algorithm that can identify cases of diabetes. To advance the mission of the DiCAYA network, University of Florida (UF) Health system researchers developed a pilot CP algorithm for identifying diabetes cases in youth. The CP algorithm was iteratively derived based on structured data from EHRs (UF Health system 2012-2020) . We randomly selected 500 presumed cases among individuals &lt; 18 years old who has (1) HbA1c ≥ 6.5%; or (2) fasting glucose ≥ 126 mg/dL; or (3) random plasma glucose ≥ 200 mg/dL; or (4) diabetes-related diagnosis code from an inpatient or outpatient encounter; or (5) prescribed, administered, or dispensed diabetes-related medication. Four reviewers independently reviewed the patient charts to determine diabetes status and type. Presumed cases without type 1 (T1D) or type 2 (T2D) diabetes diagnosis codes were categorized as nondiabetes or other types. The rest were categorized as T1D if the ratio of T1D codes to the sum of T1D and T2D codes was ≥ 0.5, or otherwise categorized as T2D. Next, we applied a list of diagnoses and procedures that can determine diabetes type (e.g., steroid use suggests induced diabetes) to correct misclassifications from step 1. Among the 500 reviewed cases, 159 and 64 had T1D and T2D. The sensitivity, specificity, and positive predictive values of the CP algorithm were 94%, 98%, and 96% for T1D; 95%, 95%, and 73% for T2D. We developed a highly accurate EHR-based CP for diabetes in youth based on EHR data from UF Health. Consistent with prior studies, T2D was more difficult to identify using these methods. A DiCAYA-wide validation and algorithm refinement process will be conducted.

Disclosure
P.Li: None. M.Prosperi: None. B.E.Dixon: Advisory Panel; Merck Sharp & Dohme Corp. D.Dabelea: None. L.H.Utidjian: None. T.L.Crume: None. L.Thorpe: None. A.D.Liese: None. D.Schatz: Advisory Panel; Abbott Diabetes, Medtronic. M.A.Atkinson: None. M.J.Haller: Advisory Panel; SAB Biotherapeutics , Consultant; MannKind Corporation, Sanofi. E.Spector: None. E.Shenkman: None. J.Bian: None. Y.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC. M.A.Atkinson: None. K.Alkhuzam: None. R.S.Patel: None. W.T.Donahoo: None. S.Bost: None. T.Lyu: None. Y.Wu: None. W.Hogan: None.

Funding
CDC/NIDDK U18DP006512
1285-P: Differentiating between Diabetic and Idiopathic Gastroparesis: A Genetic Perspective
Authors: SMIESZEK SANDRA P. 
Published: May 2022

Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, and abdominal pain. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system is likely central to the pathogenesis of gastroparesis. Most common etiologies include diabetes, post-surgical but most cases are idiopathic. Thus far, little is known about the underlying genetic risk factors for gastroparesis. We have done a genome-wide association study comparing idiopathic and diabetic cases with controls as well as contrasting idiopathic versus diabetic cases. We report a novel genetic association of SLC15A4 locus with idiopathic gastroparesis. This signal is driven by multiple variants with top missense variant SLC15A4:NM145648:exon2:c.T716C:p.V239A, rs33990080. Altogether, among EUR cohort we report 69 carriers out of 214 versus controls 165 out of 896 (MAF: cases 0.18; MAF: controls 0.09) and OR: 1.9 (p-value&lt;10^-6) . We furthermore differentiate idiopathic from diabetic gastroparesis with an established diabetes genetic risk score, - result that is statistically significant (p-value&lt;0.0004) . We also delineate a number of significant loci implicated in diabetes risk including (HLA-DQB1,HLA-DQA2, EXOC6B) in the idiopathic versus diabetic gastroparesis analysis. Of particular interest are the Exocyst complex component, 6 (EXOC6/6B) with lead variant rs41420. previously identified to play a role in insulin signaling through its interaction with the glucose transporter GLUT4. Current genetic findings suggest that a mechanism directly connected to macrophage polarization may be implicated in the etiology gastroparesis. The GWAS picture that is emerging implicates novels loci implicated in the pathophysiology of gastroparesis differentiating those of diabetic versus idiopathic etiology.

Disclosure
S.P.Smieszek: None.
1363-P: Remission of Type 2 Diabetes and Improvement in Incretins, Cardiovascular Risk Factors, and Weight Loss with a High-Protein Diet
Authors: STENTZ FRANKIE B. , AMMONS ANN , CHRISTMAN JOHN V. 
Published: May 2022

The incretins GLP-1 and GIP have important roles in insulin sensitivity and have been shown to be effective in pharmacological treatment of type 2 diabetes (T2D) . Therefore, we studied these incretin level changes with remission of T2D and weight loss using a high protein (HP) diet in 12 obese women and men with T2D. Our studies have shown that subjects with T2D on a 6 month HP diet (30%protein,30%fat, 40%CHO) had 100% remission of T2D compared to only 33% on a HC diet (15%protein,30%fat, 55%CHO) . Effects of HP and HC diets on ghrelin levels were determined since HP subjects had increased satiety compared to HC diet. GLP-1, GIP, and Ghrelin levels were determined with a Meal Tolerance Test (MTT) at baseline and after 6 mo on HP and HC diets where all food was provided. Since cardiovascular risk factors (CVRF) decreased more in the HP than the HC diet, we determined if the B-Type Natriuretic Peptide (BNP) released from the heart was affected by either diet. As shown in Table, HP diet had a greater increase in GLP-1 and GIP than the HC diet. BNP decrease demonstrates improvement in heart tissue with the HP diet having a greater effect than the HC diet. Weight loss was similar (9.8% in HP vs. 11.3% in HC, p=0.692) . this study demonstrates that the HP diet increases GLP-1 and GIP which may be responsible in part for the improved insulin sensitivity and decreased BNP with greater improvement in CVRF with remission of T2D

Disclosure
F.B.Stentz: None. A.Ammons: None. J.V.Christman: None.

Funding
AD Baskin Research Grant
1377-P: Pramlintide Lowers Postprandial Glucagon Concentrations by Inhibiting Glucagon Secretion without Altering Clearance in Type 1 Diabetes: A [13C15N]-Glucagon Study
Authors: RUCHI FNU , ROMERES DAVIDE , SCHIAVON MICHELE , RENUSE SANTOSH , PANDEY AKHILESH , MAN CHIARA DALLA , COBELLI CLAUDIO , BASU RITA , BASU ANANDA 
Published: May 2022

To determine the underlying mechanism of pramlintide effects on postprandial (PP) glucagon concentrations, we studied thirteen C-peptide negative T1D subjects (Age 35±yrs, BMI 27.6±2.2 kg/m2, fasting plasma glucose 9.4±4 mM, HbA1c 7.1±1%) on two occasions in random order, with and without 30 μg of sc pramlintide at the onset of a mixed meal (75 gm carb, 15% fat and 35% protein; 8 kcal/kg) . Subjects administered insulin bolus at meal onset. 13C15N glucagon tracer was infused intravenously to estimate PP glucagon turnover. Arterialized venous samples were drawn periodically for measurements of glucose (YSI) , 13C15N-glucagon (LC-MS/MS) and glucagon (Mercodia) concentrations. Systemic glucagon turnover was calculated using non-steady state Steele's equation after determining glucagon volume of distribution. Integrated PP glucagon concentrations were lower (p&lt;0.01) in pramlintide (Pram) than without pramlintide (No Pram) . Integrated rates of glucagon appearance and glucagon disappearance were lower (p&lt;0.01) in Pram vs. No Pram. When adjusted for plasma glucagon concentrations, glucagon clearance was not different (p=0.7) between Pram vs. No Pram. These data demonstrate that pramlintide lowers postprandial glucagon concentrations by lowering glucagon secretion without altering clearance in subjects with T1D.

Disclosure
F.Ruchi: None. D.Romeres: None. M.Schiavon: None. S.Renuse: None. A.Pandey: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. C.Cobelli: None. R.Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca. A.Basu: Speaker's Bureau; Zealand Pharma A/S.

Funding
National Institute of Health (DK 085516, DK 029953)