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TG concentrations across lipoprotein subclasses associate with diabetic kidney disease (DKD) in adults with T1D, but little is known about this relationship in youth with T1D. We evaluated cross-sectional relationships among TG concentrations across lipoprotein subclasses, intraglomerular hemodynamics, and renal oxygen availability (RO2) in youth with T1D. Glomerular filtration rate (GFR) , RO2, renal plasma flow (RPF) , afferent arteriolar resistance (RA) , efferent arteriolar resistance (RE) , intraglomerular pressure (PGLO) , and urine albumin-to-creatinine ratio (UACR) were assessed. Concentrations of lipid constituents from lipoprotein subclasses were quantified via targeted nuclear magnetic resonance spectroscopy (Nightingale Health Ltd., Helsinki, Finland) . Particle sizes for VLDL, LDL, intermediate-density lipoprotein, and HDL were measured. Fifty youth with T1D (age 16.0 ± 3.0 years, 50% female, HbA1c 8.7 ± 1.3%, T1D duration 5.7 ± 2.6 years) and 20 without T1D were included. VLDL-TG concentrations and small LDL-TG correlated with intraglomerular hemodynamic function parameters and RO2. To conclude, strong relationships were found among renal function markers and TG concentrations across lipoprotein subclasses in adolescents with T1D. Disclosure M.E.Pauley: None. K.L.Tommerdahl: None. C.Vinovskis: None. L.Pyle: None. R.Wadwa: Advisory Panel; Dompé, Consultant; Beta Bionics, Inc., Other Relationship; Tandem Diabetes Care, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Tandem Diabetes Care, Inc. R.G.Nelson: None. K.J.Nadeau: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. Funding MEP supported by NIH (T32DK063687) ; KLT supported by NIH (K23 HL159292) , Children’s Hospital Colorado Research Institute Research Scholar Award, University of Colorado Diabetes Research Center (P30 DK116073) , Ludeman Family Center for Women’s Health Research at the University of Colorado, and Dept of Pediatrics, Section of Endocrinology at University of Colorado School of Medicine; PB supported by NIDDK (RDK129211, R21 DK129720, K23 DK116720, UC DK114886, and P30 DK116073) , JDRF (2-SRA-2019-845-S-B, 3-SRA-2017-424-M-B, 3-SRA-2022-1097-M-B) , Boettcher Foundation, American Heart Association (20IPA35260142) , Ludeman Family Center for Women’s Health Research at the University of Colorado, Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine

Standardization of GFR by BSA can underestimate kidney function in overweight individuals. Standardization of GFR by ECV, rather than BSA, may be a way to avoid measurement bias. Our aim was to compare the distribution and agreement of GFR measures in people with type 1 diabetes at risk of kidney disease, and to determine associations with clinical hemodynamic measures. In this exploratory analysis of the PERL clinical trial of allopurinol, the distribution and agreement of 4 measurements for GFR were compared in 542 participants with eligible data. GFR was measured using gold-standard iohexol plasma clearance procedures, and ECV was calculated using the Jødal-Bröchner-Mortensen method, which estimates ECV using results from clearance studies. GFR was standardized using ECV corrected for 14 L of fluid volume rather than 1.73 m2 of BSA. Agreement between measurements was assessed by Bland-Altman and Spearman correlation analyses. The trial primary outcome was re-analyzed using ECV-adjusted GFR. Mean age and BMI were 51±years and 29.5±6.0 kg/m2. The distribution of normalized GFR measures overlapped and agreement was strong; GFR/ECV overestimated GFR/BSA by 2.9 numerical units (mean 70.5 ml/min/14 L vs. 67.6 ml/min/1.73 m2) . Heart rate was associated with unstandardized GFR (r=-0.10, p=0.023) . Associations between diastolic blood pressure and all measures of GFR were observed (r ranged from 0.17-0.18; p-values Disclosure L.Lovblom: None. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. S.Polsky: Advisory Panel; Medtronic, Other Relationship; diaTribe, Research Support; Dexcom, Inc., Eli Lilly and Company, Leona M. and Harry B. Helmsley Charitable Trust, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi-Aventis U.S. A.B.Karger: Consultant; Roche Diagnostics, Research Support; Kyowa Kirin Co., Ltd., Siemens. A.Galecki: None. B.A.Perkins: Advisory Panel; Abbott Diabetes, Insulet Corporation, Sanofi, Board Member; Novo Nordisk, Other Relationship; Abbott Diabetes, Insulet Corporation, Medtronic, Novo Nordisk, Research Support; BMO Bank of Montreal, Novo Nordisk. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research & Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. S.O.Lanctot: Employee; Medtronic. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. M.Mauer: None. L.Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG. S.Rosas: Advisory Panel; AstraZeneca, Teladoc Health, Other Relationship; Bayer AG, Research Support; AstraZeneca, Bayer AG. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. Funding Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171

Our objective was to compare renal hemodynamic function between obese youth with and without type 2 diabetes (T2D) and relate these measures to adipose insulin resistance (IR) . We assessed insulin sensitivity and kidney function in obese youth with (n=31, 15.8 ± 1.8 years, BMI 35.6 ± 6.6 kg/m2) , and without (n=20, 15.3 ± 2.1 years, BMI 38.2 ± 7.4 kg/m2) T2D. A hyperglycemic clamp was performed with 20% dextrose to maintain mild hyperglycemia for 240 minutes. Free fatty acids (FFA) were measured at baseline and every minutes during the steady state. FFA suppression (baseline FFA subtracted from steady state FFA) was used to estimate adipose IR. Iohexol and p-aminohippurate clearances were used to measure GFR and renal plasma flow, respectively. Renal hemodynamic parameters were calculated using Gomez equations. FFA suppression was attenuated in youth with T2D compared to obese controls (55.6% vs. 92.1%, p Youth with T2D had impaired FFA suppression compared to obese controls, indicating adipose IR. Impaired FFA suppression was associated with perturbed renal hemodynamics, indicating a potential role for adipose IR in the development of early diabetic kidney disease. Disclosure C.Platnick: None. P.V.Prasad: None. L.Li: None. L.Pyle: None. R.G.Nelson: None. D.Van raalte: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Sanofi. K.J.Nadeau: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company.

Background: Global vascular dysfunction is well-recognized in youth with type 1 diabetes (T1D) , accentuating lifetime cardiovascular event risk and making therapeutic strategies to mitigate vascular dysfunction a high priority. In the BCQR-T1D study, we tested the hypothesis that BCQR, a medication used in obese adults with type 2 diabetes, would improve vascular health in T1D youth. Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating cardiovascular and metabolic impacts of BCQR in T1D. Youth were randomized 1:1 to phase-1: 4-weeks of BCQR or placebo after which blood pressure (BP) , peripheral vascular stiffness by brachial artery distensibility (BrachD) , and central aortic stiffness by pulse wave velocity (PWV) , relative area change (RAC) and distensibility from phase-contrast MRI, were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 years, HbA1c 8.6%, BMI %ile 71.4, T1D duration 5.8 years) with T1D were enrolled. Compared to placebo, BCQR therapy decreased systolic (∆ = -5 mmHg, p Conclusions: BCQR improved BP, central and peripheral aortic stiffness and pressure hemodynamics in T1D adolescents over 4 weeks vs. placebo, even if normal weight, supporting future longer-term studies. Disclosure M.Schäfer: None. I.E.Schauer: None. K.J.Nadeau: None. L.Browne: None. U.Truong: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. A.Baumgartner: None. K.S.Hunter: None. J.Reusch: Advisory Panel; Medtronic. A.J.Barker: None. Funding JDRF BROM QR THERP3-SRA-2015-125-M-R

Diabetic kidney disease (DKD) is the leading cause of end stage kidney disease (ESKD). Higher rates of death and ESKD are seen in YO vs. AO T2D; however, no studies have evaluated differences in structural lesions from kidney biopsies in YO and AO T2D. 161 Pima Indians with T2D underwent kidney biopsies. Quantitative morphometry was performed and participants were stratified as YO ( Disclosure H. C. Looker: None. C. Severn: None. T. B. Vigers: None. L. Pyle: None. P. Saulnier: None. B. Najafian: Consultant; Self; 4DMT, Sangamo Therapeutics, Sanofi Genzyme, Research Support; Self; Amicus. M. Mauer: Consultant; Self; Freeline Therapeutics, Research Support; Self; Amicus, Sanofi Genzyme. R. G. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc., Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly Diabetes, Novo Nordisk, Research Support; Self; Horizon Therapeutics plc. Funding American Diabetes Association (1-08-CR-42 to R.G.N.); National Institute of Diabetes and Digestive and Kidney Diseases (DK116720, DK114886); JDRF (2-SRA-2019-845-S-B); Boettcher Foundation

The relationship between renal function and neuropathy is not well established in T1D. Our objective was to determine the relationship between renal hemodynamic function and neuropathy in adults with a ≥50-year history of T1D compared to nondiabetic controls. GFR (inulin), effective renal plasma flow (ERPF, p-aminohippurate) and modified Toronto Clinical Neuropathy Score (mTCNS) were measured in 66 patients with T1D for ≥50-years and in 73 patients without diabetes matched for age and sex. Afferent (RA), efferent (RE) arteriolar resistances and glomerular hydrostatic pressure (PGLO) were estimated using Gomez’s equations. Presence of DKD was defined as eGFRMDRD30mg/day at the screening visit. Linear regressions were applied to examine the relationships between renal function (dependent variable) and measures of neuropathy (independent variable), adjusted for age, sex and HbA1c in participants with T1D and for age and sex in nondiabetic controls. Greater mTCNS, a measure of neuropathy signs and symptoms, was associated with lower renal blood flow (β=-9.57±4.15, p=0.024) and greater RE (β=32.79±15.13, p=0.034) in adults with T1D after adjusting for age, sex and HbA1c. Participants with T1D and DKD had a greater mTCNS compared to those without DKD (6.3±5.2 vs. 3.8±3.6, p=0.016). In contrast, renal hemodynamic parameters did not associate with measures of neuropathy in nondiabetic controls in multivariable models. Neuropathy score was associated with lower renal perfusion in adults with longstanding T1D. Neurological dysfunction in the presence of diabetes may contribute to impaired renal perfusion resulting in ischemic injury in patients with T1D. Further work is required to understand factors - including the autonomic nervous system - that contribute to maintaining normal renal perfusion in longstanding T1D. Disclosure Y. Lytvyn: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma. L. Lovblom: None. H. Liu: None. J.A. Lovshin: Consultant; Self; AstraZeneca. Consultant; Spouse/Partner; Bayer Inc. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic. M. Farooqi: None. A. Weisman: None. H.A. Keenan: None. M.H. Brent: Advisory Panel; Self; Bayer AG, Novartis Pharmaceuticals Canada Inc., Roche Canada. N. Paul: None. V. Bril: Advisory Panel; Self; Alexion Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Takeda Canada. Consultant; Self; Akcea Therapeutics, CSL Behring, Sanofi. Research Support; Self; Biogen, Grifols, Momenta Pharmaceuticals. B.A. Perkins: Consultant; Self; Abbott, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Other Relationship; Self; Medtronic. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk.

The balance of RA and RE, a major determinant of intraglomerular pressure (P Disclosure P. Saulnier: None. H.C. Looker: None. M. Mauer: None. R.G. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma. Funding American Diabetes Association (1-08-CR-42 to R.G.N.); National Institute of Diabetes and Digestive and Kidney Diseases

Glomerular filtration rate (GFR) is a major determinant of renal energy expenditure. Animal models support a mismatch between renal oxygenation (RO2) and energy expenditure in diabetic kidney disease (DKD). The objective of this study was to compare the ratio of RO2 to GFR (RO2:GFR) in adolescents with and without type 1 diabetes (T1D) and correlate the ratio with albuminuria, effective renal plasma flow (ERPF), blood pressure, trunk mass and renal oxygen consumption. RO2 was measured by blood oxygenation level dependent (BOLD) MRI before and after 20 mg of I.V. furosemide, trunk mass by DXA, GFR by iohexol clearance, ERPF by p-aminohippurate clearance and albuminuria by urine albumin-to-creatinine ratio (UACR) in 50 adolescents with T1D (mean age 16.1±3.0 yrs, trunk mass 44.8±2.2%, HbA1c 8.6±1.2%, GFR 189±40 ml/min) and 20 non-obese controls (mean age 16.1±2.9 yrs, trunk mass 44.9±2.2%, HbA1c 5.2±0.2%, GFR 136±22 ml/min). The RO2:GFR (s/ml/min*1000) was calculated as renal oxygenation (T2*, s) divided by GFR (ml/min), and furosemide-suppressible oxygenation (FSOC) as change in RO2 in responses to furosemide. Relationships were evaluated by correlation and multivariable generalized linear regression models. RO2:GFR was 25% lower in adolescents with T1D vs. controls (mean±SD: 0.24±0.04 vs. 0.32±0.04, p Disclosure C.L. Vinovskis: None. K.J. Nadeau: None. K.L. Tommerdahl: None. P.V. Prasad: None. L. Li: None. L. Pyle: None. M. Rewers: None. M. Pragnell: None. F.H. Mahmud: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation. D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Sanofi. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. R. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc. Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Novo Nordisk Foundation. Research Support; Self; Horizon Pharma. Funding JDRF (2-SRA-2018-627-M-B); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK116720)

Elevated copeptin, a stable surrogate of vasopressin, is recognized to be higher in T1D and predicts diabetic kidney disease and cardiovascular (CV) mortality. Vasopressin increases renal oxygen consumption through enhanced sodium reabsorption and may result in renal hypoxia. Given the natriuretic and cardiorenal protective effects of SGLT2 inhibition (SGLT2i) in clinical trials, our aim was to: 1) examine serum copeptin in adults with T1D after SGLT2i with empagliflozin (EMPA) for 8-weeks; and 2) determine the relationship between copeptin and metabolic, renal and system hemodynamic parameters. In this post hoc, exploratory analysis, serum copeptin concentration, glomerular filtration rate (GFR) by inulin clearance, effective renal plasma flow (ERPF) by PAH clearance, vascular stiffness parameters, plasma RAAS markers, HbA1c, 24-hour urine volume and sodium and glucose excretion were measured in 40 participants with T1D (24.1±5.0 years, HbA1c 8.0±0.9%) during eu- and hyperglycemia at baseline and after 25 mg of daily EMPA. Copeptin concentrations increased under both eu- and hyperglycemic conditions (4.0±2.1 to 5.1±6.0 pmol/L, p=0.005 and p SGLT2i increased serum copeptin concentrations, which positively correlated with HbA1c and inversely with urine output and natriuresis, but not with renal or system hemodynamic parameters. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i; whether it is simply a marker of diuresis or may contribute to CV disease long-term. Disclosure Y. Lytvyn: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Katz: None. S.K. Singh: None. L.C. Godoy: None. L.T. Chung: None. C.L. Vinovskis: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.

To compare DKD rates over 5-years of follow-up in two cohorts of severely obese adolescents with T2D undergoing medical vs. surgical interventions. A secondary analysis of data collected by the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) and Treatment Options of type 2 diabetes in Adolescents and Youth (TODAY) studies was performed. Teen-LABS participants underwent bariatric surgery; TODAY participants were randomized to metformin alone or in combination with rosiglitazone or intensive lifestyle intervention, and insulin therapy was given when there was loss of glycemic control. TODAY participants (irrespective of treatment group assignment) were frequency matched to the 30 Teen-LABS participants with T2D by baseline age (13-18 years), ethnicity, sex, and baseline BMI (>35 kg/m2). Urinary albumin excretion (UAE), estimated glomerular filtration rate (eGFR) by creatinine and cystatin C equation, and prevalence of elevated UAE (≥ 30mg/g) and hyperfiltration (eGFR ≥ 135ml/min/1.73m2) were assessed. Thirty Teen-LABS participants with T2D (mean±SD age, 16.9±1.3 years; 70% female; 66% white; BMI 54.4 kg/m2) and 63 TODAY participants (15.3±1.3 years; 44% female; 71% white; BMI 40.5 kg/m2) were compared. During 5-years of follow-up, hyperfiltration decreased from 20% to 13% in Teen-LABS and increased from 5% to 37% in TODAY. Elevated UAE decreased from 27% to 5% in Teen-LABS and increased from 21% to 43% in TODAY. Adjusting for baseline age, sex, BMI and HbA1c, Teen-LABS participants had 15-fold lower odds of hyperfiltration (OR: 0.06, 95% CI 0.01-0.38) and 27-fold lower odds of elevated UAE (OR: 0.04, 95% 0.01-0.20) at 5-years of follow-up. Decreases in HbA1c and BMI showed the strongest associations with attenuation of hyperfiltration and elevated UAE, respectively. Compared with medical treatment, bariatric surgery of severely obese youth with T2D was associated with significantly lower odds of DKD over 5-years of follow-up. Disclosure P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. K.S. Hughan: None. M.M. Kelsey: None. A. Shah: None. J.L. Lynch: Board Member; Self; American Academy of Pediatrics. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Daiichi Sankyo Company, Limited, National Institutes of Health, Novo Nordisk Inc., Pediatric Diabetes Consortium. E. Nehus: Other Relationship; Self; Certara. M. Mitsnefes: None. T.M. Jenkins: None. P. Xu: None. C. Xie: None. T.H. Inge: Other Relationship; Self; Independent Medical Expert Consulting Services, Standard Bariatrics, UpToDate. K.J. Nadeau: None. Funding National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases

PUA is associated with renin angiotensin aldosterone system (RAAS) activation, which promotes hypertension and kidney disease in T1D. Our aims were to examine (1) the effect of an ANG II infusion on PUA and (2) the association between PUA and systemic and renal hemodynamic responses to ANG II over a wide range of T1D duration. In this post hoc analysis, blood pressure, PUA, GFRinulin and ERPFPAH were measured during a euglycemic clamp before and after an ANG II infusion (1 ng·kg-1·min-1) in participants with T1D: 49 young (26.2±5.5 years) and 62 older (66.0±7.9 years) adults and healthy controls (HC): 27 young (25.1±4.6 years), and 72 older (64.6±8.0 years) adults. ANG II infusion caused a greater decline in GFRinulin in older vs. younger adults with T1D; there was no such difference between older vs. younger HC adults. ANG II decreased PUA more in HC than T1D in both age groups (p Our findings suggest that ANG II infusion reduces PUA, potentially through direct effects on the ANG II type 1 receptor (AT1R). The presence of T1D attenuates PUA lowering effects irrespective of diabetes duration, suggesting an interaction between hyperglycemia, RAAS signaling pathways and PUA. Further studies are required to better understand the effects of AT1R receptor signaling on PUA concentrations. Disclosure Y. Lytvyn: None. J.A. Lovshin: Consultant; Self; Eli Lilly and Company, Intarcia Therapeutics, Inc., Prometic Life Sciences Inc. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. L. Lovblom: None. A. Katz: None. A. Lytvyn: None. G. Boulet: Other Relationship; Self; Medtronic. M.A. Farooqi: None. A. Weisman: None. H.A. Keenan: Employee; Self; Sanofi Genzyme. M.H. Brent: Advisory Panel; Self; AbbVie Inc., Bayer Canada, Novartis Canada. Research Support; Self; Bayer Canada, Novartis Canada, Roche Canada. N. Paul: Consultant; Self; Bayer AG. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. A. Advani: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Dexcom, Inc., Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim International GmbH. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi. Funding JDRF (17-2013-312)

In people with type 2 diabetes (T2D), SGLT2 inhibitors reduce cardiovascular risk and diabetic kidney disease (DKD) progression. Because several mechanisms of DKD progression overlap in people with T2D and T1D, our aim was to assess if sotagliflozin (SOTA), a dual SGLT1 and 2 inhibitor, had favorable renal effects suggestive of kidney protection in adults with T1D. In this 52-week pooled analysis, 1575 adults enrolled in the InTandem 1 and 2 trials were randomized to SOTA 200 mg, 400 mg, or placebo (PBO) in addition to optimized insulin therapy. Mean changes of eGFR (MDRD), urinary albumin to creatinine ratio (UACR, geometric mean), systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to week 52 were compared with PBO. From a baseline eGFR of 89.30±0.86 ml/min/1.73m2, mean eGFR reduction was -2.50±0.63 ml/min/1.73m2 vs. PBO after 4 weeks for SOTA 200 mg and similar change was observed with 400 mg (p In adults with T1D, SOTA 200 mg was associated with short and long-term hemodynamic changes in eGFR and lower UACR. SOTA 200 and 400 mg lowered SBP and DBP and induced mild hemoconcentration. These data suggest that the renal hemodynamic profile of SOTA in T1D is similar to that seen with SGLT2 inhibition in T2D. Further investigation around cardiorenal effects of SOTA in people with T1D is warranted. Disclosure D.H. van Raalte: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. F. Persson: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. R. Castro: Employee; Self; Sanofi US. S. Wang: Employee; Self; Sanofi US. D.R. Powell: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Prometic Life Sciences Inc., Sanofi.

Objective: In health, circulating growth differentiation factor (GDF)-15 is low, and concentrations are thought to increase rapidly in response to cardiac and renal injuries. GDF-15 is secreted in response to inflammation, oxidative stress and hypoxia, and therefore may be a biomarker of subclinical vascular disease. Yet, the relationships between GDF-15, coronary artery disease and diabetic kidney disease (DKD) remain incompletely understood. Accordingly, the objective of this study was to delineate these relationships in adults with T1D. Methods: Participants with (n=377, HbA1c 7.8±1.3%, duration 37.1±8.6 years) and without T1D (n=456) in the Coronary Artery Calcification in type 1 diabetes (CACTI) study were assessed for serum GDF-15, coronary artery calcification (CAC) measured using 128-slice spiral CT, urinary albumin-to-creatinine ratio (UACR) and eGFR calculated by CKD-EPI creatinine. Impaired GFR was defined as eGFR Results: Participants with T1D had greater GDF-15 concentrations than nondiabetics (666.4 [95% CI 633.9-700.5] vs. 579.1 [558.7-600.4] ng/l, p Conclusion: In this cross-sectional analysis, GDF-15 was strongly associated with DKD and coronary atherosclerosis in adults with T1D, independent of glycemic control. As a biomarker, GDF-15 holds promise to aid in risk stratification and clinical trial enrichment. Disclosure P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. R.M. Sippl: None. M. Rewers: None. J.K. Snell-Bergeon: None. Funding National Institutes of Health; JDRF

Insulin resistance (IR) and obesity are independently associated with T1D and are known risk factors for CV disease, the leading cause of mortality in T1D. We evaluated the impact of BMI on CV outcomes in T1D youth and compared obese T1D (OT1D) youth to youth with type 2 diabetes (T2D). Pubertal youth aged 12-21 years with T1D and T2D were recruited from the RESistance to InSulin in type 1 and type 2 diabetes (RESISTANT) and Effects of MEtformin on CardiovasculaR Function in AdoLescents with type 1 Diabetes (EMERALD) cohorts. Participants were stratified as lean (LT1D), overweight, or obese T1D or T2D (Table). CV outcomes included resting heart rate (HR), systolic and diastolic blood pressure (SBP, DBP), leptin, hsCRP, and adiponectin. T1D participants performed bicycle ergometry for peak oxygen consumption (VO2peak), brachial artery (BA) distensibility by Dynapulse, and aortic MRI. HR, SBP, DBP, mean arterial pressure, and prevalence of hypertension were higher and BA distensibility, descending aorta oscillatory shear index, VO2peak, leptin, and hsCRP were worsened in OT1D vs. LT1D. Beyond hypertension prevalence in OT1D vs. T2D, which was worse in OT1D, T2D did not differ significantly from OT1D. Higher BMI, which is increasingly prevalent in T1D, is associated with a worsened CV profile in T1D youth, nearly approximating the CV phenotype of T2D youth. Closer attention to lifestyle management in T1D youth is needed to help reduce CV risk. Disclosure K.L. Tommerdahl: None. K.V. Baumgartner: None. P. Bjornstad: Advisory Panel; Self; Horizon, XORTX. Consultant; Self; Bayer US, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company. A. Baumgartner: None. L. Pyle: None. J.G. Regensteiner: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. K.J. Nadeau: None. Funding American Diabetes Association (7-11-CD-08 to K.J.N.); JDRF (11-2010-343); National Institutes of Health (1R56DK088971-01)

We evaluated the performance of creatinine-based estimating equations for glomerular filtration rate (GFR) in adults with type 2 diabetes without nephropathy compared to measured GFR by gold-standard inulin clearance methods. mGFR was performed 4 times over the course of a 1 month treatment period in the context of a small randomized placebo-controlled trial measuring the intrarenal hemodynamics function responses to the dipeptidyl peptidase 4 inhibitor sitagliptin. Thirty-two adults with type 2 diabetes (randomized 1:1 to placebo or sitagliptin) completed the trial, and all participants underwent mGFR by inulin clearance and GFR estimated by serum creatinine using the MDRD (eGFRMDRD) and CKD-EPI (eGFRCKD-EPI). Performance of eGFR equations was evaluated using measurements of bias (mean difference), precision (standard deviations [SD]), and inaccuracy (defined as the proportion of eGFR that differed by >20% of mGFR). The effects of treatment and time on bias were evaluated using linear mixed effects models. Mean±SD age, diabetes duration, HbA1c, and BMI was 60±8 years, 9±7 years, 7.2±0.8%, and 31.0±6.2 kg/m2, respectively, and 12(38%) participants were female. At baseline, mean mGFR was 113±24, mean eGFRMDRD was 93±12, and mean eGFRCKD-EPI was 94±9, all in mL/min/1.73m2. When all 128 observations (32 participants measured 4 times) were evaluated, both equations substantially underestimated mGFR. For the eGFRMDRD, mean bias was -21.5 mL/min/1.73m2, precision was 22.7 mL/min/1.73m2, and 46% of observations differed by more than 20%. Results were similar for eGFRCKD-EPI. No time or treatment effects on bias were observed. In adults with type 2 diabetes, eGFR equations underestimated mGFR, lacked precision and accuracy, and had lower performance at higher ranges of mGFR. More accurate measures of kidney function may improve clinical decision-making in adults with type 2 diabetes. Disclosure J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. L. Lovblom: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. Y. Lytvyn: None. H. Rajasekeran: None. D. Scarr: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Cardiovascular disease is the leading cause of mortality in T1D and relates to IR. We demonstrated that lean and obese T1D youth have IR and that metformin improves surrogate markers of IR in obese T1D youth. Yet, little is known about vascular health in T1D youth or about the effect of metformin on directly-measured IR or vascular health. In The Effects of MEtformin on cardiovasculaR function in AdoLescents with type 1 Diabetes (EMERALD) study, we hypothesized that T1D youth have impaired vascular function and that metformin decreases IR and improves vascular health. 49 T1D youth ages 12-21 years (40% with BMI ≥ 90%ile; 44% male) and 24 controls of similar age, BMI and sex underwent phase contrast MRI of the ascending (AA) and descending aorta (DA) to determine aortic pulse wave velocity (PWV) and wall shear stress (WSS). T1D youth also had carotid intima-media thickness (cIMT) by ultrasound, DXA scan, fasting labs following overnight IV glycemic control, and a hyperinsulinemic-euglycemic clamp (80 mU/m2/min insulin) to assess IR (glucose infusion rate [mg/kg/min)]/insulin or M/I). T1D youth were then randomized 1:1 to 2g of metformin or placebo daily, and all measures repeated at 3 months. At baseline, T1D youth vs. controls had elevated aortic PWV (AA: 3.7±0.2 vs. 2.5±0.4 m/s, p Disclosure K.J. Nadeau: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. M. Sch fer: None. L. Browne: None. A. Baumgartner: None. Y. Garcia Reyes: None. A. Maniatis: None. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; MannKind Corporation, Dexcom, Inc., Xeris Pharmaceuticals, Inc., Bigfoot Biomedical. S. Nayak: None. L. Pyle: None. M. Cree-Green: None. J.E. Reusch: Research Support; Self; Merck & Co., Inc.. Board Member; Self; American Diabetes Association. Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis.

Sodium-glucose cotransporter-2 (SGLT2) inhibition reduces hyperfiltration in adults with T1D, likely by inducing natriuresis, which stimulates tubuloglomerular feedback. This exploratory analysis aimed to examine whether these renal effects occur acutely within 24 hours of SGLT2 inhibition following a single exposure to empagliflozin (EMPA) in youth with T2D. In this single-administration, open-label, randomized, parallel-group study (NCT02121483), 27 patients with T2D (mean age 14.1 years, 67% girls, mean BMI 35.5 kg/m2) received EMPA 5, 10 or 25 mg. The effects of EMPA on fractional sodium excretion (FENa+) and estimated GFR (eGFR as assessed by Zappitelli-combined creatinine and cystatin C equation) were investigated by pooling the three doses of EMPA for analyses. At baseline, mean (SD) baseline FENa+ was 0.55% (0.46), and eGFR was 123.4 ml/min/1.73m2 (15.6). After a single dose of EMPA, the adjusted mean change from baseline in FENa+ was +0.81% (95% CI 0.27, 1.36; p=0.006). The adjusted mean change from baseline in eGFR was -5.5 ml/min/1.73m2 (95% CI -8.3, -2.7; p=0.0006). In eGFR subgroups of interest, eGFR decreased by -6.7 (9.7) ml/min/1.73m2 in patients with hyperfiltration (n=8, eGFR >119.1 ml/min/1.73m2, [95th percentile of eGFR for obese youth in NHANES]) and by -5.0 (6.0) ml/min/1.73m2 in patients with normofiltration (n=19). SGLT2 inhibition following a single dose of EMPA was associated with acute natriuresis and attenuation of elevated GFR in youth with T2D, suggesting a reduction in intraglomerular pressure. Further mechanistic studies are required to define changes in renal function, and longer-term trials examining renal protective effects in youth with diabetes are needed. Disclosure P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc. G. Simons: Employee; Self; Boehringer Ingelheim GmbH. S. Hantel: Employee; Self; Boehringer Ingelheim GmbH. M. von Eynatten: Employee; Self; Boehringer Ingelheim GmbH. J.T. George: Employee; Self; Boehringer Ingelheim GmbH. J. Marquard: Employee; Self; Boehringer Ingelheim GmbH. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

We aimed to measure the prevalence of retinopathy in a T1D cohort of 75 adults with T1D duration of ≥50 years, and to determine association with other vascular complications. Participants underwent ultra-widefield retinal imaging and optimal coherence tomography. Neuropathy was characterized by electrophysiology and corneal confocal microscopy. Intrarenal hemodynamic function was determined by inulin and para-aminohippurate clearance, and arterial stiffness was measured by applanation tonometry, both at baseline and in responses to intravenous angiotensin II (ANGII). Participants were classified as having no diabetic retinopathy (ⱷDR), non-proliferative (NPDR), or proliferative (PDR), and associations were determined using multivariable linear regression adjusting for age, sex, and HbA1c. Thirty-nine (52%) participants had PDR, 24 (32%) had NPDR, and 12 (16%) had ⱷDR. Those without retinopathy had lower HbA1c vs. those with NDPR and PDR (6.7±0.6% vs. 7.4±0.7% and 7.5±0.9%, p=0.019). PDR was associated with lower corneal nerve fibre density, worse electrophysiology, and a greater number of signs and symptoms of neuropathy, but not with intrarenal hemodynamic function. Retinopathy severity was associated with greater response to ANGII for carotid-radial pulse wave velocity (mean change -4.9±11.4% vs. 8.2±18.5% vs. 12.9±20.2% for ⱷDR, NPDR, and PDR respectively, p=0.043). In longstanding T1D, retinopathy associated strongly with neuropathy and arterial stiffening, but not with renal hemodynamic function. Greater understanding of the co-occurrence of microvascular complications in patients with T1D, and relationships with macrovascular abnormalities such as arterial stiffness, may improve early detection and management of diabetes-related diseases. Disclosure J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. L. Lovblom: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. Y. Lytvyn: None. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. A. Weisman: None. V.S. Lai: None. J.M. Tse: None. L. Cham: None. A. Orszag: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Little is known about how tubular injury relates to intrarenal hemodynamic dysfunction in T1D. We sought to define the relationships between serum NGAL, a marker of tubular injury, and intrarenal hemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in T1D adults. The cohort consisted of patients with longstanding T1D (≥50 years duration); 44 Diabetic Nephropathy (DN) Resistors (eGFR >60mL/min/1.73m2 and Differences remained significant after adjusting for age, sex, HbA1c, SBP and LDL. DN Resistors had significantly lower serum NGAL vs. those with DN. Elevated NGAL is related to intrarenal hemodynamic dysfunction and afferent vasoconstriction in longstanding T1D. Disclosure P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. S.K. Singh: None. L. Lovblom: None. J.M. Tse: None. A. Orszag: None. Y. Lytvyn: None. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. L. Cham: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Our aim was to better understand kidney function changes and RAAS activation over the natural history of T1D in patients with a wide range of T1D duration. GFRinulin and ERPFPAH were measured during a euglycemic clamp before and after an angiotensin II infusion (ANGII, 3 ng·kg-1·min-1-a measure of RAAS activation) in patients with T1D: 28 adolescents (age 16.2±2.0 years), 54 young adults (25.4±5.6 years) and 66 adults with ≥50 years of T1D (65.7±7.5 years) from the Canadian Study of Longevity. Gomez’s equations were used to estimate afferent (RA) and efferent (RE) arteriolar resistances and glomerular hydrostatic pressure (PGLO). In a step-wise fashion, GFRinulin, ERPFPAH, PGLO decreased, renal vascular resistance (RVR) and RA increased in adolescents vs. young adults vs. adults with ≥50 years of T1D (Figure 1). RE was similar in adolescents vs. young adults, but was higher in patients with ≥50 years of T1D. ANGII resulted in blunted renal hemodynamic responses in patients with ≥50 years of T1D (RVR increase of 0.033±0.016 vs. 0.049±0.019mmHg/L/min in adolescents, p=0.0006) suggesting a state of enhanced RAAS activation. With longer duration of disease, patients with T1D have evidence of renal vasoconstriction, leading to lower GFRinulin, ERPFPAH, elevated RVR and RAAS activation. Further work is required to understand the potential role of non-RAAS, pharmacologic agents that target RA in patients with early T1D. Disclosure Y. Lytvyn: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. M. Farooqi: None. V.S. Lai: None. J.M. Tse: None. L. Cham: None. L. Lovblom: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. E.B. Sochett: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Higher PUA levels are associated with renal vasoconstriction, renin angiotensin aldosterone system (RAAS) activation and vascular stiffness, however the timeline for these associations in T1D is not clear. Our aim was to compare adolescents vs. young adults vs. adults with ≥50 years of T1D from the Canadian Study of Longevity to determine the relationship between PUA and changes in renal hemodynamic function, arterial stiffness and plasma renin and aldosterone over a wide range of diabetes duration. PUA, GFRinulin, ERPFPAH, vascular stiffness parameters (aortic augmentation index [AIx], carotid AIx, carotid femoral pulse wave velocity [cfPWV]), plasma renin and aldosterone were measured during a euglycemic clamp in participants with T1D: 27 adolescents (age 16.8±1.9 years), 52 young adults (25.6±5.5 years) and 66 older adults (65.7±7.5 years). PUA levels were highest in the cohort with the longest T1D duration: 197±44 in adolescents vs. 264±82µmol/L in older adults (p The relationship between higher PUA with lower GFR, increased arterial stiffness and RAAS activation was observed only in adults with longstanding T1D. T1D may modify the association between PUA, renal hemodynamic function and RAAS activation, leading to renal vasoconstriction and ischemia. Further work is required to determine whether pharmacological PUA lowering prevents injurious hemodynamic and neurohormonal sequelae of longstanding T1D, thereby improving clinical outcomes. Disclosure Y. Lytvyn: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc. G. Boulet: Advisory Panel; Self; Medtronic, Sanofi, Novo Nordisk Inc.. Other Relationship; Self; Janssen Global Services, LLC., Abbott. M. Farooqi: None. V.S. Lai: None. J.M. Tse: None. L. Cham: None. L. Lovblom: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. A. Advani: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Other Relationship; Self; Boehringer Ingelheim GmbH. E.B. Sochett: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..

Elevated SUA is increasingly recognized as a risk factor for kidney disease in adults with diabetes, yet there are limited data in youth. We hypothesized that elevated SUA would predict development of elevated UAE and HTN over time in teens with T2D. Serum creatinine, cystatin C, SUA, and urine albumin to creatinine ratio (ACR) were assessed in 539 youth, ages 12-17 with T2D duration Disclosure P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC. J.L. Lynch: Other Relationship; Self; Novo Nordisk Inc.. Research Support; Self; Daiichi Sankyo Company, Limited. L. El Ghormli: None. R.S. Weinstock: Research Support; Self; Medtronic MiniMed, Inc., Mylan, Kowa Pharmaceuticals America, Inc., Diasome Pharmaceuticals, Inc., Calibra Medical, Dexcom, Inc., Ultradian Diagnostics LLC., JAEB Center For Health Research, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases. S.E. Tollefsen: None. K.J. Nadeau: None.

Lower SUMOD correlates with decreasing kidney function and atherosclerosis in adults with T1D, but its relationship with markers of arterial stiffness in youth with T1D is unknown. We sought to evaluate the relationship between SUMOD and central arterial stiffness in youth with T1D. Participants (n=49, 12-21 years old, 51% female, BMI 25.2±4.6 kg/m2, mean HbA1c8.6±1.4) were enrolled in EMERALD, a randomized controlled trial of metformin in youth with T1D. Post-hoc SUMOD was measured using Euroimmun ELISA kits from serum from the baseline visit. Ascending (AA) and descending aortic (DA) stiffness (pulse wave velocity [PWV] and strain) were determined by MRI at baseline and 3 months of follow-up. SUMOD positively correlated with AA strain (r: 0.37, p=0.04) and negatively with AA PWV (r: -0.41, p=0.03). According to SUMOD tertiles, participants in the lower tertile had higher AA PWV vs. the middle and high tertiles (Figure). Lower baseline SUMOD also predicted worsening in AA PWV over 3 months (β±SE: -0.04±0.01, p=0.03) adjusting for age, sex, baseline AA PWV, treatment group (metformin vs. placebo) and estimated glomerular filtration rate. In T1D youth, decreased SUMOD is associated with increased aortic stiffness. Further research is needed in T1D youth to understand the pathogenesis of SUMOD in cardiovascular disease. Disclosure P. Wiromrat: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. C. Roncal-Jimenez: None. M. Schäfer: None. A. Baumgartner: None. L. Pyle: None. M. Cree-Green: None. Y. Garcia Reyes: None. L. Browne: None. R. Johnson: Board Member; Self; XORT Therapeutics. Stock/Shareholder; Self; Colorado Research Partners LLC. Consultant; Self; Danone Research Foundation. K.J. Nadeau: None.