Novo Nordisk Inc Research Articles

211-OR: Differential Cerebral Blood Flow in Controlled and Uncontrolled Patients with Type 2 Diabetes Mellitus

Introduction: Patients with type 2 diabetes mellitus (T2DM) show variable brain tissue changes and mood and cognitive symptoms, which may result from altered cerebral blood flow (CBF). However, the regional CBF status in controlled and uncontrolled T2DM patients remains unclear, which can be examined with arterial spin labeling (ASL) imaging. Our aim was to examine regional CBF between controlled and uncontrolled T2DM patients using ASL imaging procedures. Methods: We collected hemoglobin A1c (A1C) data and 3D pseudo-continuous ASL data from 32 T2DM patients (16 controlled [A1C < 7%], age, 56.5±6.5 years; BMI, 29.6±6.2 kg/m2; 8 female; 16 uncontrolled [A1C ≥ 7%], age, 57.6±7.5 years; BMI, 30.0±5.1 kg/m2; 11 female) using a 3.0-Tesla MRI. A1C was measured by point-of-care testing. Whole-brain CBF maps were calculated, normalized to a common space, smoothed, and compared between groups (controlled T2DM patients vs. uncontrolled T2DM patients) using analysis of covariance (SPM12; covariates, age and sex; p<0.05). Results: No significant differences in age or sex appeared between groups. Multiple brain areas showed decreased CBF values in the cingulate, caudate, putamen, insula, hippocampus, amygdala, thalamus, hypothalamus, midbrain, cerebellum, prefrontal and frontal, and temporal cortices in uncontrolled T2DM patients over controlled T2DM patients. However, few brain sites in controlled T2DM patients, including the cerebellum, pons, medulla, parahippocampal gyrus, and temporal cortices showed reduced CBF over uncontrolled T2DM patients. Conclusion: Uncontrolled T2DM patients show significant reduction in CBF compared to controlled T2DM in areas that are involved in mood and cognition regulation. The findings suggest that uncontrolled levels may contribute to reduce regional CBF leading to site-specific tissue changes resulting to mood and cognition deficits in the condition. Disclosure S. E. Choi: None. B. Roy: None. M. Freeby: Research Support; Self; Abbott Diabetes, Novo Nordisk Inc. R. Kumar: None. Funding National Institutes of Health (1R01NR017190-03, 3R01NR017190-03S1)

95-LB: LixilanONE CAN: Randomized Trial Comparing a Daily vs. Weekly Titration Algorithm for Switching from Basal Insulin to iGlarLixi Fixed-Ratio Combination in People with T2DM in Canada

The combination of basal insulin with a GLP-1 RA may be helpful for people with T2DM to achieve and maintain HbA1c targets compared with each used individually. This randomized, 26-week, multicenter Phase 3 study (NCT03767543) in people with T2DM included participants with HbA1c ≥7.5% and ≤10.5%, and on basal insulin for ≥6 months (dose of ≤40 units/day). In addition to background oral glucose lowering medications, all participants received once-daily iGlarLixi, a fixed-ratio combination given within 1 hour prior to their first meal of the day, and were randomized 1:1 with instructions to titrate daily using a 1 unit per day algorithm or the traditional once-weekly titration (2 or 4 units per week) with target FPG of 4.4 to 5.6 mmol/L (79.2 to 100.8 mg/dL). Daily titration of iGlarLixi was superior to a weekly titration for the primary endpoint of change from baseline in HbA1c at week 26. The proportion of participants experiencing ≥1 gastrointestinal event(s) (27.9% daily vs. 27.8% weekly titration) and incidence of hypoglycemic events (84% daily vs. 81% weekly titration) were similar between the two arms. In this randomized trial, a daily titration algorithm for iGlarLixi was demonstrated as a safe alternative to the traditional weekly titration, while allowing patients to reach their maintenance dose earlier. Disclosure I. Hramiak: Advisory Panel; Self; AstraZeneca, Bayer Inc., BI-Lilly Joint Venture (Boehringer Ingelheim and Eli Lilly), Dexcom, Inc., Insulet Corporation, Medtronic, Research Support; Self; Eli Lilly and Company, Novo Nordisk, Sanofi. H. C. Gerstein: Advisory Panel; Self; Novo Nordisk Inc., Pfizer Inc., Sanofi, Consultant; Self; Abbott, Covance Inc., Eli Lilly and Company, Kowa Company, Ltd., Sanofi, Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., DKSH, Eli Lilly and Company, Sanofi, Zuellig, Research Support; Self; AstraZeneca, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. L. A. Leiter: Advisory Panel; Self; Abbott Diabetes, Amgen Inc., AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Esperion, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Other Relationship; Self; Applied Therapeutics, Research Support; Self; Amgen Inc., AstraZeneca, Esperion, Kowa Company, Ltd., Lexicon Pharmaceuticals, Inc., Medicines Company, Novartis Pharmaceuticals Corporation, Speaker’s Bureau; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. J. Yale: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Novo Nordisk Canada Inc., Sanofi, Research Support; Self; Bayer Inc., Speaker’s Bureau; Self; Dexcom, Inc., Medtronic, Merck & Co., Inc., Omnipod. H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. J. A. Stewart: Employee; Self; Sanofi. M. Toutounji: Employee; Self; Sanofi. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi. Funding Sanofi Canada

85-OR: Semaglutide 2.4 mg Improves Patient Reported Outcome Measures of Physical Functioning in Adults with Overweight/Obesity and Type 2 Diabetes in the STEP 2 Trial

An analysis of the STEP 2 trial evaluated the effect of s.c. semaglutide 2.4 mg vs. placebo (PBO) on physical function (PF) in adults with overweight/obesity and type 2 diabetes (T2D). The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; data not shown), or PBO (N=403), plus lifestyle changes. Endpoints included change in PF (baseline-week 68) using the SF-36v2® Health Survey acute version (SF-36) and Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT), and achievement of meaningful within-person PF improvements (≥3.7 points [SF‑36]; ≥14.6 points [IWQoL-Lite-CT]). Patients were 51% female, with a mean age of 55 years, body weight 99.8 kg, and BMI 35.7 kg/m2. Body weight change at week 68 with semaglutide 2.4 mg vs. PBO was -9.6% vs. -3.4%. Semaglutide significantly improved PF vs. PBO on SF-36 and IWQoL‑Lite‑CT (Table). SF-36 and IWQoL-Lite-CT PF improvements correlated with weight loss during the trial. Proportions of patients with clinically meaningful PF improvements were greater with semaglutide vs. PBO (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved PF vs. PBO, and led to greater proportions of patients with clinically meaningful PF changes in SF-36 and IWQoL-Lite-CT. Disclosure S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. T. Kalayci oral: Employee; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S

95-OR: Safety and Feasibility Evaluation of Closed-Loop Glycemic Management in Pregnant Women with Type 1 Diabetes

Pregnancy complicated by type 1 diabetes (T1D) is associated with increased maternal and fetal morbidity and mortality. We report results from the first clinical trial testing a closed-loop control (CLC) system specifically designed for pregnant women with T1D in the United States. Eight pregnant women with T1D participated in a 48-hour clinical trial at three US sites (NCT04492566). Women were enrolled in the second trimester after organogenesis was completed. CLC sessions used the interoperable artificial pancreas system (iAPS) running a Zone-Model Predictive Control algorithm designed for stricter glycemic targets for pregnancy. Glycemic target zones were 80-110 mg/dL during the day and 80-100 mg/dL overnight, with assertive insulin delivery in the postprandial period. The primary outcome was sensor glucose time in range (TIR) for pregnancy 63-140 mg/dL as per international consensus guidelines. All enrolled subjects completed the trial. Participants had a mean age of 29.3±3.5 years, gestational age of 22.2±3.6 weeks, weight of 77±12.2 kg, and HbA1c of 5.7±0.5%. Mean sensor TIR 63-140 mg/dL was 79.3±12.8% during CLC, compared to 60.8±18.8% for the week prior in open loop at home (p=0.03, Table 1). Unrestricted carbohydrate intake at meals ranged from 7 to 78 grams during the CLC sessions. No severe hypoglycemia or adverse events occurred. CLC in pregnant women with T1D is safe and effective. Disclosure B. Ozaslan: None. M. Church: None. M. Plesser: None. S. K. Mccrady-spitzer: None. C. Bakus: None. S. J. Ogyaadu: None. K. Nelson: None. C. Reid: None. S. Deshpande: None. W. K. Kremers: Research Support; Self; AstraZeneca, Biogen, Roche Pharma. F. J. Doyle: Advisory Panel; Self; Mode AGC, Other Relationship; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care. C. J. Levy: Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Employee; Spouse/Partner; AbbVie Inc., Other Relationship; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care. B. Rosenn: None. Y. C. Kudva: Research Support; Self; Dexcom, Inc. E. Dassau: Consultant; Self; Eli Lilly and Company, Employee; Self; Eli Lilly and Company, Research Support; Self; Dexcom, Inc., Tandem Diabetes Care, Speaker’s Bureau; Self; Dexcom, Inc., Roche Diabetes Care, Stock/Shareholder; Self; Eli Lilly and Company. J. E. Pinsker: Advisory Panel; Self; Medtronic, Consultant; Self; Eli Lilly and Company, Tandem Diabetes Care, Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. G. O’malley: Research Support; Self; Abbott Diabetes, Dexcom, Inc., Horizon Therapeutics plc, Tandem Diabetes Care. R. Kaur: None. K. N. Castorino: Consultant; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Abbott Laboratories, Dexcom, Inc., Drawbridge Health, Inc., Lilly Diabetes, Medtronic, Novo Nordisk Inc. C. Levister: Research Support; Self; Abbott Diabetes, Insulet Corporation. M. Trinidad: None. D. Desjardins: None. Funding National Institutes of Health (R01DK120358); Dexcom, Inc. (AP-2020-014)

876-P: Is Telemedicine the Preferred Visit Modality in Patients with Type 1 Diabetes?

Background: The COVID-19 pandemic limits access to diabetes clinics. Remote communication by phone calls and WhatsApp messages became available in the past years. However, the current need to avoid face-to-face meetings necessitates further expansion of telemedicine services. There are limited data whether the option of virtual meetings is a preferred therapeutic modality for patients with type 1 diabetes (T1D). Objective: To assess in a cohort of T1D patients, their preference and perception of telemedicine. Methods: T1D patients who are followed in a hospital-affiliated diabetes clinic were asked to fill a structured questionnaire aimed to determine their attitude towards telemedicine and their preference of virtual versus conventional visits. The questionnaire was offered to consecutive T1D patients who visited the clinic between August to October 2020. Results: Seventy one T1D patients that fulfilled the questionnaire were included. Mean age was 42±15 years, 39% were male, and the mean duration of diabetes was 21±14 years. Fourteen percent of the participants preferred only virtual visits, 24% only conventional visits and 62% preferred a combination of these modalities. Sex, origin, education, duration of diabetes, mode of insulin treatment and distance from the clinic were not associated with patients’ preference, but older patients (≥ 61 years) tended to prefer conventional visits. Sixty-seven percent felt confident in their ability to download data from their personal medical devices. Conclusions: Patients from a wide range of treatment modalities are willing to use telemedicine. However, virtual meetings cannot fully replace conventional visits in T1D especially in the older age group. Disclosure A. Kirzhner: Speaker’s Bureau; Self; Novo Nordisk. T. Zornitzki: Speaker’s Bureau; Self; Novo Nordisk. V. Ostrovsky: None. H. Knobler: None. T. Schiller: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc.

778-P: SGLT2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors and Risk of All-Cause Hospitalization

Introduction: Clinical trials have shown cardiorenal benefits of SGLT2 inhibitors (SGLT2i). However, adoption of SGLT2i in clinical practice has been slow, perhaps in part due to safety concerns. We aimed to assess the association between SGLT2i and risk of all-cause hospitalization as the totality of severe adverse events and benefits, comparing to risks associated with DPP4 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1RA). Methods: We identified patients with type 2 diabetes who initiated SGLT2i (n=2492), DPP4i (n=4762) or GLP1RA (n=1982) between 2015 and 2018 in Geisinger and performed 1:1 propensity score matching on SGLT2i (n=2171) vs. DPP4i (n=2171) and SGLT2i (n=1605) vs. GLP1RA (n=1605). We examined all-cause hospitalization as the main outcome. We also considered two positive controls (major adverse cardiovascular event [MACE] defined as cardiovascular death, myocardial infarction, and stroke; and heart failure [HF] hospitalization), and a negative control (hospitalization due to major bleeding). Results: Mean (SD) age was 58 (13) and 56 (13) years and 46% and 53% were women in the SGLT2i-DPP4i and SGLT2i-GLP1RA matched sample, respectively. During a median follow-up of 14 months, SGLT2i had similar risk of all-cause hospitalization compared with DPP4i (HR [95% CI] 0.85 [0.72-1.01]) or GLP1RA (HR 0.93 [0.77-1.13]). SGLT2i was associated with significantly lower risk of MACE and HF hospitalization compared with DPP4i (MACE: HR 0.70 [0.37, 0.98]; HF: HR 0.61 [0.38, 0.97]) but not with GLP1RA (MACE: HR 1.02 [0.50, 2.08]; HF: HR 0.72 [0.42, 1.23]). Risk of hospitalization due to bleeding was similar between SGLT2i vs. DPP4i or SGLT2i vs. GLP1RA. Conclusions: In this real-world comparison of antidiabetes medications, SGLT2i may be as safe as DPP4i with significant cardiac benefits and have comparable risk-benefit profiles compared with GLP1RA. These results further encourage SGLT2i use in routine diabetes care, particularly among patients at high risk of MACE. Disclosure B. Lyu: None. M. Grams: None. A. R. Chang: Advisory Panel; Self; Reata Pharmaceuticals, Inc., Relypsa Inc., Research Support; Self; Novo Nordisk Inc. L. A. Inker: None. J. Coresh: Consultant; Self; Healthy. io, Research Support; Self; National Institutes of Health, National Kidney Foundation. J. Shin: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K01DK121825)

561-P: Hispanic/Latino Adults with or at Risk of Type 2 Diabetes: Adequate Activity but Not Enough Sleep?

Sufficient sleep and physical activity (PA) are key for optimal health; low PA and sleep are established risk factors for type 2 diabetes (T2D). The American Academy of Sleep Medicine and Sleep Research Society recommend 7 hours/ night for adults; less than 7 hours on a regular basis is associated with adverse health outcomes. Similarly, 8,000 steps/day is associated with 51% lower risk than 4,000 steps/day for premature death. This study assessed PA and sleep in Hispanic/Latino adults with or at risk of T2D. Sleep and PA were measured by Fitbit InspireHR worn on the non-dominant wrist 24 hours/day for 7 consecutive days by 105 Hispanic/Latino adults (mean±SD 57.4±10.3 years, 67 women, 92 with T2D, HbA1c 7.9±2.0). BMI and waist circumference (WC) differed by gender (BMI women (W) 32.3±5.9 vs. men (M) 29.2±4.8, p≤0.01; WC W 102.4±13.6 vs. M 97.1±10.2cm, p≤0.05). Sleep duration was below recommended levels in W and M. Average weekday steps differed significantly from weekend steps. In W, average steps/weekday was negatively correlated with WC -0.26, BMI -0.26, and age -0.27, all p≤0.05. In M, average steps/weekday was negatively correlated with HbA1c -0.44 and total sleep time -0.37, p≤0.05. In these Hispanic/Latino adults with or at risk of T2D, PA was within recommended levels, but sleep was low in both W and M at ~6 hours/night. More weekday steps was associated with lower WC and BMI in W and with lower HbA1c and sleep duration in M. Disclosure W. C. Bevier: Research Support; Self; Abbott Diabetes, Eli Lilly and Company. A. J. Larez: Research Support; Self; Abbott, Eli Lilly and Company. C. Conneely: Research Support; Self; Abbott, Eli Lilly and Company. N. M. Glantz: Research Support; Self; Abbott, Eli Lilly and Company. K. N. Castorino: Consultant; Self; Dexcom, Inc., Research Support; Self; Abbott Diabetes, Abbott Laboratories, Dexcom, Inc., Drawbridge Health, Inc., Lilly Diabetes, Medtronic, Novo Nordisk Inc. D. Kerr: Advisory Panel; Self; Novo Nordisk, Sanofi-Aventis, Research Support; Self; Abbott Diabetes, Elsevier, Lilly Diabetes, Stock/Shareholder; Self; Glooko, Inc. Funding Eli Lilly and Company

28-LB: RTCGM Performance at Different Sensor Wear Sites during Prolonged Aerobic Exercise

Strenuous exercise may disrupt the local equilibria between vascular and interstitial glucose concentrations. We measured interstitial glucose levels during aerobic exercise in different anatomical regions with continuous glucose monitoring (CGM) sensors and compared them to capillary blood glucose (BG) levels. We enrolled 10 individuals, 7 with type 1 diabetes (T1D) and 3 without (healthy volunteers), for a 50-mile bicycle ride. Three CGM sensors (Dexcom G6) were placed on each participant, with one each in the upper arm, abdomen and thigh. BG values were obtained at the start of the ride and every 30 minutes thereafter. Accuracy of CGM levels was assessed for each insertion site as the mean absolute relative difference (MARD) and bias versus contemporaneous BG levels. Table shows that arm-worn sensors were more accurate in terms of MARD, and also had smaller numerical bias, than sensors placed in either the abdomen or thigh. Sensor accuracy was not significantly affected by the presence or absence of a diabetes diagnosis and accuracy metrics were consistent with those reported in the device’s instructions for use. CGM users may benefit from wearing sensors on the arm during sustained bicycle rides.View largeDownload slideView largeDownload slide DisclosureM. Mueller-korbsch: Research Support; Self; Dexcom, Inc., Menarini Group, Novo Nordisk Inc. L. Fruehwald: None. M. Heer: None. G. Rega-kaun: None. M. Fangmeyer-binder: None. P. Fasching: None.

1093-P: Association between First-Line Monotherapy with Metformin and the Risk of Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus

Background: Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and is associated with an increased risk of thromboembolic events, heart failure, and frequent hospitalizations. Type 2 diabetes mellitus (T2DM) has one of the strongest associations with AF with an overall 35% increased risk. Metformin is the first-line medication for T2DM and it has been proposed to have anti-inflammatory, pro-metabolic and cardioprotective benefits, but its effect on AF is not well studied. Our objective was to investigate whether the initial metformin monotherapy was associated with reduced AF rates compared to other non-insulin agents. Methods: This retrospective cohort analysis involved adults with newly diagnosed T2DM between 2007 and 2017, without any history of arrhythmias or contraindications to metformin use including GFR less than 30 ml/min who initiated a single antidiabetes therapy (except insulin). A multivariate analysis was performed to control for other variables that may have impacted the association between initial therapy with metformin and the outcomes of interest. Results: Out of 42384 cases with newly diagnosed diabetes, 5664 patients met the inclusion criteria. The majority of patients initiated monotherapy with metformin (81%), followed by sulfonylureas (13%) and thiazolidinediones (4%). The 10-year cumulative incidence of AF in the metformin group was 5.2% vs. 8.1% with others. Competing risk analysis did not demonstrate reduced rates of AF with metformin use (HR 0.92 95% CI 0.69 to 1.21; P = 0.55). Increased age and the presence of CHF were associated with significantly higher risk of AF (HR: 1.29, 95% CI: 1.21 to 1.37; P<0.001; HR: 2.73, 95% CI: 1.62 to 4.61; P<0.001, resp). Conclusion: In this observational study following patients with newly diagnosed T2DM, first-line therapy with metformin, when compared to other non-insulin antidiabetes therapies, was not found to be associated with a decreased risk of developing AF. Disclosure Z. Tekin: None. A. Milinovich: Research Support; Self; Novartis AG, Novo Nordisk Inc. X. Ji: Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. J. Bauman: None. M. Kattan: Consultant; Self; GlaxoSmithKline plc. Research Support; Self; Boehringer Ingelheim (Canada) Ltd., Novo Nordisk Inc. K.M. Pantalone: Consultant; Self; Bayer Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc. R.S. Zimmerman: Research Support; Self; Bayer U.S., Merck & Co., Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; LifeScan, Inc., Merck & Co., Inc. Stock/Shareholder; Self; Baxter, Bristol-Myers Squibb, Pfizer Inc., Procter & Gamble Company. M.K. Chung: None. S. Kashyap: Other Relationship; Self; GI Dynamics Inc.

953-P: Real-World Effectiveness of Once-Weekly Semaglutide (Sema OW) from a U.S. Commercially Insured and Medicare Advantage Population

Background: This study presents real-world evidence on effectiveness of sema OW in a large cohort of T2D patients. Methods: Claims and lab result data were used to identify T2D patients who initiated sema OW between 2/1/18 - 4/30/19 (index as first claim). Patients selected had ≥1 A1c result within ≤3 months pre- and ≥3 months post-index. All patients and a group of patients persistent on sema OW (those with a sema OW prescription with days supply dispensed overlapping/in proximity of date of post-index A1c measurement) were assessed for A1c changes and were split into 4 subgroups: GLP-1 naïve, GLP-1 experienced and either group with pre-index A1c >9%. Results: Of 1,888 patients initiating sema OW, 57.8% were GLP-1 naïve. A1c was significantly reduced in all patients (-0.9%) and subgroups (p<0.001, Figure 1). Persistent patients achieved a 1.1% A1c reduction, with similar or greater reductions across subgroups when compared to all patients. Attainment of A1c <7% increased from 23% pre- to 49% post-index for all patients (20 to 30% pre to post increase in each subgroup, all p<0.001). Conclusion: Initiation of sema OW was associated with significant reduction in A1c and an increase in reaching A1c <7% regardless of a prior history of GLP-1 use. Sema OW also provides significant change in A1c among patients whose A1c was not controlled on their previous GLP-1. Disclosure J. Visaria: None. C. Uzoigwe: Employee; Self; Novo Nordisk Inc. C. Swift: Employee; Self; Novo Nordisk Inc. Stock/Shareholder; Self; Novo Nordisk Inc. Y.M. Paprocki: Employee; Self; Novo Nordisk Inc. Stock/Shareholder; Self; Novo Nordisk A/S. V. Willey: Employee; Self; HealthCore. Funding Novo Nordisk

2220-PUB: Renal Outcomes Associated with Canagliflozin 100mg and with Intensification of SGLT2 Inhibitor Therapy Switching to Canagliflozin 300mg in Patients with Type 2 Diabetes Mellitus in a Real-World Setting: The Renal-WECAN Study

The aim of this multicentric retrospective study was to assess in a real-world setting kidney outcomes associated with canagliflozin 100 mg/d (CANA100), as add-on to the background antihyperglycemic therapy, and with the intensification of SGLT2 inhibitor (SGLT2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. 583 patients were included, 279 with CANA100 (eGFR 86.5 ml/min, eGFR<60 12.3%, albuminuria >30 mg/g 25.7%) and 304 with CANA 300 (eGFR 84.9 ml/min, eGFR<60 9.1%, albuminuria >30 mg/g 20.7%). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. The primary outcomes of the study were changes in eGFR, albuminuria and systolic BP (SBP) over the follow-up time. CANA100 was associated to significant reductions in eGFR (-2 ml/min) and SBP (-4.8 mmHg). In those patients with SBP>140 mmHg, CANA 100 lowered SBP levels by 14.9 mmHg. No significant changes in albuminuria were observed. However, in the subset of patients with baseline albuminuria >30 mg/gr, there was a significant decrease in median albuminuria. In the second cohort, patients with prior background SGLT2i therapy switched to CANA300. Significant reductions in eGFR (-1.8 ml/min), SBP (-3.2 mmHg), and median albuminuria (from 8.1 to 5.8 mg/g) were observed over the follow-up period. In those patients with SBP>140 mmHg, CANA 300 lowered SBP levels by 15.9 mmHg. In the subset with baseline albuminuria >30 mg/g, there was a significant decrease in median albuminuria. No significant changes in anti-hypertensive medications were observed over the follow-up. There was a low rate of adverse events related to volume depletion. In summary, CANA100 (as add-on therapy) and CANA300 (switching from CANA100 or other SGLT2i) significantly decreased SBP and modestly reduced eGFR. A significant reduction in albuminuria was observed with CANA300. Disclosure J.J. Gorgojo-Martinez: Advisory Panel; Self; Abbott, AstraZeneca, Grunenthal Group, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Mundipharma International, Novo Nordisk Inc., Pfizer Inc. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Mundipharma International, Novo Nordisk Inc. M.A. Gargallo-Fernandez: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi. A. Galdon: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Mundipharma International, Novo Nordisk Inc. T. Antón-Bravo: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Mundipharma International, Novo Nordisk Inc. M. Brito-Sanfiel: Advisory Panel; Self; Abbott, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker’s Bureau; Self; Almirall, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Esteve, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mylan, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. J.E.M. Wong-Cruz: None.

1127-P: Real-World Clinical Outcomes Associated with Canagliflozin 100mg and with Intensification of SGLT2 Inhibitor Therapy Switching to Canagliflozin 300mg in Patients with Type 2 Diabetes Mellitus: The Real-WECAN Study

The aims of this multicentric retrospective study were to assess in a real-world setting the effectiveness and safety of canagliflozin 100 mg/d (CANA100) as add-on to the background antihyperglycemic therapy, and to evaluate the intensification of SGLT2 inhibitor (SGLT2i) therapy by switching to canagliflozin 300 mg/d (CANA300) in patients with T2DM. 583 patients were included, 279 in the cohort of CANA100 (men 54.8%, age 59.7 y, A1C 8.05%, weight 94.9 kg) and 304 in the cohort of CANA 300 (men 55.9%, age 61.1 y, A1C 7.51%, weight 92.0 kg). Median follow-up periods in both cohorts were 9.1 and 15.4 months respectively. The primary outcome of the study was the mean change in A1C over the follow-up time. CANA100 was associated to significant reductions in A1C (-0.90%), weight (-4.1 kg) and systolic BP (-4.8 mmHg) at the end of the follow-up. The percentage of patients with A1C<7% significantly increased from 25.2% to 50.6%. In those patients with poor glycemic control (A1C >8%, mean 9.2%) CANA100 lowered A1C levels by 1.51%. There was a significant decrease in serum uric acid and liver enzymes. In the second cohort, patients with prior background SGLT2i therapy (dapagliflozin 10 mg 51%, CANA100 30.6%, empagliflozin 10/25 mg 7.3%/11.1%) switched to CANA300. Significant improvements in A1C (-0.35%), weight (-2.1 kg) and systolic BP (-3.2 mmHg) were observed over the follow-up period. There was a significant decrease in liver enzymes after SGLT2i intensification with CANA300. The percentage of patients with A1C<7% significantly increased from 28.9% to 46.6%. In those patients with poor glycemic control (A1C >8%, mean 8.9%) CANA300 lowered A1C levels by 1.12%. No unexpected adverse events were reported. In summary, CANA100 (as add-on therapy) and CANA300 (switching from CANA100 or other SGLT2i) significantly improved several cardiometabolic parameters in patients with T2DM. Disclosure J.J. Gorgojo-Martinez: Advisory Panel; Self; Abbott, AstraZeneca, Grunenthal Group, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Mundipharma International, Novo Nordisk Inc., Pfizer Inc. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Celgene, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Mundipharma International, Novo Nordisk Inc. M.A. Gargallo-Fernandez: Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi. A. Galdon: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Mundipharma International, Novo Nordisk Inc. T. Antón-Bravo: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Mundipharma International, Novo Nordisk Inc. M. Brito-Sanfiel: Advisory Panel; Self; Abbott, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. Speaker’s Bureau; Self; Almirall, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Esteve, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mylan, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi-Aventis. J.E.M. Wong-Cruz: None.

1222-P: Implementation of an Electronic Medical Record Tool to Improve Type 2 Diabetes Management in a Large Health System

Guidelines recommend individualized treatment for patients with type 2 diabetes (T2D), avoidance of clinical inertia, and specific therapeutic choices for patients at risk for cardiovascular disease, congestive heart failure, or chronic kidney disease. However, a gap exists in translating these guidelines into practice. We created an electronic medical record (EMR) tool to improve evidence-based treatment intensification for T2D and studied its implementation in endocrinology and primary care (PC). The tool included a best practice alert (BPA) informing providers at an office visit of an A1C ≥ 8% and prompted providers, within the tool, to make therapeutic choices based upon five priority care goals- cardiovascular risk reduction, A1c lowering, low hypoglycemia risk, cost, or weight loss. After a 3-month pilot at one site, the tool was implemented using a stepped-wedge approach from March-November 2019 to all PC (N=52) and endocrinology (N=17) sites in our health system with 1903 eligible patient visits by November 2019. Within endocrinology, provider tool usage ranged from 94% of visits at the pilot site to 34% after full rollout; in PC, usage ranged from 52% during the pilot to just above 5%. Usage varied by practice site (range <1- 44%) and by provider (0 - 100%). Providers expressed interest in tool utility but reported the timing of the BPA, during a busy office visit, as a barrier to use. Of note, the BPA was deferred up to 20% of the time in PC citing patient nonadherence to current therapy. Uptake of a point of care EMR tool to promote treatment intensification for T2D in endocrinology and PC demonstrated variation at the specialty, practice site, and provider levels. Our findings also suggest that, given time pressures, provider focused point of care EMR-based interventions to improve T2D care may need to be supplemented with tools asynchronous to the office visit and should address patient factors in adherence. Further analyses will focus on tool effects on A1c control. Disclosure A.D. Misra-Hebert: Research Support; Self; Agency for Healthcare Research and Quality, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. K.M. Pantalone: Consultant; Self; Bayer Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc. S. Rajpathak: Employee; Self; Menarini Group. T. Weiss: Employee; Self; Merck & Co., Inc. M. Hamaty: Research Support; Self; Merck & Co., Inc. R.S. Zimmerman: Research Support; Self; Bayer U.S., Merck & Co., Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; LifeScan, Inc., Merck & Co., Inc. Stock/Shareholder; Self; Baxter, Bristol-Myers Squibb, Pfizer Inc., Procter & Gamble Company.

254-OR: Islet Autoimmunity Is Highly Prevalent and Associated with Diminished Beta-Cell Function in Patients with Type 2 Diabetes (T2D) in the GRADE Study

We hypothesized that islet autoimmunity, hitherto considered the pathophysiologic basis of type 1 diabetes (T1D) and latent autoimmune diabetes of adults (LADA), could contribute to ß cell dysfunction in patients with type 2 diabetes (T2D). To evaluate this question, the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study - Beta Cell Ancillary Study Network measured humoral islet autoimmunity (autoantibodies against 65 kDa glutamic acid decarboxylase (GAD65-Ab), islet autoantigen-2 (IA2-Ab) and zinc transporter-8 (ZnT8-Ab)) in 392 participants (age 57.2 ± 10.1 y; BMI 33.5 ± 6.2 kg/m2; diabetes duration 4.0 ± 3.0 y; HbA1c 7.5 ± 0.5 %; on metformin as the sole glucose-lowering medication), and cellular islet autoimmunity (T cell autoreactivity against a broad range of islet antigens) in 322 of the same participants. 41.4% had evidence of cellular islet autoimmunity and 13.5% had evidence of humoral islet autoimmunity, but only 5.4% had both. T cell autoreactivity to islet antigens, but not autoantibody-positivity, was associated with diminished ß cell function, as assessed by the ratio of incremental area under the curve (iAUC) of C-peptide to iAUC of glucose during 0-120 min of an OGTT (ß = -0.1403; se = 0.0612; p = 0.0219) or ∆C-peptide/∆glucose during 0-30 min of an OGTT (ß = -0.2113; se = 0.0728; p = 0.0037), adjusted for insulin sensitivity. T cell positive participants also had higher fasting plasma glucose (p = 0.045) and HbA1c (p = 0.001) than T cell negative participants. These findings indicate that islet autoimmunity in T2D patients is far more prevalent than previously recognized; T cell mediated islet autoimmunity is associated with diminished ß cell function. Disclosure B. Brooks-Worrell: None. C.S. Hampe: None. E.V. Gonzalez: None. B.M. Palomino: None. S.Z. Zangeneh: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. M.E. Larkin: None. M.L. Johnson: Consultant; Self; Jaeb Center for Health Research. Research Support; Self; Abbott, Dexcom, Inc., Insulet Corporation, JDRF, Lilly Diabetes, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. N. Younes: None. N. Rasouli: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Allergan plc., Novo Nordisk Inc. C. Desouza: Consultant; Self; AstraZeneca, Bayer AG, Novo Nordisk A/S. R.M. Cohen: Stock/Shareholder; Self; Bristol-Myers Squibb. J.Y. Park: None. H. Florez: None. W. Valencia: None. A. Shojaie: None. J.P. Palmer: None. A. Balasubramanyam: None. Funding National Institutes of Health (R01DK104832, U01DK098246)

64-OR: Sustained Intensive Treatment and Long-Term Effects on A1C Reduction (SILVER Study) by CGM in Persons with T1D Treated with MDI

CGM reduces A1c and time in hypoglycemia in persons with T1D treated with MDI evaluated over short time periods. It’s unclear to what extent CGM improves glucose control, treatment satisfaction, hypoglycemia fear and diabetes-related QoL long term. The GOLD trial was a 16 month randomized crossover trial of CGM use in persons with T1D treated with MDI. The SILVER study is an extension in which patients continued CGM use (DexcomG4/G5) for 1 year with clinical visits every 3 months. The primary endpoint, A1c change during long-term CGM use compared with SMBG during GOLD (from end of SMBG in GOLD until end of SILVER study/1.0-1.5 years), showed decreased A1c of 0.35% (95% CI 0.19-0.50), p<0.001. TIR increased by 8.6% (95% CI 5.1-12.0,p<0.001), from 43.0 -51.0%. Time in hypoglycemia <54 and <70 mg/dl decreased from 2.1- 0.6%, p<0.001 and from 5.4- 2.9%, p<0.001, respectively. From randomization and screening in GOLD, A1c decreased by 0.45% (p<0.001) and 0.68% (p<0.001) after 2.5 years, respectively. Wellbeing WHO-5, p<0.001, treatment satisfaction DTSQ, p<0.001 and hypoglycemia confidence, p<0.001 increased. Diabetes-distress decreased PAID, p=0.006 over the time period. The SILVER study supports beneficial long-term effects by CGM use on A1c, TIR, hypoglycemia, treatment satisfaction, wellbeing, hypoglycemia confidence and diabetes distress in persons with T1D treated with MDI. Disclosure M. Lind: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Dexcom, Inc., Novo Nordisk Inc. A.F. Olafsdottir: None. I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod. J. Bolinder: Advisory Panel; Self; Abbott. Consultant; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; AstraZeneca. S. Dahlqvist: None. A. Pivodic: None. J. Hellman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. M.O. Wijkman: None. E. Schwarcz: Advisory Panel; Self; Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H. Albrektsson: None. T. Heise: Advisory Panel; Self; Mylan, Novo Nordisk A/S. Research Support; Self; ADOCIA, Aerami, Becton, Dickinson and Company, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Merck KGaA, Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. W. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Roche Diabetes Care. Consultant; Self; Abbott, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk Inc., Onduo, Sanofi US, Xeris Pharmaceuticals, Inc. Funding Dexcom, Inc.

1839-P: Glycemic Control Impacts Severity of Hepatic Fibrosis in NAFLD/NASH

T2DM increases risk for advanced fibrosis in NAFLD, however little is known about the impact of glycemic control on fibrosis severity. Objective: To assess whether glycemic control is associated with severity of fibrosis in NAFLD. Methods: We utilized the Duke NAFLD Clinical Database to examine the association between HbA1c and fibrosis in patients with biopsy (Bx)-proven NAFLD (n=941). A generalized linear regression model was used (adjusted for age, gender, race, BMI, HLD, eGFR) to assess the association of mean HbA1c (1 year pre- to 90d post-Bx) and fibrosis severity (stage 3-4=advanced vs. 0-2=mild). Patients with ≥3 HbA1c values (n=335) were examined by group-based trajectory analysis using HbA1c over 5 yrs pre- to 90d post-Bx. Results: Every 1% increase in mean HbA1c was associated with 20% higher odds of advanced fibrosis (OR 1.20, 95%CI 1.02, 1.39 p=0.02). Group-based trajectory analysis identified three glycemic patterns - good, moderate and poor (groups 1,2,3, respectively); proportion of advanced fibrosis increased with worse glycemic control. Group 2 had higher odds of advanced fibrosis than group 1 (OR 4.46, 95%CI 2.29,8.70, p<0.01). Group 3 estimates were limited by small sample size (OR vs. group 1: 2.55, 95% CI 0.87,7.44, p<0.01). Conclusion: Glycemic control preceding Bx impacts severity of liver fibrosis. We are currently analyzing 65 patients with paired Bx to assess impact of HbA1c trends on change in fibrosis severity. Disclosure A. Alexopoulos: None. M. Crowley: None. Y. Wang: None. C.D. Guy: Consultant; Self; CymaBay, HistoIndex, Madrigal, NGM. R. Henao: None. K.A. Seymour: Other Relationship; Self; Gore, Medtronic. R. Sudan: None. D. Portenier: Consultant; Self; Medtronic. Speaker’s Bureau; Self; Novo Nordisk Inc. A. Diehl: None. M.F. Abdelmalek: None. A.D. Coviello: Consultant; Self; GI Dynamics Inc., Novo Nordisk Inc. Research Support; Self; Allergan plc., GENFIT, Orthus Health. Speaker’s Bureau; Self; Novo Nordisk Inc. Funding Endocrine Fellows Foundation

527-P: Risk Factors for Nephropathy among Children and Young Adults with Type 1 Diabetes: A Swedish Cohort

Background: Persons with diabetic nephropathy have an increased risk to progress to severe renal failure and have a high cardiovascular risk. To better understand the impact of risk factors on diabetes complications information from diagnosis and onward is needed. Less focus has been on evaluating other risk factors than HbA1c following large populations from diagnosis with repeated measurements. Therefore, we aimed to evaluate risk factors for albuminuria in children and young adults. Methods: In a population-based cohort study persons with type 1 diabetes (T1D), both children (data from SWEDIABKIDS) and adults (data from Swedish National Diabetes Registry) were included, and followed from January 1, 2001 to December 31, 2017. The association between risk factors and albuminuria was evaluated. The gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results: A total of 10398 individuals with T1D were followed, 43.4% female, mean age 14.7 years and mean HbA1c 8.0% (63.4 mmol/mol). HbA1c was the strongest risk factor with an odds ratio (OR) of 1.51 (95% 1.39-1.64, p<0.0001). After adjustment for age, sex and mean HbA1c the OR per 1 SD increase were for mean diastolic blood pressure (DBP) 1.27 (95% 1.16-1.39, p<0.0001), mean triglycerides 1.21 (95% 1.14-1.28, p<0.0001), mean systolic blood pressure (SBP) 1.21 (95% 1.10-1.33, p<0.0001), mean cholesterol 1.16 (95% 1.07-1.25, p=0.0002) and mean LDL 1.12 (95% 1.03-1.21, p=0.0051). Risk for albuminuria increased at the following levels: SBP 140 mmHg, DBP 80 mmHg, triglycerides >89 mg/dL (>1.0 mmol/L), total cholesterol >193 mg/dL (>5.0 mmol/L), LDL >135 mg/dL (>3.5 mmol/L) and BMI >30 kg/m2. Smoking showed no association. Conclusion: For individuals with type 1 diabetes, higher HbA1c, blood pressure, triglycerides, LDL and cholesterol were the most prominent risk factors for albuminuria. Blood pressure levels 140/80 mmHg were associated with increased risk of albuminuria. Disclosure S.S. Ahmadi: None. A. Pivodic: None. A. Svensson: None. H. Wedel: None. J. Ludvigsson: None. M. Lind: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Novo Nordisk Inc. Consultant; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. Research Support; Self; Dexcom, Inc., Novo Nordisk Inc. Funding Swedish Child Diabetes Foundation

491-P: Renal Hemodynamic Dysfunction and Neuropathy in Long-Standing Type 1 Diabetes (T1D): Results from the Canadian Study of Longevity in T1D

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 eGFRMDRD<60ml/min/1.73m2 or 24-hour urine albumin excretion >30mg/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.

1560-P: Impaired Glucose Tolerance: Estimates for 2019 and Projections for the Years 2030 and 2045

Background: Impaired glucose tolerance (IGT) is an important risk marker for the development of type 2 diabetes. The 9th edition of the International Diabetes Federation (IDF) Diabetes Atlas provides updated estimates on the worldwide prevalence of IGT in 2019 and its projections for the years 2030 and 2045. Methods: A literature review of studies reporting the age-specific prevalence of IGT between 1990 and 2019 was conducted. The number of studies that satisfied the selection criteria according to the analytical hierarchy process was limited to 62 studies (from 49 countries). A generalised linear regression model was used to estimate the prevalence of IGT in the world’s 211 countries and territories. IGT prevalence estimates for countries without high quality in-country data sources were extrapolated from countries deemed to be similar. Results: In 2019, the estimated global prevalence of IGT in adults aged 20-79 years is 7.5% (374 million people). The vast majority (72.2%) of people with IGT live in low- and middle-income countries and 48.1% (180 million) are under the age of 50 years. The projected prevalences for 2030 and 2045 are estimated to be 8.0% and 8.6%, respectively. The IDF North America and Caribbean Region has the highest age-adjusted comparative prevalence of IGT (12.3%) in 2019, while the Europe Region has the lowest in 2019 (4.4%). The top three countries with the largest number of people in the age group 20-79 years with IGT in 2019 are China (54.5 million), the United States of America (37.4 million) and Indonesia (29.1 million), while Papua New Guinea (29.2%), Indonesia (17.8%) and New Zealand (17.5%) have the highest age-adjusted comparative prevalences of IGT in 2019. Conclusion: The majority of people with IGT are living in low- and middle-income countries. Given that IGT signifies a risk for future diabetes, its early detection and intervention can play a crucial role in primary prevention of type 2 diabetes. Disclosure P. Saeedi: None. A. Kaundal: None. S. Karuranga: None. B. Malanda: None. A.A. Motala: None. P. Aschner: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp & Dohme Corp., Sanofi. Speaker’s Bureau; Self; Novo Nordisk A/S. W. Rathmann: Advisory Panel; Self; AstraZeneca. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Research Support; Self; Novo Nordisk Inc. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc.

1658-P: A Novel Mutation in Hepatocyte Nuclear Factor-1 Beta (HNF1B) in Maturity-Onset Diabetes of the Young 5 (MODY5)

Maturity-onset diabetes of the young (MODY) is a group of dominantly inherited non-autoimmune diabetes characterized by early onset. Delayed diagnosis or misdiagnosis as type 1 or 2 diabetes is common, but early and correct diagnosis of MODY is important because it significantly alters the management of both the patient and his or her relatives. MODY5 is caused by mutations in the HNF1B, associated with renal and pancreatic abnormalities. Recently, we had identified a novel pathogenic mutation in IVS3-1G>C of HNF1B, in a Japanese MODY family. A 30-year-old male presented to our office with a diagnosis of NIDDM at age 15; autoimmune antibodies were negative, glycemia was initially managed with basal-bolus insulin. Abdominal ultrasound showed bilateral hyperechogenic kidneys but unlike with the reported typical abnormalities in MODY5, only a few renal cysts were observed, and pancreas was intact. An initial diagnosis of early-onset type 2 diabetes was made. However, the case subsequently showed high probability of MODY, when he reported a strong family history of early-onset diabetes in his sister, his father and paternal grandmother. Genetic testing performed in him, his sister and his father revealed shared unreported gene mutation g.37731831C>G (GRCH38 Chr17) in the HNF1B gene suggesting a diagnosis of MODY5. The mutation locates in the splicing site which may result in the production of abnormal proteins or failure of protein synthesis. Our MODY5 case was unique in the point that despite the mild renal morphological abnormalities, the proband had renal dysfunction and microalbuminuria from the early stage of disease, evoking the importance of considering the possibility of monogenic diabetes even in scarce structural abnormalities but having atypical diabetes with strong family history. It also suggests the necessity of further investigation of the exact mechanism of the development of diabetes and the cause of abnormalities in the kidney by this certain mutation. Disclosure Y. Fujita: None. T. Hyo: Speaker’s Bureau; Self; ARKRAY, Kissei Pharmaceutical Co., Ltd., LifeScan, Inc., Medtronic, Novo Nordisk Inc. M. Matsubara: None. Y. Hamamoto: Research Support; Self; Sumitomo Dainippon Pharma Co., Ltd. Speaker’s Bureau; Self; Novo Nordisk Inc. D. Tanaka: None. Y. Seino: Research Support; Self; ARKRAY, Bayer Yakuhin, Ltd., Boehringer Ingelheim International GmbH, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Speaker’s Bureau; Self; Becton, Dickinson and Company, Eli Lilly Japan K.K., Kao Corporation, Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.