bluuebunny/crossref_metadata_2025 huggingface dataset:
107-LB: Variation of Measured Values Associated with Different Lots of Sensors for the Freestyle Libre
Authors: OKADA JUNICHI , OKADA SHUICHI , YAMADA MASANOBU
Published: June 2019

The FreeStyle Libre Flash glucose monitoring system is a continuous glucose monitoring system that is used worldwide for improving plasma glucose control in patients with diabetes mellitus. Although we have used six different lots of the sensors, we recently and unexpectedly noted that one of the sensors for the FreeStyle Libre system showed completely different measured values. Herein, we designated these six lots as lot A through F. We observed that 53.4% and 54.6% of repeatedly measured interstitial glucose levels by Lot A were below 80 mg/dL (We tested two of Lot A on different day to confirm reproducibility.). On the other hand, the rest of 5 Lots (Lot B through F) showed that 0% of repeatedly measured interstitial glucose levels was below 80 mg/dL. However, unexpectedly, SMBG using a FS precision electrode with using the same reader of FreeStyle Libre system measured completely different values. Thus, Lot A consistently showed lower measured values compared to with those obtained using SMBG. As measured values using the FreeStyle Libre system are considered to be accurate as well as those obtained by SMBG, we decided to simultaneously test different lots of sensors, although the arm-attached sensor for B was on a different side than that for lot A. Lot A consistently showed measured values that were 20-30 mg/dL lower than those of Lot B. It is obvious that one of the six different lots showed inappropriately lower measured values and these discrepancies were critical. Therefore, it is possible that some lots of sensors for the FreeStyle Libre system do not work correctly, and may lead to false readings of hypoglycemia and a delayed response to true hyperglycemia, which requires a rapid response.

In summary, when changing of the lots of sensors for the FreeStyle Libre glucose monitoring system, we recommended that patients double check measured values using an alternative method, such as SMBG, as soon as possible to avoid incorrect blood glucose control.

Disclosure

J. Okada: None. S. Okada: None. M. Yamada: None.
1079-P: Glycemic Control and Change in Insulin Dose with Real-Life Use of Hybrid Closed-Loop System
Authors: GIORDANO DOMINIQUE A. , SNELL-BERGEON JANET K. , JOSEPH HAL , GARG SATISH K. , AKTURK HALIS K.
Published: June 2019

Optimal glycemic control with minimal hypo- and hyperglycemia in type 1 diabetes (T1D) is difficult to achieve. New technologies such as hybrid closed loop (HCL-670G) system could help to improve glycemic control and prevent complications. We report a single-center 6-month experience regarding changes in metrics for glycemic control in adult patients with T1D on the Medtronic® 670G system. There were 139 patients (mean±SD age 41±12 years, 60% women) with T1D who were on a pump and CGM for at least 3 months prior to initiating 670G system, and who had at least six months of follow-up on 670G. We analyzed the changes in HbA1c, daily insulin dose, and BMI from baseline (just prior to initiating 670G system) at 3 and 6-months of 670G use. The mean percent time in auto-mode was 71% at 3 months and 73% at 6 months, with a range of 0-99% at both time points. Use of the 670G system significantly improved HbA1c with no change in BMI (Table). Percent time in auto-mode was significantly correlated to HbA1c at 3 (r=-0.26, p=0.009) and 6 months (r=-0.32, p=0.002). Daily bolus and total insulin dose increased at 3 months but were not significantly higher than pre-670G after 6 months of 670G use. We conclude that HCL use in real-life improves glucose control without increasing body weight or insulin dose.

Disclosure

D.A. Giordano: None. J.K. Snell-Bergeon: None. H. Joseph: None. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. H.K. Akturk: Advisory Panel; Self; Sanofi. Research Support; Self; Eli Lilly and Company, MannKind Corporation, REMD Biotherapeutics. Speaker's Bureau; Self; MannKind Corporation.
109-OR: Notch Signaling Controls Islet Architecture and ß-Cell Function in the Developed Pancreas
Authors: BARTOLOME ALBERTO , PAJVANI UTPAL
Published: June 2019

Although β cell dysfunction is a well-appreciated contributor to type 2 diabetes (T2D) pathophysiology, determinants of β cell function are incompletely understood. For instance, disrupted islet architecture is associated with T2D progression in humans and rodent models, but the identity of the molecular elements that govern islet architecture remain mostly unknown. Nevertheless, data suggest that the spatial arrangement of the different cell types that form the endocrine islets influences cell-to-cell communication and β cell function.

The Notch pathway transduces signals between neighboring cells in pancreas development, then thought to be silenced in the developed endocrine islet. However, recent reports have uncovered a maladaptive Notch response in adult β cells in T2D patients and obese rodent models. To test the repercussions of Notch activity, we created β cell-specific gain-of-function mice that express a constitutively-active Notch intracellular domain (β-NICD). β-NICD mice show a profound disorganization of islet architecture, loss of β cell maturity and marked glucose intolerance. Importantly, we generated a second model that allows doxycycline-dependent expression of NICD (β-TetO-NICD), which recapitulates the phenotypes of β-NICD mice, even when NICD is induced in adulthood. Upon doxycycline withdrawal, β-TetO-NICD mice recover markers of β cell maturity, but disrupted islet architecture and glucose intolerance persist in β-TetO-NICD mice as compared to controls. To assess the molecular mechanisms of these findings, we performed unbiased transcriptomic screening of adult islets, which identified differentially expressed pathways that regulate cell-to-cell communication in different systems.

These studies uncover β cell Notch signaling as a novel determinant of islet architecture, and suggest that Notch inhibitors repurposed from oncology pipelines may have potential application to correct obesity-related β cell dysfunction in patients with T2D.

Disclosure

A. Bartolome: None. U. Pajvani: Research Support; Self; Sanofi.

Funding

American Diabetes Association (1-17-PMF-025 to A.B.)
1099-P: Sliding Scale Insulin Use in Noncritical Care Settings: Who Can Slide?
Authors: MIGDAL ALEXANDRA , PASQUEL FRANCISCO J. , GALINDO RODOLFO J. , FAYFMAN MAYA , CARDONA SAUMETH , DAVIS GEORGIA , WANG HEQIONG , UMPIERREZ GUILLERMO E.
Published: June 2019

Despite recommendations of clinical guidelines, sliding scale insulin (SSI) is widely used for the inpatient management of patients with T2D. To understand if there is a population of patients for whom SSI may be an appropriate form of management, we utilized a large database from a single academic institution to define the frequency of SSI usage and determine factors that predict adequate glycemic control with SSI alone in the non-critical care setting. Among 15,348 patients with T2D (28% surgery, 72% medicine), 7,052 (45%) were managed with SSI and 8,296 (55%) with basal insulin. Average admission blood glucose (BG) and HbA1c were lower in patients treated with SSI (154.6±60.3 vs. 191.7±80.8 mg/dl, p<0.001; 7.0±1.5 vs. 8.5±2.1%, p<0.001). Charlson comorbidity score was higher in those treated with basal compared to SSI. Surgical patients were more likely to be treated with SSI than those on medicine services (53% vs. 43%, p<0.001). Hypoglycemia rates were lower with SSI vs. basal insulin (6.9% vs. 14%, p<0.001). Seventy-two percent of patients treated with SSI had an admission BG <180 mg/dl; of them, 93% maintained good glycemic control (mean hospital BG <180 mg/dl). After adjusting for age, gender, BMI, race, Charlson score, and setting (med vs. surg), patients treated with SSI admitted with BG <180 mg/dl had much higher odds of achieving good glycemic control compared to those admitted with BG 180-280 [OR 6.4 (95% CI 5.6, 7.3)] or >280 mg/dl [OR 42.2 (29.5, 60.5)]. Similar results were seen when comparing patients with admission A1c <7% to A1c 7-9% [OR 2.4 (1.9, 2.9)] or A1c >9% [OR 13.3 (8.8, 19.9)].

Conclusion: SSI is used in ~40% of non-critically ill patients, especially among those with mild/moderate hyperglycemia. Most patients with BG <180 mg/dl and A1c <7% treated with SSI maintain good glycemic control (mean hospital BG <180 mg/dl) while hospitalized, suggesting that basal insulin may not be necessary. Further RCT are needed to identify a subpopulation for whom SSI may be appropriate in the hospital.

Disclosure

A. Migdal: None. F.J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc. R.J. Galindo: Advisory Panel; Self; Abbott, Novo Nordisk Inc., Sanofi US. Research Support; Self; Novo Nordisk Inc. M. Fayfman: None. S. Cardona: None. G. Davis: None. H. Wang: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc., Sanofi US.
1104-P: Management of Corticosteroid-Related Hospital Hyperglycemia in the “Real-World”
Authors: PATHAM BHARGAVI , VADHARIYA AISHA , JOHNSON MICHAEL L. , YANDE SOHAM D. , SADHU ARCHANA R.
Published: June 2019

Guidelines recommend basal bolus insulin for inpatient hyperglycemia management based on studies performed in patients with type 2 diabetes without any corticosteroid therapy. However, in the “real-world,” corticosteroid use is common and complicates management. To better understand insulin use in corticosteroid related hyperglycemia, we conducted a large, retrospective study of patients who were: age >18 years, admission >48 hours, administered insulin >75% of admission, AND administered corticosteroids within the first 2 days of admission. Patients receiving IV insulin or no insulin within two days were excluded. Insulin therapy was categorized into 3 groups based on observed prescribing practices: (a) sliding scale (SS, n=481) (b) basal bolus (BB, n=356), (c) Basal plus (B+, n=386). Each group was analyzed for glucose control: days with hypoglycemia (any <70mg/dl), hyperglycemia (mean >180 mg/dl) or euglycemia (no hypo- or hyperglycemia) and clinical outcomes of length of stay (LOS), 30/60-day readmission, and hospital mortality. Patient and provider factors that influence choice of therapy were controlled using propensity score adjusted models.

BB had fewer hyperglycemic days and lower LOS, albeit more hypoglycemia than SS. B+ had higher hyperglycemic and hypoglycemic days than SS. For corticosteroid related hyperglycemia, BB was a superior insulin regimen in reducing hyperglycemia and LOS.

Disclosure

B. Patham: None. A. Vadhariya: None. M.L. Johnson: None. S.D. Yande: None. A.R. Sadhu: None.
1108-P: The Total Basal Dose (TBD) Is about 35% of Total Daily Dose (TDD) and TBD/Weight Is about 0.23U/kg: 144 Subjects Titrated by Continuous Glucose Monitoring (CGM) while under Dietary Control
Authors: KING ALLEN B.
Published: June 2019

The current dosing guidelines suggesting TBD is ~ 50% of TDD and TBD = 0.5 U/kg (in T2DM) were based on uncontrolled studies. We have previously published separate controlled studies in pump-treated type 1 (n=39) and type 2 (n=30), multiple daily dosed-treated type 1 (n=49) and basal insulin only-treated type 2 diabetes (n=29). Herein we report the pooled results from these studies. In all studies the dose was titrated by CGM, the diet was the same (50% carbohydrate:30% fat:20%protein) and one meal/d was omitted to establish basal glucose control (except basal insulin-treated T2DM study in which the evening meal was limited to < 18:00h). Carbohydrate-to-insulin (CIR) was established by adjusting the pre-meal bolus so that the 2-4th h post-meal glucose was within 20% of the pre-meal. The resulting mean 24 h basal glucose of each study varied between 100 to 130 mg/dl. There was no significant difference (p > 0.10) in the mean TBD/TDD% and the mean U/kg between groups. When all subjects were then pooled, the mean TBD/kg was 0.232 U/kg (r = 0.601, n= 144) and the TBD/TDD%, 34.5% (r = 0.894, n=115). The mean CIR, g/U = 314/TDD (r = 0.829, n = 115) and 106/TBD (r = 0.747, n = 115). Basal estimation formulas are the same for T1 and T2DM. Current dosing estimation formulas recommend excessive basal and insufficient bolus insulin.

Disclosure

A.B. King: None.
1116-P: Glycemic Outcomes and Persistence with Basal Insulin and Glucagon-Like Peptide-1 Receptor Agonists among Patients with T2D: Simultaneous vs. Sequential Initiation
Authors: PENG XUEJUN V. , AYYAGARI RAJEEV , LUBWAMA ROBERT , VAN VLEET MELVIN J. , SHI LIZHENG , PRICE-HAYWOOD EBONI G. , HOLLANDER PRISCILLA , FONSECA VIVIAN
Published: June 2019

This real-world retrospective observational analysis was conducted using data from REACHnet, a U.S. regional electronic medical records (EMR) database. Glycemic outcomes after simultaneous or sequential initiation of basal insulin (BI) and a glucagon-like peptide-1 receptor agonist (GLP-1 RA) were evaluated in patients with T2D uncontrolled (A1C ≥7.0%) on oral antidiabetes drugs (OADs). Three patient cohorts were defined: simultaneous BI and GLP-1 RA initiation (Cohort 1; n=109); initiation of BI followed by a GLP-1 RA with a gap of ≤90 days (Cohort 2; n=301); and initiation of BI followed by a GLP-1 RA with a gap of >90 days (Cohort 3; n=459). Baseline mean A1C was very similar across the cohorts (10.3%, 10.3%, and 10.2% in Cohorts 1, 2, and 3, respectively), as were comorbidities including dyslipidemia, hypertension, and obesity. Mean A1C decreased in all 3 cohorts in the 12 months from the date of first BI injection. The greatest mean A1C reductions occurred within 6 months of simultaneous administration (Cohort 1: -2.18%), followed by addition of a GLP-1 RA within 90 days (Cohort 2: -1.77%) and after 90 days (Cohort 3: -1.24%).

Results at 12 months were Cohort 1: -1.66%; Cohort 2: -1.46%; and Cohort 3: -1.32%. Persistence (i.e., non-discontinuation of index treatments) at 12 months was 74.3%, 73.8%, and 80.0% in Cohorts 1, 2, and 3, respectively. Simultaneous initiation resulted in more patients achieving A1C <7.0% at 12 months (33.4%, 24.5%, and 20.9% in Cohorts 1, 2, and 3, respectively); data were statistically significant different between Cohorts 1 and 3 (p=0.0186), but not between Cohorts 1 and 2 or Cohorts 2 and 3.

In conclusion, this retrospective analysis of real-world EMR data in patients with T2D uncontrolled on OADs suggests that simultaneous initiation of BI and a GLP-1 RA resulted in significantly better glycemic control than sequential initiation with a gap of >90 days.

Disclosure

X.V. Peng: Employee; Self; Sanofi. Stock/Shareholder; Spouse/Partner; AbbVie Inc. Stock/Shareholder; Self; AbbVie Inc., Sanofi. R. Ayyagari: Consultant; Self; Sanofi US. Other Relationship; Self; Various pharmaceutical companies. R. Lubwama: Employee; Self; Merck & Co., Inc., Sanofi. M.J. Van Vleet: Employee; Self; Sanofi US. L. Shi: None. E.G. Price-Haywood: None. P. Hollander: Advisory Panel; Self; Novo Nordisk Inc. V. Fonseca: Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Abbott, Asahi Kasei Corporation, Novo Nordisk Inc., Sanofi US, Takeda Pharmaceutical Company Limited. Research Support; Self; Bayer US. Stock/Shareholder; Self; Amgen Inc., BRAVO4HEALTH, Mellitus Health.

Funding

Sanofi U.S.
1120-P: Emotion-Focused CBT Reduces HbA1c Levels in Patients with T2D
Authors: COCCARO EMIL F. , BUSBY ANDREA K. , POTTS TIFFANY M. , PHILIPSON LOUIS H. , DROSSOS TINA
Published: June 2019

A relationship between HbA1c levels and emotional regulation in T1/T2 diabetes has been reported. Accordingly, we developed a 10-session Emotion-Focused Cognitive Behavioral Treatment (EF-CBT) program to address this issue. Twenty patients with T2D were equally randomized to EF-CBT and Treatment As Usual (TAU). While both displayed HbA1c reductions mid-trial, the EF-CBT group showed a larger reduction [-1.23 ± 1.11 (d = 1.11)] compared with TAU [-0.67 ± 1.11 (d = 0.61)]. The difference at end- (d = 0.49), but not mid- (d = 0.03) trial, is likely because most EF-CBT elements are after mid-trial. Correlations between changes in HbA1c levels and in diabetes distress (r = 0.57)/Emotion Regulation (r = -0.52), both p < 0.02), were also observed at end-trial.

Disclosure

E.F. Coccaro: Consultant; Self; Avanir, Inc. Other Relationship; Self; Azevan, Inc. A.K. Busby: None. T.M. Potts: None. L.H. Philipson: Research Support; Self; Jaeb Center for Health Research, Johnson & Johnson. T. Drossos: None.

Funding

Chicago Center for Diabetes Translation Research (P30DK092949); University of Chicago
1122-P: Physiological Effects of Pioglitazone in Ataxia-Telangiectasia
Authors: MCCREIGHT LAURA J. , MARI ANDREA , PEARSON EWAN
Published: June 2019

Aims: Ataxia telangiectasia (A-T) is a rare genetic condition associated with diabetes. OGTT data show that nondiabetic adults with A-T are insulin resistant. ATM-ko mice are glucose intolerant, insulin resistant with abnormal fat distribution, which improve with TZD treatment. The RAMP study assessed the effects of pioglitazone in A-T.

Methods: This open label, non-randomised, crossover study compared 8 nondiabetic people with A-T and 15 healthy controls. Dual tracer mixed meal tests, indirect calorimetry, and adipocyte function were used to assess response to treatment.

Results: Groups were matched for age, BMI and HbA1c. Pioglitazone reduced fasting (61 [IQR 26 - 135] to 28.0 [IQR 20.9 - 110.1] pmol/l, p=0.008) and meal (393 [IQR 275 - 2103] to 252 [IQR 195 - 823], p=0.02) insulin in the A-T group, with unchanged fasting but reduced mean glucose (6.3 [IQR 6.1 - 6.7] to 5.9 [IQR 5.7 - 6.2] mmol/l, p=0.02). Pioglitazone did not affect glucose or insulin in controls. Pioglitazone improved insulin sensitivity in the A-T group, with reduced HOMA-IR (2.19 [IQR 0.96 - 4.14] to 0.97 [IQR 0.76 - 3.54], p=0.023) and increased Matsuda index (2.7 [IQR 1.2 - 5.9] to 5.3 [IQR 1.6 - 7.1], p=0.008). Pioglitazone increased adiponectin in both groups (A-T: 2528 [IQR 2008 - 4887] to 12461 [IQR 4451 - 15843] ng/ml, p=0.008; control 6262 [IQR 4051 - 89940] to 15123 [IQR 9594 - 19384] ng/ml, p=0.001). NEFAs were reduced in A-T (0.25 [IQR 0.22 - 0.28] to 0.18 [IQR 0.14 - 0.20] mmol/l, p=0.016). Pioglitazone increased the fasting respiratory quotient (RQ) in A-T (0.9 [IQR 0.8 - 1.0] to 1.1 [IQR 1.0 - 1.2], p=0.04). A mixed effects model of insulin sensitivity identified a significant gene * drug interaction (p=0.001) between A-T and pioglitazone.

Conclusion: Pioglitazone treatment improved insulin sensitivity and adipocyte function in A-T. Pioglitazone reduced NEFAs and increased RQ, indicating a reduction in fatty acid oxidation. These data suggest that pioglitazone may be an appropriate first line treatment for diabetes in A-T.

Disclosure

L.J. McCreight: None. A. Mari: Consultant; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim International GmbH. E. Pearson: None.

Funding

UK Wellcome Trust (to E.P.)
1126-P: Comparison of Telmisartan vs. Valsartan on Cardiovascular and Renal Biomarkers in 84 Patients with T2DM with Microalbuminuria
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2019

84 T2DM with microalbuminuria (eUACR) >30 aged 18-75 years irrespective of their A1c, on standard glucose, lipid and BP lowering therapy using telmisartan (Tm) or valsartan (Vs) were followed-up for 2 years. 2 groups were identified, Tm group and Vs group. Renal (Cr, eGFR, UACR) and CV (BP, BMI, Lipid profile, hs-CRP) markers were evaluated at 3-6 month intervals for 2 years. NT-ProBNP was measured at the end of 2 years. Patients with history of major surgery, coronary intervention, IHD or hospitalization in last 1 year, eGFR <45, potassium >5.5 were excluded. Data was analyzed using PSPP version 1.0.1 and represented as Mean (SD) and independent sample t-test and paired t-test was used. P value of 0.05 was considered to be significant.

Results: Baseline therapeutic, renal and CV parameters were well matched in both groups. Mean Tm dose was 86.19mg (SD ± 69.63) and Vs 153.33mg (SD ± 83.77). Within Tm group, mean A1c 1.43% (95% CI 0.95-1.92, p-<0.001), SBP 9.19mm (95% CI 2.58-15.80, p-0.008), TC 38.68mg% (95% CI 26.73-50.63, p-<0.001), LDL 28.35 (95% CI 17.14-39.56, p-<0.001), TG 39.15 (95% CI 20.82-57.47, p-<0.001), Cr 10.66 (95% CI 5.62-15.71, p<0.001), non-HDL 49.42 (95% CI 33.79-65.05, p-<0.001), UACR 87.62 (95% CI 17.03-158.21, p-0.016) reduced significantly. Within Vs group, mean A1c 1.09% (95% CI 0.81-1.38, p-<0.001), TC 24.63mg% (95% CI 15.81-33.46, p-<0.001), LDL 16.67 (95% CI 7.07-26.28, p-0.001), TG 59.26 (95% CI 25.10-53.42, p-<0.001), Cr 15.15 (95% CI 9.28-21.02, p-<0.001), non-HDL 42.57 (95% CI 29.77-55.37, p-<0.001) reduced and HDL 5.98 (95% CI 2.81-9.14, p-0.001) increased significantly. At the end of 2 years there was no difference see in any CV or renal parameter between both groups. NT-ProBNP (Tm 149.16 (±153.36) vs. Vs 203.47 (±335.40), p 0.343) remained high in both groups.

Conclusion: Tm is as effective as Vs with respect to control of CV and renal parameters in T2DM patients with microalbuminuria however NT-ProBNP remained elevated in both groups.

Disclosure

V. Gupta: None. V. Teli: None.
1127-P: SGLT2 Inhibition (SGLT2i) Mediated Urinary Glucose Excretion (UGE) Associations with Metabolic and Renal Hemodynamic Parameters
Authors: LYTVYN YULIYA , LYTVYN ANDRIY , MUSCELLI ELZA O. , PERKINS BRUCE A. , CHERNEY DAVID , FERRANNINI ELE
Published: June 2019

The metabolic and hemodynamic correlates of SGLT2i-mediated UGE in patients with diabetes are not well understood. Accordingly, in this post hoc analysis, we measured UGE in 66 T2D, 37 T1D, and 25 nondiabetic (ND) participants under baseline conditions and following treatment with an SGLT2i (empagliflozin, 25 mg/d, EMPA). Measurements were taken during 3 h of fasting and 5 h of a mixed meal absorption (T2D and ND) or under usual clinical conditions in patients with T1D. Fractional glucose excretion (FEGlu) was obtained as the ratio of UGE to the filtered glucose load (=GFR x plasma glucose concentration [G]). In T1D participants only, ERPFPAH and GFRINULIN were measured and intraglomerular pressure (PGLO) estimated.

With EMPA, FEGlu was 38±12% and 46±11% in T2D (fasting and post meal, respectively), 26±11% and 36±8% in ND, and 45±21% in T1D. In the pooled T1D, T2D and ND cohort, overall effect of EMPA on FEGlu was 39±11%; in this model, [G] was a positive determinant (FEGlu=34% at a [G] of 100 mg/dL and 44% at a [G] of 200 mg/dL, r=0.38, p<0.0001), whereas presence of T1D, T2D or ND was not. After adjusting for [G], plasma insulin concentration was also a positive determinant of FeGlu (r=0.12, p=0.01), adding 3% to FEGlu at the mean post meal plasma insulin of 50 µU/mL in T2D and ND; likewise, in T1D, FEGlu was related to the mean daily insulin dose (r=0.41, p<0.01). As described in previous work, in T1D, EMPA decreased ERPF and increased renal vascular resistance (p<0.01). Estimated PGLO was reduced (59.0±6.7 to 56.5±4.6 mmHg, p=0.038), and its change from baseline was associated with a larger increment in FEGlu (r=0.48, p=0.003.

In conclusion, SGLT2i effects on renal glucose reabsorption are consistent across the spectrum of glucose tolerance. Moreover, FEGlu is a function of ambient hyperglycemia and, to a lesser extent, insulinemia. Finally, in T1D, decrements in renal hyperfiltration are related to greater glycosuria, possibly as a function of natriuresis.

Disclosure

Y. Lytvyn: None. A. Lytvyn: None. E.O. Muscelli: 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. E. Ferrannini: None.
1131-P: Endoscopic Duodenal Submucosal Laser Ablation for the Treatment of Type 2 Diabetes Mellitus: Results of First-in-Human Pilot Study
Authors: MRAZ MILOS , MARCOVITCH IDAN , LANKOVA IVANA , KRATOCHVILOVA HELENA , CINKAJZLOVA ANNA , BENES MAREK , KORNER JUDITH , VLASAKOVA ZUZANA , SPICAK JULIUS , PELIKANOVA TEREZIE , HALUZIK MARTIN
Published: June 2019

The duodenum has recently emerged as a key regulator in glucose metabolism via modulation of a complex network of neural and hormonal signals in response to ingested food. DiaGone™ is an endoscopic device which utilizes precisely controlled laser technology to target the duodenal submucosal neural plexi with the aim of improving glucose control by modulating the gastrointestinal neurohumoral axis. Nine subjects (5 males) with obesity (BMI 34.0 ± 4.6 kg/m2) and type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin were included in this first-in-human trial in order to assess the efficacy and safety of DiaGone™. Subjects were instructed to continue with regular diet 24h after the procedure and metformin dose was not changed during the study period. Biochemical and anthropometric parameters were assessed at baseline and 3 and 6 months after the procedure and continuous glucose monitoring (CGM) and a standard liquid meal test were performed at baseline and 3 months after the procedure. DiaGone™ significantly decreased HbA1C from 78.3 ± 13.3 mmol/mol at baseline to 64.9 ± 6.4 mmol/mol and 64.8 ± 7.1 mmol/mol at 3 and 6 months, respectively (p<0.01). Similarly, a decrease in fasting glucose levels was noted (12.4 ± 3.5 vs. 9.5 ± 2.0 vs. 9.7 ± 2.7 mmol/l, p<0.01) with no significant changes in fasting insulin levels. Glucose AUC during the 150 min meal test 3 months after the procedure showed a reduction of 20% from baseline (43,435 vs. 34,096, p<0.01). No significant changes were observed in AUC for insulin. No adverse events related to the procedure or significant changes in weight were reported throughout the 6-month period.

In conclusion, these pilot results suggest that endoscopic duodenal submucosal laser ablation using the DiaGone™ device is associated with improvements in both baseline and postprandial glycemia as well as HbA1C with no significant changes in insulin levels or body weight while having a favorable safety and tolerability profile.

Disclosure

M. Mraz: None. I. Marcovitch: Employee; Self; Digma Medical. I. Lankova: None. H. Kratochvilova: None. A. Cinkajzlova: None. M. Benes: None. J. Korner: Board Member; Self; Digma Medical. Stock/Shareholder; Self; Digma Medical. Z. Vlasakova: None. J. Spicak: None. T. Pelikanova: None. M. Haluzik: None.

Funding

MH CZ - DRO; Institute for Clinical and Experimental Medicine (IN00023001); RVO (VFN64165)
1137-P: Remission of Type 2 Diabetes (T2DM) in 33.6% (51 of 152) Hypogonadal Men Receiving Long-Term Testosterone Therapy for Up to 12 Years in a Real-Life Registry Study
Authors: HAIDER KARIM S. , HAIDER AHMAD , SAAD FARID
Published: June 2019

Background: In the 2018 ADA Standards of Medical Care in Diabetes checking testosterone in men with diabetes was added as new recommendation.

Methods: A registry of hypogonadal men (testosterone ≤12.1 nmol/L) was initiated in 2004 in a urological setting. By 2018, 324 of 823 patients (39%) had T2DM diagnosed and treated in a diabetes center. 152 of these men received testosterone undecanoate (TU) injections 1000 mg/12 weeks (T-group) following an initial 6-week interval. Anthropometric and metabolic parameters were measured at least twice a year and fasting insulin obtained from the diabetes center to calculate HOMA-IR.

Results: Mean follow-up was 7.9, maximum 12 years. 51 patients (33.6%) were in remission at the last measurement. Their average baseline age was 61±4.11 years. HbA1c dropped from 8.6±1.01% at baseline to 5.45±0.18%, fasting glucose from 7.8±1.2 mmol/L to 5.4±0.09 mmol/L. HOMA-IR dropped from 9.76±2.74 to 1.98±0.54. Triglycerides decreased from 3.41±0.57 to 2.18±0.11 mmol/L. Anthropometric parameters: Body weight declined progressively from 112.9±13.2 to 90.2±7.4 kg, waist circumference from 110.7±7.6 to 97.8±4.6 cm. All patients had been on oral antidiabetic medication (metformin) at baseline. 17 patients were on insulin at an average dose of 25.3±5.9 units per day. The average observation time was 124.1±22.7 months (10.3±1.9 years). The average time to discontinuation of diabetes medication was 107.2 months (8.9 years). Medication adherence to TU was 100% as all injections were administered in the urology office and documented.

Discussion: The registry was not designed to study the effects of testosterone on T2DM. Remission of T2DM has not been described in the literature and was unexpected.

Conclusions: Long-term testosterone treatment in hypogonadal men may result in remission of T2DM.

Disclosure

K.S. Haider: Speaker's Bureau; Self; Bayer AG. A. Haider: Research Support; Self; Bayer AG. Speaker's Bureau; Self; Bayer AG. F. Saad: Employee; Self; Bayer AG. Stock/Shareholder; Self; AbbVie Inc., Amgen Inc., Bayer AG.

Funding

Bayer AG
1143-P: Secondary Metformin Monotherapy Failure in Type 2 Diabetes Mellitus Patients
Authors: WEISS TRACEY , IGLAY KRISTY , VERMA PRIYA , RAJPATHAK SWAPNIL , YANG LINGFENG , BLONDE LAWRENCE
Published: June 2019

Clinical guidelines recommend metformin monotherapy (MM) as an initial glucose-lowering therapy for type 2 diabetes (T2D) patients [pts]. While studies have previously reported the incidence of metformin monotherapy failure, there are limited data specifically assessing the rate of “secondary” MM failure (defined as loss of control following initial achievement of glycemic control). The current study sought to characterize and evaluate factors associated with secondary failure among T2D pts on MM in a diverse U.S. population. Using the GE Centricity Electronic Medical Record database, we conducted a retrospective study of T2D pts ≥18 years initiating MM between 1/2013-5/2016 and achieving an HbA1c <7% (index date) within 6 months of initiation. Secondary MM failure was assessed at 6, 12, 18, and 24 months after index date and was defined based on HbA1c ≥7% or by treatment change (therapy switch or add-on intensification). Multivariable logistic regression was used to evaluate the factors associated with secondary MM failure. Of 4,775 pts included, 53.4% were female, the median age was 63 years and median HbA1c at index date was 6.4%. At 6 months, the proportion of pts who experienced MM failure by HbA1c ≥7% was 9.76% and by treatment change was 6.01%. At 12, 18 and 24 months, these proportions (%) were 16.20/8.00, 22.95/9.36, and 28.82/10.68, respectively. Factors positively associated with secondary MM failure (HbA1c ≥7%) at 24 months were male gender, HbA1c at index date and younger age (<65 years). These data suggest that after initially achieving an A1C <7%, a substantial proportion of pts on MM experience secondary failure within a relatively short period of time, with an increasing number experiencing failure within 2 years. Pts controlled on MM may benefit from regular HbA1c testing to ensure timely treatment modification. Further studies assessing whether initial metformin combination therapy would result in more durable glycemic control would also be of value.

Disclosure

T. Weiss: Employee; Self; Merck & Co., Inc. K. Iglay: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. P. Verma: None. S. Rajpathak: None. L. Yang: Employee; Self; Bristol-Myers Squibb Company, Merck & Co., Inc. L. Blonde: Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US.
1152-P: Erbium-Yttrium Aluminum Garnet (YAG) Laser Accelerates Healing in Indolent Diabetic Foot Ulcers
Authors: JOHNSON MATTHEW J. , LAVERY LAWRENCE A.
Published: June 2019

Aim: The objective of the study was to evaluate the effect of the Erbium-Yttrium aluminum garnet (YAG) laser on diabetic foot ulcer that had not responded to standard care.

Methods: We retrospectively evaluated 23 patients with c non-healing diabetic foot ulcers that received at least four weeks of standard wound care, demonstrated poor healing response, and were subsequently treated with YAG laser. We measure the percent wound area reduction (PWAR) for the 4 weeks prior to initiating laser therapy and the PWAR for 4 weeks following the initiation of laser therapy. YAG laser treatment consisted of two components: debridement and re-surfacing. The laser settings were the same for all treatments. We used pair t-test to compare pre versus post wound area reduction.

Results: During the 4-week period prior to the initiation of laser therapy, the average PWAR was -32.1%. During this time, the diabetic foot ulcers increased in area. After treatment with YAG laser, after 4 weeks the average PWAR was 63.5% (p<0.01), 66.7%% of patients had > 50% PAR at 4 weeks and 45.8% of patients healed by 12 weeks.

Conclusion: YAG laser therapy accelerated DFU healing in a cohort of patients with ulcers that had been unresponsive to standard of care therapy.

Disclosure

M.J. Johnson: None. L.A. Lavery: Consultant; Self; Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Medline Industries, Inc. Research Support; Self; Cardinal Health, EO2 Concepts, Integra LifeSciences, MedImmune, Osiris Therapeutics, Inc.
1163-P: Comparison of Glycemic Variability between Gemigliptin and Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Randomized, Active-Controlled, Multicenter, 12-Week Clinical Trial (STABLE II Study)
Authors: HWANG YOU CHEOL , KIM JAE HYEON , KWAK SOO HEON , KIM SANGYONG , WON JONG CHUL , BAE JI CHEOL , KIM HYUN JIN , SUH SUNGHWAN , LEE EUN YOUNG , LEE SUBIN
Published: June 2019

The aim of this study was to evaluate the effect of gemigliptin, a potent and selective dipeptidyl peptidase-4 inhibitor versus dapagliflozin, a sodium glucose co-transporter-2 inhibitor on glycemic variability in patients with type 2 diabetes mellitus (T2DM). This randomized, parallel group, blinded end-point, multicenter, 12-week clinical trial was conducted in 71 patients with T2DM inadequately controlled with metformin alone or drug naïve patients. Subjects were randomized to receive gemigliptin 50mg (N=35) or dapagliflozin 10mg (N=36) daily for 12 weeks. Glycemic variability parameters such as mean amplitude of glycemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) were evaluated during 6-day continuous glucose monitoring at baseline and after 12 weeks of treatment. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. Measures of glycemic control, oxidative stress and inflammation, as well as safety profiles were assessed. Adjusted mean change ± standard error in MAGE after 12 weeks were -27.2 ± 4.4 mg/dL (P<0.001) in the gemigliptin group and -7.9 ± 4.9 mg/dL (P=0.160) in the dapagliflozin group. The between-group comparison showed that gemigliptin group had significantly larger reduction in MAGE compared to dapagliflozin group (-19.2 mg/dL, 95% CI -31.3 to -7.2, P=0.002). Other glycemic variability parameters including SD and CV also showed significantly larger reduction in the gemigliptin group. Glycemic control estimated by HbA1c, fasting glucose and safety profiles were comparable between the two groups.

In conclusion, gemigliptin significantly improved glycemic variability than dapagliflozin with similar glycemic efficacy and safety profiles in patients with T2DM inadequately controlled with metformin alone or drug naïve patients. ClinicalTrials.gov Identifier: NCT03202563.

Disclosure

Y. Hwang: None. J. Kim: None. S. Kwak: None. S. Kim: None. J. Won: None. J. Bae: None. H. Kim: None. S. Suh: None. E. Lee: None. S. Lee: Employee; Self; LG Chem.

Funding

LG Chem, Ltd.
1167-P: Safety and Efficacy of 52 Weeks' Therapy with Hydroxychloroquine (HCQ)—First Anti-inflammatory Drug Approved in India for T2D
Authors: PAREEK ANIL , MEHTA RAVI TEJRAJ , DHARMADHIKARI SHRUTI , NAIDU KUMAR BHASKAR
Published: June 2019

Introduction: This phase 4 study enrolled 600 T2D patients uncontrolled (A1c≥7%) on metformin+SU combination to receive add-on HCQ 400mg for 52 weeks (405 patients have completed 24 weeks and 234 have completed 52 weeks of study till date). Effect on glycemic, lipid and inflammatory parameters was assessed.

Results: Efficacy was assessed in 234 patients completing 52 weeks of study. Patients were divided based on baseline hsCRP (≤3 and >3 mg/L). Enrolled population had more females and they had higher inflammatory load. HCQ significantly reduced glycemic, lipid and inflammatory parameters; with greater reduction in higher inflammatory load group. Similar effect is seen in 405 patients completing 24 weeks of study. Of the 140 AEs, most were GI related (25%), mild in intensity (84%) and unlikely related to HCQ (66%). Ten patients reported hypoglycemia; all were Level 1 as per ADA criteria. Eight NPDR cases were reported, all were mild and 7 were unlikely related to HCQ. Of the 6 SAEs reported, 5 were not related to HCQ. Causality was assessed by study investigators. T2D is characterized by chronic, low-grade inflammation, referred to as metaflammation. HCQ significantly reduced A1c (0.91%) and other glycemic parameters (comparable to other OHAs), with added benefits on lipid and inflammatory markers.

Conclusion: T2D patients have high inflammatory load and HCQ could be effective and well-tolerated option.

Disclosure

A. Pareek: Employee; Self; Ipca Laboratories Ltd. R.T. Mehta: Employee; Self; Ipca Laboratories Ltd. S. Dharmadhikari: Employee; Self; Ipca Laboratories Ltd. K.B. Naidu: Employee; Self; Ipca Laboratories Ltd.

Funding

Ipca Laboratories Limited
1168-P: The Effects of Long-Term Testosterone Therapy on A1c in Men with Co-occurring T2DM
Authors: JENKINS CRAIG , TATE JOSHUA M. , WARDIAN JANA L. , RITTEL ALEX , FOLARON IRENE
Published: June 2019

Approximately 25% of men with type 2 diabetes mellitus (T2DM) have hypogonadotropic hypogonadism. Although there is a paucity of trials evaluating testosterone therapy in relation to T2DM, there have been recent studies highlighting possible additional benefits of its use in men with T2DM. Our study aims to evaluate the effects of long-term testosterone therapy on A1c in men with co-occurring T2DM. We identified 12,125 military beneficiaries with dual diagnoses of T2DM and hypogonadism from 2005-2018. Roughly 10.5% (1,125) met inclusion criteria: testosterone treatment ≥5 years and available pre-treatment and post-treatment clinical values (A1c, serum testosterone, and BMI). Patients were categorized as follows based on testosterone adherence rates: Group 1 (≥75%; n=72), Group 2 (50-74%; n=172), Group 3 (25-49%, n=266), Group 4 (<25%; n=762). All groups showed improvement in BMI over time, although it was more substantial in Group 1. Pre- and post-treatment BMI values were 33.7 kg/m2 vs. 32.8 kg/m2 for Group 1 (-0.93 kg/m2), 33.7 kg/m2 vs. 33.5 kg/m2 for Group 2 (-0.2 kg/m2), 34.1 kg/m2 vs. 33.8 kg/m2 for Group 3 (-0.3 kg/m2), 33.8 kg/m2 vs. 33.4 kg/m2 for Group 4 (-0.4 kg/m2). Pre- and post-treatment A1c values were 6.8% vs. 6.6% for Group 1 (-0.18%), 7% vs. 7.1% for Group 2 (+0.11%), 7% vs. 7.3% in Group 3 (+0.3%), and 7.4% vs. 7.6% in Group 4 (+0.25%). Thus, the A1c improvement in Group 1 was statistically significant when compared to Group 3 (p=0.045) and Group 4 (p=0.047). Despite improvement in BMI for all groups, only Group 1 showed improvement in A1c. This speaks to the potential effect of testosterone on A1c specifically, irrespective of BMI, as evidenced by the glycemic benefit only seen in those with the highest adherence rates.

Disclosure

C. Jenkins: None. J.M. Tate: None. J.L. Wardian: None. A. Rittel: None. I. Folaron: None.
118-OR: Activation of Dopamine Signaling in the Brain Causes HAAF
Authors: DE ABREU ADRIANA VIEIRA , AGRAWAL RAHUL , MEIER ETHAN R. , CHAN OWEN , FISHER SIMON
Published: June 2019

Hypoglycemia-associated autonomic failure (HAAF) is comprised of both a blunted counterregulatory response to hypoglycemia and hypoglycemia unawareness. We previously demonstrated that both these aspects of HAAF can be reversed by treatment with the dopamine receptor antagonist, metoclopramide. These findings suggest that repetitive activation of the dopaminergic system may contribute to HAAF. We now evaluate whether both the blunted counterregulatory response to hypoglycemia and hypoglycemia unawareness are mediated by repeated activation of brain dopaminergic receptors. To test this hypothesis, male Sprague-Dawley rats were randomized to receive either the dopamine receptor agonist, bromocriptine, (Bromo; 20 µg/d) intracerebroventricularly (ICV) for 3 consecutive days or recurrent ICV saline (controls). On the fourth day, all rats underwent either, 1) a hyperinsulinemic (50 mU/kg/min) hypoglycemic (∼50 mg/dl) clamp to assess counterregulation, or 2) had food consumption measured in response to insulin-induced (15 U/kg; SQ) hypoglycemia (∼40 mg/dl) to assess hypoglycemia awareness. In response to hypoglycemia, antecedent Bromo blunted, 1) the epinephrine response by 86%* (see Fig), 2) the glucagon response by 56%§, and 3) hypoglycemia awareness by 37%§, as compared to controls (*p<0.01, §p<0.05). These findings demonstrate that dopaminergic signaling in the central nervous system contributes to the development of HAAF.

Disclosure

A. Vieira de Abreu: None. R. Agrawal: None. E.R. Meier: None. O. Chan: Research Support; Self; Zucara Therapeutics Inc. S. Fisher: None.
1186-P: Lean Women with Polycystic Ovary Syndrome and Insulin Resistance Have Normal Incretin Effect, which Is Unaffected by Metformin Therapy
Authors: VEDTOFTE LOUISE , FOGHSGAARD SIGNE , ZIERAU LOUISE , VILSBØLL TINA , KNOP FILIP K.
Published: June 2019

Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and a high risk of type 2 diabetes. We investigated the incretin effect (IE) and gastrointestinal-mediated glucose disposal (GIGD) in lean women with PCOS and IR, but normal fasting plasma glucose, and whether metformin affects the IE and GIGD in these women.

Ten normoglucose-tolerant, lean women with PCOS and IR (homeostatic model assessment (HOMA-IR) > 1.5) were randomly allocated to receive metformin (500 mg bid) or placebo for 12 weeks interposed by a 6-week wash-out period in a double-blind, cross-over design. The women underwent an OGTT and an isoglycemic intravenous glucose infusion (IIGI) at baseline and at the end of each treatment period. Ten healthy, lean women without PCOS served as controls and underwent one OGTT and one IIGI.

At baseline, the control group and the PCOS group had similar age (25±3 vs. 25±4 years (mean±SD), P=0.91), BMI (22±2 vs. 23±2 kg/m2, P=0.42), fasting plasma glucose (4.8±0.3 vs. 5.0±0.2 mmol/l, P=0.11), GIGD (58±15 vs. 59±12%, P=0.84) and IE (56±15 vs. 51±13%, P=0.45); the PCOS group had higher HOMA-IR (1.8±0.4 vs. 1.0±0.3, P<0.0001) and lower Matsuda index (6±3 vs. 9±2, P=0.03). Compared to placebo, 12 weeks’ metformin treatment had no effect on BMI (P=0.42), fasting plasma glucose (P=0.71), HOMA-IR (P=0.95) and Matsuda index (P=0.52). Compared to baseline, metformin treatment lowered the IE in the PCOS group (-9.2% [-17.8;-0.6] (mean [95% CI])), but the change was not different from the change observed after placebo treatment (0.9% [-8.2;10.1], P=0.11) and metformin treatment tended to lower the GIGD (-9.7 [-21.3; 1.9] vs. 1.9% [-10.6; 14.5], P=0.05).

We conclude that the studied lean women with PCOS and IR have similar IE and GIGD as matched, insulin-sensitive controls and, surprisingly, we observed no effect of metformin on IR, IE or GIGD in these women.

Disclosure

L. Vedtofte: None. S. Foghsgaard: None. L. Zierau: None. T. Vilsbøll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S.

Funding

Augustinus Foundation; A.P. Møller Foundation
1190-P: IFN-Alpha Kinoid: A Promising Vaccine against Type 1 Diabetes Targeting IFN-alpha in NOD Mice
Authors: CAILLOT NOÉMIE , COLAONE FABIEN , BERTRAND ROMAIN , SILVA JENNIFER DA , HAMDI SAMIR , BONNEFOY JONATHAN , LEHUEN AGNES , BOITARD BOITARD F. , GROUARD-VOGEL GÉRALDINE
Published: June 2019

Major elements highlight IFNα implication in type 1 diabetes (T1D) pathogenesis. While there is still no cure for this autoimmune disease, we aimed to evaluate the benefit of IFNα kinoid (IFN-K). This conjugated vaccine consisting of IFNα coupled to Keyhole limpet hemocyanin as a carrier protein elicits the production of polyclonal anti-IFNα neutralizing antibodies and has shown beneficial effects in a recent phase IIb trial in lupus (NCT02665364). Three independent experiments in NOD mice were performed to evaluate the activity of anti-IFNα neutralizing antibodies, conveyed either by maternal transfer or by passive or active immunization. Glycemia was monitored by a glucometer, neutralizing antibodies by the virus-induced cytopathic effect assay and H&E pancreas sections were evaluated in blind. In the first study, we compared T1D incidence in offsprings from IFN-K or KLH immunized mothers with sentinels. In the second study, mice were passively immunized with purified total IgG from sera collected in NOD mice immunized with IFN-K or KLH. Finally, active immunization was performed with IFN-K, KLH or PBS in combination with a squalene oil-in-water adjuvant. Mice were immunized at 5, 10 or 15 weeks of age. Anti-IFNα neutralizing antibodies were effectively conveyed from mothers to offspring, and levels decreased over time to completely disappear by month 3. In progeny from IFN-K immunized mice, despite transient and low amount of neutralizing antibodies, insulitis was decreased compared to control groups and T1D onset was delayed. In the second study, long-lasting administrations of total IgG comprising anti-IFNα neutralizing antibodies conferred protection towards T1D development, while total IgG from KLH-immunized mice did not. Finally, diabetes incidence was reduced when IFN K immunization started at week 10 of age. These different elements point out the need to neutralize IFNα during NOD lifetime to prevent T1D, and encourage us to evaluate IFN-K in newly diagnosed T1D patients.

Disclosure

N. Caillot: None. F. Colaone: None. R. Bertrand: None. J. Da Silva: None. S. Hamdi: None. J. Bonnefoy: None. A. Lehuen: Board Member; Spouse/Partner; Inatheris. Consultant; Self; Neovacs. B.F. Boitard: None. G. Grouard-Vogel: None.