Virginie Messier's research while affiliated with Institut de recherches cliniques de Montréal and other places

Introduction & Objective: To explore the association between using an automated insulin delivery (AID) system and physical activity (PA) frequency among people with type 1 diabetes (T1D). Methods: Cross-sectional study using the Canadian BETTER T1D registry. Inclusion criteria: T1D; aged ≥ 18 y/o; reported PA with a validated questionnaire (Canadian Community Health Survey). “PA” includes organized or unorganized sports, fitness or recreational PA lasting ≥ 10 consecutive minutes; “moderate to vigorous PA” is PA that makes participants sweat at least a little and breathe harder. Regression models (with and without adjustment for imbalanced variables - sex, age, T1D duration) were used to compare PA frequency among treatment options, with pairwise comparison between the AID group and each of the other groups. Results: Among 1213 participants, the AID group and pump+continuous glucose monitoring (CGM) group had a similar frequency of PA and moderate to vigorous PA, but these levels were higher in the AID group than those of injections+CGM and no-CGM groups (Table). Conclusion: In real-world settings, compared with injections+CGM or No-CGM, AID users within the BETTER T1D registry have a higher frequency of PA and moderate to vigorous PA. However, these frequencies are similar between AID and pump+CGM users. Disclosure Z. Wu: None. J.E. Yardley: Speaker's Bureau; Dexcom, Inc. Research Support; LifeScan Diabetes Institute. T. Chahal: None. C. Guédet: None. V. Messier: None. C. Grou: None. V. Boudreau: None. A. Brazeau: Other Relationship; Dexcom, Inc. Research Support; Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF), Diabète québec, Fonds de recherche du Québec en Santé. R. Rabasa-Lhoret: Other Relationship; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc. Research Support; Diabetes Canada. Other Relationship; Eli Lilly and Company. Research Support; Cystic Fibrosis Canada, Canadian Institutes of Health Research, FFRD - Fondation Francophone pour la Recherche du Diabète. Other Relationship; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Other Relationship; Novo Nordisk, GlaxoSmithKline plc. Consultant; HLS Therapeutics Inc., Insulet Corporation. Speaker's Bureau; CPD Networks. Other Relationship; Medtronic. Consultant; Pfizer Inc. Speaker's Bureau; Tandem Diabetes Care, Inc. Other Relationship; Sanofi. Speaker's Bureau; Vertex Pharmaceuticals Incorporated. Research Support; SFD - Société Francophone du Diabète. Funding Canadian Institutes of Health Research (JT1-157204) and Juvenile Diabetes Research Foundation (4-SRA-2018-651-Q-R)

Background: Guidelines recommend treating non-severe (NS) hypoglycemia with 15g carbohydrates (CHO) at 15minutes intervals when blood glucose (BG) falls below 72 mg/dL. No specific recommendations exist for people living with type 1 diabetes (PwTID) using continuous glucose monitoring (CGM) despite known time delays between BG and CGM values. Objective: to assess CGM data corresponding to BG values used for NS hypoglycemia management. Methods: Secondary analysis of the REVERSIBLE trial (accepted in Diabetes Care); three arms open-label crossover study assessing the efficacy of 16g oral CHO for preventing NS hypoglycemia (insulin induced) at different BG levels: <72 mg/dL (control using 15 rule), ≤80mg/dL or ≤90 mg/dL. CGM data (Dexcom G6® ) were compared to BG to assess mean absolute relative difference (MARD) at time of CHO intake. Results: Participants (n=29) were 52% male, 46.8±16.3 y.o., BMI 26.4±3.9 kg/m2, diabetes duration 26.2±15.9 years, A1c 53.4±15.5 mmol/mol and 62% insulin pump users. BG levels corresponded to higher Dexcom values for all arms at time of CHO intake (p<0.001). Participants with hypoglycemia %, BG vs. dexcom values (mean [95% CI]) and MARD were as follows: for <72 mg/dL arm, 100% participants, 64.0 [62.0-66.0] mg/dL vs. 85.5 [76.0-95.0] mg/dL, MARD 34.4 [18.1-50.6] %; for ≤80 mg/dl arm, 86% participants, 72.7 [70.4-74.9] vs. 93.1 [84.3-102.0] mg/dL, MARD 28.2 [17.1-39.3] % ; for ≤90 mg/dl arm, 34% participants; 82.8 [81.2- 84.4] vs. 99.5 [93.6-105.3] mg/dL, MARD 20.3 [13.4-27.1]. No significant rebound hyperglycemia (BG>180 mg/dl) was observed within the first hour for all arms. Conclusion: When using CGM, PwTID may need to treat NS hypoglycemia at a higher threshold than the 72mg/dl without increasing rebound hyperglycemia risks. Research is warranted to determine optimal CGM level for management and prevention of NS hypoglycemia in free living settings. Disclosure S. Al-Mahayni: None. R. Cheng: Other Relationship; Novo Nordisk. Z. Wu: None. V. Messier: None. A. Brazeau: Other Relationship; Dexcom, Inc. Research Support; Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF), Diabète québec, Fonds de recherche du Québec en Santé. R.P.R. Rabasa-Lhoret: Other Relationship; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc. Research Support; Diabetes Canada. Other Relationship; Eli Lilly and Company. Research Support; Cystic Fibrosis Canada, Canadian Institutes of Health Research, FFRD - Fondation Francophone pour la Recherche du Diabète. Other Relationship; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Other Relationship; Novo Nordisk, GlaxoSmithKline plc. Consultant; HLS Therapeutics Inc., Insulet Corporation. Speaker's Bureau; CPD Networks. Other Relationship; Medtronic. Consultant; Pfizer Inc. Speaker's Bureau; Tandem Diabetes Care, Inc. Other Relationship; Sanofi. Speaker's Bureau; Vertex Pharmaceuticals Incorporated. Research Support; SFD - Société Francophone du Diabète. N. Taleb: Other Relationship; Dexcom, Inc. Consultant; Viatris Inc. Other Relationship; Novo Nordisk. Funding Secondary analysis (primary study supported by Funding: Juvenile Diabetes Research Foundation (4-SRA-2018-651-Q-R) and CIHR/SPOR (JT1-157204).

OBJECTIVE Current guidelines recommend initiating treatment for nonsevere (NS) hypoglycemia with 15 g carbohydrates (CHO) at 15-min intervals when blood glucose (BG) reaches <70 mg/dL (3.9 mmol/L). Despite this recommendation, NS hypoglycemia management remains challenging for individuals living with type 1 diabetes (T1D). We aimed to assess the efficacy of 15 g CHO at higher BG levels. RESEARCH DESIGN AND METHODS A total of 29 individuals with T1D participated in an open-label crossover study. After an inpatient subcutaneous insulin-induced decrease in BG in the fasting state, 16 g CHO was administered orally at a plasma glucose (PG) of <70 (3.9), ≤80 (4.5), or ≤90 mg/dL (5.0 mmol/L). The primary outcome was time spent in hypoglycemia (<70 mg/dL) after initial CHO intake. RESULTS When comparing the <70 (control) with the ≤80 and ≤90 mg/dL treatment groups, 100 vs. 86 (P = 0.1201) vs. 34% (P < 0.0001) of participants reached hypoglycemia, respectively. These hypoglycemic events lasted 26.0 ± 12.6 vs. 17.9 ± 14.7 (P = 0.026) vs. 7.1 ± 11.8 min (P = 0.002), with a PG nadir of 56.57 ± 9.91 vs. 63.60 ± 7.93 (P = 0.008) vs. 73.51 ± 9.37 mg/dL (P = 0.002), respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥70 mg/dL), compared with 52% in the ≤80 mg/dL group and 31% in the ≤90 mg/dL group, with no significant rebound hyperglycemia (>180 mg/dL) within the first hour. CONCLUSIONS For some impending NS hypoglycemia episodes, individuals with TID could benefit from CHO intake at a higher BG level.

Background: Current guidelines recommend initiating the treatment of non-severe (NS) hypoglycemia with 15g of carbohydrates (CHO) at 15 minutes intervals when blood glucose (BG) reaches <72 mg/dl. Despite this recommendation, NS hypoglycemia management remains challenging for people living with type 1 diabetes (pwT1D) and more optimal treatment strategies are required. We aim to assess the efficacy of 15g of CHO at higher treatment thresholds. Methods: The REVERSIBLE Trial is an open-label, randomized, three interventions x three periods cross-over study. Following inpatient insulin-induced decrease in BG, 16g of oral carbohydrates is administered at a plasma glucose threshold of <72 mg/dl, ≤81 mg/dl or ≤90 mg/dl. The primary outcome is the time (in minutes) spent in hypoglycemia (<72 mg/dl) after the initial correction. Results: Participants (n=29) characteristics are 52% male, 46.8±16.3 years old, BMI of 26.4±3.9 kg/m2, diabetes duration of 26.2±15.9 years, A1c of 53.4±15.5 mmol/mol and 62% insulin pump users. When comparing <72 mg/dl (control) to ≤81 mg/dl and ≤90 mg/dl treatment thresholds, 100% vs. 86% (p=0.1201) vs. 34% (p<0.0001) of participants had hypoglycemia. These hypoglycemic events lasted 26.0±12.6 vs. 17.9±14.7 (p=0.026) vs. 7.1±11.8 (p=0.002) minutes, with a blood glucose nadir of 56.5±9.9 vs. 63.5±7.9 (p=0.008) vs. 73.4±9.7 mg/dl (p=0.002) respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥ 72 mg/dl) compared to 52% in the ≤81 mg/dl group and 31% in the ≤90 mg/dl group with no significant rebound hyperglycemia (>180mg/dl) within the first hour. Conclusion: Compared with <72 mg/dl, consuming 16g of oral carbohydrates at ≤81 mg/dl and ≤90 mg/dl shortened the time spent in hypoglycemia, lessened the glucose nadir and reduced the need for repetitive treatments. For some NS episodes, pwT1D could benefit from CHO intake at a higher BG threshold. Disclosure R.Cheng: None. N.Taleb: Consultant; Viatris Inc. Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)

Introduction: LADA is known for a slow progression of autoimmune destruction of beta-cells with cases that span a spectrum between classic T1D and T2D phenotypes. To date, lacking a good understanding of LADA has prohibited the release of specific clinical practice guidelines and subsequently an optimal management. Methodology: Cross-sectional analysis of online clinical questionnaires in the Canadian BETTER registry; participants can specify having received a diagnosis of LADA or T1D. Data was analyzed for the first 1464 participants; 131 (9%) reported LADA and 1333 (91%) T1D. Results: At registration; LADA vs T1D were 49 ± 13 y.o. vs 42 ± 15 y.o; 61% vs. 62% females; diabetes duration 10 ± 9 vs. 24 ± 15 years. LADA vs. T1D were older at diagnosis (39 ± 12 vs. 18 ± 12 years old; p<0.001), only half started insulin in first year of diagnosis (52 vs. 97%; p<0.001), more often reported a family history of T1D (46 vs. 32%; p=0.001). For comparable glycemic control (HbA1c < 8.6 mmol/l, <7%, 38 vs. 32%), fewer cases with LADA reported at least an episode in last month of level II hypoglycemia <54 mg/dL (3.0mmol/L) 63% vs. 77%; p= 0.004, severe hypoglycemia rates were 8% vs. 12%, p=0.15. Diabetes related hospitalizations were 10% in LADA vs. 6%, p=0.11, insulin pumps and glucagon were less used in LADA. In a matched analysis for diabetes duration and gender (1:1), glycemic control was still statistically comparable in LADA vs. T1D (HbA1c <7%: 38 vs 35%, p=0.12) as well as rates of nephropathy (6% vs. 11%, p=0.22), neuropathy (12% vs. 7%, p=0.23) and retinopathy (6% vs. 9%, p=0.07) yet with more cardiovascular disease (5% vs. 2%; p=0.02) and less coeliac disease (3 vs. 5%; p=0.001). Data analysis of 3000 participants is ongoing in early 2023. Conclusion: Reported differences may impact LADA management. This study sets the stage for building a prospective Canadian cohort of LADA to undergo deep phenotyping, genotyping and interventional trials. Disclosure M.Issa: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. S.Haag: Other Relationship; Omnipod. A.Roy-fleming: None. V.Messier: None. N.Taleb: Consultant; Viatris Inc.

Introduction: We aim to assess the difference between open-source do-it-yourself (DIY) and commercial automated insulin delivery (AID) systems in patient-reported outcomes (PRO) of adults with type 1 diabetes (T1D). Methods: Analysis from a prospective, non-inferiority, non-randomized, parallel-cohort study involving 78 non-pregnant adults with T1D, AID users ≥3 months and living in Canada. Participants (25 DIYAID and 53 commercial AID users, 60.3% females, mean age 41.2±14.6 years, mean T1D duration 27.0±14.7 years, median [Q1, Q3] duration of AID use 15.6 [7.8, 27, 4] months, mean HbA1c 6.7±0.7%, median time in range [TIR 70-180 mg/dl] 74.3% [66.8, 81.0]) completed the following validated PRO questionnaires: Diabetes Distress Scale (DDS, high distress level defined as >2.0), Diabetes Treatment Satisfaction Questionnaire (DTS-Q), An Audit of Diabetes-Dependent Quality of Life (ADD-QoL), Hypoglycemia Fear Score II (HFS-II, fear of hypoglycemia defined as scoring ≥3 in any worry subscale item), Pittsburgh Sleep Quality Index (PSQI, poor sleep defined as >5), Clarke and Gold score (hypoglycemia unawareness defined as either score ≥4). Results: DIYAID users reported better sleep quality (66.7% vs 33.3%, p=0.02) and lower HFS-II worry subscale score (28.2 vs 33.2, p=0.03) than commercial AID users, but results did not remain significant after adjusting for sex, age, level of education, T1D and AID use duration, HbA1c, and TIR. The two groups were otherwise comparable in other PROs. Overall, one third of participants reported diabetes distress, 88.3% reported poor sleep, 20.8% reported impaired hypoglycemia awareness and 80.5% reported fear of hypoglycemia. Conclusion: Similar broad QoL and other PROs were observed between DIYAID and commercial AID users, with a persistent and significant diabetes burden for all, despite advanced diabetes technology use and optimal glycemic management. Disclosure M.Lebbar: None. Z.Wu: Other Relationship; Eli Lilly and Company. A.C.Bonhoure: Consultant; Dexcom, Inc. V.Messier: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding Canadian Institutes of Health Research (148464)

Aims Non-severe hypoglycemia (NS-H) is challenging for people living with type 1 diabetes (PWT1D) and often results from relative iatrogenic hyper-insulinemia. Current guidelines recommend a one-size-fits-all approach of 15–20 g of simple carbohydrates (CHO) every 15 min regardless of the triggering conditions of the NS-H event. We aimed to test different amounts of CHO to treat insulin-induced NS-H at various glucose ranges. Methods This is a randomized, four-way, crossover study involving PWT1D, testing NS-H treatment outcomes with 16 g vs. 32 g CHO at two plasma glucose (PG) ranges: A: 3.0–3.5 mmol/L and B: <3.0 mmol/L. Across all study arms, participants consumed an additional 16 g of CHO if PG was still <3.0 mmol/L at 15 min and <4.0 mmol/L at 45 min post-initial treatment. Subcutaneous insulin was used in a fasting state to induce NS-H. Participants had frequent venous sampling of PG, insulin, and glucagon levels. Results Participants ( n = 32; 56% female participants) had a mean (SD) age of 46.1 (17.1) years, had HbA1c at 54.0 (6.8 mmol/mol) [7.1% (0.9%)], and had a diabetes duration of 27.5 (17.0) years; 56% were insulin pump users. We compared NS-H correction parameters between 16 g and 32 g of CHO for range A, 3.0–3.5 mmol/L ( n = 32), and range B, <3.0 mmol/L ( n = 29). Change in PG at 15 min for A: 0.1 (0.8) mmol/L vs. 0.6 (0.9) mmol/L, p = 0.02; and for B: 0.8 (0.9) mmol/L vs. 0.8 (1.0) mmol/L, p = 1.0. Percentage of participants with corrected episodes at 15 min: (A) 19% vs. 47%, p = 0.09; (B) 21% vs. 24%, p = 1.0. A second treatment was necessary in (A) 50% vs. 15% of participants, p = 0.001; (B) 45% vs. 34% of participants, p = 0.37. No statistically significant differences in insulin and glucagon parameters were observed. Conclusions NS-H, in the context of hyper-insulinemia, is difficult to treat in PWT1D. Initial consumption of 32 g of CHO revealed some advantages at the 3.0–3.5 mmol/L range. This was not reproduced at lower PG ranges since participants needed additional CHO regardless of the amount of initial consumption. Clinical trial registration ClinicalTrials.gov , identifier NCT03489967.