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Randomized Controlled Trial
. 2023 Jun 2:14:1186680.
doi: 10.3389/fendo.2023.1186680. eCollection 2023.

Non-severe hypoglycemia in type 1 diabetes: a randomized crossover trial comparing two quantities of oral carbohydrates at different insulin-induced hypoglycemia ranges

Nadine Taleb  1   2   3 , Véronique Gingras  1   4   5 , Ran Cheng  1   3 , Valérie Parent  1 , Virginie Messier  1 , Danijela Bovan  1 , Azadeh Shohoudi  1 , Anne-Sophie Brazeau  6   7 , Rémi Rabasa-Lhoret  1   3   5   7
Affiliations
Randomized Controlled Trial

Non-severe hypoglycemia in type 1 diabetes: a randomized crossover trial comparing two quantities of oral carbohydrates at different insulin-induced hypoglycemia ranges

Nadine Taleb et al. Front Endocrinol (Lausanne). .

Abstract

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.

Keywords: hypoglycemia treatment guidelines; non-severe hypoglycemia; oral carbohydrate; subcutaneous insulin injection; type 1 diabetes.

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Conflict of interest statement

RR-L has received research grants from Astra-Zeneca, Eli Lilly, Merck, Novo-Nordisk, and Sanofi-Aventis. He has been a consultant or member of advisory panels of Abbott, Amgen, Astra-Zeneca, Boehringer, Carlina Technology, Eli Lilly, Janssen, Medtronic, Merck, Neomed, Novo-Nordisk, Roche, Sanofi-Aventis, and Takeda. He has received honoraria for conferences by Abbott, Astra-Zeneca, Eli Lilly, Janssen, Medtronic, Merck, Novo-Nordisk, and Sanofi-Aventis. He has received in kind contributions related to closed-loop technology from Animas, Medtronic, and Roche. He also benefits from unrestricted grants for clinical and educational activities from Eli Lilly, Lifescan, Medtronic, Merck, Novo Nordisk, and Sanofi. He holds intellectual property in the field of type 2 diabetes risk biomarkers, catheter life, and the closed-loop system. RR-L and VM received purchase fees from Eli Lilly in relation with closed-loop technology. NT has received consultant fees from Dexcom, Eli Lilly, and Viatris. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Trial flowchart.
Figure 2
Figure 2
Plasma glucose profiles starting at 60 min before hypoglycemia treatment level was reached until 60 min after CHO consumption for the four trial arms.
See this image and copyright information in PMC

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