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. 2025 May;27(5):2768-2776.
doi: 10.1111/dom.16283. Epub 2025 Mar 5.

Effects of insulin-induced hypoglycaemia on cardiac function in people with type 1 and type 2 diabetes and people without diabetes

Therese Wilbek Fabricius  1   2 , Clementine Verhulst  3 , Cecilie Hornborg Svensson  1 , Malene Wienberg  4 , Anthonie L Duijnhouwer  5 , Cees J Tack  3 , Peter L Kristensen  1   6 , Bastiaan E de Galan  3   7   8 , Ulrik Pedersen-Bjergaard  1   6 ; Hypo‐RESOLVE consortium
Affiliations

Effects of insulin-induced hypoglycaemia on cardiac function in people with type 1 and type 2 diabetes and people without diabetes

Therese Wilbek Fabricius et al. Diabetes Obes Metab. 2025 May.

Abstract

Aims: Cardiovascular disease is the most common complication and cause of death in people with diabetes. Hypoglycaemia is independently associated with the development of cardiovascular complications, including death. The aim of this study was to assess changes in cardiac function and workload during acute hypoglycaemia in people with and without diabetes and to explore the role of diabetes type, magnitude of the adrenaline response, and other phenotypic traits.

Materials and method: We enrolled people with type 1 diabetes (n = 24), people with insulin-treated type 2 diabetes (n = 15) and controls without diabetes (n = 24). All participants underwent a hyperinsulinaemic-normoglycaemic-(5.3 ± 0.3 mmol/L)-hypoglycaemic (2.8 ± 0.1 mmol/L)-glucose clamp. Cardiac function was assessed by echocardiography, with left ventricular ejection fraction (LVEF) as the primary endpoint.

Results: During hypoglycaemia, LVEF increased significantly in all groups compared to baseline (6.2 ± 5.2%, p < 0.05), but the increase was significantly lower in type 1 diabetes compared to controls without diabetes (5.8 ± 3.4% vs. 9.4 ± 5.0%, p = 0.03, 95% CI difference: -5.0, -0.3). In people with type 1 diabetes, ΔLVEF was inversely associated with diabetes duration (β: -0.16, 95% CI: -0.24, -0.53, p = 0.001) and recent exposure to hypoglycaemia (β: -0.30, 95% CI: -0.53, -0.07, p = 0.015). Hypoglycaemia also increased global longitudinal strain (GLS) in controls without diabetes (p < 0.05), but this did not occur in the two diabetes subgroups (p > 0.10).

Conclusions: Hypoglycaemia increased LVEF in all groups, but the increase diminished with longer disease duration and prior exposure to hypoglycaemia in type 1 diabetes, suggesting adaptation to recurrent hypoglycaemia. The increment in GLS observed in controls was blunted in people with diabetes. More research is needed to determine the clinical relevance of these findings.

Keywords: diabetes complications; heart failure; hypoglycaemia; type 1 diabetes; type 2 diabetes.

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Conflict of interest statement

TWF has been employed by Novo Nordisk after the completion of the study. CV, MW, ALD and CHS: none. PLK has received lecture fees from AstraZeneca, Sanofi, and Novo Nordisk. BG has received research support from Novo Nordisk. UP‐B has served on advisory boards for Novo Nordisk, Sanofi‐Aventis, and Vertex and has received lecture fees from Novo Nordisk and Sanofi‐Aventis.

Figures

FIGURE 1
FIGURE 1
Glucose levels during the glucose clamp.
FIGURE 2
FIGURE 2
Cardiac function results of baseline and hypoglycaemia per subgroup for left ventricular ejection fraction (A), global longitudinal strain (B), and E/e′ (C). Data are shown in a box, representing 25th to 75th percentiles and whiskers with 10th and 90th percentiles. *p < 0.05 and **p < 0.001.
See this image and copyright information in PMC

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