Background: Insulin-induced hypoglycemia, the most common adverse event in people with diabetes treated with insulin, is associated with increased risk of cardiovascular events. The effect of hypoglycemia on cardiac function has not yet been fully clarified. Our aim was to investigate the effect of hypoglycemia on left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) in people with type 1 diabetes (T1DM) and in healthy controls (HC).

Methods: We enrolled 15 adults with T1DM (M/F 9/6, age 47±19 years, HbA1c 7.9±2.9%, diabetes duration 22.5±12.6 years) and 14 HCs (M/F 7/7, age 39±17 years). All participants underwent a hyperinsulinemic normoglycemic (5.3±0.4 mmol/L, 30 min) hypoglycemic (2.8±0.5 mmol/L, 60 min) glucose clamp. At baseline and approximately 30 min into the hypoglycemic phase (steady-state), a cardiac ultrasound was performed (by the same person), for later analysis.

Results: All participants had sinus rhythm at baseline and none developed arrhythmias during hypoglycemia. We found no difference between T1DM and HC for LVEF measured at baseline. In response to hypoglycemia, LVEF increased from 58.1±2.6% at baseline to 63.7±4.0% in the T1DM group (p<0.0005) and from 58.0±3.8% to 64.7±2.4%, (p<0.005) in the HC group. GLS was unchanged (-20.9±1.5% to -21.3±3.5% (p=0.800)) in the T1DM group, but a numerical decrease from -19.6±3.0% to -22.0±2.7% (p=0.084) was seen in the HC. Age did not modulate the effect of hypoglycemia on LVEF or GLS.

Conclusion: An event of hypoglycemia increases the LVEF significantly in people with diabetes. Presumably due to the catecholamines chronotropic, inotropic and peripheral contracting effect. The result of this would be increased cardiac output, increased oxygen consumption and metabolism and thereby increased load on the heart. This may contribute to explain the link between hypoglycemia and cardiovascular disease.

Disclosure

T. W. Fabricius: None. C. E. Verhulst: None. M. Wienberg: None. A. L. Duijnhouwer: None. P. L. Kristensen: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. B. E. De galan: Research Support; Self; Novo Nordisk. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding

Innovative Medicines Initiative 2 Joint Undertaking (777460); European Union Horizon 2020 Research and Innovation Program; European Federation of Pharmaceutical Industries and Associations; T1D Exchange; JDRF; International Diabetes Federation; The Leona M. and Harry B. Helmsley Charitable Trust

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