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

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

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.

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Diabetes Mellitus, Type 1* / blood
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 1* / physiopathology
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / physiopathology
  • Diabetic Cardiomyopathies* / physiopathology
  • Echocardiography
  • Female
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemia* / complications
  • Hypoglycemia* / physiopathology
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Insulin* / adverse effects
  • Male
  • Middle Aged
  • Stroke Volume / drug effects
  • Ventricular Function, Left / drug effects

Substances

  • Insulin
  • Hypoglycemic Agents
  • Blood Glucose