Effect of acute hyperglycemia on left ventricular contractile function in diabetic patients with and without heart failure: two randomized cross-over studies

PLoS One. 2013;8(1):e53247. doi: 10.1371/journal.pone.0053247. Epub 2013 Jan 8.


Background: It is unknown whether changes in circulating glucose levels due to short-term insulin discontinuation affect left ventricular contractile function in type 2 diabetic patients with (T2D-HF) and without (T2D-nonHF) heart failure.

Materials and methods: In two randomized cross-over-designed trials, 18 insulin-treated type 2 diabetic patients with (Ejection Fraction (EF) 36 ± 6%, n = 10) (trial 2) and without systolic heart failure (EF 60 ± 3%, n = 8) (trial 1) were subjected to hyper- and normoglycemia for 9-12 hours on two different occasions. Advanced echocardiography, bicycle exercise tests and 6-minute hall walk distance were applied.

Results: Plasma glucose levels differed between study arms (6.5 ± 0.8 mM vs 14.1 ± 2.6 mM (T2D-HF), 5.8 ± 0.4 mM vs 9.9 ± 2.1 mM (T2D-nonHF), p<0.001). Hyperglycemia was associated with an increase in several parameters: maximal global systolic tissue velocity (Vmax) (p<0.001), maximal mitral annulus velocity (S'max) (p<0.001), strain rate (p = 0.02) and strain (p = 0.05). Indices of increased myocardial systolic contractile function were significant in both T2D-HF (Vmax: 14%, p = 0.02; S'max: 10%, p = 0.04), T2D-nonHF (Vmax: 12%, p<0.01; S'max: 9%, p<0.001) and in post exercise S'max (7%, p = 0.049) during hyperglycemia as opposed to normoglycemia. LVEF did not differ between normo- and hyperglycemia (p = 0.17), and neither did peak exercise capacity nor catecholamine levels. Type 2 diabetic heart failure patients' 6-minute hall walk distance improved by 7% (p = 0.02) during hyperglycemia as compared with normoglycemia.

Conclusions: Short-term hyperglycemia by insulin discontinuation is associated with an increase in myocardial systolic contractile function in type 2 diabetic patients with and without heart failure and with a slightly prolonged walking distance in type 2 diabetic heart failure patients. (Clinicaltrials.gov identifier NCT00653510).

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Echocardiography
  • Female
  • Heart Failure, Systolic / blood
  • Heart Failure, Systolic / complications*
  • Heart Failure, Systolic / physiopathology
  • Heart Ventricles / physiopathology*
  • Hemodynamics
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / complications*
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Male
  • Middle Aged
  • Myocardial Contraction
  • Ventricular Function, Left
  • Walking


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin

Associated data

  • ClinicalTrials.gov/NCT00653510

Grant support

This study is supported by grants from the Danish Heart Foundation (R68-A2122-B983), by a grant from Food, Obesity, and Overt Cardiovascular Disease – The FOOD study group (jr. nr. 3304-FSE-06-0505-4) and Aarhus University. The authors have no disclosures. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.