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Hyperinsulinemia improves ischemic LV function in insulin resistant subjects.

Patrick M Heck¹, Stephen P Hoole, Sadia N Khan

¹Cardiovascular Medicine, ACCI, Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.

Cardiovascular Diabetology

|June 26, 2010

Summary

Metabolic manipulation using a hyperinsulinemic euglycemic clamp (HEC) improved left ventricular (LV) function during stress tests in patients with coronary artery disease and insulin resistance (IR). This approach enhances myocardial glucose utilization, offering a promising therapeutic strategy for IR.

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Area of Science:

Cardiology
Metabolic Research
Cardiovascular Physiology

Background:

Glucose is a more efficient energy source than free fatty acids (FFA) for ATP production.
Insulin resistance (IR) is associated with elevated FFA levels and reduced myocardial glucose uptake, potentially exacerbating ischemic conditions.
Left ventricular (LV) function may be compromised in patients with IR under stress.

Purpose of the Study:

To investigate the impact of metabolic manipulation via hyperinsulinemic euglycemic clamp (HEC) on LV performance during dobutamine stress echocardiography (DSE).
To determine if HEC improves LV function in patients with coronary artery disease (CAD) and IR.
To compare the effects of HEC on LV function between insulin-sensitive (IS) and insulin-resistant (IR) groups.

Main Methods:

24 subjects with normal LV function and CAD underwent two DSEs.
One DSE was preceded by HEC, involving insulin infusion and variable dextrose to maintain euglycemia.
LV function was assessed using tissue Doppler imaging to measure peak systolic velocities (Vs) and LV ejection fraction (EF) at each stress stage.

Main Results:

HEC successfully suppressed FFAs and increased myocardial glucose utilization.
LV performance significantly improved post-HEC, evidenced by increased EF and peak Vs in ischemic segments.
The improvement in LV function was more pronounced in the IR group compared to the IS group.

Conclusions:

Hyperinsulinemic euglycemic clamp-induced increase in myocardial glucose use enhances LV function under stress in patients with CAD and IR.
Targeting cardiac metabolism in individuals with IR presents a potential therapeutic avenue.
Metabolic modulation strategies may be beneficial for improving cardiac function in at-risk populations.