Hyperinsulinemia improves ischemic LV function in insulin resistant subjects.
BACKGROUND
Glucose is a more efficient substrate for ATP production than free fatty acid (FFA). Insulin resistance (IR) results in higher FFA concentrations and impaired myocardial glucose use, potentially worsening ischemia. We hypothesized that metabolic manipulation with a hyperinsulinemic euglycemic clamp (HEC) would affect a greater improvement in left ventricular (LV) performance during dobutamine stress echo (DSE) in subjects with IR.


METHODS
24 subjects with normal LV function and coronary disease (CAD) awaiting revascularization underwent 2 DSEs. Prior to one DSEs they underwent an HEC, where a primed infusion of insulin (rate 43 mU/m 2/min) was co-administered with 20% dextrose at variable rates to maintain euglycemia. At steady-state the DSE was performed and images of the LV were acquired with tissue Doppler at each stage for offline analysis. Segmental peak systolic velocities (Vs) were recorded, as well as LV ejection fraction (EF). Subjects were then divided into two groups based on their insulin sensitivity during the HEC.


RESULTS
HEC changed the metabolic environment, suppressing FFAs and thereby increasing glucose use. This resulted in improved LV performance at peak stress, measured by EF (IS group mean difference 5.3 (95% CI 2.5-8) %, p = 0.002; IR group mean difference 8.7 (95% CI 5.8-11.6) %, p < 0.0001) and peak V s in ischemic segments (IS group mean improvement 0.7(95% CI 0.07-1.58) cm/s, p = 0.07; IR group mean improvement 1.0 (95% CI 0.54-1.5) cm/s, p < 0.0001) , that was greater in the subjects with IR.


CONCLUSIONS
Increased myocardial glucose use induced by HEC improves LV function under stress in subjects with CAD and IR. Cardiac metabolic manipulation in subjects with IR is a promising target for future therapy.
Heck
Patrick M
PM
Cardiovascular Medicine, ACCI, Level 6, Box 110, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
Hoole
Stephen P
SP
Khan
Sadia N
SN
Dutka
David P
DP
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000503:physiopathology; D018618:Echocardiography, Doppler, Color; D025401:Echocardiography, Stress; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D013318:Stroke Volume; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016277:Ventricular Function, Left
D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin