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Hyperinsulinemia improves ischemic LV function in insulin resistant subjects.

Heck PM, Hoole SP, Khan SN, Dutka DP - Cardiovasc Diabetol (2010)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

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.

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Related in: MedlinePlus

Metabolic parameters during control and clamped studies. shows the glucose, c-peptide, FFA and insulin concentrations during control, graphs (a), left, and clamped studies, graphs (b), right. The black square represents the IS group and the white circle the IR group. Numbers plotted are mean values and the standard errors. Detailed description of the results is in the main text. * = p < 0.05; ** = p < 0.01 for comparison between IS and IR group.
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Figure 1: Metabolic parameters during control and clamped studies. shows the glucose, c-peptide, FFA and insulin concentrations during control, graphs (a), left, and clamped studies, graphs (b), right. The black square represents the IS group and the white circle the IR group. Numbers plotted are mean values and the standard errors. Detailed description of the results is in the main text. * = p < 0.05; ** = p < 0.01 for comparison between IS and IR group.

Mentions: The metabolic responses of both groups during the clamp are shown in Table 3 and Figure 1.


Hyperinsulinemia improves ischemic LV function in insulin resistant subjects.

Heck PM, Hoole SP, Khan SN, Dutka DP - Cardiovasc Diabetol (2010)

Metabolic parameters during control and clamped studies. shows the glucose, c-peptide, FFA and insulin concentrations during control, graphs (a), left, and clamped studies, graphs (b), right. The black square represents the IS group and the white circle the IR group. Numbers plotted are mean values and the standard errors. Detailed description of the results is in the main text. * = p < 0.05; ** = p < 0.01 for comparison between IS and IR group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2903514&req=5

Figure 1: Metabolic parameters during control and clamped studies. shows the glucose, c-peptide, FFA and insulin concentrations during control, graphs (a), left, and clamped studies, graphs (b), right. The black square represents the IS group and the white circle the IR group. Numbers plotted are mean values and the standard errors. Detailed description of the results is in the main text. * = p < 0.05; ** = p < 0.01 for comparison between IS and IR group.
Mentions: The metabolic responses of both groups during the clamp are shown in Table 3 and Figure 1.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus