c-peptide and Ventricular-Dysfunction--Left

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.. 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.. 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.. 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.

Topics: Aged; Blood Glucose; C-Peptide; Coronary Artery Disease; Echocardiography, Doppler, Color; Echocardiography, Stress; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Male; Middle Aged; Myocardium; Stroke Volume; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

The present state of knowledge unequivocally indicates that chronic diabetes is associated with impaired function of coronary vessels. Langendorff retrograde perfusion is one of the most frequently employed methods to study dysfunction of coronary vasculature in animal models of diabetes mellitus. However, because of methodological discrepancies in experimental protocols, the reliability of this technique is limited. In the current study, we propose the novel technique of vasoactive drug administration and aim to evaluate its usefulness in detecting coronary dysfunction in diabetes. Using Langendorff model, we compared the results of coronary endothelium-dependent (bradykinin) and -independent (diethylamine/nitric oxide, DEA/NO) vasodilatation obtained from experimental model utilizing automatically corrected-rate infusion with commonly used, constant-rate infusion of vasoactive drug. The infusion of bradykinin at constant rate failed to reveal coronary endothelium-dependent dysfunction typical for diabetes mellitus. Induction of endothelium-independent vasodilatation by constant infusion demonstrated augmented response in diabetic hearts. The administration of bradykinin or DEA/NO at the corrected rate was associated with significantly increased maximal responses in comparison with constant infusion experiments. This phenomenon was observed particularly in the control group. We conclude that only corrected-rate infusion of vasoactive agents to actual value of coronary flow enables the reliable detection of endothelial dysfunction in diabetes mellitus.

Topics: Animals; Blood Glucose; Bradykinin; C-Peptide; Cholesterol; Coronary Circulation; Coronary Vessels; Diabetes Mellitus, Experimental; Endothelium, Vascular; Fasting; Heart; Hydrazines; In Vitro Techniques; Infusions, Intravenous; Insulin; Male; Muscle, Smooth, Vascular; Nitric Oxide Donors; Perfusion; Rats; Rats, Wistar; Triglycerides; Vasodilation; Ventricular Dysfunction, Left

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Disease Progression; DNA, Mitochondrial; Echocardiography; Glycated Hemoglobin; Humans; Male; Mitochondrial Myopathies; Point Mutation; Ventricular Dysfunction, Left