Abstract 16723: Impaired Exercise Capacity in Diabetes: Procollagen Biomarkers Suggest Mechanism is Underlying Myocardial Fibrosis
Background: Reduced exercise capacity correlates with impaired myocardial contractility and relaxation in non-ischemic diabetic heart disease (DHD). The underlying pathophysiology of this myocardial stiffness remains undefined. Metabolic derangement is believed to Results in myocardial accumulation of types I & III collagen leading to fibrosis. We sought to explore the relationship between impaired exercise capacity, myocardial dysfunction and myocardial fibrosis in type 2 diabetes (T2DM) using procollagen biomarkers.
Methods: Anthropometric, hemodynamic and biochemical data were measured in healthy subjects with T2DM. Myocardial function was sought on resting echo with 2D and color TDI measures (early diastolic [Em] & systolic [Sm] tissue velocity, strain and strain rate [SR]) acquired in standard views. Treadmill exercise was performed to establish peak exercise capacity (VO2 max) and stress hemodynamics. Stress echo was employed to exclude ischemia and establish myocardial function at peak. Amino-terminal propeptides of procollagen type I (PINP) and type III (PIIINP) were quantitated in serum on radioimmunoassay.
Results: Of 140 subjects (80 men, 60±9 yrs), mean VO2 max was 28±7 ml/kg/min. VO2 max correlated with metabolic, hemodynamic and echo markers of DHD including: age, BMI, waist circumference, Hb, albumin, insulin resistance (HOMA-IR), arterial stiffness (aortic pulse wave velocity), systolic BP, rest & peak HR, mitral inflow ratio (E/A), Em & Sm (both rest & stress), rest & stress diastolic filling pressures (E/Em) and stress SR (p for all <0.05). A novel association between procollagen biomarkers (PINP & PIIINP) and VO2 max was established (p<0.05 for both). On linear regression analysis, PINP (Beta=-0.214, p=0.010), rest E/Em (Beta=-0.188, p=0.029), rest Sm (Beta=0.304, p=0.002), rest HR (Beta=-0.433, p=<0.001) and peak HR (Beta=0.265, p=0.002) were independently associated with VO2max (R2 = 0.419).
Conclusions: Impaired exercise capacity is related to metabolic, hemodynamic and echo characteristics of DHD. A novel association with procollagen biomarkers, PINP & PIIINP, supports that fibrosis is an important underlying mechanism responsible for myocardial stiffness and resultant impaired exercise capacity in T2DM.
- © 2010 by American Heart Association, Inc.