Abstract 19183: Insulin Resistance Develops after the Onset of Heart Failure in Dogs
Background: Heart failure (HF) is a condition associated with increased plasma norepinephrine levels. Norepinephrine is known to affect glucose homeostasis by decreasing insulin sensitivity. We have previously reported an increase in plasma norepinephrine levels in coronary microembolization-induced HF dogs. However, the status of plasma insulin and glucose levels is unknown in large animal models of HF. In the present study, we examined insulin and glucose levels in fasted plasma from dogs before and after the onset of HF.
Methods: 12 healthy mongrel dogs weighing 20-30 kg underwent serial coronary microembolization to produce HF. Embolization was performed every 1-2 weeks until angiographic left ventricular ejection fraction (LVEF) was <35%. All procedures were performed during cardiac catheterization, under general anesthesia and sterile conditions. Fasted plasma was collected before and after inducing HF and was stored at -80oC. Insulin and glucose levels were determined using commercially available ELISA kits for insulin and colorimetric assay kits for glucose, and expressed in microunits/mL and mg/dL, respectively. Homeostasis assessment model for insulin resistance (HOMA-IR) ([fasting insulin in microunits/mL * fasting glucose in mg/dL] * 0.5551/22.5) was calculated in all dogs at baseline and after inducing HF. Data were analyzed using paired t-tests.
Results: Baseline LVEF was > 55% in all dogs. Once HF was established, mean LVEF was 31 ± 1%. Baseline mean fasting blood glucose and fasting plasma insulin were 84 ± 17 mg/dL and 9.7 ± 3.6 microunits/mL, respectively. Once HF was established, fasting blood glucose rose to 161 ± 44 mg/dL (p<0.0001) and fasting plasma insulin increased to 16.5 ± 4.0 microunits/mL (p=0.0008). HOMA-IR score increased from 2.0 ± 0.8 at baseline to 6.7 ± 3.0 with HF (p=0.0002).
Conclusions: Hyperglycemia, hyperinsulinemia and insulin resistance develop after the onset of heart failure due to coronary microembolization in dogs consistent with observations previously reported in patients with chronic HF. This large animal model of HF can serve as a useful tool in exploring the underlying causes and consequences of insulin resistance in the setting of chronic HF.
- © 2012 by American Heart Association, Inc.