Introduction Hyperinsulinemia has been implicated as a possible contributing factor for increased cardiovascular risk, abnormal lipid and carbohydrate metabolism and smooth muscle cell proliferation. However, a direct causal relationship between insulin per se in hyperinsulinemic states and these factors has not been established.
Objectives The objectives of this study were 1) to develop a model of endogenous hyperinsulinemia without the use of pharmacological agents and 2) to determine the effect of hyperinsulinemia as an independent risk factor on development of coronary artery atherosclerosis.
Research Design and Methods We established hyperinsulinemia in eight dogs (group 1) by using a novel surgical technique in which endocrine secretions were diverted from the portal to systemic circulation by end to side anastomosis of the splenic and superior pancreaticoduodenal veins to the inferior vena cava. Another eight dogs served as sham operated control (group 2).
Results Presurgical baseline plasma insulin levels were not different in the two groups (5.6 μU/mL in experimental group versus 8.4 μU/mL in control), but did differ at 3 months (26.1 μU/mL in experimental group versus 6.0 μU/mL in control group, p < .001). This difference remained significant at six months (24.4 μU/mL in experimental group versus 6.1 μU/mL in control group, p < .001), and in six years (12.58 ± 4.6 μU/mL in experimental group versus 6.05 ± 1.3 μU/mL in control group, p = .005). There was a significant difference in C peptide level in the two groups (0.53 ± 0.17 ng/mL in hyperinsulinemic versus 0.32 ± 0.12 ng/mL in nonhyperinsulinemic, p = .015) at the end of six years. There was no significant difference in the level of glucose, total cholesterol, triglycerides, HDL and FFA at the end of follow-up. Coronary arteries of 6 hyperinsulinemic dogs and 4 nonhyperinsulinemic dogs at the end were available for study. Based on the reading of a pathologist who was masked to the identity of experimental versus control, there was fibrosis in muscularis mucosa of 2 out of 6 hyperinsulinemic dogs but none in four nonhyperinsulinemic dogs.
Conclusions We conclude that hyperinsulinemia per se in dogs is associated with 33% increased risk of fibrosis in muscularis mucosa of coronary arteries, despite the lack of significant differences in lipid profile.