This is another of those conceptions, like the ability of insulin to regulate blood pressure, that have been mostly neglected for decades, despite the profound implications if it’s true. The specter of this atherogenic effect of insulin is noted briefly, for example, in the fourteenth edition (2005) of Joslin’s Diabetes Mellitus. The Harvard diabetologist Edward Feener and Victor Dzau, president of the Duke University Health System, write that “the effects of insulin on [cardiovascular disease] in diabetes and insulin resistance are related to both systematic metabolic abnormalities and the direct effects of insulin action on the vasculature [blood vessels; my italics].” The second mention, by two Harvard cardiologists, acknowledges the association between insulin resistance, hyperinsulinemia, and heart disease and suggests that if insulin resistance is not the problem, then “another possibility” is that insulin itself “has direct cardiovascular effects.” Nothing more is said.

The first evidence of the potential atherogenicity of insulin emerged from precisely the kind of experiments in rabbits that initially gave credibility to the cholesterol hypothesis a century ago. Rabbits fed high-cholesterol diets develop plaques throughout their arteries, but diabetic rabbits (Type 1) will not suffer this atherosclerotic fate no matter how cholesterol-rich their diet. Infuse insulin along with the cholesterol-laden diet, however, and plaques and lesions will promptly blossom everywhere. This phenomenon was first reported in 1949 in rabbits, and then, a few years later, in chickens, by Jeremiah Stamler and his mentor Louis Katz, and later in dogs, too. Hence, insulin itself may be “one factor in the pathogenesis of the frequent, premature, severe atherosclerosis of diabetic patients,” as Stamler and his colleagues suggested.