In the late 1960s, Robert Stout of Queen’s University in Belfast published a series of studies reporting that insulin enhances the transport of cholesterol and fats into the cells of the arterial wall and stimulates the synthesis of cholesterol and fat in the arterial lining. Since a primary role of insulin is to facilitate the storage of fats in the fat tissue, Stout reasoned, it was not surprising that it would have the same effect on the lining of blood vessels. In 1969, Stout and the British diabetologist John Vallance-Owen pre-empted Reaven’s Syndrome X hypothesis by suggesting that the “ingestion of large quantities of refined carbohydrate” leads first to hyperinsulinemia and insulin resistance, and then to atherosclerosis and heart disease. In certain individuals, they suggested, the insulin secretion after eating these carbohydrates would be “disproportionately large.” “The carbohydrate is disposed of in three sites—adipose [fat] tissue, liver and arterial wall,” Stout wrote. “Obesity is produced. In the liver, triglyceride and cholesterol are synthesized and find their way into the circulation. Lipid synthesis is also stimulated in the arterial wall and is augmented by deposition of [triglycerides and cholesterol]…which in a few decades would reach significant proportions.” In 1975, Stout and the University of Washington pathologist Russell Ross reported that insulin also stimulates the proliferation of the smooth muscle cells that line the interior of arteries, a necessary step in the thickening of artery walls characteristic of both atherosclerosis and hypertension.

This insulin-atherogenesis hypothesis is the simplest possible explanation for the intimate association of diabetes and atherosclerosis: the excessive secretion of insulin accelerates atherosclerosis and perhaps other vascular complications. It also implies, as Stout suggested, that any dietary factor—refined carbohydrates in particular—that increases insulin secretion will increase risk of heart disease. This did not, however, become the preferred explanation. Even Reaven chose to ignore it.*54 But Reaven’s hypothesis proposed that heart disease was caused primarily by insulin resistance through its influence on triglycerides. He considered hyperinsulinemia to be a secondary phenomenon. Stout considered hyperinsulinemia the primary cause of atherosclerosis.

Most diabetologists have believed that diabetic complications are caused by the toxic effects of high blood sugar.*55 The means by which high blood sugar induces damage in cells, arteries, and tissues are indeed profound, and the consequences, as the carbohydrate hypothesis implies, extend far beyond diabetes itself. This line of research is pursued by only a few laboratories. As a result, its ultimate implications and validity remain to be ascertained. But it should be considered as yet another potential mechanism by which the consumption of refined carbohydrates could cause or exacerbate the entire spectrum of the chronic diseases of civilization.