achievement. A year later, Reaven received the ADA’s Banting Medal for Scientific Achievement.*52 Reaven then gave the prestigious Banting Lecture at the ADA’s annual conference and took the opportunity to extend the implications of his research. For the first time, he laid out the hypothesis of what he called Syndrome X (metabolic syndrome) and the cluster of disorders—including insulin resistance, hyperinsulinemia, high triglycerides, low HDL cholesterol, and high blood pressure—that accompanies Type 2 diabetes and obesity and plays a critical role in the genesis of heart disease even in nondiabetics. “Although this concept may seem outlandish at first blush,” Reaven said, “the notion is consistent with available experimental data.” As Reaven described it, the condition of being resistant to insulin leads to both heart disease and diabetes. But not everyone with insulin resistance becomes diabetic; some continue to secrete sufficient insulin to overcome their insulin resistance, though this hyperinsulinemia causes havoc on its own, including elevating triglyceride levels, and also further exacerbating the insulin resistance—a vicious cycle.
Reaven supported his hypothesis with the results of observational studies that had already linked hyperinsulinemia, insulin resistance, and Type 2 diabetes to high triglycerides, heart disease, obesity, stroke, and hypertension. Three large-scale Framingham-like prospective studies of healthy nondiabetic populations—in Paris, Helsinki, and in Busselton, Australia—had also reported that, the higher the insulin levels, the greater the risk of heart disease.
As DeFronzo later remarked, the conclusion that hyperinsulinemia and insulin resistance were related to “a whole host of metabolic disorders” was an obvious one, but it required that clinical investigators measure insulin resistance in human patients, which would always be the obstacle in the science of metabolic syndrome. Measuring insulin resistance requires multiple tests of blood sugar while insulin levels are held constant and precise amounts of glucose are consumed or infused into the bloodstream. This is not the kind of test that physicians can do in a checkup, at least not without going far beyond the usual practice of sending a blood sample out to a laboratory for a battery of tests. As a result, when the National Cholesterol Education Program officially acknowledged the existence of Reaven’s Syndrome X in 2002 (renaming it metabolic syndrome), neither insulin resistance nor hyperinsulinemia was included among the diagnostic criteria, despite being the fundamental defects in the syndrome itself.
Reaven’s 1988 Banting Lecture is credited as the turning point in the effort to convince diabetologists of the critical importance of insulin resistance and hyperinsulinemia, but those investigators concerned with the genesis of heart disease paid little attention, considering anything having to do with insulin to be relevant only to diabetes. This was a natural consequence of the specialization of scientific research. Through the mid-1980s, Reaven’s research had focused on diabetes and insulin, and so his publications appeared almost exclusively in journals of diabetes, endocrinology, and metabolism. Not until 1996 did Reaven publish an article on Syndrome X in the American Heart Association journal
Even the diabetes community found it easier to accept Reaven’s science than its dietary implications. Reaven’s observations and data “speak for themselves,” as Robert Silverman of the NIH suggested at a 1986 consensus conference on diabetes prevention and treatment. But they placed nutritionists in an awkward position. “High protein levels can be bad for the kidneys,” said Silverman. “High fat is bad for your heart. Now Reaven is saying not to eat high carbohydrates. We have to eat something.” “Sometimes we wish it would go away,” Silverman added, “because nobody knows how to deal with it.”
This is what psychologists call
Among the few clinical investigators working on heart disease who paid attention to Reaven’s research in the late 1980s was Ron Krauss. In 1993, Krauss and Reaven together reported that small, dense LDL was another of the metabolic abnormalities commonly found in Reaven’s Syndrome X. Small, dense LDL, they noted, was associated with insulin resistance, hyperinsulinemia, high blood sugar, hypertension, and low HDL as well. They also reported that the two best predictors of the presence of insulin resistance and the dominance of small, dense LDL are triglycerides and HDL cholesterol—the higher the triglycerides and the lower the HDL, the more likely it is that both insulin resistance and small, dense LDL are present. This offers yet another reason to believe the carbohydrate hypothesis of heart disease, since metabolic syndrome is now considered perhaps the dominant heart-disease risk factor—a “coequal partner to cigarette smoking as contributors to premature [coronary heart disease],” as the National Cholesterol Education Program describes it—and both triglycerides and HDL cholesterol are influenced by carbohydrate consumption far more than by any fat.
Nonetheless, when small, dense LDL and metabolic syndrome officially entered the orthodox wisdom as risk factors for heart disease in 2002, the cognitive dissonance was clearly present. First the National Cholesterol Education Program published its revised guidelines for cholesterol testing and treatment. This was followed in 2004 by two conference reports: one describing the conclusions of a joint NIH-AHA meeting on scientific issues related to metabolic syndrome, and the other, in which the American Diabetes Association joined in as well, describing joint treatment guidelines. Scott Grundy of the University of Texas was the primary author of all three documents. When I interviewed Grundy in May 2004, he acknowledged that metabolic syndrome was the cause of most heart disease in America, and that this syndrome is probably caused by the excessive consumption of refined carbohydrates. Yet his three reports—representing the official NIH, AHA, and ADA positions—all remained firmly wedded to the fat- cholesterol dogma. They acknowledge metabolic syndrome as an
There was no mention that carbohydrates might be responsible for causing or exacerbating either metabolic syndrome or the combination of low HDL, high triglycerides, and small, dense LDL, which is described as occurring “commonly in persons with premature [coronary heart disease].*53 In the now established version of the alternative hypothesis—that metabolic syndrome leads to heart disease—the carbohydrates that had always been considered the causative agent had been officially rendered harmless. They had been removed from the equation of nutrition and chronic disease, despite the decades of research and observations suggesting the critical causal role they played.
THE SIGNIFICANCE OF DIABETES
Does carbohydrate cause arteriosclerosis? Certainly it does if taken in such excess as to produce obesity, but
