Good Calories, Bad Calories (35 page)

From the mid-1960s onward, our understanding of the role of insulin resistance in both heart disease and diabetes was driven by the work of Stanford University diabetologist Gerald Reaven. Reaven began his investigations by measuring triglycerides and glucose tolerance in heart-attack survivors. A glucose-tolerance test is a common test given by physicians to determine if a patient is either diabetic or on the way to becoming so. The patient drinks a solution of glucose and water, and then, two hours later, the physician measures his or her blood sugar. If the blood sugar is higher than what’s considered normal, it means the patient has been unable to metabolize the glucose properly—hence, glucose intolerance—and so either lacks sufficient insulin to deal with the glucose, or is resistant to the insulin that is secreted. In 1963, Reaven reported that heart-attack survivors invariably had both high triglycerides and glucose intolerance, and this suggested that the two conditions had a common cause. Reaven considered insulin resistance to be the obvious suspect.

Working with John Farquhar, who had studied with Pete Ahrens at Rockefel er, Reaven developed a two-part hypothesis.

The first part explained why most, if not virtual y al individuals with high triglycerides had what Ahrens had cal ed carbohydrate-induced lipemia. In other words, their triglyceride levels increased with carbohydrate-rich diets and decreased when fat replaced the carbohydrates. The crucial factor, Reaven explained, is that, the more carbohydrates consumed, the more insulin is needed to transport the glucose from the carbohydrates into cel s where it can be used as fuel. This insulin, however, also prompts the liver to synthesize and secrete triglycerides for storage in the fat tissue. If someone who is already insulin-resistant consumes a carbohydrate-rich diet, according to Reaven’s hypothesis, the person wil have to secrete even more insulin to deal with the glucose, prompting in turn even greater synthesis and secretion of triglycerides by the liver, and so even higher triglyceride levels in the blood.

This, in turn, implied part two of the hypothesis: if eating a carbohydrate-rich diet in the presence of insulin resistance wil abnormal y elevate triglyceride levels, then it’s hard to avoid the implication that eating a carbohydrate-rich diet increases the risk of heart disease. Insulin resistance and carbohydrates wil also exacerbate Type 2 diabetes, according to Reaven’s hypothesis, and this would explain, as wel , why these diabetics inevitably have high triglycerides. By 1967, Reaven and Farquhar had reported that triglyceride levels, insulin resistance, and insulin levels moved up and down in concert even in healthy individuals: the more insulin secreted in response to carbohydrates, the greater the apparent insulin resistance and the higher the triglycerides.

Reaven and Farquhar spent the next twenty years working to establish the validity of the hypothesis. Much of the progress came with the development, once again, of new measuring techniques: in this case, tests that al owed investigators to measure insulin resistance directly. In 1970, Reaven and Farquhar published the details of the first such insulin-resistance test, which was then fol owed by a half-dozen more. The best of these—the “gold standard”—was developed at the NIH in the late 1960s and then refined over the next decade by a young endocrinologist named Ralph DeFronzo. It wasn’t until 1979, after DeFronzo joined the faculty at Yale Medical School and began measuring insulin resistance in human patients, that he published the details. It would take another decade for Reaven, Farqhuar, and DeFronzo, along with Eleuterio Ferrannini of the University of Pisa, among others, to convince diabetologists that resistance to insulin was the fundamental defect in Type 2 diabetes.

In 1987, the American Diabetes Association honored DeFronzo with its award for outstanding scientific 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 cal ed 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 official y 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 Circulation, the primary journal for research in heart disease. Meanwhile, his work had no influence on public-health policy or the public’s dietary consciousness. Neither the 1988 Surgeon General’s Report on Nutrition and Health nor the National Academy of Sciences’s 1989 Diet and Health mentioned insulin resistance or hyperinsulinemia in any context other than Reaven’s cautions that high-carbohydrate diets might not be ideal for Type 2 diabetics. Both reports ardently recommended low-fat, high-carbohydrate diets for the prevention of heart disease.

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 cal cognitive dissonance, or the tension that results from trying to hold two incompatible beliefs simultaneously. When the philosopher of science Thomas Kuhn discussed cognitive dissonance in scientific research—“the awareness of an anomaly in the fit between theory and nature”—he suggested that scientists wil typical y do what they have invariably done in the past in such cases: “They wil devise numerous articulations and ad hoc modifications of their theory in order to eliminate any apparent conflict.” And that’s exactly what happened with metabolic syndrome and its dietary implications. The syndrome itself was accepted as real and important; the idea that it was caused or exacerbated by the excessive consumption of carbohydrates simply vanished.

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 smal , dense LDL was another of the metabolic abnormalities commonly found in Reaven’s Syndrome X.

Smal , dense LDL, they noted, was associated with insulin resistance, hyperinsulinemia, high blood sugar, hypertension, and low HDL as wel . They also reported that the two best predictors of the presence of insulin resistance and the dominance of smal , 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 smal , 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 smal , dense LDL and metabolic syndrome official y 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 fol owed 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 wel , describing joint treatment guidelines. Scott Grundy of the University of Texas was the primary author of al 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—al remained firmly wedded to the fat-cholesterol dogma. They acknowledge metabolic syndrome as an emerging risk factor for heart disease, but identify LDL cholesterol as “the primary driving force for coronary atherogenesis.”

Thus, heart disease in America, as the National Cholesterol Education Program report put it, was stil official y caused by “mass elevations of serum LDL

cholesterol result[ing] from the habitual diet in the United States, particularly diets high in saturated fats and cholesterol.”

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 smal , 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 official y 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 except in this manner no one would attribute any such function to it…. Is a persistent [high blood sugar] a cause of arteriosclerosis in diabetes? It very likely is a cause because it is an abnormal condition and any abnormal state would tend to wear out the machine.

ELLIOTT JOSLIN, “Arteriosclerosis and Diabetes,” 1927

DESPITE NEARLY A CENTURY’S WORTH OF therapeutic innovations, the likelihood of a diabetic’s contracting coronary artery disease is no less today than it was in 1921, when insulin was first discovered. Type 2 diabetics can stil expect to die five to ten years prematurely, with much of this difference due to atherosclerosis and what Joslin’s Diabetes Mellitus has cal ed an “extraordinarily high incidence” of coronary disease.

Diabetes specialists have historical y perceived this plague of atherosclerosis among their patients as though it has little relevance to the atherosclerosis and heart disease that affect the rest of us. Textbooks would note the importance of identifying and control ing the “numerous and as yet il -defined factors general y involved in the pathogenesis of atherosclerosis,” as the 1971 edition of Joslin’s Diabetes Mellitus did, but the implication was that the requisite revelations would emerge, as they had in the past, from heart-disease researchers, as though the flow of knowledge about heart disease could proceed only from heart-disease research to diabetology and never the other way around.

The extreme example of this thinking has been the assumption that saturated fat is the nutritional agent of heart disease in diabetics, just as it supposedly is in everyone else. “The frequent cardiovascular complications seen in past years among persons with diabetes,” the 1988 Surgeon General’s Report on Nutrition and Health says, are caused by the “traditional restriction of carbohydrate intake in persons with diabetes” and thus an increased intake of fat, “usual y, saturated.” This was the logic that led the American Diabetes Association, from the early 1970s, to recommend that diabetics eat more carbohydrates rather than less, despite a complete absence of clinical trials that might demonstrate that the benefits of doing so outweigh the risks, and the decades of clinical experience establishing carbohydrate restriction as an effective method of control ing blood sugar. If atherosclerosis was accelerated in diabetics, the thinking went, it was accelerated because they ate more saturated fat than nondiabetics. Diabetologists believed they could safely prescribe a carbohydrate-rich diet to their patients, because a diet that is low in fat wil be high in carbohydrates.