Good Calories, Bad Calories (36 page)

But the research on metabolic syndrome suggests an entirely different scenario. If the risk of heart disease is elevated in metabolic syndrome and elevated stil further with diabetes, then maybe the flow of knowledge about heart disease should proceed from diabetics, who suffer the most extreme manifestation of the disease, to the rest of us, and not the other way around. Maybe diabetics have such extreme atherosclerosis because there is something about the diabetic condition that causes the disease. Perhaps the metabolic abnormalities of the diabetic condition are the essential cause of atherosclerosis and coronary heart disease in everyone, only diabetics suffer to a greater extent.

Another way to look at this is to consider that metabolic syndrome and Type 2 diabetes lie on a continuum or a curve of physical degeneration. This curve is marked by ever-worsening disturbances of carbohydrate and fat metabolism—high insulin, insulin resistance, high blood sugar, high triglycerides, low HDL, and smal , dense LDL. Atherosclerosis is one manifestation of this physical degeneration. In diabetes, the metabolic abnormalities are exacerbated—diabetics are further down the curve of physical degeneration—and the atherosclerotic process is accelerated. But we al live on the same curve. The mechanisms that cause atherosclerosis are the same in al of us; only the extent of damage differs.

Consider Keys’s cholesterol hypothesis as an example of this logic. One reason we came to believe that high cholesterol is a cause of heart disease is that severe atherosclerosis is a common symptom of genetic disorders of cholesterol metabolism. If having a cholesterol level of 1,000 mg/dl—as these individuals often do—makes atherosclerosis seemingly inevitable, the logic goes, and if higher cholesterol seems to associate with higher risk of heart disease among the rest of us, then cholesterol is a cause of heart disease, and elevating cholesterol by any amount wil increase risk. The higher the cholesterol, the greater the risk. If eating saturated fat elevates cholesterol, then that in turn causes heart disease. And this is supposedly true of diabetics as wel . Keys oversimplified the science and was wrong about the true relationship of cholesterol and heart disease, but the logic itself is otherwise sound.

The same logic holds for blood pressure and heart disease. The higher the blood pressure, the greater the risk of heart disease. If salt supposedly raises blood pressure, even if only by a few percentage points, then salt is a nutritional cause of heart disease. This, too, is held to be true for diabetics.

Thus, the atherogenic American diet, as now official y defined, the diet that clogs arteries and causes heart disease, is a diet high in saturated fat and salt.

Now let’s apply the same reasoning to metabolic syndrome and diabetes. Diabetics suffer more virulent atherosclerosis and die of heart disease more frequently than those with metabolic syndrome, and much more frequently than healthy individuals who manifest neither condition. Some aspect of the diabetic condition must be the cause—most likely, either high blood sugar, hyperinsulinemia, or insulin resistance, al three of which wil tend to be worse in diabetics than in those with metabolic syndrome. Indeed, the existence of metabolic syndrome tel s us that these same abnormalities exist in nondiabetics, although to a lesser extent, and though individuals with metabolic syndrome suffer an increased risk of heart disease, they do so to a lesser extent than diabetics. And because dietary carbohydrates and particularly refined carbohydrates elevate blood sugar and insulin and, presumably, induce insulin resistance, the implication is that eating these carbohydrates increases heart-disease risk not only in diabetics but in healthy individuals. By this reasoning, the atherogenic American diet is a carbohydrate-rich diet. Hence, cognitive dissonance.

The logic of this argument has to be taken one step further, however, even if the cognitive dissonance is elevated with it. Both diabetes and metabolic syndrome are associated with an elevated incidence of virtual y every chronic disease, not just heart disease. Moreover, the diabetic condition is associated with a host of chronic blood-vessel-related problems known as vascular complications: stroke, a stroke-related dementia cal ed vascular dementia, kidney disease, blindness, nerve damage in the extremities, and atheromatous disease in the legs that often leads to amputation. One obvious possibility is that the same metabolic and hormonal abnormalities that characterize the diabetic condition—in particular, elevated blood sugar, hyperinsulinemia, and insulin resistance—may also cause these complications and the associated chronic diseases. And otherwise healthy individuals,

therefore, would be expected to increase their risk of all these conditions by the consumption of refined and easily digestible carbohydrates, which inflict their damage first through their effects on blood sugar and insulin, and then, indirectly, through triglycerides, lipoproteins, fat accumulation, and assuredly other factors as wel .

This is a fundamental tenet of the carbohydrate hypothesis: If the risk of contracting any chronic disease or condition increases with metabolic syndrome and Type 2 diabetes, then it’s a reasonable hypothesis that insulin and/or blood sugar plays a role in the disease process. And if insulin and blood sugar do play a pathological role, then it’s a reasonable hypothesis that the same conditions can be caused or exacerbated in healthy individuals by the consumption of refined and easily digestible carbohydrates and sugars.

Among the immediate examples that fol ow from this logic is the particularly disconcerting possibility that insulin itself causes or exacerbates atherosclerosis. Since insulin resistance and hyperinsulinemia characterize Type 2 diabetes, it’s certainly possible that chronical y elevated levels of insulin are the cause of the persistently high incidence of atherosclerosis in diabetics, quite aside from any other effects insulin might have on triglycerides, lipoproteins, or blood pressure. And if this is the case, then the excessive secretion of insulin—induced by the consumption of refined carbohydrates and sugars—might be responsible for causing or exacerbating atherosclerosis in those of us who are not diabetic.

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 initial y gave credibility to the cholesterol hypothesis a century ago. Rabbits fed high-cholesterol diets develop plaques throughout their arteries, but diabetic rabbits (Type 1) wil 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 wil 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 col eagues suggested.

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 cel s of the arterial wal 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 Val ance-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 wal ,” 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 wal 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 Russel Ross reported that insulin also stimulates the proliferation of the smooth muscle cel s that line the interior of arteries, a necessary step in the thickening of artery wal s 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 wil 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 cel s, 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.

In particular, raising blood sugar wil increase the production of what are known technical y as reactive oxygen species and advanced glycation end-products, both of which are potential y toxic. The former are generated primarily by the burning of glucose (blood sugar) for fuel in the cel s, in a process that attaches electrons to oxygen atoms, transforming the oxygen from a relatively inert molecule into one that is avid to react chemical y with other molecules. This is not an ideal situation biological y. One form of reactive oxygen species is those known commonly as free radicals, and al of them together are known as oxidants, because what they do is oxidize other molecules (the same chemical reaction that causes iron to rust, and equal y deleterious). The object of oxidation slowly deteriorates. Biologists refer to this deterioration as oxidative stress. Antioxidants neutralize reactive oxygen species, which is why antioxidants have become a popular buzzword in nutrition discussions.

The potential of advanced glycation end-products (AGEs) for damage is equal y worrisome. Their formation can take years, but the process (glycation) begins simply, with the attachment of a sugar—glucose, for instance—to a protein without the benefit of an enzyme to orchestrate the reaction. That absence is critical. The role of enzymes in living organisms is to control chemical reactions to ensure that they “conform to a tightly regulated metabolic program,” as the Harvard biochemist Frank Bunn explains. When enzymes affix sugars to proteins, they do so at particular sites on the proteins, for very particular reasons. Without an enzyme overseeing the process, the sugar sticks to the protein haphazardly and sets the stage for yet more unintended particular reasons. Without an enzyme overseeing the process, the sugar sticks to the protein haphazardly and sets the stage for yet more unintended and unregulated chemical reactions.

The term glycation refers only to this initial step, a sugar molecule attaching to a protein, and this part of the process is reversible—if blood-sugar levels are low enough, the sugar and protein wil disengage, and no damage wil be done. If blood sugar is elevated, however, then the process of forming an advanced glycation end-product wil move forward. The protein and its accompanying glycated sugars wil undergo a series of reactions and rearrangements until the process culminates in the convoluted form of an advanced glycation end-product. These AGEs wil then bind easily to other AGEs and to stil more proteins through a process known as cross-linking—the sugars hooked to one protein wil bridge to another protein and lock them together. Now proteins that should ideal y have nothing to do with each other wil be inexorably joined.