Good Calories, Bad Calories (69 page)

Von Noorden suggested that obesity and diabetes are different consequences of the same underlying defects in the mechanisms that regulate carbohydrate and fat metabolism. In severe diabetes (Type 1), he noted, the patients are unable either to utilize blood sugar as a source of energy or to convert it into fat and store it. This is why the body al ows the blood sugar to overflow into the urine, which is a last resort since it wastes potential y valuable fuel. The result is glycosuria, the primary symptom of diabetes. These diabetics must be incapable of storing or maintaining fat, von Noorden noted, because they eventual y become emaciated and waste away. In obese patients, on the other hand, the ability to utilize blood sugar is impaired, but not the ability of the body to convert blood sugar into fat and store it. “Obese individuals of this type have already an altered metabolism for sugar,” von Noorden wrote, “but instead of excreting the sugar in the urine, they transfer it to the fat-producing parts of the body, whose tissues are stil wel prepared to receive it.” As the ability to burn blood sugar for energy further deteriorates and “the storage of the carbohydrates in the fat masses [also suffers] a moderate and gradual y progressing impairment,” sugar appears in the urine, and the patient becomes noticeably diabetic. Using the modern terminology, this is the route from obesity to Type 2 diabetes. “The connection between diabetes and obesity,” as von Noorden put it, “ceases in the light of my theory to be any longer an enigmatical relation, and becomes a necessary consequence of the relationship discovered in the last few years between carbohydrate transformation and formation of fat.”

After the discovery of insulin in 1921, the potential role of insulin as a fattening hormone would become a long-running controversy. Those physicians who believed, as Louis Newburgh did without reservation, that obesity was an eating disorder, rejected the idea that insulin could fatten humans, if for no other reason than that this suggested the existence of a defective hormonal mechanism that could lead to obesity. The evidence, however, suggested exactly that. When insulin was injected into diabetic dogs in the laboratory, or diabetic human patients in the clinic, they put on weight and body fat. As early as 1923, clinicians were reporting that they had successful y used insulin to fatten chronical y underweight children—patients who would be diagnosed today as anorexic—and to increase their appetite in the process.

In 1925, Wilhelm Falta, a student of von Noorden and a pioneer of the science of endocrinology in Europe, began using insulin therapy to treat underweight and anorexia in adults as wel . Falta had argued, even in the pre-insulin era, that whatever pancreatic hormone was absent or defective in diabetes governed not only the use of carbohydrates for fuel, but also the assimilation of fat in adipose tissue. “A functional y intact pancreas is necessary for fattening,” Falta wrote. He also noted that the only way to fatten anyone efficiently was to include “abundant carbohydrates in the diet.” Otherwise, the body would adjust to eating “very much more than the appetite real y craves,” by either lessening appetite stil further or creating “an increased demand for movement.” The only way to get around this natural balance of intake and expenditure is by increasing the secretion from the pancreas. “We can conceive,” Falta speculated, “that the origin of obesity may receive an impetus through a primarily strengthened function of the insular apparatus, in that the assimilation of larger amounts of food goes on abnormal y easily, and hence there does not occur the setting free of the reactions that in normal individuals work against an ingestion of food which for a long time supersedes the need.” After the discovery of insulin, Falta reported that giving it to patients would increase their appetite for carbohydrates specifical y, and the carbohydrates in turn would stimulate the patient’s own insulin production. It would create a vicious cycle—although, in the case of anorexic and underweight patients, one that might return them to a normal appetite and normal weight.

By the 1930s, clinicians throughout Europe and the United States had taken to using insulin therapy to fatten their pathological y underweight patients.

These patients could gain as much as six pounds a week eating meals “rich in carbohydrates” after receiving injections of smal doses of insulin, reported Rony, who used insulin therapy on seven anorexic patients in his own clinic; it worked on five of them. None of these patients had been able to gain weight, but now they added an average of twenty pounds each in three months. “Al reported a more or less pronounced increase of appetite,” Rony wrote, “and occasional strong feelings of hunger.” Until the 1960s, insulin was also used to treat severe depression and schizophrenia. Among the more renowned patients subjected to what was then cal ed insulin-shock therapy was the Princeton mathematician John Nash, made famous by Sylvia Nasar’s 1998 biography, A Beautiful Mind. Its efficacy for treating mental il ness was debatable, but as Nasar observed, “al the patients gained weight.” Another memorable recipient was the poet Sylvia Plath, who experienced a “drastic increase in weight” on the treatment. (In her autobiographical novel, The Bell Jar, Plath’s protagonist, Esther Greenwood, gains twenty pounds on insulin therapy—“I just grew fatter and fatter,” she says.) Insulin’s fattening properties have long been particularly obvious to diabetics and the physicians who treat them. Because diabetics wil gain weight with insulin therapy, even those who are obese to begin with, clinicians have always had difficulty convincing their patients to continue taking their insulin. When they start to fatten, they natural y want to slack off on the therapy, so the need to control blood sugar competes with the desire to remain lean, or at least relatively so. This is also a clinical dilemma, because the weight gain wil also increase the risk of heart disease. In the chapter on insulin therapy in the 1994 edition of Joslin’s Diabetes Mellitus, the Harvard diabetologist James Rosenzweig portrayed this insulin-induced weight gain as uncontroversial: “In a number of studies of patients treated with insulin for up to 12 months, weight gains of 2.0 to 4.5 kg [roughly four to ten pounds] were reported….” This weight gain, he wrote, then leads to “the often-cited vicious cycle of increased insulin resistance, leading to the need for more exogenous insulin, to further weight gain, which increases the insulin resistance even more.”*109

If insulin fattens those who receive it, as the evidence suggests, then how does it work? The prewar European clinicians who used insulin therapy to treat anorexics accepted the possibility, as Falta suggested, that the hormone can directly increase the accumulation of fat in the fat tissues. Insulin was “an excel ent fattening substance,” Erich Grafe wrote in Metabolic Diseases and Their Treatment. Grafe believed that the fattening effect of insulin is likely

“due to improved combustion of carbohydrate and increased synthesis of glycogen and fat.” In the United States, however, the conventional wisdom came from Louis Newburgh and his col eagues at the University of Michigan. When insulin increases weight, Newburgh said, it does so either through the power of suggestion—a placebo effect—or by a reduction of blood sugar to the point where the patient eats to avoid very low blood sugar (hypoglycemia) and the accompanying symptoms of dizziness, weakness, and convulsions.

When Rony reviewed the experimental and clinical reports in 1940, he considered any conclusion to be premature. Because obese individuals tend to have high blood sugar, rather than low, Rony said, it was hard to imagine how insulin, which lowered blood sugar, could cause obesity. “Stil ,” he noted, “it might be possible that in obese subjects a latent or conditional form of hyperinsulinism exists which would promote fat deposition without causing hypoglycemia.” This was not supported by conclusive evidence, he added, and so it “remains, for the time being, at best a working hypothesis.”

Only Newburgh’s interpretation of the evidence, however (and only the obesity research community in the United States), survived the war years.

Afterward, clinical investigators would state unambiguously—as Edward Rynearson and Clifford Gastineau did in their 1949 clinical manual Obesity…

—that insulin puts weight on only by lowering blood sugar to the point where patients overeat to remain conscious. This hypoglycemia was considered a rare pathological condition, one with no relevance to everyday life, and so only in that condition were elevated insulin levels to be considered a causal agent in weight gain and common obesity.

In 1992, the University of Texas diabetologist Denis McGarry published an article in Science with the memorably idiosyncratic title “What If Minkowski Had Been Ageusic? An Alternative Angle on Diabetes.” The German physiologist Oskar Minkowski was the first to identify the role of the pancreas in diabetes. The word “ageusic” refers to a condition in which the sense of taste is absent. “Legend has it,” McGarry wrote, “that on a momentous day in 1889 Oskar Minkowski noticed that urine col ected from his pancreatectomized*110 dogs attracted an inordinate number of flies. He is said (by some) to have tasted the urine and to have been struck by its sweetness. From this simple but astute observation he established for the first time that the pancreas produced some entity essential for control of the blood sugar concentration, which, when absent, resulted in diabetes mel itus.” Some thirty years later, when Frederick Banting and Charles Best in Toronto identified insulin as the relevant pancreatic secretion, McGarry wrote, they natural y did so in the context of Minkowski’s observations about blood sugar, and thus “diabetes mel itus has been viewed ever since as a disorder primarily associated with abnormal glucose metabolism.” But if Minkowski had been ageusic and so missed the sweet taste of the urine, McGarry speculated, he might have noticed instead the smel of acetone, which is produced in the liver from the conversion of fat into ketone bodies. “He would surely have concluded that removal of the pancreas causes fatty acid metabolism to go awry,” McGarry wrote. “Extending this hypothetical scenario, the major conclusion of Banting’s work might have been that the preeminent role of insulin is in the control of fat metabolism.”

McGarry’s parable focused on diabetes, but the point he made extends to virtual y everything having to with insulin. Just as diabetes has traditional y been perceived as a disorder of carbohydrate metabolism—even though fat metabolism is also dysfunctional—insulin has always been perceived as a hormone that primarily functions to regulate blood sugar, though, as we’ve discussed, it regulates the storage and use of fat and protein in the body as wel . Because blood sugar could be measured easily through the first half of the twentieth century, but not yet the fats in the blood, the focus of research rested firmly on blood sugar.

From the 1920s through the 1960s, a series of discoveries in the basic science of fat metabolism led to a revolution in the understanding of the role of insulin and the regulation of fat tissue in the human body. This era began with a handful of naïve assumptions: that fat tissue is relatively inert (a “garbage can,” in the words of the Swiss physiologist Bernard Jeanrenaud); that carbohydrates are the primary fuel for muscular activity (which is stil commonly believed today); and that fat is used for fuel only after being converted in the liver into supposedly toxic ketone bodies. The forty years of research that fol owed would overturn them al —but it would have effectively no influence on the mainstream thinking about human obesity.

Those who paid attention to this research either had no influence themselves—Alfred Pennington comes to mind—or were so convinced that obesity is caused by overeating that they couldn’t imagine why the research would be relevant. From the 1950s onward, clinical investigators studying and treating obese patients, as Hilde Bruch commented, seemed singularly uninterested in this research. “Until recently, knowledge of the synthesis and oxidation of fat was quite rudimentary,” Bruch wrote in 1957. “As long as it was not known how the body builds up and breaks down its fat deposit, the ignorance was glossed over by simply stating that food taken in excess of body needs was stored and deposited in the fat cel s, the way potatoes are put into a bag.

Obviously, this is not so.” By 1973, after details of the regulation of fat metabolism and storage had been worked out in fine detail, Bruch found it “amazing how little of this increasing awareness…is reflected in the clinical literature on obesity.”

There are three distinct phases of the revolution that converged by the mid-1960s to overturn what Bruch cal ed the “the time-honored assumption that fat tissue is metabolical y inert,” and the accompanying conviction that fat only enters the fat tissue after a meal and only leaves it when the body is in negative energy balance.

The first phase began in the 1920s, when biochemists realized that the cel s of adipose tissue have distinct structures and are not, as was previously believed, simply connective tissue stuffed with a droplet of oily fat. Researchers then demonstrated that the adipose tissue is interlaced with blood vessels such that “no marked quantity of fat cel s escapes close contact with at least one capil ary,” and that the fat cel s and these blood vessels are regulated by “abundant” nerves running from the central nervous system.

This led to the revelation that the fat in the cel s of the adipose tissue is in a continual state of flux. This was initial y the work of a German biochemist, Rudolf Schoenheimer. In the early 1930s, while working at the University of Freiburg, Schoenheimer demonstrated that animals continual y synthesize and degrade their own cholesterol, independent of the amount of cholesterol in the diet. After Hitler came to power in January 1933, Schoenheimer moved to New York, where he went to work at Columbia University. It was in New York that Schoenheimer col aborated on the development of a technique for measuring serum cholesterol and, by doing so, launched the medical profession’s obsession with cholesterol levels. Then, with David Rittenberg, he developed the technique to label or tag molecules with a heavy form of hydrogen known as deuterium*111 so that their movement through the metabolic processes of the body could be fol owed. Schoenheimer and Rittenberg put this technique to work studying the metabolism of fat, protein, and carbohydrates in the body.