Good Calories, Bad Calories

At the beginning of this century, when hormones were first discovered, it was commonly believed that obesity would be found to be due to the absolute excess or deficiency of a single hormone. When this was found to be almost never true, the popular medical position swung to the other extreme: “obesity is almost never due to hormonal disturbances; it is almost always due to overeating.” Actually, the reasonable position ought to be: “in order to be obese, you always have to eat more than you expend for a certain period. How often this is due to a slight shift of relative or absolute hormone concentrations, each one of which is in the ‘normal’ range, we don’t know.”

Among the hormones that play a role in regulating fat metabolism and thus potentially play a causative role in obesity, insulin was always an obvious choice. Some failure in what clinicians a century ago called the insular^*108 apparatus of the pancreas is the fundamental defect in diabetes, and diabetes is intimately associated with obesity in those who develop the disease as adults, and with emaciation, which was the end stage of the disease in the pre-insulin era. In 1905, Carl von Noorden invoked this intimate association between diabetes and weight to formulate the third of his speculative hypotheses of obesity, what he called diabetogenous obesity. His ideas were remarkably prescient. They received little attention because insulin had not yet been discovered, let alone the technology to measure it.

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 allows the blood sugar to overflow into the urine, which is a last resort since it wastes potentially 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 eventually 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 still well 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 gradually 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 successfully used insulin to fatten chronically underweight children—patients who would be diagnosed today as anorexic—and to increase their appetite in the process.