Drugs, Populations, and Type II Diabetes Mellitus

Abstract

Richard I. Shader, MD In this issue, our Topic Editor for Endocrinology, Diabetes, and Other Endocrine Disorders, Dr. John G. Ryan, has assembled a Diabetes Update titled “Race, Risk, and Behaviors,” a diverse group of articles related to the management and treatment of type 2 diabetes mellitus (T2DM). These articles address issues of assessment, newly available treatments, population implications, and glycemic control facilitation. As always, we welcome your responses to these articles. My own interest in T2DM dates back to the 1960s, when it became clear that changes in blood sugar levels in seriously ill psychiatric patients were more common than had been expected. Our speculation at the time was that the elevations we saw were merely a reflection of the severe emotional stress experienced by these patients. Our simple hypothesis linked stress to increased cortisol secretions and resulting glucose elevations. In a book I wrote in 1970 with my late colleague Alberto DiMascio and other associates, we included a chapter on glucose metabolism. After reviewing the literature from the pre-antipsychotic drug era, we concluded that abnormalities in glucose metabolism were more common in patients suffering from schizophrenia than in the general population. We were particularly influenced by a study from Braceland et al, who found delayed responses to insulin and DM-like glucose tolerance test results in some of their schizophrenic patients. Note that this study was published in1945, a decade before the appearance of chlorpromazine. I was pleased to see that a 2004 paper by Bushe and Holt arrived at the same conclusions we did in 1970. According to these authors, “People with schizophrenia and other serious psychiatric conditions appear to be at significant risk of developing impaired glucose tolerance and diabetes, regardless of whether they are receiving antipsychotic medication.” Unfortunately, a number of patients receiving certain currently available antipsychotic agents (eg, clozapine, olanzapine) gain weight and develop insulin resistance and T2DM. We do not know whether the metabolic abnormalities seen in the predrug era predispose some patients to these unwanted consequences. Some of you may be interested in following connections to the history of medicine. One of the coauthors on the Braceland et al study was Ladislas von Meduna, who had been the initiator of chemically induced seizure treatments for psychotic states. In the mid-1930s, Meduna had first used camphor oil and then pentylenetetrazol to induce seizures. Meduna’s approach followed shortly after Manfred Sakel began to use insulin to achieve hypoglycemic seizures as a treatment for psychosis, an approach he developed in the late 1920s and early 1930s. When I began my psychiatric training in 1961 at the Massachusetts Mental Health Center (formerly called the Boston Psychopathic Hospital), insulin coma therapy was still in use in a few places, among them McLean Hospital in Belmont, Massachusetts. Meduna’s work, in turn, influenced Ugo Cerletti of Italy; Cerletti, working with Lucino Bini, introduced electroconvulsive therapy in 1938. What a curious journey: insulin was once used as a therapy, and resistance to it is now a potential consequence of antipsychotic drug use. The treatment of DM, especially T2DM, has changed dramatically over the last 60 years. The first oral hypoglycemic agents were discovered in France in the early years of World War II. The discovery was purely by chance, as so many drug discoveries are. A French insulin researcher heard that one compound in a group of new sulfa-containing antibiotics caused blackouts, convulsions, and coma; he astutely recognized these as