Abstract
Studies conducted at the University of Michigan for 60 years and at the University of Chicago for approximately 25 years form the basis of this review. As no field of study can develop or progress in isolation, we have included selected investigations performed in other centers. In the academic year 1949–1950, one of us (S.S.F.), while a first-year Fellow in Endocrinology and Metabolism at the University of Michigan (Jerome W. Conn, Division Chief), initiated a prospective, long-term study on the diagnosis, natural history, and clinical genetics of diabetes. Starting with known diabetic patients from the Diabetes Clinic, I recruited their apparently healthy and asymptomatic first-degree relatives (parents, brothers, sisters, and children) for routine oral glucose tolerance tests (OGTTs). As control subjects, I recruited young individuals, many of them students, physicians, nurses, dietitians, and their spouses, who did not have a family history of diabetes or of large newborn babies. The initial objectives were 1 ) to define the normal range for the OGTT, 2 ) to attempt to unmask the potential diabetic subjects who manifest normal glucose tolerance by the standard OGTT and determine whether the diabetogenic activity of cortisone could be used to uncover a subclinical defect in the metabolism of glucose, and 3 ) to carry out periodic follow-up over many years of the apparently healthy first-degree relatives of diabetic patients. In our first publication in 1954 (1), 19% of 152 relatives of known diabetic patients were found to have diabetes by OGTT and, moreover, some were as young as 10 years of age. The same prevalence of 19% was found when testing a larger sample of 438 relatives of known diabetic patients (2). In 1960, we reported that mild, asymptomatic diabetes occurs in nonobese children, adolescents, and young adults. Their diabetic glucose tolerance and fasting hyperglycemia improved or normalized …
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