Genetic basis of endocrine disease. 1. Molecular genetics of insulin resistant diabetes mellitus

Genetic factors are an important determinant of whether an individual will develop noninsulindependent diabetes mellitus (NIDDM). However, the pattern of inheritance of NIDDM is complex and not well understood. In fact, the genetic complexity led one author to refer to diabetes mellitus as a “geneticist's nightmare”. Nevertheless, the pathophysiology of the disease is becoming better understood. Most patients with NIDDM are resistant to the biological actions of insulin. Prospective studies have demonstrated that insulin resistance is a prominent feature early in the natural history of the disease when the patients have impaired glucose tolerance, even before the time that they develop overt diabetes. Whether or not an insulin resistant patient develops NIDDM is determined by the capacity of the pancreatic β-cell to secrete sufficient insulin to overcome the insulin resistance. In those patients who develop insulin deficiency in addition to insulin resistance, the level of plasma glucose rises and the patient develops diabetes mellitus