Atypical Forms of Type 2 Diabetes

Abstract

Patients with "typical" type 2 diabetes are generally obese and display varying degrees of insulin resistance and insulin secretory defects. The onset of type 2 diabetes occurs mostly after the third decade of life, and these patients do not spontaneously develop ketosis or need insulin for Survival. Many other patients present with "atypical" forms of type 2 diabetes; insulin resistance or insulin secretory defects occur owing to certain other specific etiologies. These include various genetic and acquired causes leading to adipose tissue disorders, beta-cell dysfunction or impaired insulin action. Other endocrinopathies and drug therapy may also result in atypical diabetes. Lipodystrophies are characterized by selective loss of adipose tissue leading to excess fat accumulation in aberrant tissues Such as the liver and muscle, which causes insulin resistance. Although the degree of fat loss and the resultant metabolic abnormalities varies among patients with the different types of lipodystrophies, diabetes in most lipodystrophic patients is characterized by marked insulin resistance and high insulin requirements. Maturity-onset Diabetes of the Young (MODY) is a group of heterogeneous forms of monogenic diabetes characterized by autosomal dominant inheritance, young age at onset and pancreatic beta-cell dysfunction. Similarly, mutations or deletions in mitochondrial DNA also cause diabetes owing to beta-cell dysfunction, which is maternally inherited, whereas insulin receptor mutations cause autosomal dominant or recessive syndromes of extreme insulin resistance such as type-A insulin resistance syndrome, Rabson-Mendenhall syndrome, and Leprechaunism. The clinical features and management of patients with these rare syndromes are distinct from those for patients with typical type 2 diabetes. Recognition of these patients is important, as it helps to tailor therapy based on the underlying pathophysiologic process. These syndromes have also greatly contributed to our understanding of glucose homeostasis and the pathogenesis of diabetes in general.