Diagnosis, classification, and pathogenesis of diabetes mellitus

Diabetes mellitus is a metabolic disorder that is characterized by inappropriate hyperglycemia and is associated with both acute and chronic complications. Currently, diabetes mellitus is diagnosed by blood or plasma glucose levels. A random plasma glucose level > or = 200 mg/dL in an individual with classic symptoms is sufficient to make the diagnosis. Otherwise, a fasting plasma glucose level > or = 126 mg/dL or a 2-hour plasma glucose level > or = 200 mg/dL after an oral glucose challenge of 75 g on 2 occasions is sufficient evidence upon which to diagnose diabetes mellitus. The major types of diabetes mellitus are type 1 diabetes (insulin deficient) and type 2 diabetes (combination of insulin resistance and insulin deficiency). In both types, there is a genetic predisposition as well as environmental factors that contribute to the expression of the genetic predisposition. In type 1 diabetes, the primary abnormality is extensive deficiency of beta cell function. In type 2 diabetes, insulin resistance occurs, and the marked compensatory increases in insulin secretion necessary to maintain normal glucose tolerance cannot be achieved or maintained. As beta cell function continues to decrease, the individual progresses from normal glucose tolerance to impaired glucose tolerance to diabetes with primarily postprandial hyperglycemia to diabetes with fasting hyperglycemia. Drugs can cause diabetes by interfering with beta cell insulin secretion, by increasing insulin resistance, or by a combination of both. Atypical antipsychotic drugs have been reported to cause diabetic ketoacidosis, obesity and insulin resistance, type 2 diabetes, and hypertriglyceridemia. A monitoring system should be in place in patients started on treatment with these agents to detect metabolic abnormalities as they are evolving so that adequate and timely treatment can be initiated.