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Endocrine System

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classes 8 (Table 33-2). Included are the categories of type 1 diabetes (i.e., diabetes resulting from beta cell destruction and an absolute insulin deficiency); type 2 diabetes (i.e., diabetes due to insulin resistance and a relative insulin deficiency); gestational diabetes mellitus (i.e., glucose intolerance that develops during pregnancy that is not clearly overt diabetes [either type 1 or type 2]); and other specific types of diabetes, many of which occur secondary to other conditions (e.g., Cushing syn- drome, acromegaly, and pancreatitis). Categories of Risk for Diabetes The revised classification system also includes a system for diagnosing diabetes according to stages of glucose intolerance. 8–11 The system relies on two tests: (1) a fast- ing plasma glucose (FPG) test, which measures plasma glucose levels after food has been withheld for at least 8 hours, and (2) an oral glucose tolerance test (OGTT), which measures the body’s ability to remove glucose from the blood within 2 hours of consuming 75 g of glucose in 300 mL of water. A FGP below 100 mg/dL or an OGTT less than 140 mg/dL is considered normal (Table 33-3). Persons whose glucose levels, although not meeting the crite- ria for diabetes, are too high to be considered normal are classified as having impaired fasting plasma glu- cose (IFG) and/or impaired glucose tolerance (IGT). Impaired fasting glucose is defined by an elevated FPG of 100 to 125 mg/dL and IGT as plasma glucose levels of 140 to 199 mg/dL with an OGTT (see Table 33-3).

Persons with IFG and/or IGT are often referred to as having prediabetes , meaning they are at relatively high risk for the future development of diabetes as well as cardiovascular disease. 10,11 Thus, calorie restriction and weight reduction (even 5% to 10%) are important in overweight people with prediabetes. Person with a FPG greater than or equal to 126 mg/dL (7.0 mmol/L) or an OGTT 2-hour glucose level greater than or equal to 200 mg/dL (11.1 mmol/L) are considered to have provisional diabetes. 10,11 The cri- teria in Table 33-3 are used to confirm the diagnosis. Glycosylated hemoglobin (i.e., HbA 1c [A1C]) is a widely used marker for chronic hyperglycemia, reflecting aver- age blood glucose levels over a 2- to 3-month period of time (to be discussed). The A1C, which plays a critical role in the management of persons with diabetes, is now recommended for use in the diagnosis of diabetes, with a threshold of greater than 6.5%. 10,11 The test can also be used to identify persons at higher risk for developing diabetes (see Table 33-3). Type 1 Diabetes Mellitus Type 1 diabetes mellitus, which is characterized by destruction of the pancreatic beta cells and accounts for 5% to 10% of those with diabetes, is subdivided into type 1A immune-mediated diabetes and type 1B idio- pathic (non–immune-related) diabetes. 10 In the United States and Europe, approximately 90% to 95% of peo- ple with type 1 diabetes mellitus have type 1A immune- mediated diabetes. The rate of beta cell destruction is

TABLE 33-2 Etiologic Classification of Diabetes Mellitus Type Subtypes

Etiology of Glucose Intolerance

  I.Type 1*

Beta cell destruction usually leading to absolute insulin deficiency A. Immune mediated May range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance A. Genetic defects in beta cell function (e.g., glucokinase) B. Genetic defects in insulin action (e.g., leprechaunism, Rabson-Mendenhall syndrome) C. Diseases of exocrine pancreas (e.g., pancreatitis, neoplasms, cystic fibrosis) D. Endocrine disorders (e.g., acromegaly, Cushing syndrome) Any degree of glucose intolerance that develops during pregnancy that is not clearly diabetes (either type 1 or type 2) B. Idiopathic

Autoimmune destruction of beta cells

Unknown

 II.Type 2*

III. Other specific types

Dysregulation insulin secretion due to a defect in glucokinase generation Pediatric syndromes that have mutations in insulin receptors

Loss or destruction of insulin-producing beta cells

Diabetogenic effects of excess hormone levels Combination of insulin resistance and impaired insulin secretion

IV. Gestational diabetes mellitus (GDM)

*Patients with any form of diabetes may require insulin treatment at some stage of the disease. Such use of insulin does not, in itself, classify the patient. Adapted fromThe Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2004;27:S5–S10. Reprinted with permission from the American Diabetes Association. Copyright © 2004 American Diabetes Association.