Diagnosis and Classification of Diabetes Mellitus

S43 P O S I T I O N S T A T E M E N T Diagnosis and Classi?cation of Diabetes Mellitus AMERICAN DIABETES ASSOCIATION reduction, exercise, and/or oral glucose- lowering agents. These individuals there- fore do not require insulin. Other DEFINITION AND DESCRIPTION OF DIABETES MELLITUS — Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of dia- betes is associated with long-term dam- age, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. Several pathogenic processes are in- volved in the development of diabetes. These range from autoimmune destruc- tion of the -cells of the pancreas with consequent insulin de?ciency to abnor- malities that result in resistance to insulin action. The basis of the abnormalities in carbohydrate, fat, and protein metabo- lism in diabetes is de?cient action of in- sulin on target tissues. De?cient insulin action results from inadequate insulin se- cretion and/or diminished tissue re- sponses to insulin at one or more points in the complex pathways of hormone action. Impairment of insulin secretion and de- fects in insulin action frequently coexist in the same patient, and it is often unclear which abnormality, if either alone, is the primary cause of the hyperglycemia. Symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss, sometimes with polyphagia, and blurred vision. Impairment of growth and suscep- tibility to certain infections may also ac- company chronic hyperglycemia. Acute, life-threatening consequences of uncon- trolled diabetes are hyperglycemia with ketoacidosis or the nonketotic hyperos- molar syndrome. Long-term complications of diabetes include retinopathy with potential loss of vision; nephropathy leading to renal failure; peripheral neuropathy with risk of foot ul- cers, amputations, and Charcot joints; and autonomic neuropathy causing gastrointes- tinal, genitourinary, and cardiovascular symptoms and sexual dysfunction. Patients with diabetes have an increased incidence of atherosclerotic cardiovascular, periph- eral arterial, and cerebrovascular disease. Hypertension and abnormalities of lipopro- tein metabolism are often found in people with diabetes. The vast majority of cases of diabetes fall into two broad etiopathogenetic cate- gories (discussed in greater detail below). In one category, type 1 diabetes, the cause is an absolute de?ciency of insulin secre- tion. Individuals at increased risk of de- veloping this type of diabetes can often be identi?ed by serological evidence of an autoimmune pathologic process occur- ring in the pancreatic islets and by genetic markers. In the other, much more preva- lent category, type 2 diabetes, the cause is a combination of resistance to insulin ac- tion and an inadequate compensatory in- sulin secretory response. In the latter category, a degree of hyperglycemia suf?- cient to cause pathologic and functional changes in various target tissues, but without clinical symptoms, may be present for a long period of time before diabetes is detected. During this asymp- tomatic period, it is possible to demon- strate an abnormality in carbohydrate metabolism by measurement of plasma glucose in the fasting state or after a chal- lenge with an oral glucose load. The degree of hyperglycemia (if any) may change over time, depending on the extent of the underlying disease process (Fig. 1). A disease process may be present but may not have progressed far enough to cause hyperglycemia. The same disease process can cause impaired fasting glu- cose (IFG) and/or impaired glucose toler- ance (IGT) without ful?lling the criteria for the diagnosis of diabetes. In some in- dividuals with diabetes, adequate glyce- mic control can be achieved with weight individuals who have some residual insu- lin secretion but require exogenous insu- lin for adequate glycemic control can survive without it. Individuals with ex- tensive -cell destruction and therefore no residual insulin secretion require insu- lin for survival. The severity of the meta- bolic abnormality can progress, regress, or stay the same. Thus, the degree of hy- perglycemia re?ects the severity of the un- derlying metabolic process and its treatment more than the nature of the process itself. CLASSIFICATION OF DIABETES MELLITUS AND OTHER CATEGORIES OF GLUCOSE REGULATION — Assigning a type of diabetes to an individ- ual often depends on the circumstances present at the time of diagnosis, and many diabetic individuals do not easily ?t into a single class. For example, a person with gestational diabetes mellitus (GDM) may continue to be hyperglycemic after deliv- ery and may be determined to have, in fact, type 2 diabetes. Alternatively, a per- son who acquires diabetes because of large doses of exogenous steroids may be- come normoglycemic once the glucocor- ticoids are discontinued, but then may develop diabetes many years later after re- current episodes of pancreatitis. Another example would be a person treated with thiazides who develops diabetes years later. Because thiazides in themselves sel- dom cause severe hyperglycemia, such in- dividuals probably have type 2 diabetes that is exacerbated by the drug. Thus, for the clinician and patient, it is less important to label the particular type of diabetes than it is to understand the pathogenesis of the hy- perglycemia and to treat it effectively. Type 1 diabetes ( -cell destruction, usually leading to absolute insulin ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? The information that follows is based largely on the reports of the Expert Committee on the Diagnosis and Classi?cation of Diabetes (Diabetes Care 20:1183–1197, 1997, and Diab