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Classification of diabetes mellitus and genetic diabetic syndromes

David K McCulloch, MD
Section Editors
David M Nathan, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Jean E Mulder, MD


Type 2 diabetes accounts for over 90 percent of cases of diabetes in the United States, Canada, and Europe; type 1 diabetes accounts for another 5 to 10 percent, with the remainder due to other causes (table 1). New information has led to increased understanding of genetic defects related to diabetes. Monogenic causes of type 2 diabetes (eg, those causing maturity onset diabetes of the young) represent only a small fraction of cases, and commonly inherited polymorphisms individually contribute only small degrees of risk for, or protection from, diabetes. Most of the genetic risk for type 2 diabetes results from complex polygenic risk factors.

The etiologic classification of diabetes mellitus will be reviewed here. The definition and diagnostic criteria for diabetes mellitus are discussed separately. (See "Clinical presentation and diagnosis of diabetes mellitus in adults".)


Type 1 diabetes is characterized by destruction of the pancreatic beta cells, leading to absolute insulin deficiency. This is usually due to autoimmune destruction of the beta cells (type 1A). Testing for islet cell antibodies (ICA) or other islet autoantibodies (antibodies to glutamic acid decarboxylase [GAD] 65, insulin, and to the tyrosine phosphatases, insulinoma-associated protein 2 [IA-2] and IA-2 beta, and zinc transporter ZnT8) in serum may be helpful if establishing the diagnosis is important; a positive result is indicative of immune-mediated or type 1A diabetes [1]. However, the absence of pancreatic autoantibodies does not rule out the possibility of type 1 diabetes. Some patients with absolute insulin deficiency have no evidence of autoimmunity and have no other known cause for beta cell destruction. They are said to have idiopathic or type 1B diabetes mellitus. (See "Pathogenesis of type 1 diabetes mellitus".)

The current American Diabetes Association (ADA) classification of diabetes mellitus does not reflect the clinical heterogeneity of patients with diabetes and the emergence of the concept that early beta cell dysfunction is likely to be a primary defect in the pathophysiology of diabetes, regardless of “type.” Other classification schemes have been proposed, accounting for beta cell autoimmunity, beta cell function, clinical features, and body weight. The high prevalence of overweight/obesity in the population has further complicated classification systems with an added element of insulin resistance even in type 1 diabetes. (See "Syndromes of ketosis-prone diabetes mellitus", section on 'Classification'.)

It is anticipated that other subtypes of type 1 (and type 2 diabetes) will become more clearly defined in the future.


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Literature review current through: Sep 2016. | This topic last updated: Apr 1, 2016.
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