Clinical Inquiries

What is the best way to distinguish type 1 and 2 diabetes?

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EVIDENCE-BASED ANSWER

No clinical characteristic or diagnostic test is available to readily distinguish type 1 from type 2 diabetes mellitus. Although C-peptide levels, autoantibodies, and adiponectin-to-leptin ratios show some utility, they do not yet have a standard diagnostic role; research on the pathophysiology of diabetes suggests that the classic type 1 and type 2 distinctions may not be appropriate for all patients1 (strength of recommendation: C, based on expert opinion).

Evidence summary

Onset of diabetes in childhood with ketoacidosis and insulin dependency has traditionally been sufficient to diagnose type 1 diabetes, while onset in older, obese patients with primary insulin resistance suggested type 2 diabetes. Unfortunately, features of type 1 and type 2 diabetes may be present in the same patient, making differentiation difficult. No diagnostic studies in the literature were identified that definitively demonstrate how to separate type 1 from type 2 diabetes.

A patient’s age may suggest, but does not reliably distinguish, diabetes types. A study of 569 new-onset type 1 and type 2 diabetic children and adolescents showed that older age was only weakly associated with type 2 diagnosis (odds ratio [OR]= 1.4 for each 1-year increment in age; 95% confidence interval [CI], 1.3–1.6).2 In fact, newly diagnosed 12-year-old children have an equal incidence of type 1 as type 2 diabetes. Likewise, adults with type 2 phenotype (no initial insulin requirement) can present with positive autoantibodies typically found in younger type 1 patients. Older patients who fit this profile have been classified as type 1.5 diabetes or latent autoimmune disease in adults (LADA).3

A history of diabetic ketoacidosis (DKA) also does not reliably distinguish between types 1 and 2. A retrospective chart review gathered data on adults over 18 years of age who were admitted for DKA in a urban US hospital. Many patients with DKA were subsequently diagnosed with type 2 diabetes. Rates of type 2 diabetes in patients with DKA varied by race: 47% of Hispanics, 44% of African Americans, and 17% of Caucasians had type 2 diabetes.4

The overlapping presence of autoantibodies in both types of diabetes limits their use (TABLE). Autoantibodies do predict an earlier need for insulin. One prevalence study of 101 type 2 adult patients found 20% were positive for glutamic acid decarboxylase autoantibody (GADAb), which was positively associated with insulin dependence at 4 years postdiagnosis (OR=5.8; 95% CI, 1.8–18.9).5 Eighty percent of patients with autoantibodies required insulin compared with 41% of patients without autoantibodies. Another study in young adults with type 2 or unclassified diabetes from Sweden found 93% of patients who were GADAb+ required insulin at 3 years, compared with 51% who were GADAb–(OR=18.8; 95% CI, 1.8–191).6

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