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Chapter 2
The Diagnosis and Classification of Diabetes in Nonpregnant Adults
Irl B. Hirsch, MD, MACP,1 and Linda M. Gaudiani, MD, FACP, FACE2
1Professor of Medicine, University of Washington School of Medicine, Seattle, WA. 2Medical Director, Braden Diabetes Center, Marin Endocrine Care and Research, Greenbrae, CA; Associate Clinical Professor of Medicine, University California San Francisco, CA.
DOI: 10.2337/9781580406086.02
Much has been learned about the diverse pathogenesis of diabetes over the previous two decades resulting in alterations in the traditional classification of this disease. Although former classifications focused largely on age at onset of initial clinical presentations, such as acute diabetic ketoacidosis (DKA) versus chronic hyperglycemia, the newer position statements on classification by the American Diabetes Association (ADA) have focused on etiologies rather than phenotype. New genetic testing capabilities, expanded immunologic characterizations, and case reports of novel presentations in special disease states have further expanded diagnostic and classification schemes. This has resulted in nomenclature that is more complex than type 1 diabetes (T1D) and type 2 diabetes (T2D), recognizing the heterogeneous characteristics of the major classes of diabetes as well as the phenotypic and mechanistic overlap both initially and over the course of the disease state. Although assigning a type of diabetes to any given patient may be confounded by the circumstances at the time of diagnosis or by acute illness in the hospitalized patient, misdiagnosis of the type of diabetes, failure to attempt to classify the patient accurately, or failure to recognize that the hospitalized patient has diabetes all are critical errors that may affect treatment decisions in the hospital and following discharge and also may contribute to readmissions. An incorrect diabetes classification during the hospital admission and discharge could have especially significant consequences in our current protocol-driven system of diabetes management and certainly on safe transitions of aftercare.
Unfortunately, misclassification of diabetes is not uncommon. Reasons include the fact that age and obesity are traditional discriminating factors for T1D and T2D. Although the exact number is not known, it is estimated that as many as 50% of patients with T1D are diagnosed after the age of 18 years. The impact of this change in the demographics of T1D is not yet clear; however, misdiagnosis of T1D is responsible for admissions for DKA and the development of DKA in the hospital setting.
Several other issues are contributing to a more complex classification of diabetes type. The recent increase in the use of insulin to treat T2D has blurred the prior differentiating schemes based on therapy, as has the expanded uses of noninsulin injectable and oral agents to augment insulin therapy in select individuals with T1D. Additionally, the expanded descriptions and differentiations of the various forms of monogenic diabetes, pancreatic diabetes, and lipodystrophic and syndromic diabetes now often require the assistance of sophisticated laboratory testing for diagnosis1-3 and often provoke controversy even among endocrinologists. Even with appropriate genetic or antibody analysis, classification is not always clear, available, or timely, resulting in movement between diagnostic categories over time.4
It is critical that significant hyperglycemia in the hospitalized patient be promptly recognized and addressed with therapies and education to ensure safe glycemic targets that support best clinical outcomes for the admission. An adequate history must be obtained and testing tailored to guide inpatient management and discharge planning. These goals can be best met by thoughtful consideration of accurate diabetes classification and reconsideration of patients’ prior classification as they present clinically.
This chapter reviews the current diagnostic criteria and classification scheme of diabetes for nonpregnant adults with a focus on areas of special interest in the hospital setting. We also hope to acknowledge the areas of controversy and confusion in the current nomenclature and to clarify and further define the various nomenclatures in a schema that is useful, intuitive, and flexible. It is our expectation that as understanding about the pathogenesis and genetic influences of the various forms of diabetes expands, future classifications will continue to evolve.5
Diagnosis
Because more than 8 million people (nearly a third) in the U.S. with diabetes are not diagnosed,6 many patients admitted with hyperglycemia will have undiagnosed diabetes. Those with previously undiagnosed diabetes are more likely to require admission to the hospital compared with those without diabetes.7 Furthermore, at each level of hyperglycemia, those without a previous diagnosis of diabetes have been shown to be less likely to receive insulin and have greater adverse events compared with those with known diabetes before admission.8 Unfortunately, diabetes can remain undiagnosed or unattended during hospitalization9 and the nondiagnosis of diabetes or the undertreatment of stress-induced hyperglycemia in the hospital represents a “missed opportunity” and confers increased mortality risk.10
The current diagnostic criteria for diabetes mellitus pose special challenges for the admitting health-care provider. All of the three recently proposed diagnostic glucometric tests for diabetes, except for the HbA1c, are specific for nonill, nonstressed individuals, rendering a new diagnosis of diabetes during hospitalization problematic. The traditional glucose tolerance tests are impractical in the hospital setting and random plasma and fasting plasma glucose values can be distorted by dextrose-containing intravenous (IV) fluids, steroids, stress, illness, and fluctuations in nutrition. The HbA1c test has the advantages of speed, convenience (fasting is not required), and fewer perturbations from recent stress and illness. Table 2.1 notes the current ADA criteria for diabetes.5
Table 2.1—Criteria for the Diagnosis of Diabetes
HbA1c >6.5% (The test should be performed in a laboratory using a method that is National Glycohemoglobin Standardization Program certified* and standardized to the Diabetes Control and Complications Trial assay.**)
OR
Fasting plasma glucose >126 mg/dL (fasting is defined as no caloric intake for at least 8 h)
OR
2-h postprandial plasma glucose >200 mg/dL during a 75-g oral glucose tolerance test
OR
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose >200 mg/dL
*See NGSP.org; **in the absence of unequivocal hyperglycemia, the results should be confirmed
