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 by repeat testing.
Of the three diagnostic glucose tests for diabetes, all of which have limitations in hospitalized patients, the most recently added is HbA1c.5 Despite its advantages, a number of cautions still pertain to the reliability and accuracy of this test in the acutely ill population, especially when critical illness is superimposed on chronic comorbidities.11 There are numerous clinical scenarios in which the HbA1c may be falsely high or more commonly low and therefore not actually reflect the glycemic history that usually relates to changes in red blood cell survival times (Table 2.2). This obviously makes the HbA1c difficult to utilize as a diagnostic tool in the hospital setting without careful consideration. In one study, just treating an iron-deficiency anemia can lower the HbA1c from 10.1% to 8.2% in a population with diabetes and from 7.6% to 6.2% in a population without diabetes.12
Cardiac valvulopathies and valve replacements with both aortic or mitral valves can cause a microhemolysis resulting in a falsely low HbA1c.11 Thus, despite the fact many hospitals now require admission HbA1c measurements on patients with and without known diabetes entering the hospital, the test has inherent problems, resulting in the potential for misdiagnosis and mismanagement. Nonetheless, a significantly high HbA1c level (e.g., >8.0%) in the context of hyperglycemia (>180–200 mg/dL) makes the diagnosis of diabetes highly probable.
Table 2.2—Etiologies of Falsely High or Low HbA1c Levels
Falsely high
—Iron deficiency (with or without anemia)
—Anemia
—Hemoglobinopathies
—Race: African American, Hispanic, Asian
Falsely low
—Hemolysis
—Reticulocytosis
—Hemoglobinopathies
—Posthemorrhage or post-transfusion
—Drugs: iron, erythropoietin, dapsone
—Uremia
—Splenomegaly
Plasma glucose is another test that can be used for the diagnosis of diabetes. In the outpatient setting, a fasting glucose of 126 mg/dL or higher or a 75-g oral glucose tolerance test with a 2-h glucose ≥200 mg/dL confirms the diagnosis of diabetes.5 It is recommended that two such tests are performed in the absence of unequivocal hyperglycemia. The third diagnostic test using glucose is a random plasma glucose >200 mg/dL with classic symptoms of hyperglycemia (polyuria, polydipsia).5 In addition to a significantly high HbA1c, only this last diagnostic test can be used definitively to confirm the diagnosis of diabetes for the hospitalized patient.
Consider the patient with an HbA1c of 6.8%, anemia, and renal insufficiency who is admitted with pneumonia and fasting and postprandial glucose levels in the 130–140 mg/dL and 200–220 mg/dL range, respectively. This patient may or may not meet the criteria for diabetes once discharged from the hospital. Nonetheless, the inpatient strategy for the treatment of this patient’s hyperglycemia should be to meet the goals for optimal inpatient glycemic control and should not be influenced by diagnostic ambiguity. It is critical that “stress hyperglycemia versus diabetes” be included on the discharge problem list so both the patient and the outpatient care team appreciates the specific diagnosis clarifications to be investigated once the acute illness has resolved.
In addition to the diagnostic categories of diabetes and stress-induced hyperglycemia, the Expert Committee on Diagnosis and Classification of Diabetes now recognizes a significant group of patients who are at increased risk of developing future diabetes. The term “prediabetes” is used to describe these individuals with impaired fasting glucose or impaired glucose tolerance (Table 2.3).5 Although these patients do not meet the diagnostic criteria for diabetes, their glucose values are too high to be considered normal, and numerous prospective studies have shown a strong association between HbA1c and progression to diabetes. In the hospital setting, these patients can develop significant hyperglycemia and are at increased risk for complications while hospitalized and subsequently for cardiovascular disease.
Table 2.3—Categories of Increased Risk for Diabetes (Prediabetes)*