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2. Classification and Diagnosis of Diabetes Diabetes Care Volume 42, Supplement 1, January 2019 S13 2. Classification and Diagnosis of American Diabetes Association Diabetes: Standards of Medical Care in Diabetesd2019 Diabetes Care 2019;42(Suppl. 1):S13–S28 | https://doi.org/10.2337/dc19-S002 2. CLASSIFICATION AND DIAGNOSIS OF DIABETES The American Diabetes Association (ADA) “Standards of Medical Care in Diabetes” includes ADA’s current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA’s clinical practice recommendations, please refer to the Standards of Care Introduction. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC. CLASSIFICATION Diabetes can be classified into the following general categories: 1. Type 1 diabetes (due to autoimmune b-cell destruction, usually leading to absolute insulin deficiency) 2. Type 2 diabetes (due to a progressive loss of b-cell insulin secretion frequently on the background of insulin resistance) 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation) 4. Specific types of diabetes due to other causes, e.g., monogenic diabetes syndromes (such as neonatal diabetes and maturity-onset diabetes of the young [MODY]), diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of HIV/AIDS, or after organ transplantation) This section reviews most common forms of diabetes but is not comprehensive. For additional information, see the American Diabetes Association (ADA) position statement “Diagnosis and Classification of Diabetes Mellitus” (1). Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinical Suggested citation: American Diabetes Associa- presentation and disease progression may vary considerably. Classification is im- tion. 2. Classification and diagnosis of diabetes: portant for determining therapy, but some individuals cannot be clearly classified as Standards of Medical Care in Diabetesd2019. having type 1 or type 2 diabetes at the time of diagnosis. The traditional paradigms of Diabetes Care 2019;42(Suppl. 1):S13–S28 type 2 diabetes occurring only in adults and type 1 diabetes only in children are no © 2018 by the American Diabetes Association. longer accurate, as both diseases occur in both age-groups. Children with type 1 Readers may use this article as long as the work is properly cited, the use is educational and not diabetes typically present with the hallmark symptoms of polyuria/polydipsia, and for profit, and the work is not altered. More infor- approximately one-third present with diabetic ketoacidosis (DKA) (2). The onset of mation is available at http://www.diabetesjournals type 1 diabetes may be more variable in adults, and they may not present with the .org/content/license. S14 Classification and Diagnosis of Diabetes Diabetes Care Volume 42, Supplement 1, January 2019 classic symptoms seen in children. Oc- of subtypes of this heterogeneous dis- Fasting and 2-Hour Plasma Glucose casionally, patients with type 2 diabetes order have been developed and vali- The FPG and 2-h PG may be used to may present with DKA, particularly ethnic datedinScandinavianandNorthern diagnose diabetes (Table 2.2). The con- minorities (3). Although difficulties in European populations but have not cordance between the FPG and 2-h PG distinguishing diabetes type may occur in been confirmed in other ethnic and racial tests is imperfect, as is the concordance all age-groups at onset, the true diag- groups. Type 2 diabetes is primarily as- between A1C and either glucose-based nosis becomes more obvious over sociated with insulin secretory defects test.ComparedwithFPGandA1Ccut time. related to inflammation and metabolic points, the 2-h PG value diagnoses more In both type 1 and type 2 diabetes, stress among other contributors, includ- people with prediabetes and diabetes (9). various genetic and environmental fac- ing genetic factors. Future classification tors can result in the progressive loss of schemes for diabetes will likely focus A1C b-cell mass and/or function that mani- on the pathophysiology of the underly- Recommendations fests clinically as hyperglycemia. Once ing b-cell dysfunction and the stage of 2.1 To avoid misdiagnosis or missed hyperglycemia occurs, patients with all disease as indicated by glucose status diagnosis, the A1C test should be forms of diabetes are at risk for devel- (normal, impaired, or diabetes) (4). performed using a method that is oping the same chronic complications, certified by the NGSP and stan- although rates of progression may differ. DIAGNOSTIC TESTS FOR DIABETES dardized to the Diabetes Control The identification of individualized ther- Diabetes may be diagnosed based on and Complications Trial (DCCT) apies for diabetes in the future will re- plasma glucose criteria, either the fasting assay. B quire better characterization of the many plasma glucose (FPG) value or the 2-h 2.2 Marked discordance between mea- paths to b-cell demise or dysfunction (4). plasma glucose (2-h PG) value during a sured A1C and plasma glucose Characterization of the underlying 75-g oral glucose tolerance test (OGTT), levels should raise the possibility pathophysiology is more developed in or A1C criteria (6) (Table 2.2). of A1C assay interference due to type 1 diabetes than in type 2 diabetes. It Generally, FPG, 2-h PG during 75-g hemoglobin variants (i.e., hemo- is now clear from studies of first-degree OGTT, and A1C are equally appropriate globinopathies) and consider- relatives of patients with type 1 diabetes for diagnostic testing. It should be noted ation of using an assay without that the persistent presence of two or that the tests do not necessarily detect interference or plasma blood glu- more autoantibodies is an almost certain diabetes in the same individuals. The cose criteria to diagnose diabe- predictor of clinical hyperglycemia and efficacy of interventions for primary pre- tes. B diabetes. The rate of progression is de- vention of type 2 diabetes (7,8) has 2.3 In conditions associated with an pendent on the age at first detection primarily been demonstrated among in- altered relationship between A1C of antibody, number of antibodies, anti- dividuals who have impaired glucose and glycemia, such as sickle cell body specificity, and antibody titer. Glu- tolerance (IGT) with or without elevated disease, pregnancy (second and cose and A1C levels rise well before the fasting glucose, not for individuals with third trimesters and the postpar- clinical onset of diabetes, making diag- isolated impaired fasting glucose (IFG) or tum period), glucose-6-phosphate nosis feasible well before the onset of for those with prediabetes defined by dehydrogenase deficiency, HIV, DKA. Three distinct stages of type 1 di- A1C criteria. hemodialysis, recent blood loss or abetes can be identified (Table 2.1) and The same tests may be used to screen transfusion, or erythropoietin ther- serve as a framework for future research for and diagnose diabetes and to detect apy, only plasma blood glucose cri- and regulatory decision making (4,5). individuals with prediabetes. Diabetes teria should be used to diagnose The paths to b-cell demise and dys- may be identified anywhere along the diabetes. B function are less well defined in type 2 spectrum of clinical scenarios: in seem- diabetes, but deficient b-cell insulin ingly low-risk individuals who happen to The A1C test should be performed using a secretion, frequently in the setting of have glucose testing, in individuals tested method that is certified by the NGSP insulin resistance, appears to be the based on diabetes risk assessment, and (www.ngsp.org) and standardized or common denominator. Characterization in symptomatic patients. traceable to the Diabetes Control and Table 2.1—Staging of type 1 diabetes (4,5) Stage 1 Stage 2 Stage 3 Characteristics c Autoimmunity c Autoimmunity c New-onset hyperglycemia c Normoglycemia c Dysglycemia c Symptomatic c Presymptomatic c Presymptomatic Diagnostic criteria c Multiple autoantibodies c Multiple autoantibodies c Clinical symptoms c No IGT or IFG c Dysglycemia: IFG and/or IGT c Diabetes by standard criteria c FPG 100–125 mg/dL (5.6–6.9 mmol/L) c 2-h PG 140–199 mg/dL (7.8–11.0 mmol/L) c A1C 5.7–6.4% (39–47 mmol/mol) or $10% increase in A1C care.diabetesjournals.org Classification and Diagnosis of Diabetes S15 Table 2.2—Criteria for the diagnosis of diabetes FPG $126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* OR 2-h PG $200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.* OR A1C $6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose $200 mg/dL (11.1 mmol/L). *In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples. Complications Trial (DCCT) reference clinical guidance concluded that A1C, Americans may also have higher levels of assay. Although point-of-care A1C assays FPG, or 2-h PG can be used to test for fructosamine and glycated albumin and may be NGSP certified or U.S.
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