1、2. Classification and Diagnosis ofDiabetes:Standards of MedicalCare in Diabetes2022Diabetes Care 2022;45(Suppl. 1):S17S38 | https:/doi.org/10.2337/dc22-S002American Diabetes AssociationProfessional Practice Committee*The American Diabetes Association (ADA) “Standards of Medical Care in Dia-betes” in
2、cludes the ADAs current clinical practice recommendations and isintended to provide the components of diabetes care, general treatment goalsand guidelines, and tools to evaluate quality of care. Members of the ADA Profes-sional Practice Committee, a multidisciplinary expert committee (https:/doi.org
3、/10.2337/dc22-SPPC), are responsible for updating the Standards of Careannually, or more frequently as warranted. For a detailed description of ADAstandards, statements, and reports, as well as the evidence-grading system forADAs clinical practice recommendations, please refer to the Standards of Ca
4、reIntroduction (https:/doi.org/10.2337/dc22-SINT). Readers who wish to commenton the Standards of Care are invited to do so at professional.diabetes.org/SOC.CLASSIFICATIONDiabetes can be classified into the following general categories:1. Type 1 diabetes (due to autoimmune b-cell destruction, usuall
5、y leading to abso-lute insulin deficiency, including latent autoimmune diabetes of adulthood)2. Type 2 diabetes (due to a progressive loss of adequate b-cell insulin secretionfrequently on the background of insulin resistance)3. Specific types of diabetes due to other causes, e.g., monogenic diabete
6、s syn-dromes (such as neonatal diabetes and maturity-onset diabetes of the young),diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis),and drug- or chemical-induced diabetes (such as with glucocorticoid use, inthe treatment of HIV/AIDS, or after organ transplantation)4. Gesta
7、tional diabetes mellitus (diabetes diagnosed in the second or third tri-mester of pregnancy that was not clearly overt diabetes prior to gestation)This section reviews most common forms of diabetes but is not comprehensive. Foradditional information, see the American Diabetes Association (ADA) posit
8、ion state-ment “Diagnosis and Classification of Diabetes Mellitus” (1).Type 1 diabetes and type 2 diabetes are heterogeneous diseases in which clinicalpresentation and disease progression may vary considerably. Classification is impor-tant for determining therapy, but some individuals cannot be clea
9、rly classified ashaving type 1 or type 2 diabetes at the time of diagnosis.The traditional paradigmsof type 2 diabetes occurring only in adults and type 1 diabetes only in children areno longer accurate, as both diseases occur in both age-groups. Children with type1 diabetes often present with the h
10、allmark symptoms of polyuria/polydipsia, and*A complete list of members of the AmericanDiabetes Association Professional Practice Com-mittee can be found at https:/doi.org/10.2337/dc22-SPPC.Suggested citation: American Diabetes Asso-ciation Professional Practice Committee. 2. Classi-fication and dia
11、gnosis of diabetes: Standards ofMedical Care in Diabetes2022. Diabetes Care2022;45(Suppl. 1):S17S38 2021 by the American Diabetes Association.Readers may use this article as long as thework is properly cited, the use is educationaland not for profit, and the work is not altered.Moreinformationisavai
12、lableathttps:/diabetesjournals.org/journals/pages/license.2. CLASSIFICATION AND DIAGNOSIS OF DIABETESDiabetes Care Volume 45, Supplement 1, January 2022S17Downloaded from http:/diabetesjournals.org/care/article-pdf/45/Supplement_1/S17/637547/dc22s002.pdf by guest on 10 July 2022approximately half pr
13、esent with diabeticketoacidosis (DKA) (24). The onset oftype 1 diabetes may be more variablein adults; they may not present withthe classic symptoms seen in childrenand may experience temporary remis-sion from the need for insulin (57).The features most useful in discrimina-tion of type 1 diabetes i
14、nclude youngerage at diagnosis (35 years) with lowerBMI (360mg/dL (20 mmol/L) at presentation (8).Occasionally, patients with type 2 diabe-tes may present with DKA (9,10), partic-ularly ethnic and racial minorities (11).It is important for the provider to real-ize that classification of diabetes typ
15、e isnot always straightforward at presenta-tion and that misdiagnosis is common(e.g., adults with type 1 diabetes mis-diagnosed as having type 2 diabetes;individuals with maturity-onset diabetesof the young MODY misdiagnosed ashaving type 1 diabetes, etc.). Althoughdifficultiesindistinguishingdiabet
16、estype may occur in all age-groups atonset, the diagnosis becomes moreobvious over time in people with b-celldeficiency.In both type 1 and type 2 diabetes,various genetic and environmental fac-tors can result in the progressive loss ofb-cell mass and/or function that mani-fests clinically as hypergl
17、ycemia. Oncehyperglycemia occurs, people with allforms of diabetes are at risk for devel-oping the same chronic complications,although rates of progression may differ.The identification of individualized ther-apies for diabetes in the future will beinformed by better characterization ofthe many path
18、s to b-cell demise or dys-function (12). Across the globe manygroupsareworkingoncombiningclinical, pathophysiological, and geneticcharacteristics to more precisely definethe subsets of diabetes that are cur-rently clustered into the type 1 diabetesversus type 2 diabetes nomenclaturewith the goal of
19、optimizing personalizedtreatment approaches. Many of thesestudies show great promise and maysoon be incorporated into the diabetesclassification system (13).Characterizationoftheunderlyingpathophysiology is more precisely devel-oped in type 1 diabetes than in type 2diabetes. It is now clear from pro
20、spectivestudies that the persistent presence oftwo or more islet autoantibodies is anear certain predictor of clinical diabetes(14). The rate of progression is depen-dent on the age at first detection ofautoantibody, number of autoantibodies,autoantibody specificity, and autoanti-body titer. Glucose
21、 and A1C levels risewell before the clinical onset of diabetes,making diagnosis feasible well before theonset of DKA. Three distinct stages oftype 1 diabetes can be identified (Table2.1) and serve as a framework for futureresearch and regulatory decision-making(12,15). There is debate as to whethers
22、lowly progressive autoimmune diabeteswith an adult onset should be termedlatent autoimmune diabetes in adults(LADA) or type 1 diabetes. The clinicalpriority with detection of LADA is aware-ness that slow autoimmune b-cell de-struction can occur in adults leading to along duration of marginal insulin
23、 secre-tory capacity. For the purpose of thisclassification, all forms of diabetes medi-ated by autoimmune b-cell destructionare included under the rubric of type 1diabetes. Use of the term LADA is com-mon and acceptable in clinical practiceand has the practical impact of heighten-ing awareness of a
24、 population of adultslikely to have progressive autoimmuneb-cell destruction (16), thus acceleratinginsulin initiation prior to deterioration ofglucose control or development of DKA(6,17).The paths to b-cell demise and dys-function are less well defined in type 2diabetes,butdeficientb-cellinsulinsec
25、retion, frequently in the setting ofinsulin resistance, appears to be thecommon denominator.Type 2 diabetes isassociated with insulin secretory defectsrelated to genetics, inflammation, andmetabolicstress.Futureclassificationschemes for diabetes will likely focus onthe pathophysiology of the underly
26、ingb-cell dysfunction (12,13,1820).DIAGNOSTIC TESTS FOR DIABETESDiabetes may be diagnosed based onplasma glucose criteria, either the fast-ing plasma glucose (FPG) value or the2-h plasma glucose (2-h PG) value dur-ing a 75-g oral glucose tolerance test(OGTT), or A1C criteria (21) (Table 2.2).General
27、ly, FPG, 2-h PG during 75-gOGTT, and A1C are equally appropriatefor diagnostic screening. It should benoted that the screening tests do notnecessarily detect diabetes in the sameindividuals. The efficacy of interventionsfor primary prevention of type 2 diabe-tes (22,23) has mainly been demon-strated
28、 among individuals who haveimpaired glucose tolerance (IGT) with orwithout elevated fasting glucose, notfor individuals with isolated impairedfasting glucose (IFG) or for those withprediabetes defined by A1C criteria.The same tests may be used toscreen for and diagnose diabetes and todetectindividua
29、lswithprediabetes(Table 2.2 and Table 2.5) (24). Diabetesmaybeidentifiedanywherealongthe spectrum of clinical scenariosinTable 2.1Staging of type 1 diabetes (12,15)Stage 1Stage 2Stage 3Characteristics? Autoimmunity? Autoimmunity? Autoimmunity? Normoglycemia? Dysglycemia? Overt hyperglycemia? Presymp
30、tomatic? Presymptomatic? SymptomaticDiagnostic criteria? Multiple islet autoantibodies? Islet autoantibodies (usually multiple)? Autoantibodies may become absent? No IGT or IFG? Dysglycemia: IFG and/or IGT? Diabetes by standard criteria? FPG 100125 mg/dL (5.66.9 mmol/L)? 2-h PG 140199 mg/dL (7.811.0
31、 mmol/L)? A1C 5.76.4% (3947 mmol/mol) or $10%increase in A1CFPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; 2-h PG, 2-h plasma glucose.S18Classification and Diagnosis of DiabetesDiabetes Care Volume 45, Supplement 1, January 2022Downloaded from http:/diab
32、etesjournals.org/care/article-pdf/45/Supplement_1/S17/637547/dc22s002.pdf by guest on 10 July 2022seemingly low-risk individuals who hap-pen to have glucose testing, in individu-als screened based on diabetes riskassessment, and in symptomatic patients.For additional details on the evidenceused to e
33、stablish the criteria for the diag-nosis of diabetes, prediabetes and abnor-mal glucose tolerance (OFG, IGT), see theADA position statement “Diagnosis andClassification of Diabetes Mellitus” (1)and other reports (21,25,26).Fasting and 2-Hour Plasma GlucoseThe FPG and 2-h PG may be used todiagnose di
34、abetes (Table 2.2). The con-cordance between the FPG and 2-h PGtests is imperfect, as is the concordancebetween A1C and either glucose-basedtest. Compared with FPG and A1C cutpoints, the 2-h PG value diagnosesmore people with prediabetes and dia-betes (27). In people in whom there isdiscordance betw
35、een A1C values andglucose values, FPG and 2-h PG aremore accurate (28).A1CRecommendations2.1Toavoidmisdiagnosisormisseddiagnosis,theA1Ctestshouldbeperformedusing a method that is certi-fied by the NGSP and stan-dardizedtotheDiabetesControlandComplicationsTrial (DCCT) assay. B2.2Marked discordance be
36、tweenmeasured A1C and plasmaglucose levels should raisethe possibility of A1C assayinterferenceandconsider-ation of using an assay with-out interference or plasmabloodglucosecriteriatodiagnose diabetes. B2.3In conditions associated withan altered relationship betweenA1C and glycemia, such ashemoglob
37、inopathiesincludingsickle cell disease, pregnancy(second and third trimestersand the postpartum period),glucose-6-phosphatedehydro-genase deficiency, HIV, hemodi-alysis, recent blood loss ortransfusion, or erythropoietintherapy, only plasma blood glu-cose criteria should be usedto diagnose diabetes.
38、 (SeeOTHERCONDITIONS ALTERING THE RELATIONSHIPOFA1CANDGLYCEMIAbelow formore information.) B2.4Adequate carbohydrate intake(at least 150 g/day) should beassured for 3 days prior tooral glucose tolerance testingas a screen for diabetes. AThe A1C test should be performed usinga method that is certified
39、 by the NGSP(www.ngsp.org)andstandardizedortraceable to the Diabetes Control andComplicationsTrial(DCCT)referenceassay. Point-of-care A1C assays may beNGSP certified and cleared by the U.S.Food and Drug Administration (FDA) foruse in monitoring glycemic control inpeople with diabetes in both Clinica
40、lLaboratory Improvement Amendments(CLIA)-regulated and CLIA-waived set-tings. Point-of-care A1C assays have notbeen prospectively studied for the diag-nosis of diabetes and are not recom-mended for diabetes diagnosis; if used,they should be confirmed with a vali-dated measure. In the U.S., point-of-
41、care A1C is a laboratory test that limitsCLIA regulation. As discussed in Section6, “Glycemic Targets” (https:/doi.org/10.2337/dc22-S006), point-of-care A1Cassays may be more generally appliedfor assessment of glycemic control in theclinic.A1C has several advantages com-pared with FPG and OGTT, incl
42、udinggreater convenience (fasting not req-uired), greaterpreanalyticalstability,and less day-to-day perturbations dur-ing stress, changes in diet, or illness.However, these advantages may be off-set by the lower sensitivity of A1C atthe designated cut point, greater cost,limited availability of A1C
43、testing in cer-tain regions of the developing world,and the imperfect correlation betweenA1C and average glucose in certain indi-viduals. The A1C test, with a diagnosticthreshold of $6.5% (48 mmol/mol),diagnoses only 30% of the diabetescases identified collectively using A1C,FPG, or 2-h PG, accordin
44、g to NationalHealth and Nutrition Examination Sur-vey (NHANES) data (29). Despite theselimitations with A1C, in 2009 the Inter-national Expert Committee added A1Cto the diagnostic criteria with the goalof increased screening (21).When using A1C to diagnose diabe-tes, it is important to recognize tha
45、tA1C is an indirect measure of averageblood glucose levels and to take otherfactors into consideration that mayimpact hemoglobin glycation indepen-dently of glycemia, such as hemodialy-sis, pregnancy, HIV treatment (30,31),age, race/ethnicity, genetic background,and anemia/hemoglobinopathies. (SeeOT
46、HER CONDITIONS ALTERING THE RELATIONSHIP OFA1CANDGLYCEMIAbelowformoreinformation.)AgeThe epidemiologic studies that formedthe basis for recommending A1C todiagnose diabetes included only adultpopulations (29). However, recent ADATable 2.2Criteria for the diagnosis of diabetesFPG $126 mg/dL (7.0 mmol
47、/L). Fasting is defined as no caloric intake for at least 8 h.*OR2-h PG $200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as describedby WHO, using a glucose load containing the equivalent of 75 g anhydrous glucosedissolved in water.*ORA1C $6.5% (48 mmol/mol). The test should be per
48、formed in a laboratory using a methodthat is NGSP certified and standardized to the DCCT assay.*ORIn a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a randomplasma glucose $200 mg/dL (11.1 mmol/L).DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose;
49、OGTT, oral glu-cose tolerance test; WHO, World Health Organization; 2-h PG, 2-h plasma glucose. *In theabsence of unequivocal hyperglycemia, diagnosis requires two abnormal test results fromthe same sample or in two separate test samples.care.diabetesjournals.orgClassification and Diagnosis of Diabe
50、tesS19Downloaded from http:/diabetesjournals.org/care/article-pdf/45/Supplement_1/S17/637547/dc22s002.pdf by guest on 10 July 2022clinical guidance concluded that A1C,FPG, or 2-h PG can be used to test forprediabetes or type 2 diabetes in chil-dren and adolescents (seeSCREENING ANDTESTING FOR PREDIA
