1.0.0.0 CLAS­SI­FI­CA­TION

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 β-cell de­struc­tion, usu­al­ly lead­ing to ab­so­lute in­sulin deficien­cy)
2. Type 2 di­a­betes (due to a pro­gres­sive loss of β-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 pre­sen­ta­tion and dis­ease pro­gres­sion may vary con­sid­er­ably. Clas­sification is im­por­tant for de­ter­min­ing ther­a­py, but some in­di­vid­u­als can­not be clear­ly clas­sified as hav­ing type 1 or type 2 di­a­betes at the time of di­ag­no­sis. The tra­di­tion­al paradigms of type 2 di­a­betes oc­cur­ring only in adults and type 1 di­a­betes only in chil­dren are no longer ac­cu­rate, as both dis­eases occur in both age-‍groups. Chil­dren with type 1 di­a­betes typ­i­cal­ly pre­sent with the hall­mark symp­toms of polyuria/‍polydipsia, and ap­prox­i­mate­ly one-‍third pre­sent with di­a­bet­ic ke­toaci­do­sis (DKA) (2). The onset of type 1 di­a­betes may be more vari­able in adults, and they may not pre­sent with the clas­sic symp­toms seen in chil­dren. Oc­ca­sion­al­ly, pa­tients with type 2 di­a­betes may pre­sent with DKA, par­tic­u­lar­ly eth­nic mi­nori­ties (3). Al­though difficul­ties in dis­tin­guish­ing di­a­betes type may occur in all age-‍groups at onset, the true di­ag­no­sis be­comes more ob­vi­ous over time.

In both type 1 and type 2 di­a­betes, var­i­ous ge­net­ic and en­vi­ron­men­tal fac­tors can re­sult in the pro­gres­sive loss of β-cell mass and/‍or func­tion that man­i­fests clin­i­cally as hy­per­glycemia. Once hy­per­glycemia oc­curs, pa­tients with all forms of di­a­betes are at risk for de­vel­op­ing the same chron­ic com­pli­ca­tions, al­though rates of pro­gres­sion may dif­fer. The iden­tification of in­di­vid­u­al­ized ther­a­pies for di­a­betes in the fu­ture will re­quire bet­ter char­ac­ter­i­za­tion of the many paths to β-cell demise or dysfunc­tion (4).

Char­ac­ter­i­za­tion of the un­der­ly­ing patho­phys­i­ol­o­gy is more de­vel­oped in type 1 di­a­betes than in type 2 di­a­betes. It is now clear from stud­ies of first-‍de­gree rel­a­tives of pa­tients with type 1 di­a­betes that the per­sis­tent pres­ence of two or more au­toan­ti­bod­ies is an al­most cer­tain pre­dic­tor of clin­i­cal hy­per­glycemia and di­a­betes. The rate of pro­gres­sion is de­pen­dent on the age at first de­tec­tion of an­ti­body, num­ber of an­ti­bod­ies, an­ti­body specificity, and an­ti­body titer. Glu­cose and A1C lev­els rise well be­fore the clin­i­cal onset of di­a­betes, mak­ing di­ag­no­sis fea­si­ble well be­fore the onset of DKA. Three dis­tinct stages of type 1 di­a­betes can be iden­tified (Table 2.1) and serve as a frame­work for fu­ture re­search and reg­u­la­to­ry de­ci­sion mak­ing (4,5).

The paths to β-cell demise and dysfunc­tion are less well defined in type 2 di­a­betes, but deficient β-cell in­sulin se­cre­tion, fre­quent­ly in the set­ting of in­sulin re­sis­tance, ap­pears to be the com­mon de­nom­i­na­tor. Char­ac­ter­i­za­tion of sub­types of this het­ero­ge­neous dis­or­der have been de­vel­oped and val­i­dat­ed in Scan­di­na­vian and North­ern Eu­ro­pean pop­u­la­tions but have not been confirmed in other eth­nic and racial groups. Type 2 di­a­betes is pri­mar­i­ly as­so­ci­at­ed with in­sulin se­cre­to­ry de­fects re­lat­ed to inflam­ma­tion and metabol­ic stress among other con­trib­u­tors, in­clud­ing ge­net­ic fac­tors. Fu­ture clas­sification schemes for di­a­betes will like­ly focus on the patho­phys­i­ol­o­gy of the un­der­ly­ing β-cell dysfunc­tion and the stage of dis­ease as in­di­cat­ed by glu­cose sta­tus (nor­mal, im­paired, or di­a­betes) (4).

Table 2.1 - Stag­ing of type 1 di­a­betes (4,5)