6.0.0.0 CYS­TIC FI­BRO­SIS–RE­LAT­ED DI­A­BETES

Rec­om­men­da­tions

2.19 An­nu­al screen­ing for cys­tic fibro­sis–re­lat­ed di­a­betes with an oral glu­cose tol­er­ance test should begin by age 10 years in all pa­tients with cys­tic fibro­sis not pre­vi­ous­ly di­ag­nosed with cys­tic fibro­sis–re­lat­ed di­a­betes. B

2.20 A1C is not rec­om­mend­ed as a screen­ing test for cys­tic fibro­sis–re­lat­ed di­a­betes. B

2.21 Pa­tients with cys­tic fibro­sis–re­lat­ed di­a­betes should be treat­ed with in­sulin to at­tain in­di­vid­u­al­ized glycemic goals. A

2.22 Be­gin­ning 5 years after the di­ag­no­sis of cys­tic fibro­sis–re­lat­ed di­a­betes, an­nu­al mon­i­tor­ing for com­pli­ca­tions of di­a­betes is rec­om­mend­ed. E

Cys­tic fibro­sis–re­lat­ed di­a­betes (CFRD) is the most com­mon co­mor­bid­i­ty in peo­ple with cys­tic fibro­sis, oc­cur­ring in about 20% of ado­les­cents and 40–50% of adults (95). Di­a­betes in this pop­u­la­tion, com­pared with in­di­vid­u­als with type 1 or type 2 di­a­betes, is as­so­ci­at­ed with worse nu­tri­tion­al sta­tus, more se­vere inflam­ma­to­ry lung dis­ease, and greater mor­tal­i­ty. In­sulin insufficien­cy is the pri­ma­ry de­fect in CFRD. Ge­net­i­cal­ly de­ter­mined β-cell func­tion and in­sulin re­sis­tance as­so­ci­at­ed with in­fec­tion and inflam­ma­tion may also con­tribute to the de­vel­op­ment of CFRD. Milder abnor­malities of glu­cose tol­er­ance are even more com­mon and occur at ear­li­er ages than CFRD. Whether in­di­vid­u­als with IGT should be treat­ed with in­sulin re­place­ment has not cur­rently been de­ter­mined. Al­though screen­ing for di­a­betes be­fore the age of 10 years can iden­tify risk for pro­gres­sion to CFRD in those with abnor­mal glu­cose tol­er­ance, no benefit has been es­tab­lished with re­spect to weight, height, BMI, or lung func­tion. Con­tin­u­ous glu­cose mon­i­tor­ing or HOMA of β-cell func­tion (96) may be more sen­si­tive than OGTT to de­tect risk for pro­gres­sion to CFRD; how­ev­er, ev­i­dence link­ing these re­sults to long-‍term out­comes is lack­ing, and these tests are not rec­om­mend­ed for screen­ing (97).

CFRD mor­tal­i­ty has significant­ly de­creased over time, and the gap in mor­tal­i­ty be­tween cys­tic fibro­sis pa­tients with and with­out di­a­betes has con­sid­er­ably nar­rowed (98). There are lim­it­ed clin­i­cal trial data on ther­a­py for CFRD. The largest study com­pared three reg­i­mens: pre­meal in­sulin as­part, repaglin­ide, or oral place­bo in cys­tic fibro­sis pa­tients with di­a­betes or abnor­mal glu­cose tol­er­ance. Par­tic­i­pants all had weight loss in the year pre­ced­ing treat­ment; how­ev­er, in the in­sulin-‍treat­ed group, this pat­tern was re­versed, and pa­tients gained 0.39 (± 0.21) BMI units (P = 0.02). The repaglin­ide-‍treat­ed group had ini­tial weight gain, but this was not sus­tained by 6 months. The place­bo group con­tin­ued to lose weight (99). In­sulin re­mains the most wide­ly used ther­a­py for CFRD (100).

Ad­di­tion­al re­sources for the clin­i­cal man­age­ment of CFRD can be found in the po­si­tion state­ment “Clin­i­cal Care Guide­lines for Cys­tic Fibro­sis-Re­lat­ed Di­a­betes: A Po­si­tion State­ment of the Amer­i­can Di­a­betes As­so­ci­a­tion and a Clin­i­cal Prac­tice Guide­line of the Cys­tic Fibro­sis Foun­da­tion, En­dorsed by the Pe­di­atric En­docrine So­ci­ety” (101) and in the In­ter­na­tion­al So­ci­ety for Pe­di­atric and Ado­les­cent Di­a­betes’s 2014 clin­i­cal prac­tice con­sen­sus guide­lines (102).