title: Removal of Bovine Insulin From Cow's Milk Formula and Early Initiation of Beta-Cell Autoimmunity in the FINDIA Pilot Study.
abstract: OBJECTIVE To test whether weaning to a bovine insulin-free cow's milk formula (CMF) reduces type 1 diabetes mellitus-associated autoantibodies in children at genetic risk. DESIGN Randomized, double-blind pilot trial (Finnish Dietary Intervention Trial for the Prevention of Type 1 Diabetes [FINDIA]). SETTING Three pediatric hospitals in Finland from May 15, 2002, to November 22, 2005. PARTICIPANTS A total of 1113 infants with HLA-conferred susceptibility to type 1 diabetes were randomly assigned to receive study infant formulas; 908 children provided at least 1 follow-up blood sample (last follow-up, June 2009). INTERVENTION The CMF (n = 389), whey-based hydrolyzed formula (WHF) (n = 350), or whey-based FINDIA formula essentially free of bovine insulin (n = 365) during the first 6 months of life whenever breast milk was not available. MAIN OUTCOME MEASURES Primary outcome was beta-cell autoimmunity monitored at ages 3, 6, and 12 months and then annually until age 3 years. Autoantibodies to insulin, the 65-kDa isoform of glutamic acid decarboxylase, and the tyrosine phosphatase-related IA-2 molecule were screened, and islet cell autoantibodies and autoantibodies to zinc transporter 8 were analyzed in infants whose primary screening test results were positive. RESULTS In the intention-to-treat analysis, 6.3% of children in the CMF group, 4.9% of those in the WHF group, and 2.6% of children in the FINDIA group were positive for at least 1 autoantibody by age 3 years. The odds ratios were 0.75 (95% CI, 0.37-1.54) in the WHF group and 0.39 (0.17-0.91) in the FINDIA group when compared with the CMF group. In the treatment-received analysis, the corresponding odds ratios were 0.81 (95% CI, 0.37-1.76) and 0.23 (0.08-0.69). CONCLUSION In comparison with ordinary CMF, weaning to an insulin-free CMF reduced the cumulative incidence of autoantibodies by age 3 years in children at genetic risk of type 1 diabetes mellitus. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01055080.
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Terhi
authors.initials: T
authors.lastname: Ruohtula
authors.forename: Jouni
authors.initials: J
authors.lastname: Pesola
authors.forename: Suvi M
authors.initials: SM
authors.lastname: Virtanen
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Matti
authors.initials: M
authors.lastname: Koski
authors.forename: Harri
authors.initials: H
authors.lastname: Kallioinen
authors.forename: Olli
authors.initials: O
authors.lastname: Tossavainen
authors.forename: Tuija
authors.initials: T
authors.lastname: Poussa
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Järvenpää
authors.forename: Jorma
authors.initials: J
authors.lastname: Komulainen
authors.forename: Raisa
authors.initials: R
authors.lastname: Lounamaa
authors.forename: Hans K
authors.initials: HK
authors.lastname: Akerblom
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip