Virtanen S M, Hyppönen E, Läärä E, Vähäsalo P, Kulmala P, Savola K, Räsänen L, Aro A, Knip M, Akerblom H K
School of Public Health, University of Tampere, Finland. mesuri.uta.fi.
Diabet Med. 1998 Sep;15(9):730-8. doi: 10.1002/(SICI)1096-9136(199809)15:9<730::AID-DIA646>3.0.CO;2-C.
Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of diabetes-associated autoantibodies and progression to clinical Type 1 DM. A cohort of 725 initially unaffected 0 to 25-year-old siblings of 801 index children with Type 1 DM diagnosed in 1986-1989 participated in the study (82% of those invited). The siblings were observed for Type 1 DM associated autoantibodies at intervals of 3-12 months for 4 years, starting from the diagnosis of Type 1 DM in the index child. The follow-up for Type 1 DM started at the same time and ended on 31 October 1995. The combined prevalence of Type 1 DM associated autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), GAD autoantibodies (GADA), and/or antibodies to the insulinoma associated cDNA2 protein (IA-2A)) was 13.6% (95/697) at the beginning of the study. Of the initially seronegative siblings, 7.5% (45/602) converted to antibody positivity during 4 years, and of all siblings 4.6% (33/725) developed Type 1 DM during the total follow-up time. The age at introduction of supplementary milk feeding was not significantly related to seroconversion to positivity for Type 1 DM associated autoantibodies or to the development of Type 1 DM in the siblings. When adjusted for age, sex, infant feeding patterns, and maternal age and education, high milk consumption in childhood (> or =3 glasses daily) was associated with more frequent emergence of Type 1 DM-associated autoantibodies than low consumption (<3 glasses daily) (adjusted odds ratio 3.97, 95% confidence interval 1.3-11.7, p = 0.01). There was a non-significant association between high milk consumption and progression to clinical Type 1 DM (adjusted hazard ratio 2.75, 95% confidence interval 0.9-8.4, p = 0.07). To conclude, this study suggests that high consumption of cow's milk during childhood may be associated both with seroconversion to positivity for diabetes-associated autoantibodies and progression to clinical Type 1 DM among siblings of children with diabetes.
关于婴儿早期引入以牛奶为基础的配方奶粉是否具有致糖尿病性,病例对照研究的证据尚无定论。我们对1型糖尿病患儿的兄弟姐妹进行了跟踪调查,以研究婴儿期或儿童期后期饮用牛奶与糖尿病相关自身抗体的出现以及发展为临床1型糖尿病之间的可能关系。1986 - 1989年诊断出的801名1型糖尿病索引儿童的725名最初未受影响的0至25岁兄弟姐妹参与了该研究(受邀者的82%)。从索引儿童被诊断为1型糖尿病开始,对这些兄弟姐妹每隔3 - 12个月观察一次1型糖尿病相关自身抗体,持续4年。对1型糖尿病的随访同时开始,并于1995年10月31日结束。研究开始时,1型糖尿病相关自身抗体(胰岛细胞抗体(ICA)、胰岛素自身抗体(IAA)、谷氨酸脱羧酶自身抗体(GADA)和/或胰岛素瘤相关cDNA2蛋白抗体(IA - 2A))的综合患病率为13.6%(95/697)。在最初血清阴性的兄弟姐妹中,7.5%(45/602)在4年内转为抗体阳性,在所有兄弟姐妹中,4.6%(33/725)在整个随访期间发展为1型糖尿病。引入补充牛奶喂养的年龄与1型糖尿病相关自身抗体血清转化为阳性或兄弟姐妹中1型糖尿病的发展无显著相关性。在对年龄、性别、婴儿喂养方式以及母亲年龄和教育程度进行调整后,儿童期高牛奶摄入量(≥3杯/天)比低摄入量(<3杯/天)与1型糖尿病相关自身抗体更频繁出现相关(调整后的优势比为3.97,95%置信区间为1.3 - 11.7,p = 0.01)。高牛奶摄入量与发展为临床1型糖尿病之间存在非显著关联(调整后的风险比为2.75,95%置信区间为0.9 - 8.4,p = 0.07)。总之,本研究表明,儿童期高牛奶摄入量可能与糖尿病相关自身抗体血清转化为阳性以及糖尿病患儿兄弟姐妹中发展为临床1型糖尿病均有关联。