Journal Club
Knip M, Virtanen SM, Seppä K, Ilonen J, Savilahti E, Vaarala O, Reunanen
A, Teramo K, Hämäläinen AM, Paronen J, Dosch HM, Hakulinen T,
Akerblom HK; the Finnish TRIGR Study Group.
Dietary Intervention in Infancy and Later Signs of Beta-Cell Autoimmunity.
N Engl J Med. 2010 Nov 11;363(20):1900-1908.
The NS, Suchindran C, North KE, Popkin BM, Gordon-Larsen P.
Association of adolescent obesity with risk of severe obesity in adulthood.
JAMA. 2010 Nov 10;304(18):2042-7.
2010年11月18日 8:30-8:55
８階 医局
埼玉医科大学 総合医療センター 内分泌・糖尿病内科
Department of Endocrinology and Diabetes,
Saitama Medical Center, Saitama Medical University
松田 昌文
Matsuda, Masafumi
the Hospital for Children and Adolescents (M.K., E.S., J.P., H.K.Å.) and Department of Obstetrics and Gynecology (K.T.),
University of Helsinki and Helsinki University Central Hospital; the Nutrition Unit (S.M.V.), Immune Response Unit (O.V.), and
Department of Health and Functional Capacity (A.R.), National Institute for Health and Welfare; and the Finnish Cancer Registry
(K.S., T.H.) — all in Helsinki; the Department of Pediatrics (M.K.) and Research Unit (S.M.V.), Tampere University Hospital, and
the Tampere School of Public Health, University of Tampere (S.M.V.), Tampere; the Immunogenetics Laboratory, University of
Turku, Turku ( J.I.); the Department of Clinical Microbiology, University of Kuopio, Kuopio ( J.I.); the Department of Pediatrics,
Jorvi Hospital, Espoo (A.-M.H.); and the Department of Pediatrics, University of Oulu, Oulu (A.-M.H.) — all in Finland; and the
Hospital for Sick Children, Research Institute, University of Toronto, Toronto (H.-M.D.).
N Engl J Med 2010;363:1900-8.
BACKGROUND
Early exposure to complex dietary proteins
may increase the risk of beta-cell
autoimmunity and type 1 diabetes in
children with genetic susceptibility. We
tested the hypothesis that supplementing
breast milk with highly hydrolyzed milk
formula would decrease the cumulative
incidence of diabetes-associated
autoantibodies in such children.
METHODS
In this double-blind, randomized trial, we assigned 230
infants with HLA-conferred susceptibility to type 1 diabetes
and at least one family member with type 1 diabetes to
receive either a casein hydrolysate formula or a
conventional, cow’s-milk–based formula (control) whenever
breast milk was not available during the first 6 to 8 months
of life. Autoantibodies to insulin, glutamic acid
decarboxylase (GAD), the insulinoma associated 2
molecule (IA-2), and zinc transporter 8 were analyzed with
the use of radio binding assays, and islet-cell antibodies
were analyzed with the use of immunofluorescence, during
a median observation period of 10 years (mean, 7.5). The
children were monitored for incident type 1 diabetes until
they were 10 years of age.
RESULTS
The unadjusted hazard ratio for positivity for one or
more autoantibodies in the casein hydrolysate group, as
compared with the control group, was 0.54 (95%
confidence interval [CI], 0.29 to 0.95), and the hazard
ratio adjusted for an observed difference in the duration
of exposure to the study formula was 0.51 (95% CI,
0.28 to 0.91). The unadjusted hazard ratio for positivity
for two or more autoantibodies was 0.52 (95% CI, 0.21
to 1.17), and the adjusted hazard ratio was 0.47 (95%
CI, 0.19 to 1.07). The rate of reported adverse events
was similar in the two groups.
CONCLUSIONS
Dietary intervention during infancy appears
to have a long-lasting effect on markers of
beta-cell autoimmunity — markers that may
reflect an autoimmune process leading to
type 1 diabetes.
(Funded by the European Commission and others; ClinicalTrials.gov number,
NCT00570102.)
Knip et al. conducted the study in Finland, where the prevalence of type 1 diabetes
is among the highest in the world and continues to increase. In 2005, there were
64.2 cases of newly diagnosed type 1 diabetes per 100,000 Finnish children
younger than 15 years of age.6
Knip et al. enrolled 230 breast-fed newborns born at term (≥36 weeks of gestation)
who had a first-degree relative with type 1 diabetes (the mother in the case of 37%
of the children, the father in 43%, a sibling in 15%, and more than one relative in
4%) and an HLA genotype associated with the risk of type 1 diabetes.
The study’s principal finding was that at least one autoantibody developed in 17%
of the babies fed the casein hydrolysate formula, as compared with 30% of the
children fed the control formula (P = 0.02). Diabetes ultimately developed in similar
numbers of children in each group — 7 of the 113 assigned to the casein
hydrolysate formula (6%) and 9 of the 117 assigned to the cow’s-milk–based
formula (8%) (a nonsignificant difference).
Although the group assignment was randomized, the infants assigned to receive
the cow’s-milk–based formula were introduced to that formula at a median age of
1.1 months, whereas the children receiving the casein hydrolysate formula were
first given the formula at a significantly later median age of 2.6 months (P = 0.03),
raising the question of whether the results could be attributed to the timing of the
introduction of the formula rather than to the content of the formula.
Although statistical tools used to account for such differences suggest that the
control formula resulted in more autoantibody seroconversions, the possibility that
there were unmeasured confounders, such as the quantity of formula ingested,
cannot be excluded.
Increased attention has been focused on the roles of gut-associated microbiome
and gut mucosal permeability on the host immune system.7 Still other research
has suggested that oral administration of low-dose interferon- α preserves
pancreatic insulin production in persons with recent-onset type 1 diabetes, despite
the fact that such treatment did not alter circulating concentrations of interferon-α.8
it seems likely that dietary constituents, not too surprisingly, can influence the
immune system and intermediary metabolism, our knowledge of the mechanisms
at play are, at present, rudimentary.
Data from the ongoing multicenter Trial
to Reduce IDDM in the Genetically at
Risk (TRIGR; ClinicalTrials.gov number,
NCT00179777)9 should help clarify
whether hydrolyzed casein formula
exerts a protective effect against the
risk of type 1 diabetes.
Message/Comments
10年も観察！ １型糖尿病予防には赤ちゃ
んのミルクの組成から介入！
Carolina Population Center (Drs The,
Suchindran, Popkin, and Gordon-Larsen)
and Departments of Nutrition (Drs The,
Popkin, and Gordon-Larsen), Biostatistics
(Dr Suchindran), and Epidemiology (Dr
North), Gillings School of Global Public
Health, University of North Carolina,
Chapel Hill.
JAMA. 2010;304(18):2042-2047
Context Although the prevalence of obesity has
increased in recent years, individuals who are
obese early in life have not been studied over
time to determine whether they develop severe
obesity in adulthood, thus limiting effective
interventions to reduce severe obesity incidence
and its potentially life-threatening associated
conditions.
Objective To determine incidence and risk of
severe obesity in adulthood by adolescent
weight status.
Design, Setting, and Participants A cohort of 8834 individuals
aged 12 to 21 years enrolled in 1996 in wave II of the US
National Longitudinal Study of Adolescent Health, followed up
into adulthood (ages 18-27 years during wave III [2001-2002]
and ages 24-33 years during wave IV [2007-2009]). Height and
weight were obtained via anthropometry and surveys
administered in study participants’ homes using standardized
procedures.
Main Outcome Measures New cases of adult-onset severe
obesity were calculated by sex, race/ethnicity, and adolescent
weight status. Sex-stratified, discrete time hazard models
estimated the net effect of adolescent obesity (aged <20 years;
body mass index [BMI] ≥95th percentile of the sex-specific BMIfor-age growth chart or BMI ≥ 30.0) on risk of severe obesity
incidence in adulthood (aged ≥ 20 years; BMI ≥ 40.0), adjusting
for race/ethnicity and age and weighted for national
representation.
Results In 1996, 79 (1.0%; 95% confidence
interval [CI], 0.7%-1.4%) adolescents were
severely obese; 60 (70.5%; 95% CI, 57.2%83.9%) remained severely obese in adulthood.
By 2009, 703 (7.9%; 95% CI, 7.4%-8.5%) non–
severely obese adolescents had become
severely obese in adulthood, with the highest
rates for non- Hispanic black women. Obese
adolescents were significantly more likely to
develop severe obesity in young adulthood than
normal-weight or overweight adolescents
(hazard ratio, 16.0; 95% CI, 12.4-20.5).
Conclusion In this cohort, obesity
in adolescence was significantly
associated with increased risk of
incident severe obesity in
adulthood, with variations by sex
and race/ ethnicity.
Message/Comments
思春期の肥満は、大人になってからとんで
もない肥満になりやすい！
（まぁ
当たり前のようにも感じますが）