Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Seminars in Immunopathology
Published in: Seminars in Immunopathology 6/2017

01-11-2017 | Review

Early life origin of type 1 diabetes

Authors: Mikael Knip, Kristiina Luopajärvi, Taina Härkönen

Published in: Seminars in Immunopathology | Issue 6/2017

Login to get access

Abstract

Type 1 diabetes (T1D) is perceived as a chronic immune-mediated disease with a subclinical prodromal period characterized by selective loss of insulin-producing beta cells in the pancreatic islets in genetically susceptible subjects. The incidence of T1D has increased manifold in most developed countries after World War II in parallel with a series of other immune-mediated diseases. T1D results from gene-environmental interactions. The appearance of disease-associated autoantibodies into the peripheral circulation is the first detectable sign of the initiation of the disease process leading to clinical T1D. The first autoantibodies may appear already before the age of 6 months and the seroconversion rate peaks during the second year of life. This implies that exogenous factors involved in the pathogenesis of T1D must be operative in early life, some of them most likely already during pregnancy. Here, we discuss putative endogenous factors that may contribute to the development of T1D during fetal and early postnatal life. Many environmental factors operative in early life have been implicated in the pathogenesis of T1D, but relatively few have been firmly confirmed.
Literature
1.
Knip M (2002) Natural course of preclinical type 1 diabetes. Horm Res 57(Suppl. 1):6–11PubMed
2.
3.
Knip M, Siljander H, Ilonen J, Simell O, Veijola R (2016) Role of humoral beta-cell autoimmunity in type 1 diabetes. Pediatr Diabetes 17(Suppl. S22):17–24 **This paper is a major source document for the current article PubMedCrossRef
4.
Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309:2473–2479PubMedPubMedCentralCrossRef
5.
Kimpimäki T, Kulmala P, Savola K et al (2002) Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 87:4572–4579PubMedCrossRef
6.
Kukko M, Kimpimäki T, Korhonen S et al (2005) Dynamics of diabetes-associated autoantibodies in young children with human leukocyte antigen-conferred risk for type 1 diabetes recruited from the general population. J Clin Endocrinol Metab 9:2712–2717CrossRef
7.
Siljander H, Simell S, Hekkala A et al (2009) Predictive characteristics of diabetes-associated autoantibodies among children with HLA-conferred disease susceptibility in the general population. Diabetes 58:2835–2842PubMedPubMedCentralCrossRef
8.
Ilonen J, Hammais A, Laine A-P et al (2013) Patterns of β-cell autoantibody appearance and genetic associations during the first years of life. Diabetes 62:3636–3640PubMedPubMedCentralCrossRef
9.
Krischer JP, Lynch KF, Schatz DA et al (2015) The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 58:980–987PubMedPubMedCentralCrossRef
10.
Barnett AH, Eff C, Leslie RDG, Pyke DA (1981) Diabetes in identical twins: a study of 200 pairs. Diabetologia 20:87–93PubMedCrossRef
11.
Kaprio J, Tuomilehto J, Koskenvuo M et al (1992) Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 35:1060–1067PubMedCrossRef
12.
Patterson CC, Gyürüs C, Rosenbauer J et al (2012) Trends in childhood type 1 diabetes incidence in Europe during 1989–2008: evidence of non-uniformity over time in rates of increase. Diabetologia 55:2142–2147PubMedCrossRef
13.
Harjutsalo V, Sund R, Knip M, Groop PH (2013) Incidence of type 1 diabetes in Finland. JAMA 310:427–428PubMedCrossRef
14.
Knip M, Simell O (2012) Environmental triggers of type 1 diabetes. Cold Spring Harb Perspect Med 7:a007690 **This paper is a major source document for the current article
15.
Oilinki T, Otonkoski T, Ilonen J, Knip M, Miettinen PJ (2012) Prevalence and characteristics of type 1 diabetes among Somali children and adolescents living in Helsinki, Finland. Pediatr Diabetes 13:176–180PubMedCrossRef
16.
Hermann R, Knip M, Veijola R et al (2003) Temporal changes in the frequencies of HLA genotypes in patients with type 1 diabetes: indication of an increased environmental pressure? Diabetologia 46:420–425PubMedCrossRef
17.
Gillespie KM, Bain SC, Barnett AH (2004) The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes. Lancet 364:1645–1647CrossRef
18.
19.
20.
21.
Herold KC, Usmani-Brown S, Ghazi T et al (2015) β cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest 125:1163–1174PubMedPubMedCentralCrossRef
22.
Warram JH, Krolewski AS, Gottlieb MS, Kahn CR (1984) Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N Engl J Med 311:149–152PubMedCrossRef
23.
Harjutsalo V, Reunanen A, Tuomilehto J (2006) Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes 55:1517–1524PubMedCrossRef
24.
Luopajärvi K, Nieminen J, Ilonen J et al (2012) Expansion of CD4+CD25+FoxP3+ regulatory T cells in infants of mothers with type 1 diabetes. Pediatr Diabetes 13:400–407PubMedPubMedCentralCrossRef
25.
Forrest JM, Menser MA, Burgess JA (1971) High frequency of diabetes mellitus in young adults with congenital rubella. Lancet 2:332–334PubMedCrossRef
26.
Forrest JM, Turnbull FM, Sholler GF et al (2002) Gregg’s congenital rubella patients 60 years later. Med J Aust 177:664–667PubMed
27.
Viskari H, Paronen J, Keskinen P et al (2003) Humoral beta-cell autoimmunity is rare in patients with the congenital rubella syndrome. Clin Exp Immunol 133:378–383PubMedPubMedCentralCrossRef
28.
Dahlquist GG, Ivarsson S, Lindberg B, Forsgren M (1995) Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study. Diabetes 44:408–413PubMedCrossRef
29.
Viskari H, Knip M, Tauriainen S et al (2012) Maternal enterovirus infection as a risk factor for type 1 diabetes in the exposed offspring. Diabetes Care 35:1328–1332PubMedPubMedCentralCrossRef
30.
31.
Kallionpää H, Laajala E, Öling V et al (2014) The standard of hygiene and immune adaptation in newborn infants. Clin Immunol 155:136–147PubMedCrossRef
32.
Lamb MM, Myers MA, Barriga K, Zimmet PZ, Rewers M, Norris JM (2008) Maternal diet during pregnancy and islet autoimmunity in offspring. Pediatr Diabetes 9:135–141PubMedCrossRef
33.
Virtanen SM, Uusitalo L, Kenward MG et al (2011) Maternal food consumption during pregnancy and risk of advanced beta cell autoimmunity in the offspring. Pediatr Diabetes 12:95–99PubMedCrossRef
34.
Stene LC, Ulriksen J, Magnus P, Joner G (2000) Use of cod liver oil during pregnancy associated with lower risk of type 1 diabetes in the offspring. Diabetologia 43:1083–1092CrossRef
35.
Sørensen IM, Joner G, Jenum PA, Eskild A, Stene LC (2012) Serum long chain n-3 fatty acids (EPA and DHA) in the pregnant mother are independent of risk of type 1 diabetes in the offspring. Diabetes Metab Res Rev 28:431–438PubMedCrossRef
36.
Marjamäki L, Niinistö S, Kenward MG et al (2010) Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring. Diabetologia 53:1599–1607PubMedCrossRef
37.
Sørensen IM, Joner G, Jenum PA, Eskild A, Torjesen PA, Stene LC (2012) Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes 61:175–178PubMedCrossRef
38.
Miettinen ME, Reinert L, Kinnunen L et al (2012) Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring. Diabetologia 55:1291–1294PubMedCrossRef
39.
Cardwell CR, Stene LC, Joner G et al (2010) Birth weight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data. Diabetologia 53:641–651PubMedCrossRef
40.
Rasmussen T, Stene LC, Samuelsen SO et al (2009) Maternal BMI before pregnancy, maternal weight gain during pregnancy, and risk of persistent positivity for multiple diabetes-associated autoantibodies in children with the high-risk HLA genotype: the MIDIA study. Diabetes Care 32:1904–1906PubMedPubMedCentralCrossRef
41.
Arkkola T, Kautiainen S, Takkinen HM et al (2011) Relationship of maternal weight status and weight gain during pregnancy to the development of advanced beta cell autoimmunity in the offspring: a prospective birth cohort study. Pediatr Diabetes 12:478–484PubMedCrossRef
42.
Stene LV, Gale EAM (2013) The prenatal environment and type 1 diabetes. Diabetologia 56:1888–1897PubMedCrossRef
43.
Cardwell CR, Stene LC, Joner G et al (2010) Maternal age at birth and childhood type 1 diabetes: a pooled analysis of 30 observational studies. Diabetes 59:486–494PubMedCrossRef
44.
Virtanen SM, Kenward MG, Erkkola M et al (2006) Age at introduction of new foods and advanced beta-cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes. Diabetologia 49:1512–1521PubMedCrossRef
45.
Cardwell CR, Stene LC, Joner G et al (2011) Birth order and childhood type 1 diabetes risk: a pooled analysis of 31 observational studies. Int J Epidemiol 40:363–374PubMedCrossRef
46.
Cardwell CR, Stene LC, Joner G et al (2008) Caesarean section is associated with an increased risk of childhood onset type 1 diabetes: a meta-analysis of observational studies. Diabetologia 51:726–735PubMedCrossRef
47.
Bonifacio E, Warncke K, Winkler C, Wallner M, Ziegler AG (2011) Cesarean section and interferon-induced helicase gene polymorphisms combine to increase childhood type 1 diabetesrisk. Diabetes 60:3300–3306PubMedPubMedCentralCrossRef
48.
Yatsunenko T, Rey FE, Manary MJ et al (2012) Human gut microbiome viewed across age and geography. Nature 486:222–227PubMedPubMedCentral
49.
Yassour M, Vatanen T, Siljander H et al (2016) Natural history of the infant gut microbiome and impact of antibiotic treatments on bacterial strain diversity and stability. Sci Transl Med 8:343RA81PubMedPubMedCentralCrossRef
50.
Knip M, Virtanen SM, Åkerblom HK (2010) Infant feeding and risk of type 1 diabetes. Am J Clin Nutr 91(Suppl):1506S–1513SPubMedCrossRef
51.
Virtanen SM, Knip M (2003) Nutritional risk predictors of β cell autoimmunity and type 1 diabetes at a young age. Am J Clin Nutr 78:1053–1067PubMed
52.
Norris JM, Barriga K, Klingensmith G et al (2003) Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290:1713–1720PubMedCrossRef
53.
Ziegler A-G, Schmid S, Huber D, Hummel M, Bonifacio E (2003) Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA 290:1721–1728PubMedCrossRef
54.
Kimpimäki T, Erkkola M, Korhonen S et al (2001) Short exclusive breast-feeding predisposes young children with increased genetic risk of type 1 diabetes to progressive beta-cell autoimmunity. Diabetologia 44:63–69PubMedCrossRef
55.
Holmberg H, Wahlberg J, Vaarala O, Ludvigsson J, the ABIS studygroup (2007) Short duration of breast-feeding as a risk factor for b-cell autoantibodies in 5-year-old children from the general population. Br J Nutr 97:111–116PubMedCrossRef
56.
Virtanen SM, Räsänne L, Aro A et al (1991) Infant feeding in Finnish children ,7 yr of age with newly diagnosed IDDM. Diabetes Care 14:415–417PubMedCrossRef
57.
Virtanen SM, Räsänen L, Ylönen K et al (1993) Early introduction of dairy products associated with increased risk of IDDM in Finnish children. Diabetes 42:1786–1790PubMedCrossRef
58.
Kostraba JN, Cruickshanks KJ, Lawler-Heavner J et al (1993) Early exposure to cow’s milk and solid foods in infancy, genetic predisposition, and risk of IDDM. Diabetes 42:288–295PubMedCrossRef
59.
Wadsworth EJK, Shield JPH, Hunt LP, Baum J (1997) A case-control study of environmental factors associated with diabetes in the under 5s. Diabet Med 14:390–396PubMedCrossRef
60.
The EURODIAB Substudy 2 Study Group (2002) Rapid early growth is associated with increased risk of childhood type 1 diabetes in various European populations. Diabetes Care 25:1755–1760CrossRef
61.
Virtanen SM, Nevalainen J, Kronberg-Kippilä C et al (2012) Food consumption during childhood and advanced β-cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes: a nested case-control study. Am J Clin Nutr 95:471–478PubMedCrossRef
62.
Stene LC, Joner G, Norwegian Childhood Diabetes Study Group (2003) Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr 78:1128–1134PubMed
63.
Norris JM, Yin X, Lamb MM et al (2007) Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA 298:1420–1428PubMedCrossRef
64.
Niinistö S, Takkinen H-M, Erlund I et al (2017) Fatty acid status in infancy is associated with the risk of type 1 diabetes associated autoimmunity. Diabetologia 60:1233–1233CrossRef
65.
66.
Knip M, Akerblom HK, Becker D et al (2014) Hydrolyzed infant formula and early β-cell autoimmunity—a randomized clinical trial. JAMA 311:2279–2287PubMedPubMedCentralCrossRef
67.
Hummel S, Pflüger M, Hummel M, Bonifacio E, Ziegler AG (2011) Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: the BABYDIETstudy. Diabetes Care 34:1301–1305PubMedPubMedCentralCrossRef
68.
Chase HP, Lescheck R, Rafkin-Mervis L et al (2009) Nutritional intervention to prevent (NIP) type 1 diabetes: a pilot trial. Infant Child Adolesc Nutr 1:99–107CrossRef
69.
Ziegler A-G, Hummel M, Schenker M, Bonifacio E (1999) Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB study. Diabetes 48:460–468PubMedCrossRef
70.
Sabbah E, Savola K, Ebeling T et al (2000) Genetic, autoimmune, and clinical characteristics of childhood- and adult-onset type 1 diabetes mellitus. Diabetes Care 23:1326–1332PubMedCrossRef
71.
Vaarala O, Knip M, Paronen J et al (1999) Cow milk formula feeding induces primary immunization to insulin in infants at genetic risk for type 1 diabetes. Diabetes 48:1389–1394PubMedCrossRef
72.
Vaarala O, Ilonen J, Ruohtula T et al (2012) Removal of bovine insulin from cow’s milk formula and early initiation of beta-cell autoimmunity. Arch Pediatr Adolesc Med 166:608–614PubMedCrossRef
73.
Hummel M, Bonifacio E, Naserke HE, Ziegler AG (2002) Elimination of dietary gluten does not reduce titers of type 1 diabetes-associated autoantibodies in high-risk subjects. Diabetes Care 25:1111–1116PubMedCrossRef
74.
Pastore MR, Bazzigaluppi E, Belloni C, Arcovio C, Bonifacio E, Bosi E (2003) Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. J Clin Endocrinol Metab 88:162–165PubMedCrossRef
75.
The EURODIAB Substudy 2 Study Group (1999) Vitamin D supplement in early childhood and risk of type I (insulindependent) diabetes mellitus. Diabetologia 42:51–54CrossRef
76.
Hyppönen E, Läärä E, Järvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth cohort study. Lancet 358:1500–1504PubMedCrossRef
77.
Mäkinen M, Mykkänen JP, Koskinen MK et al (2016) Serum 25-hydroxyvitamin D concentrations in children with genetic type 1 diabetes susceptibility progressing to autoimmunity and clinical disease. J Clin Endocrinol Metab 101:723–729PubMedCrossRef
78.
79.
Eizirik DL, Miani M, Cardozo AK (2013) Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation. Diabetologia 56:234–241PubMedCrossRef
80.
Hyppönen E, Kenward MG, Virtanen SM et al (1999) Infant feeding, early weight gain and risk of type 1 diabetes. Diabetes Care 22:1961–1965PubMedCrossRef
81.
Hyppönen E, Virtanen SM, Kenward MG, Knip M, Åkerblom HK, the Childhood Diabetes in Finland Study Group (2000) Obesity, increased linear growth and risk of type 1 diabetes mellitus in children. Diabetes Care 23:1755–1760PubMedCrossRef
82.
Lamb MM, Yin X, Zerbe GO et al (2009) Height growth velocity, islet autoimmunity and type 1 diabetes development: the diabetes autoimmunity study in the young. Diabetologia 52:2064–2071PubMedPubMedCentralCrossRef
83.
Rasmussen T, Witso E, Tapia G, Stene LC, Ronningen KS (2011) Selfreported lower respiratory tract infections and development of islet autoimmunity in children with the type 1 diabetes high-risk HLA genotype: the MIDIA study. Diabetes Metab Res Rev 27:834–837PubMedCrossRef
84.
Beyerlein A, Wehweck F, Ziegler AG, Pflueger M (2013) Respiratory infections in early life and the development of islet autoimmunity in children at increased type 1 diabetes risk: evidence from the BABYDIET study. JAMA Pediatr 167:800–807PubMedCrossRef
85.
Beyerlein A, Donnachie E, Jergens S, Ziegler AG (2016) Infections in early life and development of type 1 diabetes. JAMA 315:1899–1901PubMedCrossRef
86.
Lönnrot M, Korpela K, Knip M et al (2000) Enterovirus infection as a risk factor for ß-cell autoimmunity in a prospectively observed birth cohort—the Finnish Diabetes Prediction and Prevention (DIPP) Study. Diabetes 49:1314–1318PubMedCrossRef
87.
Oikarinen S, Martiskainen M, Tauriainen S et al (2011) EnterovirusRNA in blood is linked to the development of type 1 diabetes. Diabetes 60:276–279PubMedCrossRef
88.
Kimpimäki T, Kupila A, Hämäläinen A-M et al (2001) The first signs of ß-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish type 1 diabetes prediction and prevention study. J Clin Endocrinol Metab 86:4782–4788PubMed
89.
Laitinen OH, Honkanen H, Tolonen O et al (2014) Coxsackievirus B1 induces beta-cell autoimmunity that portends type 1 diabetes. Diabetes 63:446–455PubMedCrossRef
90.
Fuchtenbusch M, Irnstetter A, Jager G, Ziegler AG (2001) No evidence for an association of coxsackie virus infections during pregnancy and early childhood with development of islet autoantibodies in offspring of mothers or fathers with type 1 diabetes. J Autoimmun 17:333–340PubMedCrossRef
91.
Graves PM, Rotbart HA, Nix WA et al (2003) Prospective study of enteroviral infections and development of β-cell autoimmunity. Diabetes autoimmunity study in the young (DAISY). Diabetes Res Clin Pract 59:51–61PubMedCrossRef
92.
Stene LC, Oikarinen S, Hyöty H et al (2010) Enterovirus infection and progression from islet autoimmunity to type 1 diabetes: the diabetes and autoimmunity study in the young (DAISY). Diabetes 59:3174–3180PubMedPubMedCentralCrossRef
93.
Simonen-Tikka ML, Pflueger M, Klemola P et al (2011) Human enterovirus infections in children at increased risk for type 1 diabetes: the Babydiet study. Diabetologia 54:2995–3002PubMedCrossRef
94.
Honkanen H, Oikarinen S, Nurminen N et al (2017) Detection of enteroviruses in stools precedes the appearance of islet autoimmunity with a delay of several months—possible evidence for slowly operating mechanisms in virus-induced autoimmunity. Diabetologia 60:424–431PubMedCrossRef
95.
Hyöty H, Knip M (2014) Developing a vaccine for type 1 diabetes through targeting enteroviral infections. Expert Rev Vaccines 13:989–999PubMedCrossRef
96.
Knip M, Hyöty H (2008) Environmental determinants: the role of viruses and standard of hygiene. In: Dabelea D, Klingensmith GJ (eds) Epidemiology of pediatric and adolescent diabetes. Informa Healthcare, New York, pp 63–74CrossRef
97.
Honeyman MC, Stone NL, Harrison LC (1998) T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. Mol Med 4:231–239PubMedPubMedCentral
98.
Honeyman MC, Stone NL, Falk BA, Nepom G, Harrison LC (2010) Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol 184:2204–2210PubMedCrossRef
99.
Honeyman MC, Coulson BS, Stone NL et al (1999) Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes 49:1319–1324CrossRef
100.
Blomquist M, Juhela S, Erkkilä S et al (2002) Rotavirus infections and development of diabetes-associated autoantibodies during the first 2 years of life. Clin Exp Immunol 128:511–515CrossRef
101.
102.
Knip M, Siljander H (2016) The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol 12:154–167PubMedCrossRef
103.
Matamoro S, Gras-Leguen C, Le Vacon F, Potel G, de La Cochetiere MF (2013) Development of intestinal microbiota in infants and its impact on health. Trends Microbiol 21:167–173CrossRef
104.
Mackie RI, Sghir A, Gaskins HR (1999) Developmental microbial ecology of the neonatal gastrointestinal tract. Am J Clin Nutr 69:S1035–S1045
105.
Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R (2011) Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology 140:1713–1719PubMedCrossRef
106.
Dominguez-Bello MG, Costello EK, Contreras M et al (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci U S A 107:11971–11975PubMedPubMedCentralCrossRef
107.
Biasucci G, Benenati B, Morelli L, Bessi E, Boehm G (2008) Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr 138:1796S–1800SPubMed
108.
Jakobsson HE, Abrahamsson TR, Jenmalm MC et al (2014) Decreased gut microbiota diversity, delayed Bacteroidetes colonization and reduced Th1 responses in infants delivered by caesarean section. Gut 63:559–566PubMedCrossRef
109.
Giongo A, Mukherjee N, Gano KA et al (2011) Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 5:82–91PubMedCrossRef
110.
Brown CT, Davis-Richardson AG, Giongo A et al (2011) Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PLoS One 6:e25792PubMedPubMedCentralCrossRef
111.
Kostic AD, Gevers D, Siljander H et al (2015) The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17:260–273PubMedPubMedCentralCrossRef
112.
113.
Kondrashova A, Reunanen A, Romanov A et al (2005) A sixfold gradient in the incidence of type 1 diabetes at the eastern border of Finland. Ann Med 37:67–72PubMedCrossRef
114.
Kondrashova A, Seiskari T, Ilonen J, Knip M, Hyöty H (2013) The “hygiene hypothesis” and the sharp gradient in the incidence of autoimmune and allergic diseases between Russian Karelia and Finland. APMIS 121:478–493PubMedCrossRef
115.
Davis-Richardson A, Ardissone A, Dias R et al (2014) Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes. Front Microbiol 5:678PubMedPubMedCentralCrossRef
116.
Mikkelsen KH, Knop FK, Vilsbøll T, Frost M, Hallas J, Pottegård A (2017) Use of antibiotics in childhood and risk of Type 1 diabetes: a population-based case-control study. Diabet Med 34:272–277PubMedCrossRef
117.
Clausen TD, Bergholt T, Bouaziz O (2016) Broad-spectrum antibiotic treatment and subsequent childhood type 1 diabetes: a nationwide Danish cohort study. PLoS One 11:e0161654PubMedPubMedCentralCrossRef
118.
Moulder R, Lahesmaa R (2016) Early signs of disease in type 1 diabetes. Pediatr Diabetes 17(Suppl S22):43–48PubMedCrossRef
119.
Roadmap Epigenomics Consortium, Kundaje A, Meuleman W et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330PubMedCentralCrossRef
120.
Orban T, Kis J, Szereday L et al (2007) Reduced CD4+ T-cell-specific gene expression in human type 1 diabetes mellitus. J Autoimmun 28:177–187PubMedCrossRef
121.
Figueroa-Colon R, Arani RB, Goran MI, Weinsier RL (2000) Paternal body fat is a longitudinal predictor of changes in body fat in premenarcheal girls. Am J Clin Nutr 71:829–834PubMed
122.
Penesova A, Bunt JC, Bogardus C, Krakoff J (2010) Effect of paternal diabetes on pre-diabetic phenotypes in adult offspring. Diabetes Care 33:1823–1828PubMedPubMedCentralCrossRef
123.
Wei Y-PPY, Yang C-RR, Zhao Z-A et al (2014) Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A 111:1873–1878PubMedPubMedCentralCrossRef
124.
Zhang Y, Collier F, Naselli G et al (2016) Cord blood monocyte-derived inflammatory cytokines suppress IL-2 and induce nonclassic “TH 2-type” immunity associated with development of food allergy. Sci Transl Med 8:321ra8PubMedCrossRef
125.
Jin Y, Sharma A, Bai S et al (2014) Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function. Diabetes 63:2506–2515PubMedPubMedCentralCrossRef
126.
Elo LL, Mykkanen J, Nikula T et al (2010) Early suppression of immune response pathways characterizes children with prediabetes in genome-wide gene expression profiling. J Autoimmun 35:70–76
127.
Kallionpää H, Elo LL, Laajala E et al (2014) Innate immune activity is detected prior to seroconversion in children with HLA-conferred T1D susceptibility. Diabetes 63:2402–2414PubMedCrossRef
128.
Ferreira RC, Guo H, Coulson RM et al (2014) A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes 63:2538–2550PubMedPubMedCentralCrossRef
129.
Oresic M, Simell S, Sysi-Aho M et al (2008) Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type1 diabetes. J Exp Med 205:2975–2984PubMedPubMedCentralCrossRef
130.
Oresic M, Gopalacharyulu P, Mykkanen J et al (2013) Cord serum lipidome in prediction of islet autoimmunity and type 1 diabetes. Diabetes 62:3268–3274PubMedPubMedCentralCrossRef
131.
La Torre D, Seppanen-Laakso T, Larsson HE et al (2013) Decreased cord-blood phospholipids in young age-at onset type 1 diabetes. Diabetes 62:3951–3956PubMedPubMedCentralCrossRef
132.
Metz TO, Qian WJ, Jacobs JM et al (2008) Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset. J Proteome Res 7:698–707PubMedCrossRef
133.
Zhi W, Sharma A, Purohit S et al (2011) Discovery and validation of serum protein changes in type 1 diabetes patients using high throughput two dimensional liquid chromatography-mass spectrometry and immunoassays. Mol Cell Proteomics 10:M111.012203PubMedPubMedCentralCrossRef
134.
Zhang Q, Fillmore TL, Schepmoes AA et al (2013) Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes. J Exp Med 210:191–203PubMedPubMedCentralCrossRef
135.
Moulder R, Bhosale SD, Erkkila T et al (2015) Serum proteomes distinguish children developing type 1diabetes in a cohort with HLA-conferred susceptibility. Diabetes 64:2265–2278PubMedCrossRef
136.
Parikka V, Näntö-Salonen K, Saarinen M et al (2012) Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia 55:1926–1936PubMedCrossRef
137.
Phillips JE, Couper JJ, Penno MA, Harrison LC, ENDIA Study Group (2016) Type 1 diabetes: a disease of developmental origins. Pediatr Diabetes 18:417–421PubMedCrossRef
Metadata
Title
Early life origin of type 1 diabetes
Authors
Mikael Knip
Kristiina Luopajärvi
Taina Härkönen
Publication date
01-11-2017
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 6/2017
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-017-0665-6

Other articles of this Issue 6/2017

Seminars in Immunopathology 6/2017 Go to the issue

Introduction

Immunity and immunopathology in early human life

Review

Tolerance and immunity to pathogens in early life: insights from HBV infection

Review

In utero development of memory T cells

Review

The maternal microbiome during pregnancy and allergic disease in the offspring

Review

Survival of the fetus: fetal B and T cell receptor repertoire development

Review

Vaccine responses in newborns
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits