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Diabetologia
Published in: Diabetologia 8/2005

01-08-2005 | Article

Diabetes-associated HLA genotypes affect birthweight in the general population

Authors: H. E. Larsson, K. Lynch, B. Lernmark, A. Nilsson, G. Hansson, P. Almgren, Å. Lernmark, S-A. Ivarsson, DiPiS Study Group

Published in: Diabetologia | Issue 8/2005

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Abstract

Aims/hypothesis

The aim of our study was to test the hypothesis that HLA genotypes conferring risk of diabetes, cord blood autoantibodies, or both are associated with increased birthweight.

Methods

HLA genotypes were determined in dried blood spots of cord blood from a total of 16,709 children born to healthy mothers in the Diabetes Prediction in Skåne (DiPiS) study, a population-based observational clinical investigation of newborn children. Children born to mothers with diabetes or gestational diabetes were excluded. Autoantibodies to glutamic acid decarboxylase (GAD65Ab) and insulinoma-associated protein 2 were determined in standard radioligand binding assays. Birthweight was adjusted for gestational age and divided into quartiles. The upper quartile was defined as high relative birthweight (HrBW) and the lower quartile as low relative birthweight (LrBW).

Results

Genotypes conferring risk of type 1 diabetes were strongly associated with relative birthweight (rBW) (p=0.01). The high-risk HLA-DQ2/8, DQ8/0604 and DQ8/X genotypes were associated with HrBW (odds ratio [OR] [95% CI]=1.20 [1.08–1.33], p=0.0006). The HLA-DQB1*0603 allele, which is negatively associated with type 1 diabetes, was also associated with HrBW (p=0.025), confirming a previous report on DQB1*0603-linked HLA-DR13. GAD65Ab were negatively associated with HrBW (OR [95% CI]=0.72 [0.56–0.93], p=0.01). Regression analysis showed that the HLA-associated increase in rBW was independent of confounding factors.

Conclusions/interpretation

HLA genotypes may be associated with intrauterine growth independent of type 1 diabetes risk. The epidemiological observation that high birthweight is a risk factor for type 1 diabetes could possibly result from a moderating effect on intrauterine growth of HLA genotypes conferring a high risk of diabetes.
Literature
1.
Diabetes Epidemiology Research International Group (1990) Secular trends in incidence of childhood IDDM in 10 countries. Diabetes 39:858–864
2.
Karvonen M, Tuomilehto J, Libman I et al (1993) A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. World Health Organization DIAMOND Project Group. Diabetologia 36:883–892PubMed
3.
Dahlquist G, Mustonen L (1994) Childhood onset diabetes—time trends and climatological factors. Int J Epidemiol 23:1234–1241
4.
Gardner SG, Bingley PJ, Sawtell PA et al (1997) Rising incidence of insulin dependent diabetes in children aged under 5 years in the Oxford region: time trend analysis. The Bart’s–Oxford Study Group. BMJ 315:713–717PubMed
5.
Svensson J, Carstensen B, Molbak A et al (2002) Increased risk of childhood type 1 diabetes in children born after 1985. Diabetes Care 25:2197–2201PubMed
6.
Tuomilehto J, Virtala E, Karvonen M et al (1995) Increase in incidence of insulin-dependent diabetes mellitus among children in Finland. Int J Epidemiol 24:984–992
7.
EURODIAB Ace Study Group and EURODIAB Ace Substudy 2 Study Group (1998) Familial risk of type I diabetes in European children. Diabetologia 41:1151–1156
8.
Todd JA (1995) Genetic analysis of type 1 diabetes using whole genome approaches. Proc Natl Acad Sci U S A 92:8560–8565PubMed
9.
Redondo MJ, Fain PR, Eisenbarth GS (2001) Genetics of type 1A diabetes. Recent Prog Horm Res 56:69–89CrossRefPubMed
10.
Noble JA, Valdes AM, Cook M et al (1996) The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet 59:1134–1148PubMed
11.
Kockum I, Sanjeevi CB, Eastman S et al (1995) Population analysis of protection by HLA-DR and DQ genes from insulin-dependent diabetes mellitus in Swedish children with insulin-dependent diabetes and controls. Eur J Immunogenet 22:443–465PubMed
12.
Barnett AH, Eff C, Leslie RD et al (1981) Diabetes in identical twins. A study of 200 pairs. Diabetologia 20:87–93CrossRefPubMed
13.
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 35:1060–1067PubMed
14.
Patterson CC, Dahlquist G, Soltesz G et al (2001) Is childhood-onset type I diabetes a wealth-related disease? An ecological analysis of European incidence rates. Diabetologia 44 [Suppl 3]:B9–B16PubMed
15.
Dahlquist G, Bennich SS, Kallen B (1996) Intrauterine growth pattern and risk of childhood onset insulin dependent (type I) diabetes: population based case-control study. BMJ 313:1174–1177PubMed
16.
Stene LC, Magnus P, Lie RT et al (2001) Birth weight and childhood onset type 1 diabetes: population based cohort study. BMJ 322:889–892CrossRefPubMed
17.
Verge CF, Gianani R, Kawasaki E et al (1996) Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes 45:926–933PubMed
18.
Baekkeskov S, Aanstoot HJ, Christgau S et al (1990) Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347:151–156
19.
Solimena M, Dirkx R Jr, Hermel JM et al (1996) ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules. EMBO J 15:2102–2114PubMed
20.
Saeki K, Zhu M, Kubosaki A et al (2002) Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion. Diabetes 51:1842–1850PubMed
21.
Atkinson MA, Eisenbarth GS (2001) Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358:221–229CrossRefPubMed
22.
Lindberg B, Ivarsson SA, Landin-Olsson M et al (1999) Islet autoantibodies in cord blood from children who developed type I (insulin-dependent) diabetes mellitus before 15 years of age. Diabetologia 42:181–187CrossRefPubMed
23.
Hypponen E, Virtanen SM, Kenward MG et al (2000) Obesity, increased linear growth, and risk of type 1 diabetes in children. Diabetes Care 23:1755–1760PubMed
24.
Baum JD, Ounsted M, Smith MA (1975) Letter: Weight gain in infancy and subsequent development of diabetes mellitus in childhood. Lancet 2:866
25.
Johansson C, Samuelsson U, Ludvigsson J (1994) A high weight gain early in life is associated with an increased risk of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 37:91–94PubMed
26.
Bruining GJ (2000) Association between infant growth before onset of juvenile type-1 diabetes and autoantibodies to IA-2. Netherlands Kolibrie study group of childhood diabetes. Lancet 356:655–656CrossRefPubMed
27.
Aroviita P, Partanen J, Sistonen P et al (2004) High birth weight is associated with human leukocyte antigen (HLA) DRB1*13 in full-term infants. Eur J Immunogenet 31:21–26CrossRefPubMed
28.
Sjoroos M, Iitia A, Ilonen J et al (1995) Triple-label hybridization assay for type-1 diabetes-related HLA alleles. Biotechniques 18:870–877PubMed
29.
Ilonen J, Reijonen H, Herva E et al (1996) Rapid HLA-DQB1 genotyping for four alleles in the assessment of risk for IDDM in the Finnish population. The Childhood Diabetes in Finland (DiMe) Study Group. Diabetes Care 19:795–800PubMed
30.
Hampe CS, Hammerle LP, Bekris L et al (2000) Recognition of glutamic acid decarboxylase (GAD) by autoantibodies from different GAD antibody-positive phenotypes. J Clin Endocrinol Metab 85:4671–4679CrossRefPubMed
31.
Grubin CE, Daniels T, Toivola B et al (1994) A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM. Diabetologia 37:344–350PubMed
32.
Verge CF, Stenger D, Bonifacio E et al (1998) Combined use of autoantibodies (IA-2 autoantibody, GAD autoantibody, insulin autoantibody, cytoplasmic islet cell antibodies) in type 1 diabetes: Combinatorial Islet Autoantibody Workshop. Diabetes 47:1857–1866PubMed
33.
Marsal K, Persson PH, Larsen T et al (1996) Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr 85:843–848PubMed
34.
Persson PH, Weldner BM (1986) Intra-uterine weight curves obtained by ultrasound. Acta Obstet Gynecol Scand 65:169–173PubMed
35.
Larsson K, Elding-Larsson H, Cederwall E et al (2004) Genetic and perinatal factors as risk for childhood type 1 diabetes. Diabetes Metab Res Rev 20:429–437CrossRefPubMed
36.
Lernmark B, Elding Larsson H, Hansson G et al (2004) Parent responses to participation in genetic screening for diabetes risk. Pediatr Diabetes 5:174–181CrossRefPubMed
37.
Hermann R, Turpeinen H, Laine AP et al (2003) HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families. Tissue Antigens 62:162–169CrossRefPubMed
38.
Stene LC, Magnus P, Ronningen KS et al (2001) Diabetes-associated HLA-DQ genes and birth weight. Diabetes 50:2879–2882PubMed
39.
Dahlquist G, Frisk G, Ivarsson SA et al (1995) Indications that maternal coxsackie B virus infection during pregnancy is a risk factor for childhood-onset IDDM. Diabetologia 38:1371–1373PubMed
40.
Dahlquist GG, Ivarsson S, Lindberg B et al (1995) Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study. Diabetes 44:408–413PubMed
41.
Hyoty H, Hiltunen M, Knip M et al (1995) A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes 44:652–657PubMed
42.
Dahlquist G, Blom L, Lonnberg G (1991) The Swedish Childhood Diabetes Study—a multivariate analysis of risk determinants for diabetes in different age groups. Diabetologia 34:757–762CrossRefPubMed
43.
Dahlquist GG, Blom LG, Persson LA et al (1990) Dietary factors and the risk of developing insulin dependent diabetes in childhood. BMJ 300:1302–1306PubMed
44.
Dahlquist GG, Patterson C, Soltesz G (1999) Perinatal risk factors for childhood type 1 diabetes in Europe. The EURODIAB Substudy 2 Study Group. Diabetes Care 22:1698–1702PubMed
45.
Virtanen SM, Rasanen L, Aro A et al (1992) Feeding in infancy and the risk of type 1 diabetes mellitus in Finnish children. The ‘Childhood Diabetes in Finland’ Study Group. Diabet Med 9:815–819PubMed
46.
Thernlund GM, Dahlquist G, Hansson K et al (1995) Psychological stress and the onset of IDDM in children. Diabetes Care 18:1323–1329PubMed
47.
Robinson N, Fuller JH (1985) Role of life events and difficulties in the onset of diabetes mellitus. J Psychosom Res 29:583–591CrossRefPubMed
48.
Blom L, Persson LA, Dahlquist G (1992) A high linear growth is associated with an increased risk of childhood diabetes mellitus. Diabetologia 35:528–533CrossRefPubMed
49.
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 25:1755–1760
50.
Koczwara K, Bonifacio E, Ziegler AG (2004) Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes. Diabetes 53:1–4PubMed
51.
National Board of Health and Welfare (2002) Fakta om mammor, förlossningar, nyfödda barn-Medicinska födelseregistret 1973–2000
Metadata
Title
Diabetes-associated HLA genotypes affect birthweight in the general population
Authors
H. E. Larsson
K. Lynch
B. Lernmark
A. Nilsson
G. Hansson
P. Almgren
Å. Lernmark
S-A. Ivarsson
DiPiS Study Group
Publication date
01-08-2005
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2005
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-005-1813-4

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