The Swedish childhood diabetes study ? a multivariate analysis of risk determinants for diabetes in different age groups

Dahlquist, Gisela; Blom, L.; Lönnberg, Göran

doi:10.1007/bf00401524

Cited by 87 publications

(80 citation statements)

References 16 publications

(18 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These include viral infections [39][40][41], dietary factors (cow's milk, nitrosamines, high protein intake) [42,43], neonatal jaundice and ABO incompatibility [44], neonatal respiratory disease [44], early supplementary milk-based feeding, short time of breast-feeding [42,45] and stress events such as severe life events [42,46,47]. Several studies have found that children who later develop diabetes have a higher BW than controls, and also have an increased linear growth in childhood [15,16,42,48,49]. Our finding that HLA genetic factors, which are associated with susceptibility for type 1 diabetes, are related to intrauterine growth might in fact contribute to the increased BW in type 1 diabetes children.…”

Section: Discussionmentioning

confidence: 99%

Diabetes-associated HLA genotypes affect birthweight in the general population

et al. 2005

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Diabetes-associated HLA genotypes affect birthweight in the general population

et al. 2005

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…For example, several studies have reported that gestational infections might represent a risk factor for T1D development [4][5][6]. In contrast, exposure to maternal diabetes in utero has been suggested to represent a protective factor for the offspring during the first two decades of life [5,7]. This finding is reinforced by studies indicating that children born before maternal diabetes onset have a higher risk of developing diabetes than children who are born after the onset of maternal diabetes [7].…”

Section: Introductionmentioning

confidence: 99%

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes

Holm

Svensson

Åkesson

et al. 2006

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryMaternal transmission of islet autoantibodies to children born to mothers with type 1 diabetes (T1D) has been shown to protect from autoantibodies and diabetes development later in life. However, the factors conferring disease protection are poorly understood. The aim of this study was to evaluate comparatively proinflammatory cytokines, autoantibodies and lymphocyte subsets in cord blood (CB) of children born to mothers with either T1D (n = 13), gestational diabetes (GDM) (n = 32) or healthy mothers (n = 81) in relation to transplacental passage of autoantibodies. The results are consistent with early priming of the fetal immune system only in children born to mothers with T1D. Levels of interleukin (IL)-1b (P = 0·022), tumour necrosis factor (TNF)-a (P = 0·002) and IL-8 (P = 0·0012), as well as the frequency of CD4 + CD25 + T cells (P < 0·01) were significantly increased, and the increased levels correlated positively with anti-GAD65 autoantibody (GADA) levels. Moreover, CD4+ CD25 + T cells of children born to T1D mothers exhibited a more pronounced memory phenotype with increased CCR4 expression and down-regulation of CD62L. These data suggest that early activation of the fetal immune system as a consequence of maternal autoimmunity and transplacental passage of GADA may influence the generation and expansion of fetal regulatory T cells. This might induce an early antigen-specific immunological tolerance that could protect against T1D later in life.

show abstract

“…Neither the causes of the condition, nor the causes of the increased incidence are known. Although a genetic predisposition is clearly of great importance, direct epidemiological evidence from case-control studies [3,4] and indirect epidemiological evidence from migrant studies [5,6] indicate that environmental agents are also very important.The descriptive epidemiology of Type i diabetes is an important source of information for the framing of aetiological hypotheses. Several prominent features require explanation.…”

mentioning

confidence: 99%

The epidemiology of diabetes mellitus in the United Kingdom: The Yorkshire regional childhood diabetes register

et al. 1993

View full text Add to dashboard Cite

Summary. A register of the incidence of Type 1 (insulin-dependent) diabetes mellitus in the Yorkshire region of the United Kingdom has been completed. A total of 1,490 subjects aged between 0 and 16 years were identified from 1978 to 1990, giving an incidence of 13.7 per 100,000 (ages 0-14) or 13.6 per 100,000 (ages 0-16), comparable to other recent studies in the United Kingdom. An age-period-cohort analysis shows evidence for a modest drift effect of 1.75 % per year (95% confidence interval 0.28 to 3.25%). There is a marked epidemic pattern with peaks at 4-year intervals. The age-incidence curve is similar to that reported elsewhere, having peaks in early childhood and puberty. Girls have an earlier pubertal peak than boys. There is substantial seasonal variation in incidence confined to those over 5 years of age. Ascertainment is believed to be very complete, and is estimated to be 97.6% (95% confidence interval 97.2% to 98.1%).Key words: Type 1 (insulin-dependent) diabetes mellitus, epidemiology, aetiology, disease registry, childhood, ascertainment estimates.Type 1 (insulin-dependent) diabetes mellitus is an increasingly common disorder in many European populations [1,2]. Neither the causes of the condition, nor the causes of the increased incidence are known. Although a genetic predisposition is clearly of great importance, direct epidemiological evidence from case-control studies [3,4] and indirect epidemiological evidence from migrant studies [5,6] indicate that environmental agents are also very important.The descriptive epidemiology of Type i diabetes is an important source of information for the framing of aetiological hypotheses. Several prominent features require explanation. There is great geographical variation in incidence, with as much as a 40-fold variation between countries; Finland and Sardinia have the highest incidence rates (over 30 per 100,000 per year); Japan, Africa and Korea have the lowest (0.3 to 2.5 per 100,000 per year) [7][8][9][10][11][12][13]. The age incidence curve typically shows a peak in early adolescence, and may have a secondary peak earlier in childhood. There is marked seasonality of onset in many (though not all) studies [12,[14][15][16][17], although this may relate more to infections precipitating a metabolic decompensation in prediabetic persons, than to any aetiological agent [8]. The incidence in a population may change rapidly during short periods of time, whether in the indigenous population [18], or in migrant populations [5].A necessary first step in any series of investigations of the aetiology of Type 1 diabetes is to establish a good, well-validated register. This was the aim of the Yorkshire project.

show abstract

The Swedish childhood diabetes study ? a multivariate analysis of risk determinants for diabetes in different age groups

Cited by 87 publications

References 16 publications

Diabetes-associated HLA genotypes affect birthweight in the general population

Diabetes-associated HLA genotypes affect birthweight in the general population

Evidence for immunological priming and increased frequency of CD4+ CD25+ cord blood T cells in children born to mothers with type 1 diabetes

The epidemiology of diabetes mellitus in the United Kingdom: The Yorkshire regional childhood diabetes register

Contact Info

Product

Resources

About