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ABSTRACT: To study HLA-DQB1 genes and islet cell autoantibodies against glutamic acid decarboxylase 65 (GADA) and insulinoma antigen-2 (IA-2A) in relation to diabetes post partum in mothers with diagnosed gestational diabetes mellitus (GDM).
During 2003-2004, women undergoing a 75 g oral glucose tolerance test (OGTT) during pregnancy were invited to participate in the Mamma Study. Cut-off level defining GDM was a 2-h capillary blood glucose of 7.8 mmol/L. 1-2 years after delivery a 75 g OGTT was performed, GADA and IA-2A were measured and HLA-DQB1 genes analysed. Data were available for 452 mothers with previous GDM and 168 randomly selected control subjects.
HLA-DQB1*0602 was negatively associated with GDM (p=0.033) and with development of diabetes post partum (p=0.017), whereas high risk HLA were not associated with GDM or with diabetes. The presence of GADA post partum was positively associated with diabetes post partum (p=0.0009), but not with impaired glucose tolerance.
Mothers with GDM and HLA-DQB1*0602 were less likely to develop diabetes after pregnancy, and type 1 diabetes associated high risk HLA genes did not predict type 1 diabetes post partum. Additionally, GADA were positively associated with diabetes development.
Diabetes research and clinical practice 11/2011; 95(2):260-4. · 2.16 Impact Factor
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ABSTRACT: Little is known on the possible existence of socioeconomic and geographical differences in early coeliac disease (CD) risk. Therefore, we investigated these aspects in children before age two.
Linking the Swedish Medical Birth Registry to several other national registries, we identified all singletons born in Sweden from 1987 to 1993 (n = 792,401) and followed them until 2 years of age to identify cases of CD. Applying multilevel logistic regression analysis, we investigated the association between socioeconomic position (SEP) and CD in children and also whether a possible geographical variation in CD risk was explained by individual characteristics.
Low SEP was associated with CD in boys OR 1.37 (95% CI 1.03-1.82), but not in girls OR 0.87 (95% CI 0.68-1.12). We found a considerable geographical variation in disease risk (i.e. intra-municipality correlation ≈ 10%) that was not explained by individual characteristics.
Low SEP is associated with CD in boys but not in girls. Also, CD appears to be conditioned by geographical area of residence. While our study represents an innovative contribution to the epidemiology of CD in children, the reasons for the observed geographical and socioeconomic differences could be speculated but are still unknown.
Acta Paediatrica 08/2011; 101(2):185-91. · 2.07 Impact Factor
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ABSTRACT: Adult type 2 diabetes patients with GAD65 autoantibodies (GADA) are known as latent autoimmune diabetes in adults (LADA). It has been suggested that GADA in LADA patients preferentially bind to the N-terminal end of GAD65. Using the N-terminal end extension of ³⁵S-GAD65 generated by the pEx9 plasmid, we tested the hypothesis that GADA in LADA patients preferentially react with ³⁵S-GAD65 from the pEx9 plasmid compared to the normal length pThGAD65 plasmid. Healthy control subjects (n = 250) were compared with type 1 (n = 23), type 2 (n = 290), and unspecified (n = 57) diabetes patients. In addition, radio-binding assays for GADA with ³⁵S-GAD65 generated from both the pEx9 and pThGAD65 plasmids were used in displacement assays with an excess of recombinant human GAD65 (2 μg/mL) to correct for non-specific binding. ³⁵S-GAD65 produced by either pEx9 or pThGAD65 did not differ in binding among the healthy controls and among the type 1 diabetes patients. Among the type 2 and unspecified patients, there were 4/290 and 3/57 patients, respectively, with binding to the pEx9 but not to the pThGAD65 generated ³⁵S-GAD65. In the displacement assay, we discovered 14 patients with very high-titer GADA among the type 1 (n = 3, 12,272-29,915 U/mL), type 2 (n = 7; 12,398-334,288 U/mL), and unspecified (n = 4; 20,773-4,053,580 U/mL) patients. All samples were fully displaced following appropriate dilution. We conclude that pThGAD65 is preferred for the coupled in vitro transcription translation of ³⁵S-GAD65 and that displacement with recombinant GAD65 may detect very high-titer GADA with possible clinical relevance.
Autoimmunity 03/2011; 44(2):129-36. · 2.47 Impact Factor
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ABSTRACT: Several European studies have found significant small area variation in the risk of childhood onset (type 1) diabetes (T1D) which has been interpreted as evidence for contextual determinants of T1D. However, this conclusion may be fallacious since the limited number of newborn infants and the low risk for T1D is a source of spurious variability not properly handled by usual statistical methods. This study investigates the existence of contextual effects in the genesis of T1D, compares conclusions in previous reports with results obtained in a multilevel regression framework and highlights analysis of variance as a useful approach in public health.
All singletons born in Sweden between 1987 and 1991 were identified in the Medical Birth Registry (n=560 766) and followed for diabetes until age 14 using the Hospital Discharge Registry. Area variation in the cumulative incidence of T1D was estimated by different statistical methods including multilevel logistic regression.
The risk of T1D ranged from 4.3 to 6.5 per 1000 newborns across the counties (n=24) and from 0.0 to 19.2 per 1000 newborns across the municipalities (n=284). These differences were significant in standard statistical tests (counties, p=0.02; municipalities, p=0.007). However, according to multilevel analyses, the risk of T1D ranged from 4.7 to 5.7 and from 4.4 to 6.0 per 1000 newborns in counties and municipalities, respectively, and the area variation was small and without practical relevance (counties, sigma(2)=0.006; municipalities, sigma(2)=0.017).
Previous reports based on standard statistical tests are misleading. According to multilevel analysis, administrative areas have minor relevance for individual risk of T1D in Sweden.
Journal of epidemiology and community health 10/2009; 64(9):789-95. · 3.04 Impact Factor
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ABSTRACT: Social epidemiology investigates both individuals and their collectives. Although the limits that define the individual bodies are very apparent, the collective body's geographical or cultural limits (eg "neighbourhood") are more difficult to discern. Also, epidemiologists normally investigate causation as changes in group means. However, many variables of interest in epidemiology may cause a change in the variance of the distribution of the dependent variable. In spite of that, variance is normally considered a measure of uncertainty or a nuisance rather than a source of substantive information. This reasoning is also true in many multilevel investigations, whereas understanding the distribution of variance across levels should be fundamental. This means-centric reductionism is mostly concerned with risk factors and creates a paradoxical situation, as social medicine is not only interested in increasing the (mean) health of the population, but also in understanding and decreasing inappropriate health and health care inequalities (variance).
Critical essay and literature review.
The present study promotes (a) the application of measures of variance and clustering to evaluate the boundaries one uses in defining collective levels of analysis (eg neighbourhoods), (b) the combined use of measures of variance and means-centric measures of association, and (c) the investigation of causes of health variation (variance-altering causation).
Both measures of variance and means-centric measures of association need to be included when performing contextual analyses. The variance approach, a new aspect of contextual analysis that cannot be interpreted in means-centric terms, allows perspectives to be expanded.
Journal of epidemiology and community health 09/2009; 63(12):1043-8. · 3.04 Impact Factor
