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STUDY QUESTION Is the mode of conception (natural, subfertility and non-IVF, and IVF) associated with the risk of Type 1 diabetes mellitus among offspring? SUMMARY ANSWER The risk of Type 1 diabetes in offspring does not differ among natural, subfertility and non-IVF, and IVF conceptions. WHAT IS KNOWN ALREADY Evidence has shown that children born through IVF have an increased risk of impaired metabolic function. STUDY DESIGN, SIZE, DURATION A population-based, nested case–control study was carried out, including 769 children with and 3110 children without Type 1 diabetes mellitus within the prospective cohort of 2 228 073 eligible parent-child triads between 1 January 2004 and 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Using registry data from Taiwan, the mode of conception was divided into three categories: natural conception, subfertility, and non-IVF (indicating infertility diagnosis but no IVF-facilitated conception), and IVF conception. The diagnosis of Type 1 diabetes mellitus was determined according to the International Classification of Diseases, 9th or 10th Revision, Clinical Modification. Each case was matched to four controls randomly selected after matching for child age and sex, residential township, and calendar date of Type 1 diabetes mellitus occurrence. MAIN RESULTS AND THE ROLE OF CHANCE Based on 14.3 million person-years of follow-up (median, 10 years), the incidence rates of Type 1 diabetes were 5.33, 5.61, and 4.74 per 100 000 person-years for natural, subfertility and non-IVF, and IVF conceptions, respectively. Compared with natural conception, no significant differences in the risk of Type 1 diabetes were observed for subfertility and non-IVF conception (adjusted odds ratio, 1.04 [95% CI, 0.85–1.27]) and IVF conception (adjusted odds ratio, 1.00 [95% CI, 0.50–2.03]). In addition, there were no significant differences in the risk of Type 1 diabetes according to infertility source (male/female/both) and embryo type (fresh/frozen). LIMITATIONS, REASONS FOR CAUTION Although the population-level data from Taiwanese registries was used, a limited number of exposed cases was included. We showed risk of Type 1 diabetes was not associated with infertility source or embryo type; however, caution with interpretation is required owing to the limited number of exposed events after the stratification. The exclusion criterion regarding parents’ history of diabetes mellitus was only applicable after 1997, and this might have caused residual confounding. WIDER IMPLICATIONS OF THE FINDINGS It has been reported that children born to parents who conceived through IVF had worse metabolic profiles than those who conceived naturally. Considering the findings of the present and previous studies, poor metabolic profiles may not be sufficient to develop Type 1 diabetes mellitus during childhood. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from Shin Kong Wu Ho-Su Memorial Hospital (No. 109GB006-1). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.
STUDY QUESTION Is the mode of conception (natural, subfertility and non-IVF, and IVF) associated with the risk of Type 1 diabetes mellitus among offspring? SUMMARY ANSWER The risk of Type 1 diabetes in offspring does not differ among natural, subfertility and non-IVF, and IVF conceptions. WHAT IS KNOWN ALREADY Evidence has shown that children born through IVF have an increased risk of impaired metabolic function. STUDY DESIGN, SIZE, DURATION A population-based, nested case–control study was carried out, including 769 children with and 3110 children without Type 1 diabetes mellitus within the prospective cohort of 2 228 073 eligible parent-child triads between 1 January 2004 and 31 December 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS Using registry data from Taiwan, the mode of conception was divided into three categories: natural conception, subfertility, and non-IVF (indicating infertility diagnosis but no IVF-facilitated conception), and IVF conception. The diagnosis of Type 1 diabetes mellitus was determined according to the International Classification of Diseases, 9th or 10th Revision, Clinical Modification. Each case was matched to four controls randomly selected after matching for child age and sex, residential township, and calendar date of Type 1 diabetes mellitus occurrence. MAIN RESULTS AND THE ROLE OF CHANCE Based on 14.3 million person-years of follow-up (median, 10 years), the incidence rates of Type 1 diabetes were 5.33, 5.61, and 4.74 per 100 000 person-years for natural, subfertility and non-IVF, and IVF conceptions, respectively. Compared with natural conception, no significant differences in the risk of Type 1 diabetes were observed for subfertility and non-IVF conception (adjusted odds ratio, 1.04 [95% CI, 0.85–1.27]) and IVF conception (adjusted odds ratio, 1.00 [95% CI, 0.50–2.03]). In addition, there were no significant differences in the risk of Type 1 diabetes according to infertility source (male/female/both) and embryo type (fresh/frozen). LIMITATIONS, REASONS FOR CAUTION Although the population-level data from Taiwanese registries was used, a limited number of exposed cases was included. We showed risk of Type 1 diabetes was not associated with infertility source or embryo type; however, caution with interpretation is required owing to the limited number of exposed events after the stratification. The exclusion criterion regarding parents’ history of diabetes mellitus was only applicable after 1997, and this might have caused residual confounding. WIDER IMPLICATIONS OF THE FINDINGS It has been reported that children born to parents who conceived through IVF had worse metabolic profiles than those who conceived naturally. Considering the findings of the present and previous studies, poor metabolic profiles may not be sufficient to develop Type 1 diabetes mellitus during childhood. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from Shin Kong Wu Ho-Su Memorial Hospital (No. 109GB006-1). The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER N/A.
Type 1 diabetes (T1D) and other autoimmune diseases (AIDs) co-occur in families. We studied the aggregation of 50 parental AIDs with T1D in offspring and the contribution of a shared genetic background, which was partitioned into HLA and non-HLA variation. Leveraging nationwide registers of 7.2M Finns, including 58,284 family trios, we observed that 15 parental AIDs, such as coeliac disease and rheumatoid arthritis, were associated with an increased risk of T1D in offspring. The identified epidemiological associations were then tested by comprehensive genetic analyses performed on 470K Finns genotyped in the FinnGen study (12,563 trios). The within-family genetic transmission analysis further demonstrated that the aggregation of parental AIDs with offspring T1D could be partially explained by HLA and non-HLA polymorphisms in a disease-dependent manner. For example, the associations with offspring T1D for coeliac disease and psoriasis were mainly driven by HLA while autoimmune hypothyroidism and rheumatoid arthritis also had non-HLA contributors. We, therefore, proposed a novel parental polygenic score (PGS), integrating variations in both HLA and non-HLA genes, to understand the cumulative risk pattern of T1D in offspring. This raises an intriguing possibility of considering parental PGS, in conjunction with clinical diagnoses, to inform individuals about T1D risk in their offspring.
Aim. To assess the incidence trends in type 1 diabetes among children and adolescents across Europe during the period from 1994 to 2022 using a systematic methodology. Materials and Methods. Cross-sectional or follow-up studies reporting population-based incidence rates (IRs) of European children and adolescents diagnosed aged <15 years with type 1 diabetes were included. The Mantel‒Haenszel or DerSimonian and Laird random-effects method was used to compute the pooled IR estimates and their 95% confidence intervals (CIs). Subgroup analyses were conducted by study year, biological sex, age group (0–4, 5−9, and 10–14 years), country, and European regions. Results. A total of 75 studies (219,331 children and adolescents aged 0–14 years) with data from 32 countries were included. Generally, a high overall rate of increase in type 1 diabetes incidence has been shown in most European countries from 1994 to 2022 in both sexes, with an overall increase from 10.85 (95% CI, 9.62–12.07) per 100,000 person-years from 1994 to 2003 to 20.96 (95% CI, 19.26–22.66) per 100,000 person-years from 2013 to 2022. Conclusions. There are substantial between-country differences in the current levels and trends of IR in type 1 diabetes in European children and adolescents. Our data suggest a worrying upward trend in most European countries.
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