(DCP046) GESTATIONAL DIABETES AND PARENTAL TYPE 2 DIABETES AS RISK FACTORS FOR TYPE 1 DIABETES IN OFFSPRING: A SYSTEMATIC REVIEW

Background: Maternal obesity, type 1 diabetes (T1D) and GDM have been associated with increased risk of offspring T1D. Paternal T1D is an even greater risk factor for offspring T1D. Given that paternal T1D confers this greater risk and that animal studies have demonstrated obesity in fathers to be associated with offspring dysglycemia, the relationship between paternal type 2 diabetes (T2D) and offspring T1D is of interest.

Aim: To perform a systematic review of studies evaluating associations between GDM in mothers and T1D in offspring, the associations between T2D in mothers and offspring T1D and those between paternal T2D and offspring T1D.

METHODS AND RESULTS: A systematic review was performed in which Embase, Medline, Pubmed, Cochrane and Scopus databases were searched on October 2nd, 2021 to identify relevant observational studies. We appraised all titles and abstracts for relevance and performed full text review on relevant studies.

Results: We identified 2380 unique studies. We conducted full text review on 38 studies and included 15 studies for analysis. The number of studies addressing GDM, maternal T2D and paternal T2D as exposures for offspring T1D were 13, 8 and 7, respectively. All but one study of GDM demonstrated a positive association with offspring T1D, 5 of which had effect measures reaching statistical significance, generally reflective of the higher quality studies. These consist of 2 cohort studies with hazard ratios (HR) and 95% confidence intervals (CI) of 1.3 (1-1.68) and 1.77 (1.41-2.22), 1 cohort study with incidence rate ratio (IRR) of 1.85 (95% CI 1.53-2.23) and 2 case controls with odds ratios (OR) of 4.36 (95% CI: 2.76-7.77) and 5.1 (95% CI: 3.4-6.3). Three studies of paternal T2D exposure demonstrate a significant association with development of offspring T1D, also reflective of the higher quality studies. These consist of 1 cohort study with IRR 2.47 (95% CI: 1.98-3.08) and 2 case control studies with ORs of 1.54 (95% CI 1.04-2.26) and 3.4 (95% CI: 1.5-7.9). There is insufficient high quality data to comment on an association between maternal T2D and offspring T1D.

Conclusion:

Conclusion: The specific role of dysglycemia in pregnancy on beta cell development in utero is yet to be fully understood but our study demonstrates associations between maternal GDM and offspring T1D. We also demonstrate association between paternal T2D and offspring T1D in the existing literature. There are several potential mechanisms to explain this association including genetic, epigenetic and environmental factors.