Background The UK Biobank study provides a unique opportunity to study the causes and consequences of disease. We aimed to use the UK Biobank data to study the well-established, but poorly understood, association between low birthweight and type 2 diabetes.
Methods We used logistic regression to calculate the odds ratio for participants risk of type 2 diabetes given a one standard deviation increase in birthweight. To test for an association between parental diabetes and birthweight, we performed linear regression of self-reported parental diabetes status against birthweight. We performed path and mediation analyses to test the hypothesis that birthweight partly mediates the association between parental diabetes and participant type 2 diabetes status.
Results Of the UK Biobank participants, 277 261 reported their birthweight. Of 257 715 individuals of White ethnicity and singleton pregnancies, 6576 had type 2 diabetes, 19 478 reported maternal diabetes (but not paternal), 20 057 reported paternal diabetes (but not maternal) and 2754 participants reported both parents as having diabetes. Lower birthweight was associated with type 2 diabetes in the UK Biobank participants. A one kilogram increase in birthweight was associated with a lower risk of type 2 diabetes (odds ratio: 0.74; 95% CI: 0.71, 0.76; P = 2 10-57). Paternal diabetes was associated with lower birthweight (45 g lower; 95% CI: 36, 54; P = 2 10-23) relative to individuals with no parental diabetes. Maternal diabetes was associated with higher birthweight (59 g increase; 95% CI: 50, 68; P = 3 10-37). Participants lower birthweight was a mediator of the association between reported paternal diabetes and participants type 2 diabetes status, explaining 1.1% of the association, and participants higher birthweight was a mediator of the association between reported maternal diabetes and participants type 2 diabetes status, explaining 1.2% of the association.
Conclusions Data from the UK Biobank provides the strongest evidence by far that paternal diabetes is associated with lower birthweight, whereas maternal diabetes is associated with increased birthweight. Our findings with paternal diabetes are consistent with a role for the same genetic factors influencing foetal growth and type 2 diabetes.
Jessica S Tyrrell, Hanieh Yaghootkar, Rachel M Freathy, Andrew T Hattersley, Timothy M Frayling; Parental diabetes and birthweight in 236 030 individuals in the UK Biobank Study. Int J Epidemiol 2013; 42 (6): 1714-1723. doi: 10.1093/ije/dyt220
Risk of type 2 Diabetes and development of disease
Type 2 diabetes is a significant health burden worldwide and research is underway to determine how this burden can be reduced. Approximately fifty percent of diabetic patients die prematurely of stroke and heart disease. It is a complex disease, and a greater understanding of the disease is important for improving treatment regimens and public health interventions.
The size of the UK Biobank provides a unique opportunity to investigate individuals at the extremes of normal distributions. In this proposal we would like to identify individuals who are at high risk of type 2 diabetes but have not developed the condition, and those who are at low risk of disease who have developed the condition. We will investigate common risk factors (including anthropometric, early life, lifestyle, family history and dietary factors) to identify individuals at the extremes of the normal distribution. We will request funding to extend this work, investigating whether genetic variation has contributed to an individual?s presence within these ?paradoxical? extremes. This specific proposal uses baseline data on the full cohort on measures related to medical conditions and lifestyle factors, anthropometry, early life factors and ethnicity.
|Lead investigator:||Dr Jess Tyrrell|
|Lead institution:||University of Exeter|