Birth at 33-38 Weeks Equals Higher Risk of Type 1 Diabetes

Becky McCall

November 18, 2015

Gestational age and type 1 diabetes appear to be linked, independent of familial factors, say researchers who conducted an extensive study on nearly all births in Sweden over 4 decades.

The link could be related to insulin resistance developing as a consequence of early-life growth restriction or attributed to altered gut microbiota, lead author Dr Ali Khashan, PhD, an epidemiologist from University College Cork, Ireland, told Medscape Medical News.

"Our study provides new and intriguing data on the early life influences on the risk of developing diabetes," he added.

The work was published online October 30 in Diabetes Care.

Dr Khashan highlighted the three key findings. First, late preterm birth and early-term birth babies are at increased risk of type 1 diabetes. "This association, although small, cannot be explained by unmeasured familial confounding factors, such as genetic and lifestyle factors, shared by siblings," he pointed out.

Second, an association seen between large-for-gestational-age babies and increased risk for type 1 diabetes is unlikely to be causal and may be explained by familial factors shared by siblings, he said.

Third, and conversely, the researchers found that babies born before 33 gestation weeks (very preterm) and/or with birth weight of less than 1500 g, or small for gestational age, seem to be protected against type 1 diabetes.

"This is intriguing and deserves further investigation, as it may help [us to] understand the fetal programming effect on the development of type 1 diabetes," he noted.

Novel Sibling Control Study

Explaining the reasons for conducting the study, Dr Khashan said existing data on the potential association between gestational age, birth weight, and type 1 diabetes is inconsistent and contradictory, so his team wanted to examine these associations using the largest cohort study to date, which included more than three million births.

"In addition to using a very large population-based study and adjusting for several important potential confounders, we were able to examine the effects of very preterm birth and very low birth weight on type 1 diabetes," he noted.

"We were also able to conduct a sibling control study, which may have allowed us to, indirectly, account for unmeasured genetic and environmental factors shared by siblings."

The analytical approach was based on two steps: a population-based cohort study which included nearly all live singleton births in Sweden between 1973 and 2009, sourced from the Swedish Medical Birth Register, widely considered a high-quality data source; and within this, a nested case-control study where children with a diagnosis of type 1 diabetes were identified (from the Swedish National Patient Register) and matched with their siblings who did not have diabetes, as controls.

The cohort study consisted of 3,624,675 singleton live children, of which 13,944 were diagnosed with type 1 diabetes. The sibling-matched case-control study included 82% of the type 1 diabetes cases (11,403 of 13,944) matched with 17,920 sibling controls.

Statistical modeling was used to identify the relative risks for developing type 1 diabetes according to different criteria.

The study did not include information on possible confounders due to maternal lifestyle during pregnancy.

But using the sibling controls "allowed us to adjust for unmeasured factors that are shared by siblings, such as family environment, diet, lifestyle, maternal characteristics, and genetic factors," the researchers explain.

Preterm and Early-Term Birth Increase Risk; Very Preterm Reduces Risk

"We found a small but significantly increased risk of type 1 diabetes in relation to preterm (33 to 36 weeks' gestation; relative risk [RR] of diabetes, 1.18) and early term (37 to 38 weeks; RR, 1.12) birth, and this remained significant after accounting for sibling controls," reported Dr Khashan.

The researchers also found that very low birth weight (RR, 0.66), small for gestational age (RR, 0.83), and very preterm birth (less than 33 weeks' gestation) (RR, 0.67) conversely appeared to be associated with a reduced risk of type 1 diabetes.

Babies that were large for gestational age had an increased risk of type 1 diabetes (RR, 1.14), but this effect disappeared once familial factors were accounted for in the sibling controls, explained Dr Khashan.

With respect to possible mechanisms driving the observed associations, the authors write, "It is possible that preterm birth is associated with structural change within organ systems and epigenetic changes leading to higher risk of type 1 diabetes."

The authors declare no relevant financial relationships.

Diabetes Care. Published online October 30, 2015. Abstract


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