Low Birthweight Independently Linked to Increased Risk of Type 2 Diabetes

Rasmus Wibaek, PhD

Credit: Copenhagen University Hospitals

Low birth weight is independently linked to an increased risk of type 2 diabetes (T2D), as well as younger age and a lower prevalence of obesity at diagnosis, according to new research.¹

The findings, obtained from 2 studies at the Steno Diabetes Center Copenhagen, suggested patients with T2D and lower birthweight show higher use of diabetes drugs than those with normal birthweight, as well as a larger number of comorbidities including high blood pressure, at the time of diagnosis.

“Taken together, the two studies collectively provide strong support for the following conclusions: an adverse fetal environment reflected by low birthweight is a strong and non-genetic risk factor not only of developing T2D, per se, but in addition for the development of a relatively more severe subtype of T2D - with earlier disease onset, more complications, and co-morbidities, as well as with an increased need for clinical care and medical treatments," wrote the investigative team.

In the first study, led by Rasmus Wibaek, PhD, adults aged 30 – 60 years enrolled in the Danish Inter99 cohort in 1999–2001 (baseline examination), with information on birthweight from original birth records from 1939–1971 and without diabetes at baseline.² Birth records were linked with individual-level data on age at diabetes diagnosis. The analysis estimated incidence rates of T2D by age, sex, and birthweight using statistical modeling, adjusting for prematurity status at birth, birth order, genetic risk scores for birthweight and T2D, maternal and paternal diabetes history, socioeconomic status, and adult body mass index (BMI).

Among 4590 participants, there were 492 incident T2D cases during an average follow-up of 19 years. The analysis showed T2D incidence rates increased with age, were higher in male participants, and decreased linearly with increasing birthweight, with each extra kg of birthweight linked to a 40% reduced risk of T2D, which continued into the highest birthweight. The absolute rate of increase in T2D increase across ages was steeper in those born with lower birth weights compared with higher birth weights.

Results from the analysis suggested the effect of birth weight on T2D risk is distinct and independent of genetic susceptibility to T2D and adult adiposity, and that low birth weight as a proxy of an adverse fetal environment is of similar etiological importance to that of genotype.

For the second study, led by Aleksander L. Hansen, MD, investigators analyzed midwife records for 6866 individuals with T2D in the Danish Center for Strategic Research.³ Investigators assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables, and family history of T2D in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000 - 37000 g (the middle 50% of birthweights) using statistical modeling.

The team additionally assessed continuous relationships across the entire birthweight spectrum and calculated weighted polygenic scores for T2D and birthweight to assess the impact of genetic predispositions. Data showed each 1 kg decrease in birthweight was associated with a 3.3-year younger age of diabetes onset, 1.5 kg/m2 lower BMI, and 3.9 cm smaller waist circumference.

When compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity, with a 36% higher chance of having ≥3 comorbidities and a 26% higher chance of having a systolic blood pressure >155 mmHg. Compared with birthweight 3000 - 3700 g, birthweight <3000 g was associated with younger age at T2D diagnosis. Those with low birth weight had a 28% increased risk of being diagnosed with T2D under 45 years (more likely to be diagnosed younger) and a 30% lower risk of being diagnosed over 75 years (less likely to be diagnosed older).

Moreover, birthweight under 3kg was associated with reporting fewer individuals with a family history of T2D and a slight (7%) increased chance of reporting no T2D-affected relatives, but a 33% reduced risk of reporting ≥3 relatives with T2D. Additionally, birthweight under 3kg was associated with a lower BMI, with a 12% increased chance of being in the normal weight category (BMI <25 kg/m²), decreasing to a 43% reduced risk of having severe obesity (BMI ≥40).

Investigators noted the associations between birthweight and adult BMI were linear across the entire birthweight spectrum. They indicated other factors linked to a lower birthweight were a lower prevalence of diabetes-associated neurological diseases, as well as a 33% increased risk of using ≥3 glucose-lowering drugs.

Overall, the investigative team suggested the impact of low birthweight appears to be independent of genetics and obesity, which is why people with low birthweight are at a relatively increased risk for T2D for any increase in BMI.

“Low birthweight should therefore be considered as a criterion for screening for T2D with the same importance as that of a positive family history of diabetes,” investigators wrote.

References

1. Low birthweight is independently linked to increased risk of type 2 diabetes, and a particular presentation including lower age at diagnosis. EurekAlert! June 12, 2023. Accessed June 16, 2023. https://www.eurekalert.org/news-releases/991877.
2. Wibaek, R., Andersen, G.S., Linneberg, A. et al. Low birthweight is associated with a higher incidence of type 2 diabetes over two decades independent of adult BMI and genetic predisposition. Diabetologia (2023). https://doi.org/10.1007/s00125-023-05937-0
3. Hansen, A.L., Thomsen, R.W., Brøns, C. et al. Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes. Diabetologia (2023). https://doi.org/10.1007/s00125-023-05936-1