Lower birthweight an independent risk factor for T2D: Study

Matt Woodley

15/06/2023 5:02:19 PM

It is also linked to diagnosis at a younger age, a lower prevalence of overweight/obesity, and fewer family members with a history of diabetes.

Small baby
Type 2 diabetes incidence rate decreased linearly with increasing birthweight, with each extra kilogram linked to a 40% reduced risk of T2D.

Two new studies indicate that lower birthweight is an independent risk factor for type 2 diabetes (T2D), as well as the development of a ‘more severe’ subtype of the disease.
The papers, published in Diabetologia, have also linked lower birthweight with a ‘distinct’ presentation of T2D at the time of diagnosis, including younger age, a lower prevalence of overweight/obesity, and fewer people in the family with T2D.
These patients also tend to require higher use of diabetes drugs than those with normal birthweight and have a larger number of comorbidities, including high blood pressure, at the time of diagnosis.
The authors say that the studies collectively provide ‘strong support’ for considering lower birthweight as a criterion for T2D screening, on par with a positive family history of diabetes.
‘Low birthweight is a strong and non-genetic risk factor not only of developing T2D … [and] for the development of a relatively more severe subtype of type 2 diabetes – with earlier disease onset, more complications, and co-morbidities, as well as with an increased need for clinical care and medical treatments,’ they said.
Dr Gary Deed, Chair of RACGP Specific Interests Diabetes, told newsGP the findings support previous research that associated lower birthweight with T2D and other chronic diseases.
‘GPs should consider gathering information on birthweight – if available – in people with newly diagnosed diabetes,’ he said.
‘[This is more important] in populations with higher observed risks, such as First Nations people and younger adults presenting with diabetes between the ages of 18–30 years, which have been observed to have more aggressive complication development.’
The research
The first study included adults aged 30–60 years enrolled in the Danish Inter99 cohort from 1999–2001, without diabetes at baseline.
Birthweight, taken from original birth records, was linked with individual-level data on age at diabetes diagnosis. Incidence rates of T2D by age, sex and birthweight were estimated using statistical modelling, adjusting for:

  • prematurity status at birth
  • birth order (position in the birth order among any siblings)
  • genetic risk scores for birthweight and T2D
  • maternal and paternal diabetes history
  • socioeconomic status
  • adult body mass index (BMI). 
The authors found that, among 4590 participants, there were 492 incident T2D cases during an average follow-up of 19 years. T2D incidence rate increased with age, was higher in male participants, and decreased linearly with increasing birthweight, with each extra kilogram linked to a 40% reduced risk of T2D.
Notably, the researchers identified that the absolute rate of increase in T2D incidence across age was markedly steeper in people with lower birthweights.
The authors say the findings indicate that birthweight has a distinct impact on T2D risk independent of genetic susceptibility and adult adiposity, and that low birthweight as a proxy of an adverse fetal environment is of similar aetiological importance to that of genotype.
The second study, which shares many of the same authors, analysed midwife records for 6866 individuals with T2D, tracking:
  • age at diagnosis
  • anthropomorphic measures (body dimensions)
  • comorbidities
  • medications
  • metabolic variables
  • family history of T2D.
These were then compared between individuals in the lowest (<3000 g) and highest (>3700 g) quartiles for birthweight, with those in the middle 50% (3000–3700 g) used as a reference.
Continuous relationships across the entire birthweight spectrum were also assessed, while weighted polygenic scores for T2D and birthweight were calculated to assess the impact of genetic predispositions.
The analysis found that 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.
Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity, a 36% higher chance of having three or more comorbidities, and a 26% higher chance of having a systolic blood pressure above 155 mm Hg (severe hypertension).
Those with low birthweight also had a 28% increased risk of being diagnosed with T2D aged under 45 years, and a 30% lower risk of being diagnosed aged over 75 years, meaning they were more likely to be diagnosed at a younger age.
Birthweight under 3 kg was likewise associated with reporting fewer individuals with a family history of T2D, with a slight (7%) increased chance of reporting no T2D-affected relatives, but a 33% reduced risk of reporting three or more relatives with T2D.
Other factors linked to a lower birthweight were a lower prevalence of diabetes-associated neurological disease and a 33% increased risk of using three or more glucose-lowering drugs.
Clinically defined low birthweight (below 2.5kg) yielded stronger associations, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions.
However, the authors add that neither people with a lower birthweight, nor those with a high genetic risk of T2D have a ‘particularly very high absolute risk’ of developing the disease if they are able to maintain a healthy BMI throughout their lives.
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