Cumulative early-life risk factors such as low birth weight, lack of breastfeeding, and maternal smoking are independently and additively associated with increased risk for type 2 diabetes (T2D) in adulthood regardless of genetic predisposition or adult lifestyle, although healthy behaviors in adulthood may attenuate the risk, according to study results published in BMC Medicine.
Researchers conducted a prospective cohort study to evaluate the relationship between cumulative early-life modifiable risk factors and T2D development in adulthood on the basis of genetic predisposition or later-life healthy lifestyle behaviors. Participants from the UK Biobank were aged 40 to 69 years at enrollment.
Three early-life factors, including low birth weight (<2.5 kg), maternal smoking during pregnancy, and lack of breastfeeding, were used to compute an early-life risk score (ERS). Genetic predisposition was quantified using a standard polygenic risk score (T2D-PRS), and adult lifestyle was assessed using a modifiable healthy lifestyle score (MHS) based on the American Heart Association’s “Life’s Essential 8” metrics (diet, physical activity, nicotine exposure, and sleep).
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These results underscore the importance of effective intervention strategies in early life for the prevention of T2D across life-course.
Among this large UK Biobank cohort of 148,621 participants (mean age, 55.4 years), 7408 had T2D either at baseline or during a median follow-up of 12.5 years. T2D prevalence was 4.98% and higher among men (6.11%) than women (4.25%).
The researchers observed a dose-response association between cumulative ERS and T2D risk. Compared with individuals with no early-life risk factors, those with 1, 2, or 3 factors had a 16% (hazard ratio [HR], 1.16), 26% (HR, 1.26), and 93% (HR, 1.93) higher risk for T2D, respectively. Participants in the highest tertile of T2D-PRS had a 3.28-fold higher risk than those in the lowest tertile, and the highest joint risk was observed among individuals with an ERS of 3 and high T2D-PRS (HR, 6.67).
A healthy adult lifestyle, measured by MHS, was associated with a significantly lower T2D risk. Individuals with healthy vs unhealthy lifestyle scores had a 53% reduced risk (HR, 0.47). Although ERS was associated with higher T2D risk at all lifestyle levels, the researchers observed no significant interactions between ERS and MHS. The highest combined risk occurred among individuals with an ERS of 3 and an unhealthy lifestyle (HR, 4.99).
Sensitivity analyses confirmed these associations across sex, BMI, genetic ancestry, and alternate birth weight definitions. All combinations of early-life risk factors, except non-breastfeeding alone, were associated with increased T2D risk.
Study limitations include a lack of generalizability of the findings, selection biases, and the assessment of only 3 early-life risk factors.
The study authors concluded, “These results underscore the importance of effective intervention strategies in early life for the prevention of T2D across life-course.”