Obesity in childhood that lasts into adulthood may be associated with an increased risk of coronary artery disease (CAD) and type 2 diabetes in adulthood; reaching a normal body weight in adulthood, however, may mitigate these risks, according to results from a study published in The BMJ.
Researchers also found that obesity in childhood had a protective effect on breast cancer risk that was independent of adult body size, but that neither had any effects on the risks of prostate cancer.
“Having a high body mass index (BMI) in early life is thought to increase the risk of various health conditions, such as coronary artery disease, type 2 diabetes, and different types of cancer, in later life. Whether an individual can reverse the impact of childhood obesity through lifestyle modifications is unclear, particularly as those who are obese in early life tend to remain obese as adults,” wrote these authors, led by Tom G. Richardson, BSc, MSc, of the Bristol Medical School, University of Bristol, Bristol, UK.
“This makes it challenging to discern whether early life adiposity has an independent and lasting influence on disease risk or if its effect is entirely mediated by later life adiposity. If the latter is the case, then the potential adverse consequences of childhood obesity could be avoided by attaining and maintaining a healthy weight in adulthood,” they added.
To assess whether early-life body size affects the risk of disease in later life and whether these effects are somehow mediated by adult body size, Richardson and colleagues conducted this two-sample univariable and multivariable Mendelian randomization study.
Using data from 453,169 participants from the UK Biobank prospective cohort study and from over 700,000 participants from four large scale genome-wide association study (GWAS) consortiums, they calculated measured BMI during adulthood and self-reported perceived body size at age 10. Richardson et al then analyzed the associations between genetic variants across the human genome and body size, and calculated the genetic correlation between early life and adult body size results.
Among the UK Biobank participants, researchers detected 295 independent associations with early life, and 557 independent associations with adult body size.
Upon Mendelian randomization analyses, they found that having a larger genetically predicted early-life body size was associated with an increased odds of CAD (OR: 1.49 for each change in body-size category; 95% CI: 1.33-1.68) and type 2 diabetes (OR: 2.32; 95% CI: 1.76-3.05). But upon multivariable Mendelian randomization analysis, there was scant evidence of a direct effect on CAD (CAD: OR: 1.02; 95% CI: 0.86-1.22) or type 2 diabetes (OR: 1.16; 95% CI: 0.74-1.82).
Researchers next assessed the possible associations between body size in early life and adulthood and breast and prostate cancers. Upon multivariable Mendelian randomization analysis of breast cancer risk, they found strong evidence that larger body size in early life had a protective direct effect (OR: 0.59; 95% CI: 0.50-0.71), whereas there was less evidence of such in relation to adult body size (OR: 1.08; 95% CI: 0.93-1.27).
When they included age at menarche, the evidence of a total casual effect was weak (univariable Mendelian randomization OR: 0.98: 95% CI: 0.91-1.06). But, upon multivariable Mendelian randomization analysis, they found strong evidence of a direct causal effect that was independent of both early and adult body size (OR: 0.90; 95% CI: 0.85-0.95).
Finally, Richardson and fellow researchers found no strong evidence of a causal effect of either early (OR: 1.06; 95% CI: 0.81-1.40) or later life (OR: 0.87; 95% CI: 0.70-1.08) measures on prostate cancer.
Limitations of the study include its reliance on retrospective self-reported early life size and the reliance of univariable Mendelian randomization analyses on single nucleotide polymorphisms, which may considerably overlap at early- and later-life time points. In addition, genetically determined body size may not directly equate to weight losses or gains from lifestyle modifications. Survival bias has also been shown to skew findings from Mendelian randomization analyses. Researchers also noted that there may have been overlapping exposure and outcome samples due to the possible inclusion of UK Biobank participants in the large-scale GWAS. Finally, they stressed the difficulty of capturing non-linear effects between body size at different time points in life and disease outcomes.
In an accompanying editorial, C. Mary Schooling, MSc, PhD, of the University of Hong Kong, Hong Kong, China and the City University of New York Graduate School of Public Health and Health Policy, New York, NY, applauded Richardson and colleagues for their sophisticated Mendelian randomization methods, but urged caution in applying these results to population health.
However, she stressed the importance of their finding regarding the health benefits of achieving and maintaining normal body weight in the transition from childhood to adulthood.
“Taking the evidence together, the possibility remains that childhood adiposity has little long-term effect if followed by normal BMI later in adolescence, making the transition from childhood to adulthood a key point of intervention,” she concluded.
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The associations between childhood obesity and coronary artery disease and type 2 diabetes may be mitigated by achieving and maintaining normal body mass index in adulthood.
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Note that researchers found obesity in childhood had a protective effect on breast cancer risk that was independent of adult body size, but that neither had any effects on the risks of prostate cancer.
E.C. Meszaros, Contributing Writer, BreakingMED™
This study was supported by the Integrative Epidemiology Unit, which receives funding from the UK Medical Research Council and the University of Bristol.
Richardson has received grants from the Medical Research Council and Health Data Research UK for this study.
Cat ID: 12
Topic ID: 76,12,730,914,12,13,795,252,518,669,917,918
