Childhood BMI and adult type 2 diabetes, coronary artery diseases, chronic kidney disease, and cardiometabolic traits: a Mendelian randomization analysis

Authors: GENG, TINGTING - National University Of Singapore; SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LI, CHANGWEI - University Of Georgia; HAUNG, TAO - National University Of Singapore

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/4/2018
Publication Date: 5/1/2018
Citation: Geng, T., Smith, C.E., Li, C., Haung, T. 2018. Childhood BMI and adult type 2 diabetes, coronary artery diseases, chronic kidney disease, and cardiometabolic traits: a Mendelian randomization analysis. Diabetes Care. 41:1089-1096. https://doi.org/10.2337/dc17-2141.
DOI: https://doi.org/10.2337/dc17-2141

Interpretive Summary: Obesity is well-established as a strong contributor to chronic diseases of aging such as type 2 diabetes, heart disease and kidney disease. Because these diseases are more frequent in older adults, most research has focused on adults. However, obesity during childhood may contribute to these chronic adult diseases, because obese children often become obese adults. Few studies have examined childhood obesity and diseases of aging because of the challenges of following individuals over the decades between childhood and older age. The current study used a relatively new, genetically-based approach to investigate the relationship between childhood obesity and chronic diseases that tend to occur later in life. Instead of following people from childhood to older ages, the authors looked at the relationship between 15 genetic mutations that are associated with childhood obesity and their relationship to adult disease. Because mutations are present from birth throughout the lifetime, any health risks associated with the SNPs are theoretically also occurring throughout the lifetime. The investigators reported that adults carrying these mutations showed higher probability of several diseases (type 2 diabetes, heart disease) and metabolic conditions that contribute to these diseases (obesity, higher insulin, insulin resistance and higher triglyceride). The results from this study strengthen support for this genetic approach to studying the relationship between childhood obesity and diseases that usually occur later in life. They also suggest that the prevention of obesity in children may be an important way to reduce adult disease.

Technical Abstract: OBJECTIVE: To test the causal effect of childhood BMI on adult cardiometabolic diseases using a Mendelian randomization analysis. RESEARCH DESIGN AND METHODS: We used 15 single nucleotide polymorphisms as instrumental variables for childhood BMI to test the causal effect of childhood BMI on cardiometabolic diseases using summary-level data from consortia. RESULTS: We found that a 1-SD increase in childhood BMI (kg/m^2) was associated with an 83% increase in risk of type 2 diabetes (odds ratio [OR] 1.83 [95% CI 1.46, 2.30]; P = 2.5 x 10^-7) and a 28% increase in risk of coronary artery disease (CAD) (OR 1.28 [95% CI 1.17, 1.39]; P = 2.1 x 10^-8) at the Bonferroni-adjusted level of significance (P < 0.017) in adults. In addition, a 1-SD increase in childhood BMI was associated with a 0.587-SD increase in adulthood BMI (kg/m^2), a 0.062-SD increase in hip circumference (cm), a 0.602-SD increase in waist circumference (cm), a 0.111 pmol/L increase in log fasting insulin, a 0.068 increase in log-transformed HOMA of b-cell function (%), a 0.126 increase in log-transformed HOMA of insulin resistance (%), and a 0.109-SD increase in triglyceride (mg/dL) but a 0.138-SD decrease in HDL (mg/dL) in adults at the Bonferroni-adjusted level of significance (P < 0.0026). CONCLUSIONS: A genetic predisposition to higher childhood BMI was associated with increased risk of type 2 diabetes and CAD in adult life. These results provide evidence supportive of a causal association between childhood BMI and these outcomes.