ESPEYB15 12 Type 2 Diabetes, Metabolic Syndrome and Lipid Metabolism New Paradigm (1 abstracts)
Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore
To read the full abstract: Diabetes Care 2018;41:1089-1096
These findings show that a 1-SD increase in childhood BMI was associated with a 47–83% increased relative risk of T2DM and a 28% increased relative risk of CAD in adult life, yet childhood BMI was not associated with adult chronic kidney disease. This is the first study to examine the causal relationship between childhood BMI and cardio-metabolic diseases in adult life using Mendelian randomization. Mendelian randomization uses genetic variants to determine whether an observational association between a risk factor and an outcome is consistent with a causal effect.3 The method is analogous to a randomized controlled trial in which randomization to genotype takes place and is less likely to be affected by confounding and reverse causation. Individuals who carry more genetic BMI-increasing variants are compared to those who carry fewer and are assessed for the development of the outcome of interest. Since these genetic variants are typically unassociated with confounders, differences in the outcome between genetic groups can be directly attributed to causal differences in the risk factor, here BMI. In the current study, 15 single nucleotide polymorphisms (SNPs) were used to create a genetic risk score that summed the number of BMI-increasing alleles. Results demonstrated that childhood BMI is itself a causal factor for T2DM and CAD, further stressing the public health impact of childhood BMI modification. Based on two meta-analyses of RCTs of lifestyle interventions for children with obesity that resulted in -0.29 to -0.63 SD reductions in BMI, with better results in children younger than 12 years, the authors calculated that such a decrease in childhood BMI could translate into a reduction in adult T2DM and CAD risks of up to 27% and 9%, respectively.
3. Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA 2017; 318(19): 1925-1926.