Childhood obesity is associated with an increased risk of four of the five subtypes of adult-onset diabetes, according to new research using data from the UK Biobank and Mendelian randomization (MR). The authors say their study potentially reveals different mechanisms linking childhood adiposity to different diabetes subtypes.
The study was led by Yuxia Wei, Institute of Environmental Medicine, Karolinska Institutet, Stockholm and was published in Diabetologia.
The prevalence of childhood obesity is rising worldwide. WHO estimates that, in 2019 more than 38 million children under the age of five years were overweight or obese. Childhood adiposity has been linked to several chronic diseases, including type 1 and type 2 diabetes. However, it has never been investigated in relation to the recently proposed subtypes of adult-onset diabetes.
In 2018, a ground-breaking study identified five novel subtypes of adult-onset diabetes: severe autoimmune diabetes which includes type 1 diabetes and latent autoimmune diabetes (LADA), and four subtypes of type 2 diabetes: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD).
SIDD, SIRD, MOD and MARD are currently collectively classed as type 2 diabetes. These subtypes of diabetes differ in their clinical characteristics, complications and genetic backgrounds. It is unclear if they also differ in modifiable risk factors.
In this study, the authors aimed to compare the effects of childhood body size on the risk of different diabetes subtypes occurring in adults.
The authors used UK Biobank data to extract summary statistics for childhood body size from a genome-wide association study of 453,169 European participants who self-reported body size (thinner, about average, and plumper/bigger) at the age of 10 years. The study incorporated more than 200 genetic mutations as indicators of childhood body size and linked them to LADA (267) and the other types of diabetes (275).
The results showed higher levels of childhood adiposity were linked to a 62% increased risk of LADA, a doubling of the risk of SIDD, a near-trebling of the risk of SIRD, and a 7-times increased risk of MOD. The only diabetes subtype showing no association with childhood obesity was MARD.
Previous studies of this kind have found that childhood body size is linked to a doubling of risk for both type 1 diabetes (mean age of diagnosis 16 years) and type 2 diabetes. The authors say: “We extend these findings by demonstrating that childhood adiposity is a risk factor for four out of the five recently proposed diabetes subtypes.”
The link between childhood body size and SIRD or MOD was expected, given the adverse effects of adiposity on insulin sensitivity. Interestingly, children with higher levels of adiposity also had higher risks of LADA and SIDD, both of which are characterized by insulin deficiency. This phenomenon may be explained by the fact that impaired insulin secretion is affected by both excess fat around the pancreas and insulin resistance.
The authors conclude: “Our analyses indicate that childhood obesity is a risk factor for four of the five proposed novel subtypes of adult-onset diabetes, regardless of whether they are classified as being primarily characterized by autoimmunity, insulin deficiency, insulin resistance or obesity. Childhood obesity appears to be a risk factor for essentially all types of diabetes in adults, except for mild age-related diabetes. This stresses the importance of preventing obesity in children.”
