The influence of clinical and genetic factors on the development of obesity in children with type 1 diabetes

Abstract

The exact cause of the obesity epidemic remains unknown; however, both environmental and genetic factors are involved. People at risk of developing obesity include children with type 1 diabetes mellitus (T1DM), which in turn increases their cardiovascular disease risk. Here, we discuss the clinical and genetic factors influencing weight in patients with T1DM. In children with T1DM, the presence of obesity depends mainly on sex, metabolic control, and disease duration. However, genetic factors, including the fat mass and obesity-associated (FTO) gene, are also associated with body weight. Indeed, children with the FTO gene rs9939609 obesity-risk allele (homozygous = AA or heterozygous = AT) are predisposed to a higher body mass index and have a greater risk of being overweight or obese. However, in this review, we show that FTO gene polymorphisms only have a small effect on body weight in children, much weaker than the effect of clinical factors. The association between FTO gene polymorphisms and body weight is only statistically significant in children without severe obesity. Moreover, other genetic factors had no effect on weight in patients with T1DM, and further research involving larger populations is required to confirm the genetic basis of diabetes and obesity. Therefore, identifying the clinical features of children with T1DM, such as their initial body mass index, sex, metabolic control, and disease duration, will still have the strongest effect on reducing risk factors for cardiovascular diseases. Physicians should pay close attention to modifiable elements of these relationships, for example, metabolic control and energy and insulin intake, when caring for patients with T1DM. Copyright © 2016 John Wiley & Sons, Ltd.

Association between glycaemic outcome and BMI in Danish children with type 1 diabetes in 2000–2018: a nationwide population‐based study

“…Higher peripheral insulinaemia than that which is normally secreted by the pancreas of children without diabetes could also promote the disposition of fat 18 . Our finding of a higher BMIz in children with type 1 diabetes compared to the background population, and further increased levels in girls compared to boys is consistent with the findings of other studies, 9,17 and excessive fat storage in the abdomen of girls with type 1 diabetes has been suggested as an explanation for this 16 …”

“…During the last decade, treatment of children with type 1 diabetes has mainly focused on optimizing HbA 1c levels and avoiding severe hypoglycaemic events, and decreasing trends over time in these measures are evident 14,15 . A simultaneous rise in BMI among children with type 1 diabetes can be related both to the general development of obesity caused by environmental or behavioural factors and to intensified diabetes treatment and management aimed at achieving lower HbA 1c goals while preventing severe hypoglycaemia 16 . Earlier studies on the association between HbA 1c and BMI 9,17,18 have reported conflicting results.…”

The Double Whammy of Obesity and Diabetes on Female Reproductive Health

“…Even then, FTO gene polymorphisms have only a small effect on body weight, compared with clinical factors such as sex and metabolic control, which appear to drive the obese phenotype to a larger extent. 23,24 Unlike genetics, which are the "biological fingerprints" of a unique individual, epigenetics does not alter DNA sequence, but affects gene expression through modifications to DNA and histones. 25 Such disruptions occur in the critical period between in utero development and the early postnatal period, and may ultimately affect susceptibility and pathogenesis of diabetes and obesity.…”