Type 2 diabetes in prepubertal children

Authors: ASTUDILLO, MARCELA - Baylor College Of Medicine; TOSUR, MUSTAFA - Baylor College Of Medicine; CASTILLO, BEATRIZ - Baylor College Of Medicine; RAFAEY, AHMAD - University Of Houston; SILLER, ALEJANDRO - Baylor College Of Medicine; NIETO, JACOBO - Rice University; SISLEY, STEPHANIE - Children'S Nutrition Research Center (CNRC); MCKAY, SIRIPOOM - Baylor College Of Medicine; NELLA, AIKATERINI - Baylor College Of Medicine; BALASUBRAMANYAM, ASHOK - Baylor College Of Medicine; BACHA, FIDA - Baylor College Of Medicine; REDONDO, MARIA - Baylor College Of Medicine

Submitted to: Pediatric Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/28/2021
Publication Date: 8/7/2021
Citation: Astudillo, M., Tosur, M., Castillo, B., Rafaey, A., Siller, A., Nieto, J., Sisley, S., McKay, S., Nella, A., Balasubramanyam, A., Bacha, F., Redondo, M. 2021. Type 2 diabetes in prepubertal children. Pediatric Diabetes. https://doi.org/10.1111/pedi.13254 .
DOI: https://doi.org/10.1111/pedi.13254

Interpretive Summary: The development of type 2 diabetes (T2D) in children before puberty is very rare. Thus, there has not been a good study to understand what factors might make children more susceptible to T2D prior to puberty. We compared all children with T2D at our center over a three year time period who were prepubertal vs. those who were pubertal. Although prepubertal T2D is rare, 35 prepubertal children had T2D in our center and strikingly, ten of them were diagnosed before 10 years of age. In this study, we found that at diagnosis, children with T2D who were prepubertal had higher body mass index z-scores (a marker for obesity), higher levels of c-peptide (a marker for insulin production), and all had lipid abnormalities. Thus, our research shows that prepubertal children with T2D have more severe obesity, greater insulin resistance, and more frequent lipid abnormalities than children diagnosed later in childhood. This suggests that children with prepubertal T2D are at an increased risk for associated morbidity compared to older youth and underscores the need to prevent and treat obesity in childhood.

Technical Abstract: Puberty-induced insulin resistance is considered critical in the pathogenesis of type 2 diabetes (T2D) in youth. The development of T2D before puberty suggests distinct risk factors and pathophysiology but, because of its rarity, this has not been well studied. We aimed to describe the clinical characteristics of children with T2D diagnosed before the onset of puberty. We retrospectively studied all children with autoantibody-negative T2D and available pubertal development assessment seen at our center between July 2016 and July 2019, and compared characteristics of those at Tanner stage I (prepubertal, n = 35) versus those at Tanner II–V of pubertal development (n = 341). At T2D diagnosis, prepubertal children compared with those at Tanner II–V had higher body mass index z-score (p = 0.003) and higher C-peptide (p = 0.003)(while glucose levels were not significantly different), with differences retaining significance after adjustment for glucose, race/ethnicity and sex. Dyslipidemia occurred in 100% of prepubertal children versus 89.7% of those diagnosed later (p = 0.036). Of the prepubertal children diagnosed under age 10 (n = 13), 69.2% were female, 100% racial/ethnic minority, 100% had obesity with history of dyslipidemia and none with diabetic ketoacidosis. T2D, although rarely, can develop before puberty. Children with T2D diagnosed in the prepubertal period have more severe obesity, greater insulin resistance, and more frequent dyslipidemia than older youth. These findings suggest that children with prepubertal T2D are at increased risk for associated morbidity compared with older youth and underscore the significance of interventions to prevent and treat obesity in early childhood.