Clinical and Metabolic Profile and Cognitive Functions in Children and Adolescents with Carbohydrate Metabolism Disorders Depending on Body Weight

Abstract

INTRODUCTION: Hyperglycemia causes glucotoxicity of neurons via different mechanisms, and, in combination with obesity, is a strong predictor of cognitive dysfunction. Free fatty acids and circulating cytokines cross the blood-brain barrier leading to neuroinflammation and proliferation of microglia. These alterations can be detected using neuroimaging methods. Thus, evaluation of cognitive functions and glycemic profile seems relevant in children with disorders of carbohydrate metabolism and different weights.

AIM: To analyze clinical and metabolic profile and cognitive functions in children and adolescents with carbohydrate metabolism disorders depending on body weight.

MATERIALS AND METHODS: A prospective, open, controlled study was conducted in 2022–2023. The study included 53 children aged from 7 to 18 years with carbohydrate metabolism disorders with duration of the disease of 1 to 7 years: group 1 — children with excessive body weight or obesity (n=33) and group 2 (n=20) — children with normal body weight. The work included evaluation of anthropometric parameters, carbohydrate metabolism disorders (glycemia and its variability, determination of glycated hemoglobin, immunoreactive insulin, and C-peptide), lipid spectrum, verification of non-alcoholic fatty liver disease, and testing using children’s version of Wechsler questionnaire.

RESULTS: Children with carbohydrate metabolism disorders and overweight or obesity more often had relatives with overweight (p=0.04), or diabetes mellitus (p=0.03) and were more often diagnosed with lipidemia (p=0.048) and fatty hepatosis (p=0.031). Children with carbohydrate metabolism disorders, both normal and overweight, showed statistically significant differences in the immunoreactive insulin index: among boys (p=0.030, p=0.001) and girls (р=0.020, р=0.002). Glycemia before bedtime and the time of glycemia above the target range were higher in overweight children (p=0.029, p=0.002). In Wechsler test, children with overweight or obesity and normal body weight children differed in the following parameters: vocabulary (speech function), letter-digit test, Kohs Block Design Test (constructional-spatial praxis; p=0.043, p=0.008 and p=0.005 respectively).

CONCLUSIONS: Children with carbohydrate metabolism disorders in combination with excessive body weight and obesity are characterized by impairment of some cognitive functions associated with asymptomatic glycemic variability.

Keywords

obesity / hyperglycemia / cognitive functions / children and adolescents

References

[1] Kleinridders A, Ferris HA, Cai W, et al. Insulin action in brain regulates systemic metabolism and brain function. Diabetes. 2014;63(7):2232–2243. doi: 10.2337/db14-0568

[2] Kwon H, Pessin JE. Chapter 39. Insulin-Mediated PI3K and AKT Signaling. In: Arias IM, Alter HJ, Boyer JL, editors. The Liver: Biology and Pathobiology. 6th ed. John Wiley & Sons, Ltd; 2020. Pt 3. P: 485–495. doi: 10.1002/9781119436812.ch39

[3] Milstein JL, Ferris HA. The brain as an insulin-sensitive metabolic organ. Mol Metab. 2021;52:101234. doi: 10.1016/j.molmet.2021.101234 EDN: SJHHNZ

[4] Pignalosa FC, Desiderio A, Mirra P, et al. Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction. Int J Mol Sci. 2021;22(22):12366. doi: 10.3390/ijms222212366 EDN: PZJSAK

[5] Kiseleva NG, Taranushenko TE, Lopatina OL, et al. Assessment of “metabolic memory” as a significant predictor of glucose toxicity and risk of vascular complications in children with diabetes mellitus. Siberian Medical Review. 2023;(2):44–52. doi: 10.20333/25000136-2023-2-44-52 EDN: GFPXGO

[6] Miller AA, Spencer SJ. Obesity and neuroinflammation: a pathway to cognitive impairment. Brain Behav Immun. 2014;42:10–21. doi: 10.1016/j.bbi.2014.04.001

[7] Tanaka H, Gourley DD, Dekhtyar M, et al. Cognition, Brain Structure, and Brain Function in Individuals with Obesity and Related Disorders. Curr Obes Rep. 2020;9(4):544–549. doi: 10.1007/s13679-020-00412-y EDN: NVARAV

[8] Koutny F, Weghuber D, Bollow E, et al. Prevalence of prediabetes and type 2 diabetes in children with obesity and increased transaminases in European German-speaking countries. Analysis of the APV initiative. Pediatr Obes. 2020;15(4):e12601. doi: 10.1111/ijpo.12601

[9] Dedov II, Shestakova MV, Mayorov Ayu, et al. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV, Mayorov AYu. 10th edition. Diabetes Mellitus. 2021;24(1S):1–148. doi: 10.14341/DM12802 EDN: ISOZCM

[10] Samoylova YuG, Oleynik OA, Matveyeva MV, et al. Klinicheskaya endokrinologiya detey i podrostkov. Moscow: INFRA-M; 2023. Pt 1. (In Russ.)

[11] Troshina MS, Denisova DV. Dyslipidemia in children and adolescents. Ateroskleroz. 2019;15(4):85–90. doi: 10.15372/ATER20190409 EDN: QSLAPL

[12] Ezhov MV, Kukharchuk VV, Sergienko IV, et al. Disorders of lipid metabolism. Clinical Guidelines 2023. Russian Journal of Cardiology. 2023;28(5):5471. doi: 10.15829/1560-4071-2023-5471 EDN: YVZOWJ

[13] Daniels SR. Guidelines for Screening, Prevention, Diagnosis and Treatment of Dyslipidemia in Children and Adolescents. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. Available from: https://pubmed.ncbi.nlm.nih.gov/27809440/. Accessed: 08.02.2025.

[14] Pavlovskaya EV, Strokova TV, Pyriva EA, et al. Non-alcoholic fatty liver disease in obese children: modern aspects of diagnosis and treatment. Pediatric Nutrition. 2021;19(2):53–61. doi: 10.20953/1727-5784-2021-2-53-61 EDN: PDJKRB

[15] Shah J, Okubote T, Alkhouri N. Overview of Updated Practice Guidelines for Pediatric Nonalcoholic Fatty Liver Disease. Gastroenterol Hepatol (N Y). 2018;14(7):407–414.

[16] Ciba I, Warnakulasuriya LS, Adikaram AVN, et al. Prevalence of different states of glucose intolerance in Sri Lankan children and adolescents with obesity and its relation to other comorbidities. Pediatr Diabetes. 2021;22(2):168–181. doi: 10.1111/pedi.13145 EDN: UOTPJG

[17] Vitebskaya AV, Popovich AV. Impairment of carbohydrate metabolism in children and adolescents with obesity. Medical Council. 2021;(11):174–182. doi: 10.21518/2079-701X-2021-11-174-182 EDN: VAPXYM

[18] Kinlen D, Cody D, O'Shea D. Complications of obesity. QJM. 2018;111(7): 437–443. doi: 10.1093/qjmed/hcx152

[19] Minyaylova NN, Rovda YuI, Shishkova YN, et al. Forms and peculiarities of eating disorders in adolescents with excess adipopexis. Mother and Baby in Kuzbass. 2017;(2):8–13. EDN: YUHNCX

[20] Nikishina EI, Nikishina VB, Petrash EA. Correcting eating disorders in obese adolescents. Russian Bulletin of Perinatology and Pediatrics. 2021;66(4):81–88. doi: 10.21508/1027-4065-2021-66-4-81-88 EDN: NIKAJA

[21] Panasenko LM, Nefedova JV, Kartseva TV, et al. Obesity and its role in the development of metabolic syndrome in children. Russian Bulletin of Perinatology and Pediatrics. 2020;65(2):125–132. doi: 10.21508/1027-4065-2020-65-2-125-132 EDN: JTBMYD

[22] Bray GA, Heisel WE, Afshin A, et al. The Science of Obesity Management: An Endocrine Society Scientific Statement. Endocr Rev. 2018;39(2):79–132. doi: 10.1210/er.2017-00253 EDN: PFIJMA

[23] Assunção SNF, Boa Sorte NCA, Alves CAD, et al. Glucose alteration and insulin resistance in asymptomatic obese children and adolescents. J Pediatr (Rio J). 2018;94(3):268–272. doi: 10.1016/j.jped.2017.06.008

[24] Watt C, Sanchez-Rangel E, Hwang JJ. Glycemic Variability and CNS Inflammation: Reviewing the Connection. Nutrients. 2020;12(12):3906. doi: 10.3390/nu12123906 EDN: EAKJWM

[25] Martí-Nicolovius M. [Effects of overweight and obesity on cognitive functions of children and adolescents]. Rev Neurol. 2022;75(3):59–65. (In Spanish) doi: 10.33588/rn.7503.2022173 EDN: EAXFES

[26] Jones A, Hardman CA, Lawrence N, et al. Cognitive training as a potential treatment for overweight and obesity: A critical review of the evidence. Appetite. 2018;124:50–67. doi: 10.1016/j.appet.2017.05.032

[27] Memarian S, Moradi A, Hasani J, et al. Can sweet food-specific inhibitory control training via a mobile application improve eating behavior in children with obesity? Br J Health Psychol. 2022;27(3):645–665. doi: 10.1111/bjhp.12566 EDN: JVVDFS

RIGHTS & PERMISSIONS

Eco-Vector