Youth-Onset Type 2 Diabetes and the Developing Brain
Purpose of Review
This review describes the literature evaluating the potential adverse effects of youth-onset type 2 diabetes on the developing brain. A summary of recently published articles and the current state of knowledge are covered succinctly in this manuscript.
Current literature suggests both cognitive and brain structural differences are found in youth with type 2 diabetes. Studies have shown poorer scores in a number of neurocognitive domains, particularly in areas of executive functioning and memory. Additionally, imaging studies have found differences in brain gray matter volume, white matter volume, and microstructural integrity. These findings are largely consistent with the adult literature.
Youth with type 2 diabetes demonstrate lower cognitive scores and structural brain differences. Although causality has not yet been established, these findings are important because these individuals are still undergoing neurodevelopmental maturation.
KeywordsType 2 diabetes Youth-onset diabetes Cognitive function Brain Central nervous system
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 3.Imperatore G, Boyle JP, Thompson TJ, Case D, Dabelea D, Hamman RF, et al. Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth. Diabetes Care. 2012;35(12):2515–20. https://doi.org/10.2337/dc12-0669.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Kavey RE, Allada V, Daniels SR, Hayman LL, McCrindle BW, Newburger JW, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research. J Cardiovasc Nurs. 2007;22(3):218–53. https://doi.org/10.1097/01.jcn.0000267827.50320.85.CrossRefPubMedGoogle Scholar
- 9.Constantino MI, Molyneaux L, Limacher-Gisler F, Al-Saeed A, Luo C, Wu T, et al. Long-term complications and mortality in young-onset diabetes: type 2 diabetes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36(12):3863–9. https://doi.org/10.2337/dc12-2455.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Dabelea D, Stafford JM, Mayer-Davis EJ, D’Agostino R Jr, Dolan L, Imperatore G, et al. Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and adolescence with complications during teenage years and young adulthood. JAMA. 2017;317(8):825–35. https://doi.org/10.1001/jama.2017.0686.CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) study, 1987-1993. Am J Epidemiol. 1997;146(6):483–94.CrossRefGoogle Scholar
- 13.O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular health study collaborative research group. N Engl J Med. 1999;340(1):14–22. https://doi.org/10.1056/nejm199901073400103.CrossRefPubMedGoogle Scholar
- 21.Levitt Katz L, Gidding SS, Bacha F, Hirst K, McKay S, Pyle L, et al. Alterations in left ventricular, left atrial, and right ventricular structure and function to cardiovascular risk factors in adolescents with type 2 diabetes participating in the TODAY clinical trial. Pediatr Diabetes. 2015;16(1):39–47. https://doi.org/10.1111/pedi.12119.CrossRefPubMedGoogle Scholar
- 34.Espeland MA, Bryan RN, Goveas JS, Robinson JG, Siddiqui MS, Liu S, et al. Influence of type 2 diabetes on brain volumes and changes in brain volumes: results from the Women’s Health Initiative magnetic resonance imaging studies. Diabetes Care. 2013;36(1):90–7. https://doi.org/10.2337/dc12-0555.CrossRefPubMedGoogle Scholar
- 35.Xiong Y, Sui Y, Xu Z, Zhang Q, Karaman MM, Cai K, et al. A diffusion tensor imaging study on white matter abnormalities in patients with type 2 diabetes using tract-based spatial statistics. AJNR Am J Neuroradiol. 2016;37(8):1462–9. https://doi.org/10.3174/ajnr.A4740.CrossRefPubMedPubMedCentralGoogle Scholar
- 40.•• Yau PL, Javier DC, Ryan CM, Tsui WH, Ardekani BA, Ten S, et al. Preliminary evidence for brain complications in obese adolescents with type 2 diabetes mellitus. Diabetologia. 2010;53(11):2298–306. https://doi.org/10.1007/s00125-010-1857-y This manuscript was the first report of cognitive function differences and brain volume differences in youth with type 2 diabetes. CrossRefPubMedPubMedCentralGoogle Scholar
- 41.• Brady CC, Vannest JJ, Dolan LM, Kadis DS, Lee GR, Holland SK, et al. Obese adolescents with type 2 diabetes perform worse than controls on cognitive and behavioral assessments. Pediatr Diabetes. 2017;18(4):297–303. https://doi.org/10.1111/pedi.12383 This paper found differences in neurocognitive and behavioral domains not previously reported, and demonstrated correlations between duration of diabetes and poorer scores in working memory and processing speed. CrossRefPubMedGoogle Scholar
- 47.Rofey DL, Arslanian SA, El Nokali NE, Verstynen T, Watt JC, Black JJ, et al. Brain volume and white matter in youth with type 2 diabetes compared to obese and normal weight, non-diabetic peers: a pilot study. Int J Dev Neurosci. 2015;46:88–91. https://doi.org/10.1016/j.ijdevneu.2015.07.003.CrossRefPubMedGoogle Scholar
- 48.• Nouwen A, Chambers A, Chechlacz M, Higgs S, Blissett J, Barrett TG, et al. Microstructural abnormalities in white and gray matter in obese adolescents with and without type 2 diabetes. Neuroimage Clin. 2017;16:43–51. https://doi.org/10.1016/j.nicl.2017.07.004 This study found regional differences in gray matter volumes and white matter integrity between youth with type 2 diabetes and lean controls. CrossRefPubMedPubMedCentralGoogle Scholar
- 49.• Redel JM, DiFrancesco M, Vannest J, Altaye M, Beebe D, Khoury J, et al. Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot study. J Pediatr Endocrinol Metab. 2018;31(3):261–8. https://doi.org/10.1515/jpem-2017-0349 This paper describes differences in both global and regional brain gray matter volumes in youth with type 2 diabetes. In the regional analysis, there were 14 clusters of lower gray matter volume, but also 6 clusters of increased gray matter volume when compared to lean controls. CrossRefPubMedGoogle Scholar
- 51.Bangen KJ, Werhane ML, Weigand AJ, Edmonds EC, Delano-Wood L, Thomas KR, et al. Reduced regional cerebral blood flow relates to poorer cognition in older adults with type 2 diabetes. Front Aging Neurosci. 2018;10:270. https://doi.org/10.3389/fnagi.2018.00270.CrossRefPubMedPubMedCentralGoogle Scholar
- 52.van Meer F, van der Laan LN, Viergever MA, Adan RAH, Smeets PAM, Consortium IF. Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults. NeuroImage. 2017;159:325–33. https://doi.org/10.1016/j.neuroimage.2017.08.007.CrossRefPubMedGoogle Scholar