Skip to main content
SpringerLink
Log in

Youth-Onset Type 2 Diabetes and the Developing Brain

  • Pediatric Type 2 and Monogenic Diabetes (O Pinhas-Hamiel, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

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.

Recent Findings

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.

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dabelea D, Mayer-Davis EJ, Saydah S, Imperatore G, Linder B, Divers J, et al. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA. 2014;311(17):1778–86. https://doi.org/10.1001/jama.2014.3201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med. 2017;376(15):1419–29. https://doi.org/10.1056/NEJMoa1610187.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dabelea D, Hanson RL, Bennett PH, Roumain J, Knowler WC, Pettitt DJ. Increasing prevalence of type II diabetes in American Indian children. Diabetologia. 1998;41(8):904–10. https://doi.org/10.1007/s001250051006.

    Article  CAS  PubMed  Google Scholar 

  5. Arslanian S, Kim JY, Nasr A, Bacha F, Tfayli H, Lee S, et al. Insulin sensitivity across the lifespan from obese adolescents to obese adults with impaired glucose tolerance: who is worse off? Pediatr Diabetes. 2018;19(2):205–11. https://doi.org/10.1111/pedi.12562.

    Article  CAS  PubMed  Google Scholar 

  6. Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, Arslanian S, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012;366(24):2247–56. https://doi.org/10.1056/NEJMoa1109333.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  8. Dart AB, Martens PJ, Rigatto C, Brownell MD, Dean HJ, Sellers EA. Earlier onset of complications in youth with type 2 diabetes. Diabetes Care. 2014;37(2):436–43. https://doi.org/10.2337/dc13-0954.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Eppens MC, Craig ME, Cusumano J, Hing S, Chan AK, Howard NJ, et al. Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes. Diabetes Care. 2006;29(6):1300–6. https://doi.org/10.2337/dc05-2470.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  CAS  Google 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.

    Article  PubMed  Google Scholar 

  14. Simons PC, Algra A, Bots ML, Grobbee DE, van der Graaf Y. Common carotid intima-media thickness and arterial stiffness: indicators of cardiovascular risk in high-risk patients. The SMART study (second manifestations of ARTerial disease). Circulation. 1999;100(9):951–7.

    Article  CAS  Google Scholar 

  15. Brinton TJ, Cotter B, Kailasam MT, Brown DL, Chio SS, O’Connor DT, et al. Development and validation of a noninvasive method to determine arterial pressure and vascular compliance. Am J Cardiol. 1997;80(3):323–30.

    Article  CAS  Google Scholar 

  16. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588–605.

    Article  Google Scholar 

  17. Kotb NA, Gaber R, Salama M, Nagy HM, Elhendy A. Clinical and biochemical predictors of increased carotid intima-media thickness in overweight and obese adolescents with type 2 diabetes. Diab Vasc Dis Res. 2012;9(1):35–41. https://doi.org/10.1177/1479164111421804.

    Article  PubMed  Google Scholar 

  18. Urbina EM, Kimball TR, Khoury PR, Daniels SR, Dolan LM. Increased arterial stiffness is found in adolescents with obesity or obesity-related type 2 diabetes mellitus. J Hypertens. 2010;28(8):1692–8. https://doi.org/10.1097/HJH.0b013e32833a6132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Urbina EM, Kimball TR, McCoy CE, Khoury PR, Daniels SR, Dolan LM. Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation. 2009;119(22):2913–9.

    Article  CAS  Google Scholar 

  20. Shah AS, Khoury PR, Dolan LM, Ippisch HM, Urbina EM, Daniels SR, et al. The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults. Diabetologia. 2011;54(4):722–30. https://doi.org/10.1007/s00125-010-1974-7.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  22. Manschot SM, Brands AM, van der Grond J, Kessels RP, Algra A, Kappelle LJ, et al. Brain magnetic resonance imaging correlates of impaired cognition in patients with type 2 diabetes. Diabetes. 2006;55(4):1106–13.

    Article  CAS  Google Scholar 

  23. Awad N, Gagnon M, Messier C. The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol. 2004;26(8):1044–80. https://doi.org/10.1080/13803390490514875.

    Article  PubMed  Google Scholar 

  24. Cukierman T, Gerstein HC, Williamson JD. Cognitive decline and dementia in diabetes--systematic overview of prospective observational studies. Diabetologia. 2005;48(12):2460–9. https://doi.org/10.1007/s00125-005-0023-4.

    Article  CAS  PubMed  Google Scholar 

  25. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5(1):64–74. https://doi.org/10.1016/s1474-4422(05)70284-2.

    Article  PubMed  Google Scholar 

  26. Ruis C, Biessels GJ, Gorter KJ, van den Donk M, Kappelle LJ, Rutten GE. Cognition in the early stage of type 2 diabetes. Diabetes Care. 2009;32(7):1261–5. https://doi.org/10.2337/dc08-2143.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: the Rotterdam study. Neurology. 1999;53(9):1937–42.

    Article  CAS  Google Scholar 

  28. van Elderen SG, de Roos A, de Craen AJ, Westendorp RG, Blauw GJ, Jukema JW, et al. Progression of brain atrophy and cognitive decline in diabetes mellitus: a 3-year follow-up. Neurology. 2010;75(11):997–1002. https://doi.org/10.1212/WNL.0b013e3181f25f06.

    Article  PubMed  Google Scholar 

  29. Hsu JL, Chen YL, Leu JG, Jaw FS, Lee CH, Tsai YF, et al. Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study. NeuroImage. 2012;59(2):1098–105. https://doi.org/10.1016/j.neuroimage.2011.09.041.

    Article  PubMed  Google Scholar 

  30. Reijmer YD, Brundel M, de Bresser J, Kappelle LJ, Leemans A, Biessels GJ. Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study. Diabetes Care. 2013;36(1):137–44. https://doi.org/10.2337/dc12-0493.

    Article  PubMed  Google Scholar 

  31. van Bloemendaal L, Ijzerman RG, Ten Kulve JS, Barkhof F, Diamant M, Veltman DJ, et al. Alterations in white matter volume and integrity in obesity and type 2 diabetes. Metab Brain Dis. 2016;31(3):621–9. https://doi.org/10.1007/s11011-016-9792-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. de Bresser J, Tiehuis AM, van den Berg E, Reijmer YD, Jongen C, Kappelle LJ, et al. Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care. 2010;33(6):1309–14. https://doi.org/10.2337/dc09-1923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kumar A, Haroon E, Darwin C, Pham D, Ajilore O, Rodriguez G, et al. Gray matter prefrontal changes in type 2 diabetes detected using MRI. J Magn Reson Imaging. 2008;27(1):14–9. https://doi.org/10.1002/jmri.21224.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Allen KV, Frier BM, Strachan MW. The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations. Eur J Pharmacol. 2004;490(1–3):169–75. https://doi.org/10.1016/j.ejphar.2004.02.054.

    Article  CAS  PubMed  Google Scholar 

  37. Stewart R, Liolitsa D. Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med. 1999;16(2):93–112.

    Article  CAS  Google Scholar 

  38. Strachan MW, Deary IJ, Ewing FM, Frier BM. Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care. 1997;20(3):438–45.

    Article  CAS  Google Scholar 

  39. Ferguson SC, Blane A, Wardlaw J, Frier BM, Perros P, McCrimmon RJ, et al. Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function. Diabetes Care. 2005;28(6):1431–7.

    Article  Google 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.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  Google Scholar 

  42. Yau PL, Castro MG, Tagani A, Tsui WH, Convit A. Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics. 2012;130(4):e856–64. https://doi.org/10.1542/peds.2012-0324.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Rees DA, Udiawar M, Berlot R, Jones DK, O’Sullivan MJ. White matter microstructure and cognitive function in young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2016;101(1):314–23. https://doi.org/10.1210/jc.2015-2318.

    Article  CAS  PubMed  Google Scholar 

  44. Liang J, Matheson BE, Kaye WH, Boutelle KN. Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents. Int J Obes. 2014;38(4):494–506. https://doi.org/10.1038/ijo.2013.142.

    Article  CAS  Google Scholar 

  45. Olsson GM, Hulting AL, Montgomery SM. Cognitive function in children and subsequent type 2 diabetes. Diabetes Care. 2008;31(3):514–6. https://doi.org/10.2337/dc07-1399.

    Article  PubMed  Google Scholar 

  46. Bruehl H, Sweat V, Tirsi A, Shah B, Convit A. Obese adolescents with type 2 diabetes mellitus have hippocampal and frontal lobe volume reductions. Neurosci Med. 2011;2(1):34–42. https://doi.org/10.4236/nm.2011.21005.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  Google Scholar 

  50. Bobb JF, Schwartz BS, Davatzikos C, Caffo B. Cross-sectional and longitudinal association of body mass index and brain volume. Hum Brain Mapp. 2014;35(1):75–88. https://doi.org/10.1002/hbm.22159.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google 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.

    Article  PubMed  Google Scholar 

  53. Carnell S, Benson L, Chang KV, Wang Z, Huo Y, Geliebter A, et al. Neural correlates of familial obesity risk and overweight in adolescence. NeuroImage. 2017;159:236–47. https://doi.org/10.1016/j.neuroimage.2017.07.052.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Biessels GJ, Reijmer YD. Brain changes underlying cognitive dysfunction in diabetes: what can we learn from MRI? Diabetes. 2014;63(7):2244–52. https://doi.org/10.2337/db14-0348.

    Article  PubMed  Google Scholar 

  55. Marder TJ, Flores VL, Bolo NR, Hoogenboom WS, Simonson DC, Jacobson AM, et al. Task-induced brain activity patterns in type 2 diabetes: a potential biomarker for cognitive decline. Diabetes. 2014;63(9):3112–9. https://doi.org/10.2337/db13-1783.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Macpherson H, Formica M, Harris E, Daly RM. Brain functional alterations in type 2 diabetes - a systematic review of fMRI studies. Front Neuroendocrinol. 2017;47:34–46. https://doi.org/10.1016/j.yfrne.2017.07.001.

    Article  CAS  PubMed  Google Scholar 

  57. Johnson SB, Blum RW, Giedd JN. Adolescent maturity and the brain: the promise and pitfalls of neuroscience research in adolescent health policy. J Adolesc Health. 2009;45(3):216–21. https://doi.org/10.1016/j.jadohealth.2009.05.016.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Jacob M. Redel, Lawrence M. Dolan, Jennifer Vannest & Amy S. Shah

  2. Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave. MLC 7012, Cincinnati, OH, 45229, USA

    Jacob M. Redel, Lawrence M. Dolan & Amy S. Shah

  3. Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Mark DiFrancesco

  4. Pediatric Neuroimaging Research Consortium, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA

    Mark DiFrancesco & Jennifer Vannest

  5. Division of Neurology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA

    Jennifer Vannest

Authors
  1. Jacob M. Redel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lawrence M. Dolan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark DiFrancesco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jennifer Vannest
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Amy S. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jacob M. Redel.

Ethics declarations

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Pediatric Type 2 and Monogenic Diabetes

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Redel, J.M., Dolan, L.M., DiFrancesco, M. et al. Youth-Onset Type 2 Diabetes and the Developing Brain. Curr Diab Rep 19, 3 (2019). https://doi.org/10.1007/s11892-019-1120-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11892-019-1120-y

Keywords

Search

Navigation