Brain neuroimaging technologies in diabetes
M.V. Matveeva, Yu.G. Samoilova, N.G. Zhukova, I.V. Tolmachov, K.S. Brazovskiy, O.P. Leiman, N.Yu. Fimushkina, M.A. Rotkank
Sibir State Medical University, Tomsk
Diabetes is a chronic metabolic disorder associated with brain structural changes and mild-to-moderate cognitive impairments assessed by neuropsychological testing. Cognitive dysfunction associated with diabetes will have a major impact on global health in the future as diabetes is a growing epidemic and many people live to old ages. Type 1 and type 2 diabetes share common important risk factors, i.e., chronic hyperglycemia, severe episodes of hypoglycemia, and microvascular complications. To diagnose cognitive impairments in diabetes more carefully, practitioners use brain imaging technologies which evaluate morphology, volumetric parameters, macrostructural changes, functional connectivity of signal fluctuations, and metabolites.
This paper reviews the studies over the last two decades to improve our understanding how diadetes, blood glucose, and complications affect brain function and structure. We also describe abnormalities revealed by magnetic resonance imaging and proton magnetic resonance spectroscopy which are typical of type 1 and type 2 diabetes.
Keywords: diabetes, cognitive impairments, neuroimaging technologies.
For citation: Matveeva M.V., Samoilova Yu.G., Zhukova N.G. et al. Brain neuroimaging technologies in diabetes. RMJ. Medical Review. 2019;7:8–10.
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17. Antenor-Dorsey J.A.V., Meyer E., Rutlin J. et al. White matter microstructural integrity in youth with type 1 diabetes. Diabetes. 2013;62:581–589.
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28. Van Duinkerken E., Schoonheim M.M., IJzerman R.G. et al. Altered eigenvector centrality is related to local resting-state network functional connectivity in patients with longstanding type 1 diabetes mellitus. Hum Brain Mapp. 2017;38:3623–3636.
29. Demuru M., van Duinkerken E., Fraschini M. et al. Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients. Neuroimage Clin. 2014;5:69–76.
30. Mangia S., Kumar A.F., Moheet A.A. et al. Neurochemical profile of patients with type 1 diabetes measured by H-MRS at 4 T. J Cereb Blood Flow Metab. 2013;33(5):754–759. DOI: 10.1038/jcbfm.2013.13.
31. Heikkila O., Lundbom N., Timonen M. et al. Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain. Diabetologia. 2009;52(3):534–540. DOI: 10.1007/s00125-008-1242-2.
32. Seaquist E.R., Tkac I., Damberg G. et al. Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy. Metabolism. 2005;54:1008–1013. DOI: 10.1016/j.metabol.2005.02.018.
33. Sarac K., Akinci A., Alkan A. et al. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus. Neuroradiology. 2005;47:562–565. DOI: 10.1007/s00234-005-1387-3.
34. Biessels G.J., Staekenborg S., Brunner E. et al. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5(1):64–74.
35. Exalto L.G., Whitmer R.A., Kappele L.J., Biessels G.J. An update on type 2 diabetes, vascular dementia and Alzheimer’s disease. Exp Gerontol. 2012; 47 (11):858–864.
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37. Yates K.F., Sweat V., Yau P.L. et al. Impact of metabolic syndrome on cognition and brain: a selected review of the literature. Arterioscler Thromb Vasc Biol. 2012;32(9):2060–7. DOI: 10.1161/ATVBAHA.112.252759.
38. Geijselaers S.L.C., Sep S.J.S., Stehouwer C.D.A., Biessels G.J. Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review. Lancet Diabetes Endocrinol. 2015;3(1):75–89. DOI: 10.1016/S2213-8587 (14) 70148-2.
39. Van Harten B., de Leeuw F.E., Weinstein H.C. et al. Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 2006;29:2539–2548.
40. De Bresser J., Tiehuis A.M., van den Berg E. et al., Utrecht Diabetic Encephalopathy Study Group. Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care. 2010;33:1309–1314.
41. Kooistra M., Geerlings M.I., Mali W.P. et al. Diabetes mellitus and progression of vascular brain lesions and brain atrophy in patients with symptomatic atherosclerotic disease. The SMART-MR study. J Neurol Sci. 2013;332:69–74.
42. Musen G., Jacobson A.M., Bolo N.R. et al. Resting-state brain functional connectivity is altered in type 2 diabetes. Diabetes. 2012;61:2375–2379.
43. Sinha S., Ekka M., Sharma U. et al. Assessment of changes in brain metabolites in Indian patients with type-2 diabetes mellitus using proton magnetic resonance spectroscopy. BMC Res Notes. 2014;7:41. DOI: 10.1186/1756-0500-7-41.
44. Sahin I., Alkan A., Keskin L. et al. Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus. J Diabetes Complications. 2008;22(4):254–260. DOI: 10.1016/j.jdiacomp.2007.03.007.
45. Groeneveld O., Reijmer Y., Heinen R. et al. COG-ID study group.Brain imaging correlates of mild cognitive impairment and early dementia in patients with type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2018;28(12):1253–1260. DOI: 10.1016/j.numecd.2018.07.008.
46. Macpherson H., Formica M., Harris E., Daly R.M. Brain functional alterations in Type 2 Diabetes — A systematic review of fMRI studies. Front Neuroendocrinol. 2017;47:34–46. DOI: 10.1016/j.yfrne.2017.07.001.
47. Rae C.D. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res. 2014;39(1):1–36.
48. Gujar S.K., Maheshwari S., Björkman-Burtscher I., Sundgren P.C. Magnetic resonance spectroscopy.J Neuroophthalmol. 2005;25(3):217–226.
49. Ross B., Bluml S. Magnetic resonance spectroscopy of the human brain. Anat Rec. 2001;265(2):54—84.
2. McCall A.L. The impact of diabetes on the CNS. Diabetes. 1992;41(5):557–570.
3. Strachan M.W., Price J.F., Frier B.M. Diabetes, cognitive impairment, and dementia. BMJ. 2008;336(7634):6.
4. Mukesh G. Gohel. Evaluation of glycemic control in patients with type 2 diabetes mellitus with and without microvascular complications International. Int J Pharm Bio Sci. 2013;4(4):794–802.
5. Kodl C.T., Seaquist E.R. Cognitive dysfunction and diabetes mellitus. Endocr Rev. 2008;29(4):494–511.
6. Bangen K.J., Werhane M.L., Weigand A.J. et al. Reduced Regional Cerebral Blood Flow Relates to Poorer Cognition in Older Adults With Type 2 Diabetes. Front Aging Neurosci. 2018;10:270. DOI: 10.3389/fnagi.2018.00270. eCollection 2018.
7. Chen Y., Liu Z., Zhang J. et al. Altered brain activation patterns under different working memory loads in patients with type 2 diabetes. Diabetes Care. 2014;37:3157–3163.
8. Bertholdo D., Watcharakorn A., Castillo M. Brain proton magnetic resonance spectroscopy: introduction and overview. Neuroimaging Clin N Am. 2013; 23 (3):359–380.
9. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54:1615–1625.
10. Brands A.M., Biessels G.J., De Haan E.H. et al. The effects of type 1 diabetes on cognitive performance: a meta-analysis. Diabetes Care. 2005;28:726–735.
11. Broadley M.M., White M.J., Andrew B. A Systematic Review and Meta-analysis of Executive Function Performance in Type 1 Diabetes Mellitus. Psychosom Med. 2017;79:684–696.
12. Gaudieri P.A., Chen R., Greer T.F., Holmes C.S. Cognitive function in children with type 1 diabetes: a meta-analysis. Diabetes Care. 2008;31:1892–1897.
13. Brands A.M., Kessels R.P., Hoogma R.P. et al. Cognitive performance, psychological well-being, and brain magnetic resonance imaging in older patients with type 1 diabetes. Diabetes. 2006;55:1800–1806.
14. Northam E.A., Anderson P.J., Werther G.A. et al. Neuropsychological complications of IDDM in children 2 years after disease onset. Diabetes Care. 1998;21:379–384.
15. Lyoo I.K., Yoon S., Renshaw P.F. et al. Network-level structural abnormalities of cerebral cortex in type 1 diabetes mellitus. PLoS One. 2013;8: e71304.
16. Van Duinkerken E., Ijzerman R.G., Klein M. et al. Disrupted subject-specific gray matter network properties and cognitive dysfunction in type 1 diabetes patients with and without proliferative retinopathy. Hum Brain Mapp. 2016;37:1194–1208.
17. Antenor-Dorsey J.A.V., Meyer E., Rutlin J. et al. White matter microstructural integrity in youth with type 1 diabetes. Diabetes. 2013;62:581–589.
18. Musen G., Lyoo I.K., Sparks C.R. et al. Effects of type 1 diabetes on gray matter density as measured by voxel-based morphometry. Diabetes. 2006;55:326–333.
19. Northam E.A., Rankins D., Lin A. et al. Central nervous system function in youth with type 1 diabetes 12 years after disease onset. Diabetes Care. 2009;32:445–450.
20. Perantie D.C., Wu J., Koller J.M. et al. Regional brain volume differences associated with hyperglycemia and severe hypoglycemia in youth with type 1 diabetes. Diabetes Care. 2007;30:2331–2337.
21. Hershey T., Perantie D.C., Wu J. et al. Hippocampal volumes in youth with type 1 diabetes. Diabetes. 2010;59:236–241.
22. Marzelli M.J., Mazaika P.K., Barnea-Goraly N., et al., Diabetes Research in Children Network. Neuroanatomical correlates of dysglycemia in young children with type 1 diabetes. Diabetes. 2014;63:343–353.
23. Northam E.A., Rankins D., Lin A. et al. Central nervous system function in youth with type 1 diabetes 12 years after disease onset. Diabetes Care. 2009;32:445–450.
24. Kodl C.T., Franc D.T., Rao J.P. et al. Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function. Diabetes. 2008;57:3083–3089.
25. Van Duinkerken E., Schoonheim M.M., Sanz-Arigita E.J. et al. Resting-state brain networks in type 1 diabetic patients with and without microangiopathy and their relation to cognitive functions and disease variables. Diabetes. 2012;61:1814–1821.
26. Van Duinkerken E., Ryan C.M., Schoonheim M.M. et al. Subgenual cingulate cortex functional connectivity in relation to depressive symptoms and cognitive functioning in type 1 diabetes mellitus patients. Psychosom Med. 2016;78:740–749.
27. Ryan J.P., Aizenstein H.J., Orchard T.J. et al. Age of childhood onset in type 1 diabetes and functional brain connectivity in midlife. Psychosom Med. 2015;77:622.
28. Van Duinkerken E., Schoonheim M.M., IJzerman R.G. et al. Altered eigenvector centrality is related to local resting-state network functional connectivity in patients with longstanding type 1 diabetes mellitus. Hum Brain Mapp. 2017;38:3623–3636.
29. Demuru M., van Duinkerken E., Fraschini M. et al. Changes in MEG resting-state networks are related to cognitive decline in type 1 diabetes mellitus patients. Neuroimage Clin. 2014;5:69–76.
30. Mangia S., Kumar A.F., Moheet A.A. et al. Neurochemical profile of patients with type 1 diabetes measured by H-MRS at 4 T. J Cereb Blood Flow Metab. 2013;33(5):754–759. DOI: 10.1038/jcbfm.2013.13.
31. Heikkila O., Lundbom N., Timonen M. et al. Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain. Diabetologia. 2009;52(3):534–540. DOI: 10.1007/s00125-008-1242-2.
32. Seaquist E.R., Tkac I., Damberg G. et al. Brain glucose concentrations in poorly controlled diabetes mellitus as measured by high-field magnetic resonance spectroscopy. Metabolism. 2005;54:1008–1013. DOI: 10.1016/j.metabol.2005.02.018.
33. Sarac K., Akinci A., Alkan A. et al. Brain metabolite changes on proton magnetic resonance spectroscopy in children with poorly controlled type 1 diabetes mellitus. Neuroradiology. 2005;47:562–565. DOI: 10.1007/s00234-005-1387-3.
34. Biessels G.J., Staekenborg S., Brunner E. et al. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5(1):64–74.
35. Exalto L.G., Whitmer R.A., Kappele L.J., Biessels G.J. An update on type 2 diabetes, vascular dementia and Alzheimer’s disease. Exp Gerontol. 2012; 47 (11):858–864.
36. Exalto L.G., Whitmer R.A., Kappele L.J. et al. An update on type 2 diabetes, vascular dementia and Alzheimer’s disease. 2012;47(11):858–864. DOI: 10.1016/j.exger.2012.07.014.
37. Yates K.F., Sweat V., Yau P.L. et al. Impact of metabolic syndrome on cognition and brain: a selected review of the literature. Arterioscler Thromb Vasc Biol. 2012;32(9):2060–7. DOI: 10.1161/ATVBAHA.112.252759.
38. Geijselaers S.L.C., Sep S.J.S., Stehouwer C.D.A., Biessels G.J. Glucose regulation, cognition, and brain MRI in type 2 diabetes: a systematic review. Lancet Diabetes Endocrinol. 2015;3(1):75–89. DOI: 10.1016/S2213-8587 (14) 70148-2.
39. Van Harten B., de Leeuw F.E., Weinstein H.C. et al. Brain imaging in patients with diabetes: a systematic review. Diabetes Care. 2006;29:2539–2548.
40. De Bresser J., Tiehuis A.M., van den Berg E. et al., Utrecht Diabetic Encephalopathy Study Group. Progression of cerebral atrophy and white matter hyperintensities in patients with type 2 diabetes. Diabetes Care. 2010;33:1309–1314.
41. Kooistra M., Geerlings M.I., Mali W.P. et al. Diabetes mellitus and progression of vascular brain lesions and brain atrophy in patients with symptomatic atherosclerotic disease. The SMART-MR study. J Neurol Sci. 2013;332:69–74.
42. Musen G., Jacobson A.M., Bolo N.R. et al. Resting-state brain functional connectivity is altered in type 2 diabetes. Diabetes. 2012;61:2375–2379.
43. Sinha S., Ekka M., Sharma U. et al. Assessment of changes in brain metabolites in Indian patients with type-2 diabetes mellitus using proton magnetic resonance spectroscopy. BMC Res Notes. 2014;7:41. DOI: 10.1186/1756-0500-7-41.
44. Sahin I., Alkan A., Keskin L. et al. Evaluation of in vivo cerebral metabolism on proton magnetic resonance spectroscopy in patients with impaired glucose tolerance and type 2 diabetes mellitus. J Diabetes Complications. 2008;22(4):254–260. DOI: 10.1016/j.jdiacomp.2007.03.007.
45. Groeneveld O., Reijmer Y., Heinen R. et al. COG-ID study group.Brain imaging correlates of mild cognitive impairment and early dementia in patients with type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2018;28(12):1253–1260. DOI: 10.1016/j.numecd.2018.07.008.
46. Macpherson H., Formica M., Harris E., Daly R.M. Brain functional alterations in Type 2 Diabetes — A systematic review of fMRI studies. Front Neuroendocrinol. 2017;47:34–46. DOI: 10.1016/j.yfrne.2017.07.001.
47. Rae C.D. A guide to the metabolic pathways and function of metabolites observed in human brain 1H magnetic resonance spectra. Neurochem Res. 2014;39(1):1–36.
48. Gujar S.K., Maheshwari S., Björkman-Burtscher I., Sundgren P.C. Magnetic resonance spectroscopy.J Neuroophthalmol. 2005;25(3):217–226.
49. Ross B., Bluml S. Magnetic resonance spectroscopy of the human brain. Anat Rec. 2001;265(2):54—84.
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