The Role of a Ketogenic Diet in the Treatment of Dementia in Type 2 Diabetes Mellitus.

Lin Bai, Yue Zhou, Jie Zhang, Junpeng Ma
Author Information
  1. Lin Bai: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610041, China.
  2. Yue Zhou: Department of Pharmacy, Xindu District People's Hospital of Chengdu, Chengdu 610500, China.
  3. Jie Zhang: Key Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital of Sichuan University, Chengdu 610041, China.
  4. Junpeng Ma: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610041, China.

Abstract

Type 2 diabetes mellitus (T2DM) shares a common molecular mechanism and underlying pathology with dementia, and studies indicate that dementia is widespread in people with T2DM. Currently, T2DM-induced cognitive impairment is characterized by altered insulin and cerebral glucose metabolism, leading to a shorter life span. Increasing evidence indicates that nutritional and metabolic treatments can possibly alleviate these issues, as there is a lack of efficient preventative and treatment methods. The ketogenic diet (KD) is a very high-fat, low-carbohydrate diet that induces ketosis in the body by producing a fasting-like effect, and neurons in the aged brain are protected from damage by ketone bodies. Moreover, the creation of ketone bodies may improve brain neuronal function, decrease inflammatory expression and reactive oxygen species (ROS) production, and restore neuronal metabolism. As a result, the KD has drawn attention as a potential treatment for neurological diseases, such as T2DM-induced dementia. This review aims to examine the role of the KD in the prevention of dementia risk in T2DM patients and to outline specific aspects of the neuroprotective effects of the KD, providing a rationale for the implementation of dietary interventions as a therapeutic strategy for T2DM-induced dementia in the future.

Keywords

References

  1. Mol Med Rep. 2022 Apr;25(4): [PMID: 35119079]
  2. Diabetes. 2004 Feb;53(2):474-81 [PMID: 14747300]
  3. Soc Psychiatry Psychiatr Epidemiol. 2018 Nov;53(11):1149-1160 [PMID: 30182156]
  4. Acta Diabetol. 2021 Jun;58(6):671-685 [PMID: 33417039]
  5. J Dairy Res. 2016 Nov;83(4):442-446 [PMID: 27692001]
  6. J Diabetes Res. 2021 Jun 28;2021:9999612 [PMID: 34258295]
  7. Nutrition. 2019 Apr;60:118-121 [PMID: 30554068]
  8. Exp Mol Med. 2020 Apr;52(4):548-555 [PMID: 32269287]
  9. Mediators Inflamm. 2015;2015:105828 [PMID: 26693205]
  10. Neurochem Res. 2022 Feb;47(2):279-294 [PMID: 34480710]
  11. J Biol Chem. 2005 Jul 22;280(29):26649-52 [PMID: 15929991]
  12. Intern Med J. 2012 May;42(5):484-91 [PMID: 22372522]
  13. JMIR Diabetes. 2017 Mar 07;2(1):e5 [PMID: 30291062]
  14. Neurosci Biobehav Rev. 2018 Nov;94:11-16 [PMID: 30075165]
  15. PLoS One. 2012;7(5):e35476 [PMID: 22567104]
  16. Metabolism. 2016 Feb;65(2):102-13 [PMID: 26773933]
  17. Brain Sci. 2018 Aug 08;8(8): [PMID: 30096755]
  18. Neuropathol Appl Neurobiol. 2022 Apr;48(3):e12782 [PMID: 34823269]
  19. Cell Physiol Biochem. 2014;33(4):920-32 [PMID: 24713665]
  20. Curr Alzheimer Res. 2019;16(14):1254-1268 [PMID: 31902364]
  21. Cardiovasc Diabetol. 2020 Dec 8;19(1):208 [PMID: 33292205]
  22. Front Neurosci. 2021 Aug 19;15:688090 [PMID: 34489623]
  23. Nutr Metab (Lond). 2009 Aug 10;6:31 [PMID: 19664276]
  24. J Cereb Blood Flow Metab. 2015 Nov;35(11):1783-9 [PMID: 26058697]
  25. Neurobiol Dis. 2010 Oct;40(1):238-44 [PMID: 20594978]
  26. J Physiol Pharmacol. 1996 Jun;47(2):361-71 [PMID: 8807563]
  27. Prostaglandins Leukot Essent Fatty Acids. 2004 Mar;70(3):253-64 [PMID: 14769484]
  28. J Neurochem. 2016 Dec;139(5):769-781 [PMID: 27739595]
  29. Brain Res Rev. 2009 Mar;59(2):293-315 [PMID: 18845187]
  30. Mol Brain. 2011 Jan 07;4:3 [PMID: 21214928]
  31. Life Sci. 2020 Aug 1;254:117771 [PMID: 32437791]
  32. Neurology. 2018 Jul 10;91(2):e139-e142 [PMID: 29898968]
  33. Nat Rev Endocrinol. 2018 Oct;14(10):591-604 [PMID: 30022099]
  34. Antioxidants (Basel). 2018 Apr 28;7(5): [PMID: 29710809]
  35. PLoS One. 2009;4(1):e4144 [PMID: 19127292]
  36. Ageing Res Rev. 2019 Nov;55:100944 [PMID: 31430566]
  37. Eur J Nutr. 2016 Apr;55(3):931-40 [PMID: 25911003]
  38. Nat Med. 2015 Mar;21(3):263-9 [PMID: 25686106]
  39. Ann N Y Acad Sci. 2015 Sep;1353:60-71 [PMID: 26132277]
  40. Epilepsy Res. 2012 Jul;100(3):295-303 [PMID: 22078747]
  41. Cell Metab. 2017 Aug 1;26(2):394-406.e6 [PMID: 28768177]
  42. Epilepsia. 2015 Jul;56(7):e95-8 [PMID: 26011473]
  43. Invest Ophthalmol Vis Sci. 2012 Apr 24;53(4):2208-17 [PMID: 22427566]
  44. Metabolites. 2020 Dec 10;10(12): [PMID: 33321705]
  45. Prog Neurobiol. 2013 Jul-Aug;106-107:17-32 [PMID: 23643800]
  46. Neurobiol Aging. 2016 Mar;39:25-37 [PMID: 26923399]
  47. Psychiatry Res. 2016 Jun 30;240:42-46 [PMID: 27082868]
  48. Am J Physiol Regul Integr Comp Physiol. 2013 May 15;304(10):R829-36 [PMID: 23552496]
  49. Lancet Neurol. 2006 Jan;5(1):64-74 [PMID: 16361024]
  50. Neurobiol Aging. 2016 Dec;48:34-47 [PMID: 27639119]
  51. Lancet Public Health. 2022 Feb;7(2):e105-e125 [PMID: 34998485]
  52. Mediators Inflamm. 2014;2014:983401 [PMID: 24803746]
  53. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5440-4 [PMID: 10805800]
  54. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jul 13;101:109913 [PMID: 32151695]
  55. Curr Neuropharmacol. 2022 Nov 15;20(12):2303-2319 [PMID: 36043794]
  56. J Nutr Metab. 2018 Feb 11;2018:5157645 [PMID: 29607218]
  57. Int Rev Neurobiol. 2020;154:79-110 [PMID: 32739015]
  58. Int J Mol Sci. 2020 Jan 31;21(3): [PMID: 32023814]
  59. Front Endocrinol (Lausanne). 2019 Jun 05;10:348 [PMID: 31231311]
  60. Front Neurosci. 2020 Aug 06;14:764 [PMID: 32903669]
  61. Int J Mol Sci. 2022 May 30;23(11): [PMID: 35682821]
  62. Toxicol In Vitro. 2017 Aug;42:337-347 [PMID: 28526448]
  63. Nat Commun. 2014 May 21;5:3944 [PMID: 24845831]
  64. Ann Neurol. 2006 Aug;60(2):223-35 [PMID: 16807920]
  65. Cardiovasc Res. 2019 Sep 1;115(11):1606-1616 [PMID: 30778524]
  66. Nat Rev Endocrinol. 2021 Mar;17(3):150-161 [PMID: 33293704]
  67. Biochem J. 2009 Jan 1;417(1):1-13 [PMID: 19061483]
  68. Nature. 2004 Jun 17;429(6993):771-6 [PMID: 15175761]
  69. Sci Rep. 2020 Apr 29;10(1):7274 [PMID: 32350344]
  70. Lipids. 2006 Feb;41(2):207-12 [PMID: 17707987]
  71. Nutr Rev. 2022 Mar 10;80(4):774-785 [PMID: 34957519]
  72. Nutrients. 2022 Sep 01;14(17): [PMID: 36079870]
  73. Br J Pharmacol. 2008 Nov;155(5):623-40 [PMID: 18794892]
  74. Cell Physiol Biochem. 2015;35(1):364-73 [PMID: 25591777]
  75. PLoS One. 2014 Jan 29;9(1):e87095 [PMID: 24489845]
  76. J Int Neuropsychol Soc. 2019 Feb;25(2):215-229 [PMID: 30575498]
  77. Cell Metab. 2017 Feb 7;25(2):262-284 [PMID: 28178565]
  78. Diabetes Ther. 2018 Apr;9(2):583-612 [PMID: 29417495]
  79. Neuroimage Clin. 2020;27:102302 [PMID: 32521474]
  80. Cell Death Dis. 2022 Jan 10;13(1):40 [PMID: 35013137]
  81. Neurochem Int. 2005 Jul;47(1-2):119-28 [PMID: 15888376]
  82. Nutrients. 2022 Feb 22;14(5): [PMID: 35267893]
  83. Am J Physiol. 1995 Jun;268(6 Pt 1):E1161-6 [PMID: 7611392]
  84. Vet J. 2013 Dec;198(3):696-701 [PMID: 24210276]
  85. Front Mol Neurosci. 2017 Nov 14;10:377 [PMID: 29184484]
  86. Psychoneuroendocrinology. 2013 Nov;38(11):2462-75 [PMID: 23790682]
  87. Front Cell Neurosci. 2018 Jul 18;12:214 [PMID: 30072873]
  88. Curr Med Chem. 2017;24(12):1170-1185 [PMID: 28093985]
  89. Front Mol Neurosci. 2018 Jan 26;11:15 [PMID: 29434537]
  90. Eur J Appl Physiol. 2023 Feb 19;: [PMID: 36801969]
  91. Prog Retin Eye Res. 2015 Sep;48:40-61 [PMID: 25975734]
  92. Oxid Med Cell Longev. 2016;2016:9730467 [PMID: 26770661]
  93. Exp Neurol. 2008 May;211(1):85-96 [PMID: 18339375]
  94. JAMA. 2014 Dec 17;312(23):2551-61 [PMID: 25514304]
  95. Neurobiol Aging. 2010 Dec;31(12):2047-57 [PMID: 19111937]
  96. Int J Mol Sci. 2020 Aug 30;21(17): [PMID: 32872570]
  97. Neurobiol Aging. 2013 Jun;34(6):1530-9 [PMID: 23276384]
  98. J Mol Neurosci. 2010 Oct;42(2):145-53 [PMID: 20333481]
  99. Lancet Diabetes Endocrinol. 2021 Mar;9(3):165-173 [PMID: 33549162]
  100. Int J Mol Sci. 2020 Nov 20;21(22): [PMID: 33233502]
  101. PLoS One. 2015 May 29;10(5):e0128274 [PMID: 26023930]
  102. Nutrients. 2019 Jan 15;11(1): [PMID: 30650523]

Grants

  1. 2020JDRC0102/Sichuan Science and Technology Program
  2. 2020YFS0223/the Key R&D Project of Sichuan Provincial Department of Science and Technology

MeSH Term

Humans
Aged
Diabetes Mellitus, Type 2
Diet, Ketogenic
Ketone Bodies
Ketosis
Dementia

Chemicals

Ketone Bodies

Word Cloud

Created with Highcharts 10.0.0dementiaKD2T2DMT2DM-induceddietTypediabetesmellitusmetabolismtreatmentketogenicbrainketonebodiesneuronalneuroprotectivesharescommonmolecularmechanismunderlyingpathologystudiesindicatewidespreadpeopleCurrentlycognitiveimpairmentcharacterizedalteredinsulincerebralglucoseleadingshorterlifespanIncreasingevidenceindicatesnutritionalmetabolictreatmentscanpossiblyalleviateissueslackefficientpreventativemethodshigh-fatlow-carbohydrateinducesketosisbodyproducingfasting-likeeffectneuronsagedprotecteddamageMoreovercreationmayimprovefunctiondecreaseinflammatoryexpressionreactiveoxygenspeciesROSproductionrestoreresultdrawnattentionpotentialneurologicaldiseasesreviewaimsexaminerolepreventionriskpatientsoutlinespecificaspectseffectsprovidingrationaleimplementationdietaryinterventionstherapeuticstrategyfutureRoleKetogenicDietTreatmentDementiaDiabetesMellitustype

Similar Articles

Cited By