Efficacy of Delicious energy bites agonist pioglitazone in mild Ckntrol disease. Diabetes causes insulin resistance, Blood sugar control and cognitive function in brain energy metabolism, cognitiev in the regional cerebral blood flow, and osmotic effects on neurons, all of which damage brain health [ 33 ]. Characteristics of study population. The brain is dependent on sugar as its main fuel Vera Novak, MD, PhD.

Blood sugar control and cognitive function -

Cummings, J. Cognitive effects of the BET protein inhibitor Apabetalone: a Prespecified Montreal cognitive assessment analysis nested in the BETonMACE randomized controlled trial. Alzheimers Dis. de la Monte, S. Alzheimer's disease is type 3 diabetes-evidence reviewed. Diabetes Sci. Duarte, A. Insulin in central nervous system: more than just a peripheral hormone.

Aging Res. Furie, K. Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial. Psychiatry 89, 21— Ganguli, M. Aging, diabetes, obesity, and cognitive decline: a population-based study.

Gerstein, H. The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial. Ghetti, S. Cognitive function following diabetic ketoacidosis in children with new-onset or previously diagnosed type 1 diabetes.

Diabetes Care 43, — Gudala, K. Diabetes mellitus and risk of dementia: a meta-analysis of prospective observational studies. Diabetes Investig. Guo, M. Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus.

Hanyu, H. Pioglitazone improved cognition in a pilot study on patients with Alzheimer's disease and mild cognitive impairment with diabetes mellitus. He, J. Vascular risk factors and Alzheimer's disease: blood-brain barrier disruption, metabolic syndromes, and molecular links.

Isik, A. The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer's disease. Diabetes Res. Jash, K.

Cognitive dysfunction: a growing link between diabetes and Alzheimer's disease. Drug Dev. Köbe, T. Impact of resveratrol on glucose control, hippocampal structure and connectivity, and memory performance in patients with mild cognitive impairment.

Lacy, M. Severe hypoglycemia and cognitive function in older adults with type 1 diabetes: the study of longevity in diabetes SOLID. Lester-Coll, N. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. Li, Q. Activation of glucagon-like Peptide-1 receptor ameliorates cognitive decline in type 2 diabetes mellitus through a metabolism-independent pathway.

Heart Assoc. Lin, Y. Evaluation of metformin on cognitive improvement in patients with non-dementia vascular cognitive impairment and abnormal glucose metabolism. Aging Neurosci. McMillan, J. Impact of pharmacological treatment of diabetes mellitus on dementia risk: systematic review and meta-analysis.

BMJ Open Diabetes Res. Care 6:e Milstein, J. The brain as an insulin-sensitive metabolic organ. Moore, E. Increased risk of cognitive impairment in patients with diabetes is associated with metformin.

Diabetes Care 36, — Morris, J. Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin. Aging 39, 19— Pignalosa, F. Diabetes and cognitive impairment: a role for Glucotoxicity and dopaminergic dysfunction. Plastino, M.

Effects of insulinic therapy on cognitive impairment in patients with Alzheimer disease and diabetes mellitus type Sato, T. Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease.

Aging 32, — Tahmi, M. Metabolic syndrome and cognitive function. Umegaki, H. The associations among insulin resistance, hyperglycemia, physical performance, diabetes mellitus, and cognitive function in relatively healthy older adults with subtle cognitive dysfunction.

van Sloten, T. Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression. Xu, W. Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces Alzheimer disease-associated tau hyperphosphorylation in the hippocampus of rats with type 2 diabetes.

Xue, M. Diabetes mellitus and risks of cognitive impairment and dementia: a systematic review and meta-analysis of prospective studies. Ageing Res. Sagittal, Coronal and Axial Representations of Glucose-related Regional Grey A and White B Matter Volumes.

Table 2. Atlas Coordinates, Cluster Extents, P and T Values and Regional Descriptions. Table 3. The relationship between regional brain volumes and cognitive test performance. Discussion This study investigated the association between normal blood glucose levels and grey and white matter regional volumes across the whole brain and its association with cognitive performance in a large, community-based sample of cognitively healthy individuals without diabetes, glucose intolerance or metabolic syndrome.

Acknowledgments The authors are grateful to Patricia Jacomb, Karen Maxwell, Peter Butterworth, Simon Easteal, Helen Christensen, and the PATH interviewers. Author Contributions Conceived and designed the experiments: MEM ALJ KJA PSS NC. References 1.

Manschot SM, Brands AM, van der Grond J, Kessels RP, Algra A, et al. Diabetes — View Article Google Scholar 2. DeVisser A, Yang C, Herring A, Martinez JA, Rosales-Hernandez A, et al.

Neurobiol Dis — View Article Google Scholar 3. den Heijer T, Vermeer SE, van Dijk EJ, Prins ND, Koudstaal PJ, et al. Diabetologia — View Article Google Scholar 4. Araki Y, Nomura M, Tanaka H, Yamamoto H, Yamamoto T, et al.

Neuroradiology — View Article Google Scholar 5. Vermeer SE, Den Heijer T, Koudstaal PJ, Oudkerk M, Hofman A, et al. Stroke — View Article Google Scholar 6. Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort.

Am J Epidemiol — View Article Google Scholar 7. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, et al. Neurology — View Article Google Scholar 8.

Launer LJ Diabetes: vascular or neurodegenerative: an epidemiologic perspective. Stroke S53— View Article Google Scholar 9. Awad N, Gagnon M, Messier C The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol — View Article Google Scholar Messier C, Tsiakas M, Gagnon M, Desrochers A, Awad N Effect of age and glucoregulation on cognitive performance.

Neurobiol Aging — Vanhanen M, Koivisto K, Kuusisto J, Mykkanen L, Helkala EL, et al. Diabetes Care — Cherbuin N, Sachdev P, Anstey KJ Higher normal fasting plasma glucose is associated with hippocampal atrophy: The PATH Study.

Johansen FF, Diemer NH Influence of the plasma glucose level on brain damage after systemic kainic acid injection in the rat. Acta Neuropathol 46— van der Borght K, Kohnke R, Goransson N, Deierborg T, Brundin P, et al. Regul Pept 26— Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann RS, et al.

Hippocampus — Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, et al. Circulation — Haffner SM The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease.

Am J Cardiol 3A—11A. Vaidyula VR, Rao AK, Mozzoli M, Homko C, Cheung P, et al. Kopelman TR, O'Neill PJ, Kanneganti SR, Davis KM, Drachman DA The relationship of plasma glucose and glycosylated hemoglobin A1C levels among nondiabetic trauma patients.

J Trauma 30—33; discussion 33— Anstey KJ, Christensen H, Butterworth P, Easteal S, Mackinnon A, et al.. International Journal of Epidemiology. Saunders JB, Aasland OG, Babor TF, de la FuenteJR, Grant M Development of the Alcohol Use Disorders Identification Test AUDIT : WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption—II.

Addiction — Wechsler D A standardized memory scale for clinical use. Journal of Psychology 87— Smith A Symbol Digit Modalities Test SDM manual. Los Angeles: Western Psychological Sciences. Delis DC, Freeland J, Kramer JH, Kaplan E Integrating clinical assessment with cognitive neuroscience: construct validation of the California Verbal Learning Test.

J Consult Clin Psychol — Mack WJ, Freed DM, Williams BW, Henderson VW Boston Naming Test: shortened versions for use in Alzheimer's disease. J Gerontol P— Janke AL, Budge M, Rodell A ANDI — The Australian normative and dementia imaging collaborative network: Tools and methods for amalgamating large neuroimaging databases.

International Conference on Alzheimer's Disease. Vienna, Austria. Sled JG, Zijdenbos AP, Evans AC A nonparametric method for automatic correction of intensity nonuniformity in MRI data.

IEEE Trans Med Imaging 87— Ashburner J, Friston KJ Unified segmentation. Neuroimage — Ashburner J A fast diffeomorphic image registration algorithm. Neuroimage 95— Bergouignan L, Chupin M, Czechowska Y, Kinkingnehun S, Lemogne C, et al.

Neuroimage 29— Klein A, Andersson J, Ardekani BA, Ashburner J, Avants B, et al. van Harmelen AL, van Tol MJ, van der Wee NJ, Veltman DJ, Aleman A, et al. Biol Psychiatry — Yuan Y, Zhu W, Zhang Z, Bai F, Yu H, et al. Vasic N, Walter H, Hose A, Wolf RC Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study.

J Affect Disord — Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain.

J Neurosci — Savage CR, Deckersbach T, Heckers S, Wagner AD, Schacter DL, et al. Brain — Halliday GM, Double KL, Macdonald V, Kril JJ Identifying severely atrophic cortical subregions in Alzheimer's disease. Scahill RI, Schott JM, Stevens JM, Rossor MN, Fox NC Mapping the evolution of regional atrophy in Alzheimer's disease: unbiased analysis of fluid-registered serial MRI.

Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes Obes Metab. International Hypoglycaemia Study Group. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management.

Lancet Diabet Endocrinol. Biessels GJ, Strachan MW, Visseren FL, et al. Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions.

Lancet Diabetes Endocrinol. Hölscher C. Hong M, Lee VM. Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons. J Biol Chem. Russo VC, Higgins S, Werther GA, et al. Effects of fluctuating glucose levels on neuronal cells in vitro.

Neurochem Res. Schisano B, Tripathi G, Mcgee K, et al. Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells.

Jacobson AM, Musen G, Ryan CM, et al. Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med. Willette A, Xu G, Johnson S, et al.

Insulin resistance, brain atrophy, and cognitive performance in late middle-aged adults. Raffield L, Cox A, Freedman B, et al. Analysis of the relationships between type 2 diabetes status, glycemic control, and neuroimaging measures in the Diabetes Heart Study Mind.

Nanayakkara G, Kariharan T, Wang L, et al. The cardio-protective signaling and mechanisms of adiponectin. Am J Cardiovasc Dis. CAS PubMed PubMed Central Google Scholar. Rizzi L, Rosset I, Roriz-Cruz M. Biomed Res Int. Holman RR, Paul SK, Bethel MA, et al.

Rawlings AM, Sharrett AR, Mosley TH, et al. Glucose peaks and the risk of dementia and year cognitive decline. Terry T, Raravikar K, Chokrungvaranon N, et al. Does aggressive glycemic control benefit macrovascular and microvascular disease in type 2 diabetes?

Insights from ACCORD, ADVANCE, and VADT. Curr Cardiol Rep. Whitmer RA, Karter AJ, Yaffe K, et al. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. Zhou J, Tang X, Han M, et al.

Impact of antidiabetic agents on dementia risk: a Bayesian network meta-analysis. Bohlken J, Jacob L, Kostev K. Association between the use of antihyperglycemic drugs and dementia risk: a case-control study.

Wium-Andersen I, Osler M, Jørgensen M, et al. Antidiabetic medication and risk of dementia in patients with type 2 diabetes: a nested case-control study. Eur J Endocrinol. Cheng C, Lin C, Tsai Y, et al. Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis. J Gerontol.

Download references. This work was supported by the National Natural Science Foundation of China No. Capital's Funds for Health Improvement and Research The Rapid Service Fee was funded by the authors. All named authors meet the International Committee of Medical Journal Editors ICMJE criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents. Xingyao Tang, Marly A. Cardoso, Jinkui Yang, Jian-Bo Zhou, and Rafael Simó have no disclosures to declare.

Beijing Tongren Hospital, Capital Medical University, Beijing, China. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. Department of Nutrition, School of Public Health, University of Sao Paulo, Sao Paulo, Brazil.

Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas CIBERDEM , Instituto de Salud Carlos III ISCIII , Madrid, Spain. You can also search for this author in PubMed Google Scholar. Correspondence to Jian-Bo Zhou. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.

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et al. Impact of Intensive Glucose Control on Brain Health: Meta-Analysis of Cumulative Data from 16, Patients with Type 2 Diabetes Mellitus.

Diabetes Ther 12 , — Download citation. Received : 01 November Accepted : 23 January Published : 06 February Issue Date : March Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Download PDF. Abstract Introduction Despite growing evidence that type 2 diabetes is associated with dementia, the question of whether intensive glucose control can prevent or arrest cognitive decline remains unanswered.

Methods We searched the PubMed and Embase databases, the Web of Science website, and the Clinicaltrial. Results Six studies 5 different RCTs with 16, participants were included in this meta-analysis.

Conclusion This meta-analysis suggests that intensive glucose control in patients with type 2 diabetes can slow down cognitive decline, especially the decline in composite cognition and memory function.

ACCORDION MIND: results of the observational extension of the ACCORD MIND randomised trial Article 20 October A Prospective Longitudinal Study on the Relationship Between Glucose Fluctuation and Cognitive Function in Type 2 Diabetes: PROPOSAL Study Protocol Article Open access 05 September Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities ARIC cohort study Article 30 June Use our pre-submission checklist Avoid common mistakes on your manuscript.

FormalPara Key Summary Points Why carry out this study? What was learned from the study? Digital Features This article is published with digital features, including a summary slide, to facilitate understanding of the article.

Introduction Type 2 diabetes is a significant health challenge worldwide, and the prevalence of diabetes in adults is predicted to increase to Methods Study Inclusion The PubMed and Embase databases, the Web of Science website, and the Clinicaltrial.

Data Extraction and Quality Assessment The literature search was performed in July Statistical Analysis Heterogeneity between the studies was evaluated using the I 2 metric, and the variance between studies was evaluated using the Tau-squared Tau 2 metric.

Results Literature Search Outcomes and Validity Assessment The search strategy identified potentially relevant reports, of which were excluded due to duplication. Full size image. Table 1 Characteristics of studies included in the meta-analysis on the effects of intensive and conventional glucose control on brain health Full size table.

Table 2 Risk of bias assessment Newcastle—Ottawa Quality Assessment Scale criteria of studies on the association between intensive and conventional glucose control on brain health included in the meta-analysis Full size table.

Discussion A total of six studies involving five cohorts were included in our meta-analysis. Potential Mechanisms Various mechanisms may have the potential to contribute to the association between elevated blood glucose levels, glucose variability, and brain health.

Public Health Impact With the rapid increase in aging populations worldwide, diabetes [ 41 ] and dementia [ 42 ] have become an increasing burden for society. Strengths and Limitations of the Study Although our meta-analysis considered the entire spectrum from pre-dementia to dementia and extracted valuable information regarding associations between intensive and conventional glucose control with brain health among patients with diabetes, its essential strengths and limitations merit mention.

Conclusions The current study suggests that intensive glucose control in persons with type 2 diabetes can slow down cognitive decline, especially the decline in composite and memory function. References Ogurtsova K, Da Rocha FJD, Huang Y, et al.

Article CAS PubMed Google Scholar Bunn F, Burn AM, Goodman C, et al. Article PubMed PubMed Central Google Scholar Wild S, Roglic G, Green A, et al.

Article PubMed Google Scholar Biessels GJ, Despa F. Article PubMed PubMed Central Google Scholar Exalto LG, Whitmer RA, Kappele LJ, et al. Article CAS PubMed Google Scholar Chang CM, Hsieh CJ, Huang JC, et al.

Article PubMed Google Scholar Wardlaw JM, Smith C, Dichgans M. Article PubMed Google Scholar Cavalot F, Petrelli A, Traversa M, et al.

Article CAS PubMed Google Scholar Zoppini G, Verlato G, Targher G, et al. Article PubMed Google Scholar Murray AM, Hsu FC, Williamson JD, et al.

Article CAS PubMed Google Scholar Kirkman MS, Mahmud H, Korytkowski MT. Article Google Scholar Naor M, Steingrüber HJ, Westhoff K, et al. Article CAS Google Scholar Ryan CM, Freed MI, Rood JA, et al.

Article PubMed Google Scholar Peñaherrera-Oviedo C, Moreno-Zambrano D, Palacios M, et al. PubMed PubMed Central Google Scholar Stroup DF, Berlin JA, Morton SC, et al.

Article CAS PubMed Google Scholar Knobloch K, Yoon U, Vogt PM. Article PubMed Google Scholar Stang A. Article PubMed Google Scholar Folstein MF, Folstein SE, Mchugh PR. Article CAS PubMed Google Scholar Gurland B, Kuriansky J, Sharpe L, et al.

Article PubMed Google Scholar Da W. Google Scholar Schmidt M. Article CAS PubMed Google Scholar Houx PJ, Jolles J, Vreeling FW. Article CAS PubMed Google Scholar Silverstein AB. Article Google Scholar Egger M, Davey Smith G, Schneider M, et al. Article CAS PubMed PubMed Central Google Scholar Launer LJ, Miller ME, Williamson JD, et al.

Alex J. GravelingIan Fubction. DearyCognitivw M. Frier; Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes. Diabetes Care 1 October ; 36 10 : — Acute hypoglycemia impairs cognitive function in several domains. Aging gracefully 30, - By Erin Digitale. Sugr a continuous blood glucose monitor, which helps keep snd sugar levels in normal wugar, is associated with Enhance cognitive performance strategies performance on Blood sugar control and cognitive function tests, Stanford researchers and their colleagues have found. The study published online Aug. It is the most detailed study showing that brain structure and function can be improved in teens with diabetes via better control of blood sugar. The finding follows decades of evidence that better blood sugar control prevents long-term diabetes complications in other organs.