Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial

2021 ◽  
pp. 1-11
Author(s):  
Roni Lotan ◽  
Ithamar Ganmore ◽  
Abigail Livny ◽  
Nofar Itzhaki ◽  
Mark Waserman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Pilot Trial ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Global Cognition

Background: Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. Objective: The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). Methods: The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. Results: At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. Conclusion: The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.

scholarly journals Long Term Dietary Restriction of Advanced Glycation End-Products (AGEs) in Older Adults with Type 2 Diabetes Is Feasible and Efficacious-Results from a Pilot RCT

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3143
Author(s):  
Roni Lotan ◽  
Ithamar Ganmore ◽  
Shahar Shelly ◽  
Moran Zacharia ◽  
Jaime Uribarri ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Adults ◽  
Advanced Glycation End Products ◽  
Dietary Intervention ◽  
Advanced Glycation ◽  
Increased Risk ◽  
Glycation End Products ◽  
End Products

Introduction: High serum concentrations of advanced glycation end-products (AGEs) in older adults and diabetics are associated with an increased risk of cognitive impairment. The aim of this pilot study was to assess the feasibility of long-term adherence to a dietary intervention designed to decrease intake and exposure to circulating AGEs among older adults with type 2 diabetes. Methods: Herein, 75 participants were randomized to either a standard of care (SOC) control arm or to an intervention arm receiving instruction on reducing dietary AGEs intake. The primary outcome was a change in serum AGEs at the end of the intervention. Secondary and exploratory outcomes included adherence to diet and its association with circulating AGEs. Cognitive function and brain imaging were also assessed but were out of the scope of this article (ClinicalTrials.gov Identifier: NCT02739971). Results: The intervention resulted in a significant change over time in several serum AGEs compared to the SOC guidelines. Very high adherence (above 80%) to the AGE-lowering diet was associated with a greater reduction in serum AGEs levels. There were no significant differences between the two arms in any other metabolic markers. Conclusions: A long-term dietary intervention to reduce circulating AGEs is feasible in older adults with type 2 diabetes, especially in those who are highly adherent to the AGE-lowering diet.

Levels of Receptor for Advanced Glycation End Products and Glyoxalase-1 in the Total Circulating Extracellular Vesicles from Mild Cognitive Impairment and Different Stages of Alzheimer’s Disease Patients

2021 ◽  
pp. 1-11
Author(s):  
Mohamed Haddad ◽  
Morgane Perrotte ◽  
Mohamed Raâfet Ben Khedher ◽  
Elise Madec ◽  
Aurelie Lepage ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Extracellular Vesicles ◽  
Advanced Glycation End Products ◽  
Neuronal Cells ◽  
Advanced Glycation ◽  
Glyoxalase 1 ◽  
Glycation End Products ◽  
End Products

Background: Growing evidence supports that receptor for advanced glycation end products (RAGE) and glyoxalase-1 (GLO-1) are implicated in the pathophysiology of Alzheimer’s disease (AD). Extracellular vesicles (EVs) are nanovesicles secreted by almost all cell types, contribute to cellular communication, and are implicated in AD pathology. Recently, EVs are considered as promising tools to identify reliable biomarkers in AD. Objective: The aim of our study was to determine the levels of RAGE and GLO-1 in circulating EVs from mild cognitive impairment (MCI) and AD patients and to analyze their correlation with the clinical Mini-Mental State Examination and Montreal Cognitive Assessment scores. We have studied the possibility that neuronal cells could release and transfer GLO-1 through EVs. Methods: RAGE and GLO-1 levels were measured in circulating EVs, respectively, by Luminex assay and western blot. Released-EVs from SK-N-SH neuronal cells were isolated and GLO-1 levels were determined by western bot. Results: Our data showed higher levels of RAGE in EVs from late AD patients while GLO-1 levels in EVs from early AD were lower as compared to control and MCI patients. Interestingly, levels of RAGE and GLO-1 in EVs were correlated with the cognitive scores regardless of age. For the first time, we demonstrated that GLO-1 was released from neuronal cells through EVs. Conclusion: Although more samples will be needed, our preliminary results support the use of peripheral EVs cargo as new tools for the discovery of peripheral AD biomarkers.

scholarly journals Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications

2004 ◽  
Vol 5 (2) ◽  
pp. 163-169 ◽  
Author(s):  
A. E. Buchs ◽  
A. Kornberg ◽  
M. Zahavi ◽  
D. Aharoni ◽  
C. Zarfati ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Advanced Glycation End Products ◽  
Mononuclear Cells ◽  
Vascular Complications ◽  
Advanced Glycation ◽  
Peripheral Blood Mononuclear ◽  
Glycation End Products ◽  
End Products ◽  
Blood Mononuclear Cells

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P= .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29 in patients with complications and 0.21 ± 0.18 in patients without complications (P= .003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/106PBMCs) was 18.4 ± 13.2 in patients with complications and 6.96 ± 5.2 in patients without complications (P= .003). It increased 3-fold in both groups after stimulation (P= .001). TF antigen (pg/106PBMCs) was 33.7 ± 28.6 in patients with complications, 10.4 ± 7.8 in patients without complications (P= .02). Stimulation tripled TF antigen in both groups of patients (P= .001). The RAGE/TF axis is up-regulated inT2Dpatients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.

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