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Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction

The magnitude of type 2 diabetes mellitus (T2DM) is ever-increasing in India, and at present, ~77 million people live with diabetes. Studies have established that T2DM increases the risk of neurodegenerative disorders. This study aimed to determine the age-related prevalence of mild cognitive impair...

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Autores principales: Chakraborty, Arpita, Hegde, Sumukha, Praharaj, Samir K., Prabhu, Krishnananda, Patole, Chhaya, Shetty, Ashok K., Mayya, Shreemathi S., Acharya, Raviraj V., Hande, H. Manjunath, Prabhu, M. Mukhyaprana, Upadhya, Dinesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758578/
https://www.ncbi.nlm.nih.gov/pubmed/35035379
http://dx.doi.org/10.3389/fendo.2021.798652
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author Chakraborty, Arpita
Hegde, Sumukha
Praharaj, Samir K.
Prabhu, Krishnananda
Patole, Chhaya
Shetty, Ashok K.
Mayya, Shreemathi S.
Acharya, Raviraj V.
Hande, H. Manjunath
Prabhu, M. Mukhyaprana
Upadhya, Dinesh
author_facet Chakraborty, Arpita
Hegde, Sumukha
Praharaj, Samir K.
Prabhu, Krishnananda
Patole, Chhaya
Shetty, Ashok K.
Mayya, Shreemathi S.
Acharya, Raviraj V.
Hande, H. Manjunath
Prabhu, M. Mukhyaprana
Upadhya, Dinesh
author_sort Chakraborty, Arpita
collection PubMed
description The magnitude of type 2 diabetes mellitus (T2DM) is ever-increasing in India, and at present, ~77 million people live with diabetes. Studies have established that T2DM increases the risk of neurodegenerative disorders. This study aimed to determine the age-related prevalence of mild cognitive impairment (MCI) in T2DM patients in the Indian population and to identify link between cognitive dysfunction in T2DM patients and serum lipid composition through untargeted and targeted lipidomic studies. Using a cross-sectional study, we evaluated 1278 T2DM patients with Montreal cognitive assessment test (MoCA) and digit symbol substitution test (DSST) for cognitive functions. As per MoCA, the prevalences of MCI in T2DM patients in age groups below 40, 41-50, 51-60, 61-70, 71-80 and 81-90 years were 13.7, 20.5, 33.5, 43.7, 57.1 and 75% with DSST scores of 45.8, 41.7, 34.4, 30.5, 24.2 and 18.8% respectively. Binomial logistic regression analysis revealed serum HbA1c ≥ 7.51, duration of T2DM over 20 years, age above 41 years, and females were independent contributors for cognitive dysfunction in T2DM patients. Preliminary studies with untargeted lipidomics of the serum from 20 T2DM patients, including MCI and normal cognition (NC) group, identified a total of 646 lipids. Among the identified lipids, 33 lipids were significantly different between MCI and NC group, which comprised of triglycerides (TGs, 14), sphingolipids (SL, 11), and phosphatidylcholines (PC, 5). Importantly, 10 TGs and 3 PCs containing long-chain polyunsaturated fatty acids (PUFA) were lower, while 8 sphingolipids were increased in the MCI group. Since brain-derived sphingolipids are known to get enriched in the serum, we further quantified sphingolipids from the same 20 serum samples through targeted lipidomic analysis, which identified a total of 173 lipids. Quantitation revealed elevation of 3 species of ceramides, namely Cer (d18:1_24:1), Hex1Cer (d16:0_22:6), and Hex2Cer (d28:1) in the MCI group compared to the NC group of T2DM patients. Overall, this study demonstrated an age-related prevalence of MCI in T2DM patients and highlighted reduced levels of several species of PUFA containing TGs and PCs and increased levels of specific ceramides in T2DM patients exhibiting MCI. Large-scale lipidomic studies in future could help understand the cognitive dysfunction domain in T2DM patients, while studies with preclinical models are required to understand the functional significance of the identified lipids.
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spelling pubmed-87585782022-01-15 Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction Chakraborty, Arpita Hegde, Sumukha Praharaj, Samir K. Prabhu, Krishnananda Patole, Chhaya Shetty, Ashok K. Mayya, Shreemathi S. Acharya, Raviraj V. Hande, H. Manjunath Prabhu, M. Mukhyaprana Upadhya, Dinesh Front Endocrinol (Lausanne) Endocrinology The magnitude of type 2 diabetes mellitus (T2DM) is ever-increasing in India, and at present, ~77 million people live with diabetes. Studies have established that T2DM increases the risk of neurodegenerative disorders. This study aimed to determine the age-related prevalence of mild cognitive impairment (MCI) in T2DM patients in the Indian population and to identify link between cognitive dysfunction in T2DM patients and serum lipid composition through untargeted and targeted lipidomic studies. Using a cross-sectional study, we evaluated 1278 T2DM patients with Montreal cognitive assessment test (MoCA) and digit symbol substitution test (DSST) for cognitive functions. As per MoCA, the prevalences of MCI in T2DM patients in age groups below 40, 41-50, 51-60, 61-70, 71-80 and 81-90 years were 13.7, 20.5, 33.5, 43.7, 57.1 and 75% with DSST scores of 45.8, 41.7, 34.4, 30.5, 24.2 and 18.8% respectively. Binomial logistic regression analysis revealed serum HbA1c ≥ 7.51, duration of T2DM over 20 years, age above 41 years, and females were independent contributors for cognitive dysfunction in T2DM patients. Preliminary studies with untargeted lipidomics of the serum from 20 T2DM patients, including MCI and normal cognition (NC) group, identified a total of 646 lipids. Among the identified lipids, 33 lipids were significantly different between MCI and NC group, which comprised of triglycerides (TGs, 14), sphingolipids (SL, 11), and phosphatidylcholines (PC, 5). Importantly, 10 TGs and 3 PCs containing long-chain polyunsaturated fatty acids (PUFA) were lower, while 8 sphingolipids were increased in the MCI group. Since brain-derived sphingolipids are known to get enriched in the serum, we further quantified sphingolipids from the same 20 serum samples through targeted lipidomic analysis, which identified a total of 173 lipids. Quantitation revealed elevation of 3 species of ceramides, namely Cer (d18:1_24:1), Hex1Cer (d16:0_22:6), and Hex2Cer (d28:1) in the MCI group compared to the NC group of T2DM patients. Overall, this study demonstrated an age-related prevalence of MCI in T2DM patients and highlighted reduced levels of several species of PUFA containing TGs and PCs and increased levels of specific ceramides in T2DM patients exhibiting MCI. Large-scale lipidomic studies in future could help understand the cognitive dysfunction domain in T2DM patients, while studies with preclinical models are required to understand the functional significance of the identified lipids. Frontiers Media S.A. 2021-12-31 /pmc/articles/PMC8758578/ /pubmed/35035379 http://dx.doi.org/10.3389/fendo.2021.798652 Text en Copyright © 2021 Chakraborty, Hegde, Praharaj, Prabhu, Patole, Shetty, Mayya, Acharya, Hande, Prabhu and Upadhya https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Chakraborty, Arpita
Hegde, Sumukha
Praharaj, Samir K.
Prabhu, Krishnananda
Patole, Chhaya
Shetty, Ashok K.
Mayya, Shreemathi S.
Acharya, Raviraj V.
Hande, H. Manjunath
Prabhu, M. Mukhyaprana
Upadhya, Dinesh
Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction
title Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction
title_full Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction
title_fullStr Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction
title_full_unstemmed Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction
title_short Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction
title_sort age related prevalence of mild cognitive impairment in type 2 diabetes mellitus patients in the indian population and association of serum lipids with cognitive dysfunction
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8758578/
https://www.ncbi.nlm.nih.gov/pubmed/35035379
http://dx.doi.org/10.3389/fendo.2021.798652
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