TİP 2 DİYABETLİ HASTALARDA IL-6 DÜZEYLERİ VE KOGNİTİF KOMPLİKASYONLAR: KESİTSEL BİR ÇALIŞMA
Year 2024,
Volume: 48 Issue: 3, 1033 - 1040, 10.09.2024
Hümeyra İvecek
,
Abdüsselam Şekerci
,
Betül Sümbül Şekerci
Abstract
Amaç: Tip 2 diyabette (T2DM) önemli mortalite ve morbidite nedenleri olan makrovasküler ve mikrovasküler komplikasyonların izlenmesi ve yönetilmesi önemlidir. Diyabetle ilişkili kognitif bozukluk son dönemler daha fazla dikkat çeken önemli bir komplikasyondur, ancak patofizyolojisi ve klinik özellikleri net olarak bilinmemektedir. Bu çalışmanın amacı diyabetle ilişkili kognitif bozuklukta inflamasyonun potansiyel rolünü değerlendirmektir.
Gereç ve Yöntem: Bu kesitsel gözlemsel klinik çalışmaya toplam 122 katılımcı (67 T2DM hastası ve 55 kontrol) dahil edilmiştir. Bilişsel performans Montreal Kognitif Değerlendirme (MoCA) testi kullanılarak değerlendirilmiştir. IL-6 düzeyleri katılımcılardan alınan kan örneklerinde ELISA yöntemi kullanılarak ölçülmüştür.
Sonuç ve Tartışma: IL-6 düzeyleri diyabet ve bilişsel bozuklukla birlikte artmasına rağmen, gruplar arasında anlamlı bir fark yoktu (p>0.05). Dikkat ve oryantasyon dışında, T2DM hastalarında kognitif performansın anlamlı olarak daha fazla bozulduğunu gözlemledik. MoCA toplam skoru yaş, eğitim düzeyi, açlık glukozu, HbA1c ve D vitamini düzeyleri ile anlamlı korelasyon gösterdi (p<0.05) Sonuçlarımız IL-6'nın T2DM'de kognitif bozukluğun patofizyolojisinde rol oynadığına dair bir kanıt bulmadı dakat bu bulgular diyabetle ilişkili komplikasyonların izlenmesinde kognitif taramanın önemini vurgulamaktadır.
Project Number
grant numbers: 1919B012224507
References
- 1. Tripathi, B.K., Srivastava, A.K. (2006). Diabetes mellitus: Complications and therapeutics. Medical Science Monitor, 12, 130-147.
- 2. Sami, W., Ansari, T., Butt, N.S., Hamid, M.R.A. (2017). Effect of diet on type 2 diabetes mellitus: A review. International Journal of Health Sciences (Qassim,) 11, 65-71.
- 3. Izzo, A., Massimino, E., Riccardi, G., Della Pepa G. (2021). A narrative review on sarcopenia in type 2 diabetes mellitus: Prevalence and associated factors. Nutrients 13(1), 183. [CrossRef]
- 4. Litwak, L., Goh, S.Y., Hussein, Z., Malek, R., Prusty, V., Khamseh, M.E. (2013). Prevalence of diabetes complications in people with type 2 diabetes mellitus and its association with baseline characteristics in the multinational A1chieve study. Diabetology & Metabolic Syndrome, 5, 57. [CrossRef]
- 5. Hardigan, T., Ward, R., Ergul, A. (2016). Cerebrovascular complications of diabetes: Focus on cognitive dysfunction. Clinical Science (Lond), 130, 1807-1822. [CrossRef]
- 6. Cukierman-Yaffe, T., Gerstein, H.C., Colhoun, H.M., Diaz, R., García-Pérez, L.E., Lakshmanan, M,. Bethel, A., Xavier, D., Probstfield, J., Riddle, M.C., Rydén, L., Atisso, C.M., Hall, S., Rao-Melacini, P., Basile, J., Cushman, W.C., Franek, E., Keltai, M., Lanas, F., Leiter, L.A., Lopez-Jaramillo, P., Pirags, V., Pogosova, N., Raubenheimer, P.J., Shaw, J.E., Sheu, W.H., Temelkova-Kurktschiev, T. (2020). Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial. Lancet Neurology, 19, 582-590. [CrossRef]
- 7. Qiu, C., Sigurdsson, S., Zhang, Q., Jonsdottir, M.K., Kjartansson, O., Eiriksdottir, G., Garcia, M.E., Harris, T.B., van Buchem, M.A., Gudnason, V., Launer, L.J. (2014). Diabetes, markers of brain pathology and cognitive function: The Age, Gene/Environment Susceptibility-Reykjavik Study. Annual Neurology, 75, 138-146. [CrossRef]
- 8. Profenno, L.A., Porsteinsson, A.P., Faraone, S.V. (2010). Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biological Psychiatry 67, 505-512. [CrossRef]
- 9. Dybjer, E., Nilsson, P.M., Engström, G., Helmer, C., Nägga, K. (2018). Pre-diabetes and diabetes are independently associated with adverse cognitive test results: a cross-sectional, population-based study. BMC Endocrinology Disorder, 18, 91. [CrossRef]
- 10. Tangestani Fard, M., Stough, C. (2019). A review and hypothesized model of the mechanisms that underpin the relationship between inflammation and cognition in the elderly. Frontiers Aging Neuroscience, 11, 56. [CrossRef]
- 11. Ehtewish, H., Arredouani, A., El-Agnaf, O. (2022). Diagnostic, prognostic, and mechanistic biomarkers of diabetes mellitus-associated cognitive decline. International Journal of Molecular Sciences, 23(11), 6144. [CrossRef]
- 12. Rehman, K., Akash, M.S.H., Liaqat, A., Kamal, S., Qadir, M.I., Rasul, A. (2017). Role of Interleukin-6 in development of insulin resistance and type 2 diabetes mellitus. Critical Reviews in Eukaryotic Gene Expression, 27, 229-236. [CrossRef]
- 13. Kipinoinen, T., Toppala, S., Rinne, J.O., Viitanen, M.H., Jula, A.M., Ekblad, L.L. (2022.). Association of midlife inflammatory markers with cognitive performance at 10-year follow-up. Neurology 99, e2294-e2302. [CrossRef]
- 14. Nasreddine, Z.S., Phillips, N.A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J.L., Chertkow, H. (2005.) The montreal cognitive assessment, moca: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53, 695-699. [CrossRef]
- 15. Ozdilek, B., Kenangil, G. (2014). Validation of the turkish version of the montreal cognitive assessment scale (moca-tr) in patients with parkinson's disease. Clinical Neuropsychology, 28, 333-343. [CrossRef]
- 16. Bashir, H., Ahmad Bhat, S., Majid, S., Hamid, R., Koul, R.K., Rehman, M.U., Din, I., Ahmad Bhat, J., Qadir, J., Masood, A. (2020). Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Medical Journal of the Islamic Republic of Iran, 34, 5. [CrossRef]
- 17. Goldberg, R.B. (2009). Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. Journal of Clinical Endocrinology Metabolism, 94, 3171-3182. [CrossRef]
- 18. Launer, L.J. (2020). Interrelationships among central insulin signalling, diabetes, and cognitive impairment. Lancet Neurology, 19, 640-642. [CrossRef]
- 19. Chung, C.C., Pimentel, D., Jordan, A.J., Hao, Y., Milberg, W., Novak, V. (2015). Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology 85, 450-458. [CrossRef]
- 20. Leonardo, S., Fregni, F.. (2023). Association of inflammation and cognition in the elderly: A systematic review and meta-analysis. Frontiers in Aging Neuroscience, 15, 1069439. [CrossRef]
- 21. Yang, X., Chen, Y., Zhang, W., Zhang, Z., Yang, X., Wang, P., Yuan, H. (2020). Association between inflammatory biomarkers and cognitive dysfunction analyzed by MRI in diabetes patients. Diabetes Metabolic Syndrome and Obesity, 13, 4059-4065. [CrossRef]
- 22. Zheng, M., Chang, B., Tian, L., Shan, C., Chen, H., Gao, Y., Huang, G., Zhang, M. (2019). Relationship between inflammatory markers and mild cognitive impairment in Chinese patients with type 2 diabetes: A case-control study. BMC Endocrinology Disorder, 19, 73. [CrossRef]
- 23. Dyer, A.H., McKenna, L., Batten, I., Jones, K., Widdowson, M., Dunne, J., Conlon, N., Reilly, R., Woods, C.P., O’Neill, D., Gibney, J., Bourke, N.M., Kennelly, SP. (2020). Peripheral inflammation and cognitive performance in middle-aged adults with and without type 2 diabetes: Results from the ENBIND study. Frontiers Aging Neuroscience, 12, 605878. [CrossRef]
- 24. Groeneveld, O.N., van den Berg, E., Johansen, O.E., Schnaidt, S., Hermansson, K., Zinman, B., Espeland, M.A., Biessels, G.J. (2019). Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes. Diabetes and Vascular Disease Research, 16, 577-581. [CrossRef]
- 25. Moulton, C.D., Stewart, R., Amiel, S.A., Laake, J.P., Ismail, K. (2016). Factors associated with cognitive impairment in patients with newly diagnosed type 2 diabetes: A cross-sectional study. Aging Mental Health, 20, 840-847. [CrossRef]
- 26. Sluiman, A.J., McLachlan, S., Forster, R.B., Strachan, M.W.J., Deary, I.J., Price, J.F. (2022). Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes: Year 10 follow-up of the Edinburgh Type 2 Diabetes Study. Diabetologia 65, 467-476. [CrossRef]
- 27. Biessels, G.J., Despa, F. (2018). Cognitive decline and dementia in diabetes mellitus: Mechanisms and clinical implications. Nature Reviews Endocrinology, 14, 591-604. [CrossRef]
- 28. Biessels, G.J., Whitmer, R.A. (2020). Cognitive dysfunction in diabetes: How to implement emerging guidelines. Diabetologia, 63, 3-9. [CrossRef]
- 29. Garczorz, W., Gallego-Colon, E., Kosowska, A., Kłych-Ratuszny, A., Woźniak, M., Marcol, W., Niesner, K.J., Francuz, T. (2018). Exenatide exhibits anti-inflammatory properties and modulates endothelial response to tumor necrosis factor α-mediated activation. Cardiovascular Therapeutics, 36 (2). [CrossRef]
- 30. Luna-Marco, C., de Marañon, A.M., Hermo-Argibay, A., Rodriguez-Hernandez, Y., Hermenejildo, J., Fernandez-Reyes, M., Apostolova, N., Vila, J., Sola, E., Morillas, C., Rovira-Llopis, S., Rocha, M., Victor, V.M. (2023). Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes. Redox Biology, 66, 102849. [CrossRef]
- 31. Lund, S.S., Tarnow, L., Stehouwer, C.D., Schalkwijk, C.G., Teerlink, T., Gram, J., Winther, K., Frandsen, M., Smidt, U.M., Pedersen, O., Parving, H.H., Vaag, A.A. (2008). Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. European Journal of Endocrinology, 158, 631-641. [CrossRef]
IL-6 LEVELS AND COGNITIVE COMPLICATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A CROSS SECTIONAL STUDY
Year 2024,
Volume: 48 Issue: 3, 1033 - 1040, 10.09.2024
Hümeyra İvecek
,
Abdüsselam Şekerci
,
Betül Sümbül Şekerci
Abstract
Objective: It is important to monitor and manage macrovascular and microvascular complications, which are significant causes of mortality and morbidity in type 2 diabetes (T2DM). Diabetes-related cognitive impairment is an important complication that has recently attracted more attention, but its pathophysiology and clinical features are not known. The aim of this study was to evaluate the potential role of inflammation in diabetes-related cognitive impairment.
Material and Method: A total of 122 participants (67 patients with T2DM and 55 controls) took part in this cross-sectional observational clinical study. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. IL-6 levels were measured using the ELISA method on blood samples obtained from the participants.
Result and Discussion: Although IL-6 levels increased with diabetes and cognitive impairment, there was no significant difference between the groups (p>0.05). Except for attention and orientation, we observed significantly more impaired cognitive performance in T2DM patients. The MoCA total score was significantly correlated with age, education level, fasting glucose, HbA1c, and vitamin D levels (p<0.05). Our results found no evidence that IL-6 is involved in the pathophysiology of cognitive impairment in T2DM, but these findings the importance of cognitive screening in monitoring complications associated with diabetes.
Ethical Statement
The studies involving human participants were reviewed and approved by Bezmialem Vakif University Clinical Research Ethics Committee (05.04.2023/07-2)
Supporting Institution
Tubitak 2209-A Research Project Support Programme for Undergraduate Students
Project Number
grant numbers: 1919B012224507
References
- 1. Tripathi, B.K., Srivastava, A.K. (2006). Diabetes mellitus: Complications and therapeutics. Medical Science Monitor, 12, 130-147.
- 2. Sami, W., Ansari, T., Butt, N.S., Hamid, M.R.A. (2017). Effect of diet on type 2 diabetes mellitus: A review. International Journal of Health Sciences (Qassim,) 11, 65-71.
- 3. Izzo, A., Massimino, E., Riccardi, G., Della Pepa G. (2021). A narrative review on sarcopenia in type 2 diabetes mellitus: Prevalence and associated factors. Nutrients 13(1), 183. [CrossRef]
- 4. Litwak, L., Goh, S.Y., Hussein, Z., Malek, R., Prusty, V., Khamseh, M.E. (2013). Prevalence of diabetes complications in people with type 2 diabetes mellitus and its association with baseline characteristics in the multinational A1chieve study. Diabetology & Metabolic Syndrome, 5, 57. [CrossRef]
- 5. Hardigan, T., Ward, R., Ergul, A. (2016). Cerebrovascular complications of diabetes: Focus on cognitive dysfunction. Clinical Science (Lond), 130, 1807-1822. [CrossRef]
- 6. Cukierman-Yaffe, T., Gerstein, H.C., Colhoun, H.M., Diaz, R., García-Pérez, L.E., Lakshmanan, M,. Bethel, A., Xavier, D., Probstfield, J., Riddle, M.C., Rydén, L., Atisso, C.M., Hall, S., Rao-Melacini, P., Basile, J., Cushman, W.C., Franek, E., Keltai, M., Lanas, F., Leiter, L.A., Lopez-Jaramillo, P., Pirags, V., Pogosova, N., Raubenheimer, P.J., Shaw, J.E., Sheu, W.H., Temelkova-Kurktschiev, T. (2020). Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial. Lancet Neurology, 19, 582-590. [CrossRef]
- 7. Qiu, C., Sigurdsson, S., Zhang, Q., Jonsdottir, M.K., Kjartansson, O., Eiriksdottir, G., Garcia, M.E., Harris, T.B., van Buchem, M.A., Gudnason, V., Launer, L.J. (2014). Diabetes, markers of brain pathology and cognitive function: The Age, Gene/Environment Susceptibility-Reykjavik Study. Annual Neurology, 75, 138-146. [CrossRef]
- 8. Profenno, L.A., Porsteinsson, A.P., Faraone, S.V. (2010). Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biological Psychiatry 67, 505-512. [CrossRef]
- 9. Dybjer, E., Nilsson, P.M., Engström, G., Helmer, C., Nägga, K. (2018). Pre-diabetes and diabetes are independently associated with adverse cognitive test results: a cross-sectional, population-based study. BMC Endocrinology Disorder, 18, 91. [CrossRef]
- 10. Tangestani Fard, M., Stough, C. (2019). A review and hypothesized model of the mechanisms that underpin the relationship between inflammation and cognition in the elderly. Frontiers Aging Neuroscience, 11, 56. [CrossRef]
- 11. Ehtewish, H., Arredouani, A., El-Agnaf, O. (2022). Diagnostic, prognostic, and mechanistic biomarkers of diabetes mellitus-associated cognitive decline. International Journal of Molecular Sciences, 23(11), 6144. [CrossRef]
- 12. Rehman, K., Akash, M.S.H., Liaqat, A., Kamal, S., Qadir, M.I., Rasul, A. (2017). Role of Interleukin-6 in development of insulin resistance and type 2 diabetes mellitus. Critical Reviews in Eukaryotic Gene Expression, 27, 229-236. [CrossRef]
- 13. Kipinoinen, T., Toppala, S., Rinne, J.O., Viitanen, M.H., Jula, A.M., Ekblad, L.L. (2022.). Association of midlife inflammatory markers with cognitive performance at 10-year follow-up. Neurology 99, e2294-e2302. [CrossRef]
- 14. Nasreddine, Z.S., Phillips, N.A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., Cummings, J.L., Chertkow, H. (2005.) The montreal cognitive assessment, moca: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53, 695-699. [CrossRef]
- 15. Ozdilek, B., Kenangil, G. (2014). Validation of the turkish version of the montreal cognitive assessment scale (moca-tr) in patients with parkinson's disease. Clinical Neuropsychology, 28, 333-343. [CrossRef]
- 16. Bashir, H., Ahmad Bhat, S., Majid, S., Hamid, R., Koul, R.K., Rehman, M.U., Din, I., Ahmad Bhat, J., Qadir, J., Masood, A. (2020). Role of inflammatory mediators (TNF-α, IL-6, CRP), biochemical and hematological parameters in type 2 diabetes mellitus patients of Kashmir, India. Medical Journal of the Islamic Republic of Iran, 34, 5. [CrossRef]
- 17. Goldberg, R.B. (2009). Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. Journal of Clinical Endocrinology Metabolism, 94, 3171-3182. [CrossRef]
- 18. Launer, L.J. (2020). Interrelationships among central insulin signalling, diabetes, and cognitive impairment. Lancet Neurology, 19, 640-642. [CrossRef]
- 19. Chung, C.C., Pimentel, D., Jordan, A.J., Hao, Y., Milberg, W., Novak, V. (2015). Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes. Neurology 85, 450-458. [CrossRef]
- 20. Leonardo, S., Fregni, F.. (2023). Association of inflammation and cognition in the elderly: A systematic review and meta-analysis. Frontiers in Aging Neuroscience, 15, 1069439. [CrossRef]
- 21. Yang, X., Chen, Y., Zhang, W., Zhang, Z., Yang, X., Wang, P., Yuan, H. (2020). Association between inflammatory biomarkers and cognitive dysfunction analyzed by MRI in diabetes patients. Diabetes Metabolic Syndrome and Obesity, 13, 4059-4065. [CrossRef]
- 22. Zheng, M., Chang, B., Tian, L., Shan, C., Chen, H., Gao, Y., Huang, G., Zhang, M. (2019). Relationship between inflammatory markers and mild cognitive impairment in Chinese patients with type 2 diabetes: A case-control study. BMC Endocrinology Disorder, 19, 73. [CrossRef]
- 23. Dyer, A.H., McKenna, L., Batten, I., Jones, K., Widdowson, M., Dunne, J., Conlon, N., Reilly, R., Woods, C.P., O’Neill, D., Gibney, J., Bourke, N.M., Kennelly, SP. (2020). Peripheral inflammation and cognitive performance in middle-aged adults with and without type 2 diabetes: Results from the ENBIND study. Frontiers Aging Neuroscience, 12, 605878. [CrossRef]
- 24. Groeneveld, O.N., van den Berg, E., Johansen, O.E., Schnaidt, S., Hermansson, K., Zinman, B., Espeland, M.A., Biessels, G.J. (2019). Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes. Diabetes and Vascular Disease Research, 16, 577-581. [CrossRef]
- 25. Moulton, C.D., Stewart, R., Amiel, S.A., Laake, J.P., Ismail, K. (2016). Factors associated with cognitive impairment in patients with newly diagnosed type 2 diabetes: A cross-sectional study. Aging Mental Health, 20, 840-847. [CrossRef]
- 26. Sluiman, A.J., McLachlan, S., Forster, R.B., Strachan, M.W.J., Deary, I.J., Price, J.F. (2022). Higher baseline inflammatory marker levels predict greater cognitive decline in older people with type 2 diabetes: Year 10 follow-up of the Edinburgh Type 2 Diabetes Study. Diabetologia 65, 467-476. [CrossRef]
- 27. Biessels, G.J., Despa, F. (2018). Cognitive decline and dementia in diabetes mellitus: Mechanisms and clinical implications. Nature Reviews Endocrinology, 14, 591-604. [CrossRef]
- 28. Biessels, G.J., Whitmer, R.A. (2020). Cognitive dysfunction in diabetes: How to implement emerging guidelines. Diabetologia, 63, 3-9. [CrossRef]
- 29. Garczorz, W., Gallego-Colon, E., Kosowska, A., Kłych-Ratuszny, A., Woźniak, M., Marcol, W., Niesner, K.J., Francuz, T. (2018). Exenatide exhibits anti-inflammatory properties and modulates endothelial response to tumor necrosis factor α-mediated activation. Cardiovascular Therapeutics, 36 (2). [CrossRef]
- 30. Luna-Marco, C., de Marañon, A.M., Hermo-Argibay, A., Rodriguez-Hernandez, Y., Hermenejildo, J., Fernandez-Reyes, M., Apostolova, N., Vila, J., Sola, E., Morillas, C., Rovira-Llopis, S., Rocha, M., Victor, V.M. (2023). Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes. Redox Biology, 66, 102849. [CrossRef]
- 31. Lund, S.S., Tarnow, L., Stehouwer, C.D., Schalkwijk, C.G., Teerlink, T., Gram, J., Winther, K., Frandsen, M., Smidt, U.M., Pedersen, O., Parving, H.H., Vaag, A.A. (2008). Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes. European Journal of Endocrinology, 158, 631-641. [CrossRef]