Short-Term Effects of Metformin and Diabetic Diet on Cognitive Functions in Newly Diagnosed Type 2 Diabetes Mellitus Patients

Year 2020, Volume: 4 Issue: 3, 150 - 157, 31.12.2020

Ceyda Tanoğlu , Yıldız Kaya , Ülkü Sibel Benli , Neslihan Başçıl Tütüncü

Abstract

Objective: We aimed to investigate the effects of metformin or dietary treatment on cognitive functions in newly diagnosed Type 2 Diabetes Mellitus patients.
Materials and Methods: Our study was designed prospective. The study included 64 healthy controls and 72 newly diagnosed Type 2 Diabetes Mellitus patients. Metformin treatment for thirty-seven patients and dietary treatment for thirty-five patients were administered by a single endocrinologist. Rey Auditory Verbal Learning Test, Rey Complex Figure Test, Digit Span Test and Trail Making Test for all patients were performed at the time of diagnosis and at the sixth- month of the treatment by a blinded neurologist.
Results: At the time of diagnosis, we observed that verbal memory scores in the diabetes group were significantly lower than healthy controls (p= 0.03 in dietary, p= 0.044 in metformin group). Sixth- month evaluation revealed that dietary treatment improved only immediate verbal memory scores (p= 0.041). Metformin treatment, along with verbal memory scores, also significantly improved visual spatial memory (p = 0.014) and processing memory and executive functions (p = 0.036 and p = 0.001).
Conclusion: We determined a statistically significant improvement in verbal memory, visual spatial memory and processing speed & executive function scores with metformin treatment, while dietary treatment improved only verbal memory scores.

Keywords

diabetes mellitus, metformin, trail making test, neuropsychological tests

Yeni Tanı Tip 2 Diabetes Mellitus Hastalarında Metformin ve Diabetik Diyetin Bilişsel Fonksiyonlara Kısa Dönem Etkisi

Abstract

Amaç: Çalışmamızda yeni tanı konmuş Tip 2 Diabetes Mellitus hastalarında metformin veya diyet tedavisinin bilişsel işlevler üzerindeki etkilerini araştırmayı amaçladık.
Gereç ve Yöntem: Çalışmamız prospektif olarak tasarlandı. Çalışmaya 64 sağlıklı kontrol ve 72 yeni tanı Tip 2 Diabetes Mellitus hastası dahil edildi. Otuz yedi hasta için metformin tedavisi ve otuz beş hasta için diyet tedavisi tek bir endokrinolog tarafından başlandı. Tüm hastalar için Rey İşitsel Sözel Öğrenme Testi, Rey Kompleks Figur Testi, Sayı Dizisi Testi ve İz Sürme Testi, tanı anında ve tedavinin altıncı ayında tedaviye kör bir nörolog tarafından yapıldı.
Bulgular: Sözel bellek skorlarının tanı anında diyabet grubunda sağlıklı kontrollerden anlamlı derecede düşük olduğunu gözlemledik (diyet p = 0.03, metformin p = 0.044). Altıncı ay değerlendirilmesinde diyet tedavisinin sadece anlık sözel bellek skorlarını anlamlı iyileştirdiği görüldü (p = 0,041). Metformin tedavisi sözel bellek skorları ile beraber ayrıca görsel uzamsal belleği (p = 0.014) ve işlem belleği ve yürütücü fonksiyonları (p = 0.036 ve p = 0.001) anlamlı iyileştirmişti.
Sonuç: Yeni tanı alan Tip 2 Diyabetes Mellitus hastalarında metformin tedavisi ile sözel bellek, görsel uzamsal bellek ve işleme hızı ve yürütücü işlev skorlarında istatistiksel olarak anlamlı bir iyileşme tespit ederken, diyet tedavisi sadece sözel bellek skorlarını iyileştirdi.

Keywords

Diabetes Mellitus, Metformin, İz sürme testi, Nöropsikolojik test

References

• 1. Songer T.J , Zimmet P.Z., Epidemiology of type II diabetes: an international perspective, Pharmacoeconomics 1995; 8: Suppl 1, 1-11.
• 2. Gispen W. H. , Biessels G.J. , Cognition and synaptic plasticity in diabetes mellitus, Trends Neurosci 2000; 23 (11), 542-549.
• 3. Nandipati S. , et al. Cognition in non-demented diabetic older adults, Curr. Aging Sci. 2012; 5(2), 131-135.
• 4. Saczynski J.S. , et al. Cognitive impairment: an increasingly important complication of type 2 diabetes: the age, gene/environment susceptibility--Reykjavik study, Am. J. Epidemiol. 2008; 168(10), 1132-1139.
• 5. Qiu C. , et al. Diabetes, markers of brain pathology and cognitive function: the Age, Gene/Environment Susceptibility-Reykjavik Study, Ann Neurol 2014; 75(1), 138-146.
• 6. Kloppenborg R.P. , et al. Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review, Eur. J. Pharmacol 2008; 585(1), 97-108.
• 7. Kroner Z. , The relationship between Alzheimer's disease and diabetes: Type 3 diabetes?,Altern Med Rev 2009; 14(4), 373-379.
• 8. de la Monte S.M , et al., Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer's disease, J Alzheimers Dis 2006; 10(1), 89-109.
• 9. Herath P.M. , et al., The Effect of Diabetes Medication on Cognitive Function: Evidence from the PATH Through Life Study, Biomed Res Int. 2016, 7208429. 10. Sims-Robinson C. , et al, How does diabetes accelerate Alzheimer disease pathology?, Nat. Rev. Neurol. 2010; 6(10), 551-559.
• 11. Rivera E.J. , et al., Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine, J Alzheimers Dis. 2005; 8(3), 247-268.
• 12. Biessels G.J. , et al., Risk of dementia in diabetes mellitus: a systematic review, Lancet Neurol. 2006; 5(1), 64-74.
• 13. Cheng C. , et al., Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis, J Gerontol A-Biol. 2014; 69(10), 1299-1305.
• 14. Bozoki A. , et al., Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss, Arch. Neurol. 2001; 58(3), 411-416.
• 15. Brookmeyer R. , et al., Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset, Am. J. Public Health 1998; 88(9), 1337-1342.
• 16. Kirpichnikov D. , et al., Metformin: an update, Ann. Intern. Med. 2002; 137(1), 25-33.
• 17. Adak T. , et al., A reappraisal on metformin, Regul. Toxicol. Pharmacol. 2018; 92, 324-332.
• 18. Ng T.P. , et al., Long-term metformin usage and cognitive function among older adults with diabetes, J Alzheimers Dis. 2014; 41(1), 61-68.
• 19. Kickstein E. , et al., Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling, Proc. Natl. Acad. Sci. U. S. A. 2010; 107(50), 21830-2185.
• 20. Wang J. , et al., Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation, Cell stem cell 2012; 11(1), 23-35.
• 21. Chen F. , et al., Antidiabetic drugs restore abnormal transport of amyloid-beta across the blood-brain barrier and memory impairment in db/db mice, Neuropharmacology 2016; 101, 123-136.
• 22. Taylor M.K. , et al., A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults, Am J Clin Nutr. 2017; 106(6), 1463-1470.
• 23. Dong W. , et al., Influence of age-related learning and memory capacity of mice: different effects of a high and low caloric diet, Aging Clin Exp Res 2016; 28(2), 303-311.
• 24. Garber A. , et al., Association between glycemic load and cognitive function in community-dwelling older adults: Results from the Brain in Motion study, Clin Nutr. 2018; 37(5), 1690-1699.
• 25. Cheatham R.A., et al, Long-term effects of provided low and high glycemic load low energy diets on mood and cognition, Physiol Behav. 2009; 98(3), 374-379.
• 26. AbbatecolaA.M. , et al., Rosiglitazone and cognitive stability in older individuals with type 2 diabetes and mild cognitive impairment, Diabetes care, 2010, 33(8), 1706-1711.
• 27. Wennberg A.M.V., et al., Association of antidiabetic medication use, cognitive decline, and risk of cognitive impairment in older people with type 2 diabetes: Results from the population-based Mayo Clinic Study of Aging, Int J Geriatr Psych. 2018; 33(8), 1114-1120.
• 28. Mahler R.J. , Adler M.L. , Clinical review 102: Type 2 diabetes mellitus: update on diagnosis, pathophysiology, and treatment, J Clin Endocrinol Metab. 1999; 84(4), 1165-1171.
• 29. Lezak M. , Neuropsychological testing, University Press, Oxford, 1995.
• 30. Boone K.B. , et al., Rey-Osterrieth Complex Figure performance in healthy, older adults: Relationship to age, education, sex, and IQ, The Clinical Neuropsychologist 1993; 7(1), 22-28.
• 31. Hale J.B. , et al. Analyzing digit span components for assessment of attention processes, J. Psychoeduc. Assess. 2002; 20(2), 128-143.
• 32. King H. , et al., Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections, Diabetes care 1998; 21(9), 1414-1431.
• 33. Gupta A. , et al., Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer's-like changes, Neuropharmacology 2011; 60(6), 910-920.
• 34. Koenig A.M. , et al., Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study, Alz Dis Assoc Dis. 2017; 31(2), 107-113.
• 35. Chen Y., et al., Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, P Natl Acad Sci USA. 2009; 106(10), 3907-3912.
• 36. Thangthaeng N., et al., Metformin Impairs Spatial Memory and Visual Acuity in Old Male Mice, Aging Dis. 2017; 8(1), 17-30.
• 37. Imfeld P., et al., Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study, J Am Geriatr Soc. 2012; 60(5), 916-921.
• 38. Kuan Y.C., et al., Effects of metformin exposure on neurodegenerative diseases in elderly patients with type 2 diabetes mellitus, Prog Neuro-Psychoph. 2017; 79(Pt B), 77-83.
• 39. Moore E.M., et al., Increased risk of cognitive impairment in patients with diabetes is associated with metformin, Diabetes care 2013; 36(10), 2981-2987.