Gerontology

Clinical Section: Research Article

The Association between Antidiabetic Agents and Leukocyte Telomere Length in the Novel Classification of Type 2 Diabetes Mellitus

Huang J. · Peng X. · Dong K. · Tao J. · Yang Y.

Author affiliations

Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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Gerontology 2021;67:60–68

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Article / Publication Details

First-Page Preview
Abstract of Clinical Section: Research Article

Received: July 13, 2020
Accepted: September 05, 2020
Published online: December 15, 2020
Issue release date: January 2021

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 3

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: https://www.karger.com/GER

Abstract

Aims: This study aimed to explore the new role of telomere length (TL) in the novel classification of type 2 diabetes mellitus (T2DM) patients driven by cluster analysis. Materials and Methods: A total of 541 T2DM patients were divided into 4 subgroups by k-means analysis: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), and mild age-related diabetes (MARD). After patients with insufficient data were excluded, further analysis was conducted on 246 T2DM patients. The TL was detected using telomere restriction fragment, and the related diabetic indexes were also measured by clinical standard procedures. Results: The MARD group had significantly shorter TLs than the MOD and SIDD groups. Then, we subdivided all T2DM patients into the MARD and NONMARD groups, which included the MOD, SIDD, and SIRD groups. The TLs of the MARD group, associated with age, were discovered to be significantly shorter than those of the NONMARD group (p = 0.0012), and this difference in TL disappeared after metformin (p = 0.880) and acarbose treatment (p = 0.058). The linear analysis showed that metformin can more obviously reduce telomere shortening in the MARD group (r = 0.030, 95% CI 0.010–0.051, p = 0.004), and acarbose can more apparently promote telomere attrition in the SIRD group (r = –0.069, 95% CI –0.100 to –0.039, p< 0.001) compared with other T2DM patients after adjusting for age and gender. Conclusions: The MARD group was found to have shorter TLs and benefit more from the antiaging effect of metformin than other T2DM. Shorter TLs were observed in the SIRD group after acarbose use.

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References

  1. International Diabetes Federation. IDF Diabetes Atlas. 9th ed. Brussels: International Diabetes Federation; 2019.
  2. Ahlqvist E, Storm P, Käräjämäki A, Martinell M, Dorkhan M, Carlsson A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018 May;6(5):361–9.
  3. Zou X, Zhou X, Zhu Z, Ji L. Novel subgroups of patients with adult-onset diabetes in Chinese and US populations. Lancet Diabetes Endocrinol. 2019 Jan;7(1):9–11.
  4. Shampay J, Blackburn EH. Tetrahymena micronuclear sequences that function as telomeres in yeast. Nucleic Acids Res. 1989 Apr;17(8):3247–60.
  5. Sanchez M, Hoang S, Kannengiesser C, Potier L, Hadjadj S, Marre M, et al. Leukocyte Telomere Length, DNA Oxidation, and Risk of Lower-Extremity Amputation in Patients With Long-standing Type 1 Diabetes. Diabetes Care. 2020 Apr;43(4):828–34.
  6. Mitteldorf JJ. Telomere biology: cancer firewall or aging clock? Biochemistry (Mosc). 2013 Sep;78(9):1054–60.
  7. Liu M, Huo YR, Wang J, Wang C, Liu S, Liu S, et al. Telomere Shortening in Alzheimer’s Disease Patients. Ann Clin Lab Sci. 2016 May;46(3):260–5.
    External Resources
  8. Zhan Y, Hägg S. Telomere length and cardiovascular disease risk. Curr Opin Cardiol. 2019 May;34(3):270–4.
  9. Hamel FG. Telomeres and type 2 diabetes. Transl Res. 2010 Apr;155(4):164–5.
  10. Chang AM, Halter JB. Aging and insulin secretion. Am J Physiol Endocrinol Metab. 2003 Jan;284(1):E7–12.
  11. Geloneze B, de Oliveira MS, Vasques AC, Novaes FS, Pareja JC, Tambascia MA. Impaired incretin secretion and pancreatic dysfunction with older age and diabetes. Metabolism. 2014 Jul;63(7):922–9.
  12. Rosa EC, Dos Santos RR, Fernandes LF, Neves FA, Coelho MS, Amato AA. Leukocyte telomere length correlates with glucose control in adults with recently diagnosed type 2 diabetes. Diabetes Res Clin Pract. 2018 Jan;135:30–6.
  13. Bell WR, Meeker AK, Rizzo A, Rajpara S, Rosenthal IM, Flores Bellver M, et al. A unique telomere DNA expansion phenotype in human retinal rod photoreceptors associated with aging and disease. Brain Pathol. 2019 Jan;29(1):45–52.
  14. Xiong Y, Zhou L. The Signaling of Cellular Senescence in Diabetic Nephropathy. Oxid Med Cell Longev. 2019 Oct;2019:7495629.
  15. Ma D, Zhu W, Hu S, Yu X, Yang Y. Association between oxidative stress and telomere length in Type 1 and Type 2 diabetic patients. J Endocrinol Invest. 2013 Dec;36(11):1032–7.
    External Resources
  16. Campbell JM, Bellman SM, Stephenson MD, Lisy K. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Ageing Res Rev. 2017 Nov;40:31–44.
  17. Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell Metab. 2016 Jun;23(6):1060–5.
  18. Jiang X, Ruan XL, Xue YX, Yang S, Shi M, Wang LN. Metformin Reduces the Senescence of Renal Tubular Epithelial Cells in Diabetic Nephropathy via the MBNL1/miR-130a-3p/STAT3 Pathway. Oxid Med Cell Longev. 2020 Feb;2020:8708236.
  19. Cameron AR, Morrison VL, Levin D, Mohan M, Forteath C, Beall C, et al. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016 Aug;119(5):652–65.
  20. Valencia WM, Palacio A, Tamariz L, Florez H. Metformin and ageing: improving ageing outcomes beyond glycaemic control. Diabetologia. 2017 Sep;60(9):1630–8.
  21. de Kreutzenberg SV, Ceolotto G, Cattelan A, Pagnin E, Mazzucato M, Garagnani P, et al. Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A randomized controlled trial. Nutr Metab Cardiovasc Dis. 2015 Jul;25(7):686–93.
  22. Ma D, Yu Y, Yu X, Zhang M, Yang Y. The changes of leukocyte telomere length and telomerase activity after sitagliptin intervention in newly diagnosed type 2 diabetes. Diabetes Metab Res Rev. 2015 Mar;31(3):256–61.
  23. Liu J, Ge Y, Wu S, Ma D, Xu W, Zhang Y, et al. Association between antidiabetic agents use and leukocyte telomere shortening rates in patients with type 2 diabetes. Aging (Albany NY). 2019 Jan;11(2):741–55.
  24. American Diabetes Association. Standards of medical care in diabetes–2010. Diabetes Care. 2010 Jan;33(suppl 1):S11–61.
  25. Ouellette MM, Liao M, Herbert BS, Johnson M, Holt SE, Liss HS, et al. Subsenescent telomere lengths in fibroblasts immortalized by limiting amounts of telomerase. J Biol Chem. 2000 Apr;275(14):10072–6.
  26. Jamieson AR, Giger ML, Drukker K, Li H, Yuan Y, Bhooshan N. Exploring nonlinear feature space dimension reduction and data representation in breast Cadx with Laplacian eigenmaps and t-SNE. Med Phys. 2010 Jan;37(1):339–51.
  27. Zhu Y, Liu X, Ding X, Wang F, Geng X. Telomere and its role in the aging pathways: telomere shortening, cell senescence and mitochondria dysfunction. Biogerontology. 2019 Feb;20(1):1–16.
  28. Zee RY, Castonguay AJ, Barton NS, Germer S, Martin M. Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study. Transl Res. 2010 Apr;155(4):166–9.
  29. Tamura Y, Takubo K, Aida J, Araki A, Ito H. Telomere attrition and diabetes mellitus. Geriatr Gerontol Int. 2016 Mar;16(Suppl 1):66–74.
  30. Savage N. New tricks from old dogs join the fight against ageing. Nature. 2017 Dec 14;552(7684):S57–S59.
  31. Diman A, Boros J, Poulain F, Rodriguez J, Purnelle M, Episkopou H, et al. Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription. Sci Adv. 2016 Jul;2(7):e1600031.
  32. Kulkarni AS, Gubbi S, Barzilai N. Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab. 2020 Jul;32(1):15–30.
  33. Aulinas A, Ramírez MJ, Barahona MJ, Valassi E, Resmini E, Mato E, et al. Dyslipidemia and chronic inflammation markers are correlated with telomere length shortening in Cushing’s syndrome. PLoS One. 2015 Mar;10(3):e0120185.
  34. Sharma R, Gupta A, Thungapathra M, Bansal R. Telomere mean length in patients with diabetic retinopathy. Sci Rep. 2015 Dec;5(1):18368.
  35. Tentolouris N, Nzietchueng R, Cattan V, Poitevin G, Lacolley P, Papazafiropoulou A, et al. White blood cells telomere length is shorter in males with type 2 diabetes and microalbuminuria. Diabetes Care. 2007 Nov;30(11):2909–15.
  36. Guadagnini D, Rocha GZ, Santos A, Assalin HB, Hirabara SM, Curi R, et al. Microbiota determines insulin sensitivity in TLR2-KO mice. Life Sci. 2019 Oct;234:116793.
  37. Winer DA, Luck H, Tsai S, Winer S. The Intestinal Immune System in Obesity and Insulin Resistance. Cell Metab. 2016 Mar;23(3):413–26.
  38. Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci USA. 2019 Jun;116(26):12672–7.
  39. Zhang M, Feng R, Yang M, Qian C, Wang Z, Liu W, et al. Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats. BMJ Open Diabetes Res Care. 2019 Sep;7(1):e000717.
  40. Valdes AM, Andrew T, Gardner JP, Kimura M, Oelsner E, Cherkas LF, et al. Obesity, cigarette smoking, and telomere length in women. Lancet. 2005 Aug;366(9486):662–4.
  41. Vasan RS, Demissie S, Kimura M, Cupples LA, Rifai N, White C, et al. Association of leukocyte telomere length with circulating biomarkers of the renin-angiotensin-aldosterone system: the Framingham Heart Study. Circulation. 2008 Mar;117(9):1138–44.
  42. Kimura M, Stone RC, Hunt SC, Skurnick J, Lu X, Cao X, et al. Measurement of telomere length by the Southern blot analysis of terminal restriction fragment lengths. Nat Protoc. 2010 Sep;5(9):1596–607.
  43. Montpetit AJ, Alhareeri AA, Montpetit M, Starkweather AR, Elmore LW, Filler K, et al. Telomere length: a review of methods for measurement. Nurs Res. 2014 Jul-Aug;63(4):289–99.

Article / Publication Details

First-Page Preview
Abstract of Clinical Section: Research Article

Received: July 13, 2020
Accepted: September 05, 2020
Published online: December 15, 2020
Issue release date: January 2021

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 3

ISSN: 0304-324X (Print)
eISSN: 1423-0003 (Online)

For additional information: https://www.karger.com/GER


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