Risk factors and adverse outcomes of hypoglycemia in older patients with type 2 diabetes mellitus (review)
https://doi.org/10.37586/2686-8636-1-2024-30-39
Abstract
Currently, the world is experiencing a steady increase in the number of patients with type 2 diabetes mellitus (T2DM); this disease is recognized as a global medical and social problem of the 21st century. There is also a trend towards increasing life expectancy and, as a result, an aging population. Accordingly, the number of older patients with T2DM is increasing. Hypoglycemia, a serious complication of T2DM, is quite common among this category of patients. Hypoglycemia leads to worsening glycemic control, cognitive deficits, and an increased risk of adverse cardiovascular outcomes in older patients. This review examines the risk factors for hypoglycemic conditions that must be taken into account when prescribing glucose-lowering therapy to older patients and their prognostic significance in assessing the risk of hypoglycemia. The possible negative consequences of hypoglycemia are described and the importance of individual goals for glycemic control in older patients is emphasized.
About the Authors
S. V. Bulgakova
Samara State Medical University
Russian Federation
Russian Federation
Bulgakova Svetlana V., MD, PhD, professor, Head of the Department of Endocrinology and Geriatrics
Samara
P. Ya. Merzlova
Samara State Medical University
Russian Federation
Russian Federation
Merzlova Polina Y., MD, assistant professor, the Department of Endocrinology and Geriatrics
Samara
D. P. Kurmaev
Samara State Medical University
Russian Federation
Russian Federation
Kurmaev Dmitry P., MD, PhD, assistant professor in Endocrinology and Geriatrics Department
Samara
E. V. Treneva
Samara State Medical University
Russian Federation
Russian Federation
Treneva Ekaterina V. , MD, PhD, associate professor, Department of Endocrinology and Geriatrics
Samara
References
1. Dedov I.I., Shestakova M.V., Mayorov A.U., et al. Diabetes mellitus type 2 in adults. Diabetes mellitus. 2020;23(2S):4– 102. (In Russ.)] https://doi.org/10.14341/DM12507
2. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 [published correction appears in Diabetes Res Clin Pract. 2023 Oct;204:110945]. Diabetes Res Clin Pract. 2022;183:109119. https://doi.org/10.1016/j.diabres.2021.109119
3. Dedov I.I., Shestakova M.V., Mayorov A.U. et al. Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 9th edition. Diabetes mellitus. 2019;22(1S1):1–144 (in Russ.)] https://doi.org/10.14341/DM221S1
4. Akhundova K.R., Dudinskaya E.N., Tkacheva O.N. Geriatric aspects of diabetes mellitus. Russian Journal of Geriatric Medicine. 2020;(3):250–259. (In Russ.)] https://doi.org/10.37586/2686-8636-3-2020-250-259
5. Dedov I.I., Shestakova M.V., Vikulova O.K., et al. Diabetes mellitus in the Russian Federation: dynamics of epidemiological indicators according to the Federal Register of Diabetes Mellitus for the period 2010–2022. Diabetes mellitus. 2023;26(2):104–123. (In Russ.)] https://doi.org/10.14341/DM13035
6. Dedov I.I., Shestakova M.V., Vikulova O.K., et al. Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal Diabetes Register, status 2017. Diabetes mellitus. 2018;21(3):144–159. (In Russ.)] https://doi.org/10.14341/DM9686
7. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) [published correction appears in Lancet 1999 Aug 14;354(9178):602]. Lancet.1998;352(9131):837–853. https://doi.org/10.1016/S0140-6736(98)07019-6
8. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545– 2559. https://doi.org/10.1056/NEJMoa0802743
9. ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560–2572. https://doi.org/10.1056/NEJMoa0802987
10. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [published correction appears in Diabetes Care. 2013 Feb;36(2):490]. Diabetes Care.2012;35(6):1364–1379. https://doi.org/10.2337/dc12-0413
11. Tkacheva O.N., Tutelyan V.A., Shestopalov A.E., et al. Nutritional insufficiency (malnutrition) in older adults. Clinical recommendations. Russian Journal of Geriatric Medicine. 2021;(1):15– 34. (In Russ.)] https://doi.org/10.37586/2686-8636-1-2021-15-34
12. Verbovaya N.I., Dolgikh Yu.A., Verbovoy A.F., Galkin R.A. Microvascular complications of diabetes mellitus (lecture). Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2019; 8(4):44–54.(in Russ.)] https://doi.org/10.24411/2304-9529-2019-14006
13. Haneda M, Morikawa A. Which hypoglycaemic agents to use in type 2 diabetic subjects with CKD and how?. Nephrol Dial Transplant. 2009;24(2):338–341. https://doi.org/10.1093/ndt/gfn616
14. Weir MA, Gomes T, Mamdani M, et al. Impaired renal function modifies the risk of severe hypoglycaemia among users of insulin but not glyburide: a population-based nested case-control study. Nephrol Dial Transplant. 2011;26(6):1888–1894. https://doi.org/10.1093/ndt/gfq649
15. Miller ME, Bonds DE, Gerstein HC, et al. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ. 2010;340:b5444. Published 2010 Jan 8. https://doi.org/10.1136/bmj.b5444
16. Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med. 2010;363(15):1410– 1418. https://doi.org/10.1056/NEJMoa1003795
17. Davis TM, Brown SG, Jacobs IG, et al. Determinants of severe hypoglycemia complicating type 2 diabetes: the Fremantle diabetes study. J Clin Endocrinol Metab. 2010;95(5):2240–2247. https://doi.org/10.1210/jc.2009–2828
18. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes [published correction appears in N Engl J Med. 2009 Sep 3;361(10):1028] [published correction appears in N Engl J Med. 2009 Sep 3;361(10):1024–5]. N Engl J Med. 2009;360(2):129–139. https://doi.org/10.1056/NEJMoa0808431
19. Tkacheva O.N., Kotovskaya Yu.V., Runikhina N.K., et al. Clinical guidelines frailty. Russian Journal of Geriatric Medicine. 2020;(1):11–46. (In Russ.)] https://doi.org/10.37586/2686-8636-2-2020-115-130
20. Merkusheva L.I., Runikhina N.K., Tkacheva O.N. Kidney aging. Geriatric view. Russian Journal of Geriatric Medicine. 2021;(1):76–81. (In Russ.)] https://doi.org/10.37586/2686-8636-1-2021-76-81
21. Frier BM. Hypoglycaemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014;10(12):711– 722. https://doi.org/10.1038/nrendo.2014.170
22. Cukierman-Yaffe T, Gerstein HC, Williamson JD, et al. Relationship between baseline glycemic control and cognitive function in individuals with type 2 diabetes and other cardiovascular risk factors: the action to control cardiovascular risk in diabetes-memory in diabetes (ACCORD-MIND) trial. Diabetes Care. 2009;32(2):221–226. https://doi.org/10.2337/dc08-1153
23. Punthakee Z, Miller ME, Launer LJ, et al. Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care. 2012;35(4):787–793. https://doi.org/10.2337/dc11-1855
24. de Galan BE, Zoungas S, Chalmers J, et al. Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Diabetologia. 2009;52(11):2328–2336. https://doi.org/10.1007/s00125-009-1484-7
25. Mkrtumyan A.M., Markova T.N., Mishchenko N.K. The role of the kidneys in glucose homeostasis. Problems of Endocrinology. 2017;63(6):385–391(In Russ.)] https://doi.org/10.14341/probl2017636385-391
26. Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. 2007;261(1):32–43. https://doi.org/10.1111/j.1365-2796.2006.01746.x
27. Edridge CL, Dunkley AJ, Bodicoat DH, et al. Prevalence and Incidence of Hypoglycaemia in 532,542 People with Type 2 Diabetes on Oral Therapies and Insulin: A Systematic Review and Meta-Analysis of Population Based Studies. PLoS One. 2015;10(6):e0126427. Published 2015 Jun 10. https://doi.org/10.1371/journal.pone.0126427
28. Watts AG, Donovan CM. Sweet talk in the brain: glucosensing, neural networks, and hypoglycemic counterregulation. Front Neuroendocrinol. 2010;31(1):32–43. https://doi.org/10.1016/j.yfrne.2009.10.006
29. McNeilly AD, McCrimmon RJ. Impaired hypoglycaemia awareness in type 1 diabetes: lessons from the lab. Diabetologia. 2018;61(4):743–750. https://doi.org/10.1007/s00125-018-4548-8
30. Sherwin RS. Bringing Light to the Dark Side of Insulin. Diabetes. 2008;57(9):2259–2268. https://doi.org/10.2337/db08-9023
31. Stanley S, Moheet A, Seaquist ER. Central Mechanisms of Glucose Sensing and Counterregulation in Defense of Hypoglycemia. Endocr Rev. 2019;40(3):768–788. https://doi.org/10.1210/er.2018-00226
32. Bradley C, Eschwège E, de Pablos-Velasco P, et al. Predictors of Quality of Life and Other Patient-Reported Outcomes in the PANORAMA Multinational Study of People With Type 2 Diabetes. Diabetes Care. 2018;41(2):267–276. https://doi.org/10.2337/dc16-2655
33. Rehni AK, Dave KR. Impact of Hypoglycemia on Brain Metabolism During Diabetes. Mol Neurobiol. 2018;55(12):9075– 9088. https://doi.org/10.1007/s12035-018-1044-6
34. Martín-Timón I, Del Cañizo-Gómez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes. 2015;6(7):912–926. https://doi.org/10.4239/wjd.v6.i7.912
35. McCrimmon RJ. Consequences of recurrent hypoglycaemia on brain function in diabetes. Diabetologia.2021;64(5):971–977. https://doi.org/10.1007/s00125-020-05369-0
36. Schopman JE, Geddes J, Frier BM. Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulintreated Type 2 diabetes. Diabetes Res Clin Pract. 2010;87(1):64–68. https://doi.org/10.1016/j.diabres.2009.10.013
37. Quilliam BJ, Simeone JC, Ozbay AB. Risk factors for hypoglycemia-related hospitalization in patients with type 2 diabetes: a nested case-control study. Clin Ther. 2011;33(11):1781– 1791. https://doi.org/10.1016/j.clinthera.2011.09.020
38. Languren G, Montiel T, Ramírez-Lugo L, et al. Recurrent moderate hypoglycemia exacerbates oxidative damage and neuronal death leading to cognitive dysfunction after the hypoglycemic coma. J Cereb Blood Flow Metab. 2019;39(5):808– 821. https://doi.org/10.1177/0271678X17733640
39. Dimitriadis GD, Maratou E, Kountouri A, Board M, Lambadiari V. Regulation of Postabsorptive and Postprandial Glucose Metabolism by Insulin-Dependent and Insulin-Independent Mechanisms: An Integrative Approach. Nutrients. 2021;13(1):159. Published 2021 Jan 6. https://doi.org/10.3390/nu13010159
40. Antonova K.V., Lagoda O.V., Tanashyan M.M. Hypoglycemia in type 2 diabetes mellitus patients — cerebral, cognitive, psychosocial and clinical aspects. Diabetes mellitus. 2022;25(3):288–298. (In Russ.)] https://doi.org/10.14341/DM12840
41. Chadt A, Al-Hasani H. Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease. Pflugers Arch. 2020;472(9):1273–1298. https://doi.org/10.1007/s00424-020-02417-x
42. Bulgakova SV, Kurmaev DP, Treneva EV, et al. Sarcopenia in elderly patients with type 2 diabetes: Risk factors. Aspirantskiy vestnik Povolzhiya. 2023;23(2):66–73(In Russ.)] https://doi.org/10.55531/2072-2354.2023.23.2.66-73
43. Yoon JW, Ha YC, Kim KM, et al. Hyperglycemia Is Associated with Impaired Muscle Quality in Older Men with Diabetes: The Korean Longitudinal Study on Health and Aging. Diabetes Metab J. 2016;40(2):140–146. https://doi.org/10.4093/dmj.2016.40.2.140
44. Ogama N, Sakurai T, Kawashima S, et al. Association of Glucose Fluctuations with Sarcopenia in Older Adults with Type 2 Diabetes Mellitus. J Clin Med. 2019;8(3):319. Published 2019 Mar 6. https://doi.org/10.3390/jcm8030319
45. Chen DS, Zhu YQ, Ni WJ, et al. Hand grip strength is inversely associated with total daily insulin dose requirement in patients with type 2 diabetes mellitus: a cross-sectional study. PeerJ. 2023;11:e15761. Published 2023 Jul 20. https://doi.org/10.7717/peerj.15761
46. Yun JS, Park YM, Han K, Cha SA, Ahn YB, Ko SH. Association between BMI and risk of severe hypoglycaemia in type 2 diabetes. Diabetes Metab. 2019;45(1):19–25. https://doi.org/10.1016/j.diabet.2018.03.006
47. Yun JS, Ko SH. Risk Factors and Adverse Outcomes of Severe Hypoglycemia in Type 2 Diabetes Mellitus. Diabetes Metab J. 2016;40(6):423–432. https://doi.org/10.4093/dmj.2016.40.6.423
48. Ikeda Y, Kubo T, Oda E, Abe M, Tokita S. Incidence rate and patient characteristics of severe hypoglycemia in treated type 2 diabetes mellitus patients in Japan: Retrospective Diagnosis Procedure Combination database analysis. J Diabetes Investig. 2018;9(4):925–936. https://doi.org/10.1111/jdi.12778
49. Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults: a consensus report. J Am Geriatr Soc. 2012;60(12):2342– 2356. https://doi.org/10.1111/jgs.12035
50. Mattishent K, Loke YK. Meta-Analysis: Association Between Hypoglycemia and Serious Adverse Events in Older Patients Treated With Glucose-Lowering Agents. Front Endocrinol (Lausanne). 2021;12:571568. https://doi.org/10.3389/fendo.2021.571568
51. González-Saldivar G, González-González JG, Chow DR, et al. Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call. Int J Clin Pract. 2023;2023:9928582. Published 2023 Oct 16. https://doi.org/10.1155/2023/9928582
52. Laptev D.N., Shmushkovich I.A. Arrhythmogenic effects of hypoglycemia. Diabetes mellitus. 2012;15(1):25–30. (In Russ.)] https://doi.org/10.14341/2072-0351-5975
53. Li G, Zhong S, Wang X, Zhuge F. Association of hypoglycaemia with the risks of arrhythmia and mortality in individuals with diabetes — a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:1222409. Published 2023 Aug 14. https://doi.org/10.3389/fendo.2023.1222409
54. Heller SR, Peyrot M, Oates SK, Taylor AD. Hypoglycemia in patient with type 2 diabetes treated with insulin: it can happen. BMJ Open Diabetes Res Care. 2020;8(1):e001194. https://doi.org/10.1136/bmjdrc-2020-001194
55. Nilsson M, Jensen N, Gejl M, et al. Experimental non-severe hypoglycaemia substantially impairs cognitive function in type 2 diabetes: a randomised crossover trial. Diabetologia. 2019;62(10):1948–1958. https://doi.org/10.1007/s00125-019-4964-4
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For citations:
Bulgakova S.V., Merzlova P.Ya., Kurmaev D.P., Treneva E.V. Risk factors and adverse outcomes of hypoglycemia in older patients with type 2 diabetes mellitus (review). Russian Journal of Geriatric Medicine. 2024;(1):30-39. (In Russ.) https://doi.org/10.37586/2686-8636-1-2024-30-39
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