Hypoglycemia in type 2 diabetes patients treated with insulin: the advantages of continuous glucose monitoring
https://doi.org/10.14341/DM2014175-80
Abstract
Aims.
To determine the incidence and risk factors for hypoglycemia in elderly insulin-treated type 2 diabetes mellitus (T2DM) patients by means of continuous glucose monitoring (CGM).
Materials and Methods.
We observed seventy-six hospitalized patients with T2DM, aged 65 to 79 years. Treatment with basal insulin (n=36), premixed insulin (n=12) or basal-bolus insulin regimen (n=28) was followed by metformin (n=44), glimepiride (n=14) and dipeptidyl peptidase-4 inhibitors (n=14). 2-days CGM with retrospective data analysis was performed in all patients. During CGM, three fasting and three 2-h postprandial finger-prick glucose values were obtained daily with portable glucose meter.
Results.
Hypoglycemia (identified as blood glucose <3.9 mmol/l) was registered in 17 (22%) patients by glucose meter and in 55 (72%) patients by CGM. Most of the CGM-registered hypoglycemic events (72%) were not recognized by patients. Nocturnal hypoglycemic events were revealed in 48 subjects (63%). Patients with hypoglycemia had lower interstitial glucose (median, 25?75 percentile: 7.0, 6.4?8.3 vs. 8.3, 7.4?8.5 mmol/l, p=0.01) and higher glucose variability (2.5, 1.9?3.1 vs. 1.8, 1.4?2.2 mmol/l, respectively; p=0.0008). There was no significant difference between the groups regarding daily insulin dose, HbA1c or T2DM duration. In a model of stepwise discriminant analysis, age, duration of insulin therapy, mean interstitial glucose levels and glycemic variability showed associations with hypoglycemia (accuracy rate 97.5%, p=0.005).
Conclusion.
The unrecognized hypoglycemia is a common complication in elderly T2DM patients on insulin therapy. Compared to conventional blood glucose monitoring, two-day CGM is superior in detection of asymptomatic hypoglycemia in this patient group. Age, duration of insulin therapy, mean glucose levels and glucose variability were associated with hypoglycemic events in elderly patients with T2DM.
To determine the incidence and risk factors for hypoglycemia in elderly insulin-treated type 2 diabetes mellitus (T2DM) patients by means of continuous glucose monitoring (CGM).
Materials and Methods.
We observed seventy-six hospitalized patients with T2DM, aged 65 to 79 years. Treatment with basal insulin (n=36), premixed insulin (n=12) or basal-bolus insulin regimen (n=28) was followed by metformin (n=44), glimepiride (n=14) and dipeptidyl peptidase-4 inhibitors (n=14). 2-days CGM with retrospective data analysis was performed in all patients. During CGM, three fasting and three 2-h postprandial finger-prick glucose values were obtained daily with portable glucose meter.
Results.
Hypoglycemia (identified as blood glucose <3.9 mmol/l) was registered in 17 (22%) patients by glucose meter and in 55 (72%) patients by CGM. Most of the CGM-registered hypoglycemic events (72%) were not recognized by patients. Nocturnal hypoglycemic events were revealed in 48 subjects (63%). Patients with hypoglycemia had lower interstitial glucose (median, 25?75 percentile: 7.0, 6.4?8.3 vs. 8.3, 7.4?8.5 mmol/l, p=0.01) and higher glucose variability (2.5, 1.9?3.1 vs. 1.8, 1.4?2.2 mmol/l, respectively; p=0.0008). There was no significant difference between the groups regarding daily insulin dose, HbA1c or T2DM duration. In a model of stepwise discriminant analysis, age, duration of insulin therapy, mean interstitial glucose levels and glycemic variability showed associations with hypoglycemia (accuracy rate 97.5%, p=0.005).
Conclusion.
The unrecognized hypoglycemia is a common complication in elderly T2DM patients on insulin therapy. Compared to conventional blood glucose monitoring, two-day CGM is superior in detection of asymptomatic hypoglycemia in this patient group. Age, duration of insulin therapy, mean glucose levels and glucose variability were associated with hypoglycemic events in elderly patients with T2DM.
About the Authors
Vadim Valer'evich Klimontov
Institute of Clinical and Experimental Lymphology, Novosibirsk
Russian Federation
MD, PhD, Hed of the Endocrinology laboratory
Russian Federation
MD, PhD, Hed of the Endocrinology laboratory
Alexander Ivanovich Tsiberkin
Institute of Clinical and Experimental Lymphology, Novosibirsk
Russian Federation
Assistant, Endocrinology laboratory
Russian Federation
Assistant, Endocrinology laboratory
Olga Nikolaevna Fazullina
Institute of Clinical and Experimental Lymphology, Novosibirsk
Russian Federation
Junior Researcher, Endocrinology laboratory
Russian Federation
Junior Researcher, Endocrinology laboratory
Marina Alekseevna Prudnikova
Institute of Clinical and Experimental Lymphology, Novosibirsk
Russian Federation
Junior Researcher, Endocrinology laboratory
Russian Federation
Junior Researcher, Endocrinology laboratory
Nadezhda Viktorovna Tyan
Institute of Clinical and Experimental Lymphology, Novosibirsk
Russian Federation
Junior Researcher, Endocrinology laboratory
Russian Federation
Junior Researcher, Endocrinology laboratory
Vladimir Iosifovich Konenkov
Institute of Clinical and Experimental Lymphology, Novosibirsk
Russian Federation
MD, PhD, Professor, fellow of russian Academy of Sciences, Head of Institute
Russian Federation
MD, PhD, Professor, fellow of russian Academy of Sciences, Head of Institute
References
1. Cryer PE. The barrier of hypoglycemia in diabetes.. Diabetes 2008;57(12):3169-3176. Available from: http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=19033403 PubMed PMID: 19033403. doi: 10.2337/db08-1084.
2. Seaquist ER, AndersonJ, ChildsB, CryerP, Dagogo-JackS, FishL , et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. DiabetesCare 2013;36(5):1384-1395. doi: 10.2337/dc12-2480.
3. KlonoffDC, BuckinghamB, ChristiansenJS, MontoriVM, TamborlaneWV, VigerskyRA , et al. Continuous glucose monitoring: an Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism 2011;96(10):2968-2979. doi: 10.1210/jc.2010-2756.
4. Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008;94(3):709-728. Available from: http://www.nlm.nih.gov/medlineplus/hypoglycemia.html PubMed PMID: 19088155. doi: 10.1210/jc.2008-1410.
5. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013;36(5):1384-1395. Available from: http://www.nlm.nih.gov/medlineplus/diabetes.html PubMed PMID: 23589542. doi: 10.2337/dc12-2480.
6. Miller ME, Bonds DE, Gerstein HC, Seaquist ER, Bergenstal RM, Calles-Escandon J, 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. Available from: http://www.bmj.com/cgi/pmidlookup?view=long&pmid=20061360 PubMed PMID: 20061360.
7. Zoungas S, Patel A, Chalmers J, de Galan BE, Li Q, Billot L, et al. Severe Hypoglycemia and Risks of Vascular Events and Death. N Engl J Med 2010;363(15):1410-1418. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa1003795 PubMed PMID: 20925543. doi: 10.1056/NEJMoa1003795.
8. Shorr RI. Incidence and Risk Factors for Serious Hypoglycemia in Older Persons Using Insulin or Sulfonylureas. Arch Intern Med 1997;157(15):1681-1686. Available from: http://archinte.jamanetwork.com/article.aspx?doi=10.1001/archinte.1997.00440360095010 PubMed PMID: 9250229. doi: 10.1001/archinte.1997.00440360095010.
9. Davis TME, Brown SGA, Jacobs IG, Bulsara M, Bruce DG, Davis WA. Determinants of severe hypoglycemia complicating type 2 diabetes: the Fremantle diabetes study. J Clin Endocrinol Metab 2010;95(5):2240-2247. Available from: http://www.nlm.nih.gov/medlineplus/diabetestype2.html PubMed PMID: 20305006. doi: 10.1210/jc.2009-2828.
10. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50(6):1140-1147. Available from: http://www.nlm.nih.gov/medlineplus/diabetesmedicines.html PubMed PMID: 17415551. doi: 10.1007/s00125-007-0599-y.
11. Monnier L, Wojtusciszyn A, Colette C, Owens D. The Contribution of Glucose Variability to Asymptomatic Hypoglycemia in Persons with Type 2 Diabetes. Diabetes Technology & Therapeutics 2011;13(8):813-818. Available from: http://online.liebertpub.com/doi/abs/10.1089/dia.2011.0049 PubMed PMID: 21561372. doi: 10.1089/dia.2011.0049.
12. Qu Y, Jacober SJ, Zhang Q, Wolka LL, DeVries, J. Hans . Rate of Hypoglycemia in Insulin-Treated Patients with Type 2 Diabetes Can Be Predicted from Glycemic Variability Data. Diabetes Technology and Therapeutics 2012;14(11):1008-1012. Available from: http://online.liebertpub.com/doi/abs/10.1089/dia.2012.0099 PubMed PMID: 23101951. doi: 10.1089/dia.2012.0099.
13. Dailey GE, Gao L, Aurand L, Garg SK. Impact of diabetes duration on hypoglycaemia in patients with type 2 diabetes treated with insulinglargine or NPH insulin. Diabetes, Obesity and Metabolism 2013;15(12):1082-1085. doi: 10.1111/dom.1213.
14. Akram K, Pedersen-Bjergaard U, Carstensen B, Borch-Johnsen K, Thorsteinsson B. Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes: a cross-sectional survey. Diabet Med 2006;23(7):750-756. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=16842479 PubMed PMID: 16842479. doi: 10.1111/j.1464-5491.2006.01880.x.
15. Engler B, Koehler C, Hoffmann C, Landgraf W, Bilz S, Schoner C, et al. Relationship between HbA1c on target, risk of silent hypoglycemia and glycemic variability in patients with type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 2011;119(1):59-61. Available from: http://www.nlm.nih.gov/medlineplus/bloodsugar.html PubMed PMID: 21246466. doi: 10.1055/s-0030-1262874.
16. Berlin I, Sachon CI, Grimaldi A. Identification of factors associated with impaired hypoglycaemia awareness in patients with type 1 and type 2 diabetes mellitus. Diabetes Metab 2005;31(3 Pt 1):246-251. Available from: http://www.masson.fr/masson/MDOI-DM-06-2005-31-3-1262-3636-101019-200514506 PubMed PMID: 16142015. doi: DM-06-2005-31-3-1262-3636-101019-200514506.
17. Bremer JP, Jauch-Chara K, Hallschmid M, Schmid S, Schultes B. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care 2009;32(8):1513-1517. Available from: http://europepmc.org/abstract/MED/19487634 PubMed PMID: 19487634. doi: 10.2337/dc09-0114.
18. Hermanides J, Phillip M, DeVries JH. Current Application of Continuous Glucose Monitoring in the Treatment of Diabetes: Pros and cons. Diabetes Care 2011;34(Supplement 2). PubMed PMID: 21525455. doi: 10.2337/dc11-s219.
19. Rebrin K, Steil GM. Can interstitial glucose assessment replace blood glucose measurements?. Diabetes Technol Ther 2000;2(3):461-472. Available from: http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@rn+50-99-7 PubMed PMID: 11467349. doi: 10.1089/15209150050194332.
20. Choudhary P, Lonnen K, Emery CJ, Freeman JV, McLeod KM, Heller SR. Relationship Between Interstitial and Blood Glucose During Hypoglycemia in Subjects with Type 2 Diabetes. Diabetes Technology and Therapeutics 2011;13(11):1121-1127. Available from: http://online.liebertpub.com/doi/abs/10.1089/dia.2011.0059 doi: 10.1089/dia.2011.0059.
21. Bonds DE, Miller ME, Bergenstal RM, Buse JB, Byington RP, Cutler JA. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ;2010(340):4909. doi: 10.1136/bmj.b4909
22. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. N Engl J Med 2009;360(2):129-139. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0808431 PubMed PMID: 19092145. doi: 10.1056/NEJMoa0808431.
23. Landstedt-Hallin L, Englund A, Adamson U, Lins PE. Increased QT dispersion during hypoglycaemia in patients with type 2 diabetes mellitus. J Intern Med 1999;246(3):299-307. Available from: http://www.nlm.nih.gov/medlineplus/arrhythmia.html PubMed PMID: 10475998. doi: -2796.1999.00528.x.
24. Torimoto K, Okada Y, Mori H, Tanaka Y. Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus. Cardiovasc Diabetol 2013;12:1. Available from: http://www.cardiab.com/content/12//1 PubMed PMID: 23280391. doi: 10.1186/1475-2840-12-1.
25. Desouza C, Salazar H, Cheong B, Murgo J, Fonseca V. Association of Hypoglycemia and Cardiac Ischemia: A study based on continuous monitoring. Diabetes Care 2003;26(5):1485-1489. Available from: http://dx.doi.org/10.2337/diacare.26.5.1485 PubMed PMID: 12716809. doi: 10.2337/diacare.26.5.1485.
26. Дедов ИИ, Шестакова МВ, Аметов АС, Анциферов МБ, Галстян ГР, Майоров АЮ, Мкртумян АМ, Петунина НА, Сухарева ОЮ. Консенсус совета экспертов Российской ассоциации эндокринологов по инициации и интенсификации сахароснижающей терапии у больных сахарным диабетом 2 типа. Сахарный диабет. 2011;(4):6-17. [Dedov I.I., Shestakova M.V., Ametov A.S., Antsiferov M.B., Galstyan G.R., Mayorov A.Y., Mkrtumyan A.M., Petunina N.A., Sukhareva O.Y. Diabetes mellitus Russian Association of Endocrinologists expert consensus document on initiation and intensification of antyhyperglycaemic therapy in type 2 diabetes mellitus. Diabetes mellitus.2011;(4):6-17.] DOI: http://dx.doi.org/10.14341/2072-0351-5810
27. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, 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. Diabetes Care 2012;35(6):1364-1379. doi: 10.2337/dc12-0413.
Supplementary files
Review
For citations:
Klimontov V.V., Tsiberkin A.I., Fazullina O.N., Prudnikova M.A., Tyan N.V., Konenkov V.I. Hypoglycemia in type 2 diabetes patients treated with insulin: the advantages of continuous glucose monitoring. Diabetes mellitus. 2014;17(1):75-80. (In Russ.) https://doi.org/10.14341/DM2014175-80
Views:
1376
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
