To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Patients
2.2. Glycemic Variability Assessment
2.3. Clinical, Biological, and Laboratory Assessments
2.4. Statistical Analysis
3. Results
HbA1c and Glycemic Variability
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Saudek, C.D.; Brick, J.C. The Clinical Use of Hemoglobin A1c. J. Diabetes Sci. Technol. 2009, 3, 629–634. [Google Scholar] [CrossRef]
- ElSayed, N.A.; Aleppo, G.; Bannuru, R.R.; Bruemmer, D.; Collins, B.S.; Ekhlaspour, L.; Hilliard, M.E.; Johnson, E.L.; Khunti, K.; Lingvay, I.; et al. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2024. Diabetes Care 2024, 47 (Suppl. S1), S111–S125. [Google Scholar] [CrossRef]
- American Diabetes Association Professional Practice Committee. 6. Glycemic Targets: Standards of Medical Care in Diabetes—2022. Diabetes Care 2022, 45, S83–S96. [Google Scholar] [CrossRef]
- Radin, M.S. Pitfalls in Hemoglobin A1c Measurement: When Results May Be Misleading. J. Gen. Intern. Med. 2014, 29, 388–394. [Google Scholar] [CrossRef]
- Aldasouqi, S.A.; Gossain, V.V. Hemoglobin A1c: Past, Present and Future. Ann. Saudi Med. 2008, 28, 411–419. [Google Scholar] [CrossRef]
- Edelman, D.; Olsen, M.K.; Dudley, T.K.; Harris, A.C.; Oddone, E.Z. Utility of Hemoglobin A1c in Predicting Diabetes Risk. J. Gen. Intern. Med. 2004, 19, 1175–1180. [Google Scholar] [CrossRef]
- Beck, R.W.; Connor, C.G.; Mullen, D.M.; Wesley, D.M.; Bergenstal, R.M. The Fallacy of Average: How Using HbA1c Alone to Assess Glycemic Control Can Be Misleading. Diabetes Care 2017, 40, 994–999. [Google Scholar] [CrossRef]
- Van Belle, T.L.; Coppieters, K.T.; Von Herrath, M.G. Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies. Physiol. Rev. 2011, 91, 79–118. [Google Scholar] [CrossRef]
- Giwa, A.M.; Ahmed, R.; Omidian, Z.; Majety, N.; Karakus, K.E.; Omer, S.M.; Donner, T.; Hamad, A.R.A. Current Understandings of the Pathogenesis of Type 1 Diabetes: Genetics to Environment. World J. Diabetes 2020, 11, 13–25. [Google Scholar] [CrossRef]
- Holt, R.I.G.; DeVries, J.H.; Hess-Fischl, A.; Hirsch, I.B.; Kirkman, M.S.; Klupa, T.; Ludwig, B.; Nørgaard, K.; Pettus, J.; Renard, E.; et al. The Management of Type 1 Diabetes in Adults. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2021, 64, 2609–2652. [Google Scholar] [CrossRef]
- Šoupal, J.; Škrha, J.; Fajmon, M.; Horová, E.; Mráz, M.; Škrha, J.; Prázný, M. Glycemic Variability Is Higher in Type 1 Diabetes Patients with Microvascular Complications Irrespective of Glycemic Control. Diabetes Technol. Ther. 2014, 16, 198–203. [Google Scholar] [CrossRef]
- Picconi, F.; Parravano, M.; Ylli, D.; Pasqualetti, P.; Coluzzi, S.; Giordani, I.; Malandrucco, I.; Lauro, D.; Scarinci, F.; Giorno, P.; et al. Retinal Neurodegeneration in Patients with Type 1 Diabetes Mellitus: The Role of Glycemic Variability. Acta Diabetol. 2017, 54, 489–497. [Google Scholar] [CrossRef]
- Firouzabadi, M.D.; Poopak, A.; Sheikhy, A.; Samimi, S.; Nakhaei, P.; Firouzabadi, F.D.; Moosaie, F.; Rabizadeh, S.; Nakhjavani, M.; Esteghamati, A. Glycemic Profile Variability: An Independent Risk Factor for Diabetic Neuropathy in Patients with Type 2 Diabetes. Prim. Care Diabetes 2023, 17, 38–42. [Google Scholar] [CrossRef]
- Tang, X.; Li, S.; Wang, Y.; Wang, M.; Yin, Q.; Mu, P.; Lin, S.; Qian, X.; Ye, X.; Chen, Y. Glycemic Variability Evaluated by Continuous Glucose Monitoring System Is Associated with the 10-y Cardiovascular Risk of Diabetic Patients with Well-Controlled HbA1c. Clin. Chim. Acta 2016, 461, 146–150. [Google Scholar] [CrossRef]
- Schreur, V.; van Asten, F.; Ng, H.; Weeda, J.; Groenewoud, J.M.M.; Tack, C.J.; Hoyng, C.B.; de Jong, E.K.; Klaver, C.C.W.; Jeroen Klevering, B. Risk Factors for Development and Progression of Diabetic Retinopathy in Dutch Patients with Type 1 Diabetes Mellitus. Acta Ophthalmol. 2018, 96, 459–464. [Google Scholar] [CrossRef]
- Lipska, K.J.; Warton, E.M.; Huang, E.S.; Moffet, H.H.; Inzucchi, S.E.; Krumholz, H.M.; Karter, A.J. HbA1c and Risk of Severe Hypoglycemia in Type 2 Diabetes. Diabetes Care 2013, 36, 3535–3542. [Google Scholar] [CrossRef]
- Kilpatrick, E.S.; Rigby, A.S.; Goode, K.; Atkin, S.L. Relating Mean Blood Glucose and Glucose Variability to the Risk of Multiple Episodes of Hypoglycaemia in Type 1 Diabetes. Diabetologia 2007, 50, 2553–2561. [Google Scholar] [CrossRef]
- The Diabetes Control and Complications Trial Research Group. The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus. N. Engl. J. Med. 1993, 329, 977–986. [Google Scholar] [CrossRef]
- Frier, B.M.; Schernthaner, G.; Heller, S.R. Hypoglycemia and Cardiovascular Risks. Diabetes Care 2011, 34 (Suppl. S2), S132–S137. [Google Scholar] [CrossRef]
- Kong, A.P.S.; Chan, J.C.N. Hypoglycemia and Comorbidities in Type 2 Diabetes. Curr. Diab Rep. 2015, 15, 80. [Google Scholar] [CrossRef]
- Kahal, H.; Halama, A.; Aburima, A.; Bhagwat, A.M.; Butler, A.E.; Graumann, J.; Suhre, K.; Sathyapalan, T.; Atkin, S.L. Effect of Induced Hypoglycemia on Inflammation and Oxidative Stress in Type 2 Diabetes and Control Subjects. Sci. Rep. 2020, 10, 4750. [Google Scholar] [CrossRef] [PubMed]
- Giacco, F.; Brownlee, M. Oxidative Stress and Diabetic Complications. Circ. Res. 2010, 107, 1058–1070. [Google Scholar] [CrossRef] [PubMed]
- Leibovitz, E.; Khanimov, I.; Wainstein, J.; Boaz, M. Documented Hypoglycemia Is Associated with Poor Short and Long Term Prognosis among Patients Admitted to General Internal Medicine Departments. Diabetes Metab. Syndr. Clin. Res. Rev. 2019, 13, 222–226. [Google Scholar] [CrossRef]
- Jafar, N.; Edriss, H.; Nugent, K. The Effect of Short-Term Hyperglycemia on the Innate Immune System. Am. J. Med. Sci. 2016, 351, 201–211. [Google Scholar] [CrossRef]
- Flynn, M.C.; Kraakman, M.J.; Tikellis, C.; Lee, M.K.S.; Hanssen, N.M.J.; Kammoun, H.L.; Pickering, R.J.; Dragoljevic, D.; Al-Sharea, A.; Barrett, T.J.; et al. Transient Intermittent Hyperglycemia Accelerates Atherosclerosis by Promoting Myelopoiesis. Circ. Res. 2020, 127, 877–892. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.-L.; Sheu, W.H.-H.; Lee, I.-T.; Lin, S.-Y.; Liang, W.-M.; Wang, J.-S.; Li, Y.-F. Trajectories of Fasting Plasma Glucose Variability and Mortality in Type 2 Diabetes. Diabetes Metab. 2018, 44, 121–128. [Google Scholar] [CrossRef]
- Ceriello, A.; Esposito, K.; Piconi, L.; Ihnat, M.; Thorpe, J.; Testa, R.; Bonfigli, A.R.; Giugliano, D. Glucose “Peak” and Glucose “Spike”: Impact on Endothelial Function and Oxidative Stress. Diabetes Res. Clin. Pract. 2008, 82, 262–267. [Google Scholar] [CrossRef]
- Satya Krishna, S.; Kota, S.; Modi, K. Glycemic Variability: Clinical Implications. Indian. J. Endocrinol. Metab. 2013, 17, 611–619. [Google Scholar] [CrossRef]
- Suh, S.; Kim, J.H. Glycemic Variability: How Do We Measure It and Why Is It Important? Diabetes Metab. J. 2015, 39, 273. [Google Scholar] [CrossRef] [PubMed]
- Kusunoki, Y.; Konishi, K.; Tsunoda, T.; Koyama, H. Significance of Glycemic Variability in Diabetes Mellitus. Intern. Med. 2022, 61, 281–290. [Google Scholar] [CrossRef]
- Gómez, A.; Henao-Carillo, D.; Taboada, L.; Fuentes, O.; Lucero, O.; Sanko, A.; Robledo, M.; Muñoz, O.; Rondón, M.; García-Jaramillo, M.; et al. Clinical Factors Associated with High Glycemic Variability Defined by Coefficient of Variation in Patients with Type 2 Diabetes. Med. Devices Evid. Res. 2021, 14, 97–103. [Google Scholar] [CrossRef]
- Toschi, E.; Slyne, C.; Dufour, A.B.; Atakov-Castillo, A.; Carl, S.; Sifre, K.; Greenberg, J.; Munshi, M. Usefulness of Coefficient of Variation (CV) to Assess Hypoglycemia in Older Adults with Type 1 Diabetes (T1D). Diabetes 2019, 68 (Suppl. S1), 297-OR. [Google Scholar] [CrossRef]
- Chun, J.H.; O’Neill, M.S. Optimizing Diabetes Care with the Standardized Continuous Glucose Monitoring Report. Clin. Diabetes 2020, 38, 194–200. [Google Scholar] [CrossRef]
- Rodbard, D. The Challenges of Measuring Glycemic Variability. J. Diabetes Sci. Technol. 2012, 6, 712–715. [Google Scholar] [CrossRef]
- Czerwoniuk, D.; Fendler, W.; Walenciak, L.; Mlynarski, W. GlyCulator: A Glycemic Variability Calculation Tool for Continuous Glucose Monitoring Data. J. Diabetes Sci. Technol. 2011, 5, 447–451. [Google Scholar] [CrossRef]
- Gerbaud, E.; Darier, R.; Montaudon, M.; Beauvieux, M.-C.; Coffin-Boutreux, C.; Coste, P.; Douard, H.; Ouattara, A.; Catargi, B. Glycemic Variability Is a Powerful Independent Predictive Factor of Midterm Major Adverse Cardiac Events in Patients with Diabetes with Acute Coronary Syndrome. Diabetes Care 2019, 42, 674–681. [Google Scholar] [CrossRef]
- Gabbay, M.A.L.; Rodacki, M.; Calliari, L.E.; Vianna, A.G.D.; Krakauer, M.; Pinto, M.S.; Reis, J.S.; Puñales, M.; Miranda, L.G.; Ramalho, A.C.; et al. Time in Range: A New Parameter to Evaluate Blood Glucose Control in Patients with Diabetes. Diabetol. Metab. Syndr. 2020, 12, 22. [Google Scholar] [CrossRef]
- Wright, E.E.; Morgan, K.; Fu, D.K.; Wilkins, N.; Guffey, W.J. Time in Range: How to Measure It, How to Report It, and Its Practical Application in Clinical Decision-Making. Clin. Diabetes 2020, 38, 439–448. [Google Scholar] [CrossRef]
- Saboo, B.; Kesavadev, J.; Shankar, A.; Krishna, M.B.; Sheth, S.; Patel, V.; Krishnan, G. Time-in-Range as a Target in Type 2 Diabetes: An Urgent Need. Heliyon 2021, 7, e05967. [Google Scholar] [CrossRef]
- El Malahi, A.; Van Elsen, M.; Charleer, S.; Dirinck, E.; Ledeganck, K.; Keymeulen, B.; Crenier, L.; Radermecker, R.; Taes, Y.; Vercammen, C.; et al. Relationship Between Time in Range, Glycemic Variability, HbA1c, and Complications in Adults with Type 1 Diabetes Mellitus. J. Clin. Endocrinol. Metab. 2022, 107, e570–e581. [Google Scholar] [CrossRef]
- Huang, L.; Pan, Y.; Zhou, K.; Liu, H.; Zhong, S. Correlation Between Glycemic Variability and Diabetic Complications: A Narrative Review. Int. J. Gen. Med. 2023, 16, 3083–3094. [Google Scholar] [CrossRef] [PubMed]
- Piona, C.; Marigliano, M.; Mozzillo, E.; Rosanio, F.; Zanfardino, A.; Iafusco, D.; Maltoni, G.; Zucchini, S.; Piccinno, E.; Delvecchio, M.; et al. Relationships between HbA1c and Continuous Glucose Monitoring Metrics of Glycaemic Control and Glucose Variability in a Large Cohort of Children and Adolescents with Type 1 Diabetes. Diabetes Res. Clin. Pract. 2021, 177, 108933. [Google Scholar] [CrossRef] [PubMed]
- Kuenen, J.C.; Borg, R.; Kuik, D.J.; Zheng, H.; Schoenfeld, D.; Diamant, M.; Nathan, D.M.; Heine, R.J. Does Glucose Variability Influence the Relationship Between Mean Plasma Glucose and HbA1c Levels in Type 1 and Type 2 Diabetic Patients? Diabetes Care 2011, 34, 1843–1847. [Google Scholar] [CrossRef]
- Yamada, M.; Okada, S.; Oda, H.; Nakajima, Y.; Bastie, C.C.; Kasai, Y.; Osaki, A.; Shimoda, Y.; Shibusawa, R.; Uehara, R.; et al. Evaluation of the Relationship between Glycated Hemoglobin A1c and Mean Glucose Levels Derived from the Professional Continuous Flash Glucose Monitoring System. Endocr. J. 2020, 67, 531–536. [Google Scholar] [CrossRef] [PubMed]
- Vigersky, R.A.; McMahon, C. The Relationship of Hemoglobin A1C to Time-in-Range in Patients with Diabetes. Diabetes Technol. Ther. 2019, 21, 81–85. [Google Scholar] [CrossRef]
- Hirsch, I.B.; Sherr, J.L.; Hood, K.K. Connecting the Dots: Validation of Time in Range Metrics with Microvascular Outcomes. Diabetes Care 2019, 42, 345–348. [Google Scholar] [CrossRef]
- Castañeda, J.; Arrieta, A.; van den Heuvel, T.; Cohen, O. The Significance of Coefficient of Variation as a Measure of Hypoglycaemia Risk and Glycaemic Control in Real World Users of the Automated Insulin Delivery MiniMed 780G System. Diabetes Obes. Metab. 2023, 25, 2545–2552. [Google Scholar] [CrossRef]
HbA1c < 7% (n = 79) | HbA1c ≥ 7% (n = 68) | p-Value | |
---|---|---|---|
TIR ≥ 70% target achievement a | 59 (74.7%) | 8 (11.8%) | <0.001 * |
CV ≤ 36% target achievement a | 48 (60.8%) | 26 (38.2%) | 0.005 * |
TIR (percentage points) b | 78 [70 to 85] | 58 [50 to 66] | <0.001 * |
CV (percentage points) b | 34.1 [31.3 to 37.7] | 38.0 [33.6 to 40.1] | <0.001 * |
Standard Deviation of Glycemia b | 48 [41 to 57] | 60 [57 to 69] | <0.001 * |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lazar, S.; Ionita, I.; Reurean-Pintilei, D.; Timar, R.; Luca, S.A.; Timar, B. To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study. J. Clin. Med. 2024, 13, 450. https://doi.org/10.3390/jcm13020450
Lazar S, Ionita I, Reurean-Pintilei D, Timar R, Luca SA, Timar B. To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study. Journal of Clinical Medicine. 2024; 13(2):450. https://doi.org/10.3390/jcm13020450
Chicago/Turabian StyleLazar, Sandra, Ioana Ionita, Delia Reurean-Pintilei, Romulus Timar, Silvia Ana Luca, and Bogdan Timar. 2024. "To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study" Journal of Clinical Medicine 13, no. 2: 450. https://doi.org/10.3390/jcm13020450
APA StyleLazar, S., Ionita, I., Reurean-Pintilei, D., Timar, R., Luca, S. A., & Timar, B. (2024). To What Extent Is HbA1c Associated with Glycemic Variability in Patients with Type 1 Diabetes? A Retrospective, Noninterventional Study. Journal of Clinical Medicine, 13(2), 450. https://doi.org/10.3390/jcm13020450