A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes
Open accessAbstract
OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C. RESULTS—Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63–3.14], P < 0.0001) and nephropathy (1.80 [1.37–2.42], P < 0.0001), with the relationship a feature in conventionally treated patients in particular. CONCLUSIONS—This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.
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Data from the Diabetes Complications Control Trial showed a positive relationship between higher HbA1c levels and glycemic variability and rate of complications.
“Data from the Diabetes Complications Control Trial clearly showed the positive relationship between higher HbA1c levels and GV and rate of complications.43”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [43]
The risk of nephropathy and albuminuria is increased up to 80% for each increase in SD.
“The risk of nephropathy and albuminuria has also been shown to be remarkably increased (up to 80%) for each increase in SD.43”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [43]
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(1993) · New England Journal of Medicine · doi:10.1056/nejm199309303291401 · Cited by 24,667 · see citing works
Stratton, I. M. (2000) · BMJ · doi:10.1136/bmj.321.7258.405 · Cited by 9,059 · see citing works
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
(2005) · New England Journal of Medicine · doi:10.1056/nejmoa052187 · Cited by 5,138 · see citing works
Gupta, A., & Uribarri, J. (2016) · Hormone Research in Paediatrics · doi:10.1159/000444053 · Cited by 4,019 · see citing works
Monnier, L., Mas, E., Ginet, C., Michel, F., Villon, L., Cristol, J.-P., & Colette, C. (2006) · JAMA · doi:10.1001/jama.295.14.1681 · Cited by 2,444 · see citing works
The Diabetes Control and Complications Trial Research Group (1995) · Diabetes · doi:10.2337/diab.44.8.968 · Cited by 1,301 · see citing works
Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus
The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group (2002) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.287.19.2563 · Cited by 941 · see citing works
Quagliaro, L., Piconi, L., Assaloni, R., Martinelli, L., Motz, E., & Ceriello, A. (2003) · Diabetes · doi:10.2337/diabetes.52.11.2795 · Cited by 771 · see citing works
Davı̀, G., Ciabattoni, G., Consoli, A., Mezzetti, A., Falco, A., Santarone, S., Pennese, E., Vitacolonna, E., Bucciarelli, T., Costantini, F., et al. (1999) · Circulation · doi:10.1161/01.cir.99.2.224 · Cited by 742 · see citing works
Lachin, J. M., Genuth, S., Nathan, D. M., Zinman, B., Rutledge, B. N., & for the DCCT/EDIC Research Group (2008) · Diabetes · doi:10.2337/db07-1618 · Cited by 555 · see citing works
Early Worsening of Diabetic Retinopathy in the Diabetes Control and Complications Trial
(1998) · Archives of Ophthalmology · doi:10.1001/archopht.116.7.874 · Cited by 509 · see citing works
Glycemic Variability: A Hemoglobin A<sub>1c</sub>–Independent Risk Factor for Diabetic Complications
Brownlee, M., & Hirsch, I. B. (2006) · JAMA · doi:10.1001/jama.295.14.1707 · Cited by 482 · see citing works
Blood Glucose Control and the Evolution of Diabetic Retinopathy and Albuminuria
The Kroc Collaborative Study Group* (1984) · New England Journal of Medicine · doi:10.1056/nejm198408093110604 · Cited by 466 · see citing works
Essential Role of Growth Hormone in Ischemia-Induced Retinal Neovascularization
Smith, L. E. H., Kopchick, J. J., Chen, W., Knapp, J., Kinose, F., Daley, D., Foley, E., Smith, R. G., & Schaeffer, J. M. (1997) · Science · doi:10.1126/science.276.5319.1706 · Cited by 392 · see citing works
Diabetes Control and Complications Trial Research Group (2000) · Diabetes Care · doi:10.2337/diacare.23.8.1084 · Cited by 385 · see citing works
The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes
Kilpatrick, E. S., Rigby, A. S., & Atkin, S. L. (2006) · Diabetes Care · doi:10.2337/dc06-0293 · Cited by 376 · see citing works
Self-citationMonnier, L., & Colette, C. (2008) · Diabetes Care · doi:10.2337/dc08-s241 · Cited by 267 · see citing works
Predictive Accuracy and Explained Variation in Cox Regression
SCHEMPER, M., & Henderson, R. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00249.x · Cited by 221 · see citing works
Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes
Wentholt, I. M. E., Kulik, W., Michels, R. P. J., Hoekstra, J. B. L., & DeVries, J. H. (2007) · Diabetologia · doi:10.1007/s00125-007-0842-6 · Cited by 203 · see citing works
Hypothesis: the ‘metabolic memory’, the new challenge of diabetes
Ihnat, M. A., Thorpe, J. E., & Ceriello, A. (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02138.x · Cited by 167 · see citing works
McCarter, R., Hempe, J. M., & Chalew, S. A. (2006) · Diabetes Care · doi:10.2337/diacare.29.02.06.dc05-1594 · Cited by 126 · see citing works
Prince, C. T., Becker, D. J., Costacou, T., Miller, R. G., & Orchard, T. J. (2007) · Diabetologia · doi:10.1007/s00125-007-0797-7 · Cited by 115 · see citing works
Service, F. J., & O'Brien, P. C. (2001) · Diabetologia · doi:10.1007/s001250100635 · Cited by 106 · see citing works
Kilpatrick, E. S., Rigby, A. S., & Atkin, S. L. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2006.079756 · Cited by 96 · see citing works
Self-citationKilpatrick, E. S., Rigby, A. S., & Atkin, S. L. (2007) · Diabetologia · doi:10.1007/s00125-007-0883-x · Cited by 85 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
A practical review of C-peptide testing in diabetes
Leighton, E., Sainsbury, C. A., & Jones, G. C. (2017) · Diabetes Therapy · doi:10.1007/s13300-017-0265-4 · Cited by 773 · see citing works
Glycaemic variability in diabetes: clinical and therapeutic implications
Ceriello, A., Monnier, L., & Owens, D. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30136-0 · Cited by 588 · see citing works
Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis
Gorst, C., Kwok, C. S., Aslam, S., Buchan, I., Kontopantelis, E., Myint, P. K., Heatlie, G., Loke, Y., Rutter, M. K., & Mamas, M. A. (2015) · Diabetes Care · doi:10.2337/dc15-1188 · Cited by 530 · see citing works
Lu, J., Ma, X., Zhou, J., Zhang, L., Mo, Y., Ying, L., Lu, W., Zhu, W., Bao, Y., Vigersky, R. A., et al. (2018) · Diabetes Care · doi:10.2337/dc18-1131 · Cited by 517 · see citing works
Glucose Variability; Does It Matter?
Siegelaar, S. E., Holleman, F., Hoekstra, J. B. L., & DeVries, J. H. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0021 · Cited by 409 · see citing works
Lenoir, O., Jasiek, M., Hénique, C., Guyonnet, L., Hartleben, B., Bork, T., Chipont, A., Flosseau, K., Bensaada, I., Schmitt, A., et al. (2015) · Autophagy · doi:10.1080/15548627.2015.1049799 · Cited by 296 · see citing works
Cardoso, C. R. L., Leite, N. C., Moram, C. B. M., & Salles, G. F. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0677-0 · Cited by 222 · see citing works
Sun, B., Luo, Z., & Zhou, J. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-020-01200-7 · Cited by 168 · see citing works
Xu, F., Zhao, L.-H., Su, J.-B., Chen, T., Wang, X.-Q., Chen, J.-F., Wu, G., Jin, Y., & Wang, X.-H. (2014) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-6-139 · Cited by 159 · see citing works
Glycemic variability and cardiovascular disease in patients with type 2 diabetes
Martinez, M., Santamarina, J., Pavesi, A., Musso, C., & Umpierrez, G. E. (2021) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2020-002032 · Cited by 155 · see citing works
Glycemic Variation and Cardiovascular Risk in the Veterans Affairs Diabetes Trial
Zhou, J. J., Schwenke, D. C., Bahn, G., & Reaven, P. (2018) · Diabetes Care · doi:10.2337/dc18-0548 · Cited by 131 · see citing works
Glycemic Variability: Both Sides of the Story
Ceriello, A., & Kilpatrick, E. S. (2013) · Diabetes Care · doi:10.2337/dcs13-2030 · Cited by 111 · see citing works
Self-citationVirk, S. A., Donaghue, K. C., Cho, Y. H., Benitez-Aguirre, P., Hing, S., Pryke, A., Chan, A., & Craig, M. E. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-3604 · Cited by 109 · see citing works
Tumminia, A., Crimi, S., Sciacca, L., Buscema, M., Frittitta, L., Squatrito, S., Vigneri, R., & Tomaselli, L. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2557 · Cited by 100 · see citing works
Famulla, S., Pieber, T. R., Eilbracht, J., Neubacher, D., Soleymanlou, N., Woerle, H. J., Broedl, U. C., & Kaspers, S. (2017) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2016.0261 · Cited by 53 · see citing works
The impact of glycemic variability on diabetic peripheral neuropathy
Jin, H. Y., Lee, K. A., & Park, T. S. (2016) · Endocrine · doi:10.1007/s12020-016-1005-7 · Cited by 49 · see citing works
Significance of Glycemic Variability in Diabetes Mellitus
Kusunoki, Y., Konishi, K., Tsunoda, T., & Koyama, H. (2022) · Internal Medicine · doi:10.2169/internalmedicine.8424-21 · Cited by 40 · see citing works
Livingstone, R., Boyle, J. G., & Petrie, J. R. (2020) · Diabetic Medicine · doi:10.1111/dme.13911 · Cited by 34 · see citing works
Han, X., Zhang, X., Liu, Z., Fan, H., Guo, C., Wang, H., Gu, Y., & Zhang, T. (2024) · Journal of Diabetes · doi:10.1111/1753-0407.13564 · Cited by 11 · see citing works
- Authors
- Kilpatrick, E. S., Rigby, A. S., & Atkin, S. L.
- Affiliations
- Hull Royal Infirmary (GB)
- University of Hull (GB)
- Hull York Medical School (GB)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2008-11-01
- Volume
- 31
- Issue
- 11
- Pages
- 2198-2202
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC2571045
- OpenAlex
- W1992458693
- Cited by
- 420
- References
- 26
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 20 · 2023: 17 · 2022: 18 · 2021: 30 · 2020: 25 · 2019: 30 · 2018: 49 · 2017: 26 · 2016: 25 · 2015: 28 · 2014: 23 · 2013: 22 · 2012: 22
- FWCI
- 15.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, other-oa)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
- Keywords
- glycemic variability, HbA1c variability, type 1 diabetes, diabetic retinopathy, diabetic nephropathy, microvascular complications, glycemic control, Diabetes Control and Complications Trial
- MeSH terms
- Diabetes Mellitus, Type 1, Diabetic Neuropathies, Diabetic Retinopathy, Glycated Hemoglobin, Humans, Risk Factors, Proportional Hazards Models, Disease Progression, Risk Assessment
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