CoChat
Sign Up
Cited by 70Diabetes Treatment and ManagementHeart Failure Treatment and ManagementDiabetes Management and Research

Association of Long-term Change and Variability in Glycemia With Risk of Incident Heart Failure Among Patients With Type 2 Diabetes: A Secondary Analysis of the ACCORD Trial

Open access
Segar, Matthew W., Patel, Kershaw V., Vaduganathan, Muthiah, Caughey, Melissa C., Butler, Javed, Fonarow, Gregg C., Grodin, Justin L., McGuire, Darren K. +1 more·2020·Diabetes Care
DOI 10.2337/dc19-2541PMC PMC7876556
Open this paper in CoChat — free account

Abstract

OBJECTIVE: To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF. RESULTS: The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08–1.75] and for ≥10% increase 1.55 [1.19–2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17–1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability. CONCLUSIONS: Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.2337/dc19-2541

Cites

0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • People with diabetes are at particularly high risk for progression from asymptomatic stage A and B to symptomatic stage C and D heart failure.

    “People with diabetes are at particularly high risk for progression from asymptomatic stage A and B to symptomatic stage C and D heart failure (219,220).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [219]

    The Conclusions (p. 2) say heart failure is common among adults with type 2 diabetes, and the Results (p. 4) document incident heart-failure events in participants without prior heart failure. The paper does not classify participants by heart-failure stage or establish that people with diabetes are particularly likely, relative to others, to progress from stages A or B to C or D. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • People with diabetes are at particularly high risk for progression from asymptomatic stage A and B to symptomatic stage C and D heart failure.

    “People with diabetes are at particularly high risk for progression from asymptomatic stage A and B to symptomatic stage C and D heart failure (208,209).”

    From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [208]

    The Study Population section (p. 3) says participants had type 2 diabetes and no history of heart failure, and the outcome section (p. 3) tracks incident heart failure. The paper also says heart failure is common in adults with type 2 diabetes (Conclusions, p. 2). It does not establish a particularly high risk relative to people without diabetes or assess progression through stages A/B to C/D. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 30

  1. [1]1. BertoniAG,HundleyWG,MassingMW,Bonds DE,BurkeGL,GoffDCJr.Heartfailureprevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care 2004;27:699 -703
  2. [2]2. Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care 2004;27:1879 -1884
  3. [3]3. Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people. Lancet Diabetes Endocrinol 2015;3:105 -113
  4. [4]4. Pandey A, Patel KV, Bahnson JL, et al.; Look AHEADResearch Group. Association of intensive lifestyle intervention, fi tness, and body mass index with risk of heart failure in overweight or obese adults with type 2 diabetes mellitus: an analysis from the Look AHEAD trial. Circulation 2020;141:1295 -1306
  5. [5]5. Segar MW, Vaduganathan M, Patel KV, et al. Machine learning to predict the risk of incident heart failure hospitalization among patients with diabetes: the WATCH-DM Risk Score. Diabetes Care 2019;42:2298 -2306
  6. [6]6. Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001;103:2668 -2673
  7. [7]7. Thrainsdottir IS, Aspelund T, Thorgeirsson G, et al. The association between glucose abnormalitiesandheartfailureinthepopulationbased Reykjavik study. Diabetes Care 2005;28: 612 -616
  8. [9]9. Gerstein HC, Miller ME, Byington RP, et al.; Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358: 2545 -2559
  9. [10]10. Patel A, MacMahon S, Chalmers J, et al.; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358:2560 -2572
  10. [12]12. Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care 2010;33:1389 -1394
  11. [13]13. Zoungas S, Patel A, Chalmers J, et al.; ADVANCE Collaborative Group. Severe hypoglycemiaandrisksofvasculareventsanddeath.NEngl J Med 2010;363:1410 -1418
  12. [15]15. Gorst C, Kwok CS, Aslam S, et al. Long-term glycemicvariabilityandriskofadverseoutcomes: a systematic review and meta-analysis. Diabetes Care 2015;38:2354 -2369
  13. [16]16. CushmanWC,EvansGW,ByingtonRP,etal.; ACCORDStudyGroup.Effectsof intensive bloodpressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575 -1585
  14. [17]17. Buse JB, Bigger JT, Byington RP, et al.; ACCORD Study Group. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol 2007;99:21i -33i
  15. [19]19. Echouffo-Tcheugui JB, Zhao S, Brock G, Matsouaka RA, Kline D, Joseph JJ. Visit-to-visit glycemic variability and risks of cardiovascular events and all-cause mortality: the ALLHAT study. Diabetes Care 2019;42:486 -493
  16. [20]20. BondsDE,KurashigeEM, Bergenstal R, et al.; ACCORD Study Group. Severe hypoglycemia monitoring and risk management procedures in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 2007;99: 80i -89i
  17. [21]21. Pandey A, Keshvani N, Ayers C, et al. Association of cardiac injury and malignant left ventricular hypertrophy with risk of heart failure in African Americans: the Jackson Heart Study. JAMA Cardiol 2019;4:51 -58
  18. [22]22. WangJ, Shi X, Ma C, et al. Visit-to-visit blood pressure variability is a risk factor for all-cause mortality and cardiovascular disease: a systematic review and meta-analysis. J Hypertens 2017; 35:10 -17
  19. [23]23. Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 2001;24:1614 -1619
  20. [24]24. Parry HM, Deshmukh H, Levin D, et al. Both high and low HbA1c predict incident heart failure in type 2 diabetes mellitus. Circ Heart Fail 2015; 8:236 -242
  21. [25]25. MonnierL,MasE,GinetC,etal.Activation of oxidative stress by acute glucose fl uctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006;295: 1681 -1687
  22. [27]27. Nalysnyk L, Hernandez-Medina M, Krishnarajah G. Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature. Diabetes Obes Metab 2010;12:288 -298
  23. [28]28. Muggeo M, Verlato G, Bonora E, Zoppini G, Corbellini M, de Marco R. Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona Diabetes Study. Circulation 1997;96: 1750 -1754
  24. [29]29. Kwon S, Lee SR, Choi EK, et al. Visit-to-visit variability of metabolic parameters and risk of heart failure: a nationwide population-based study. Int J Cardiol 2019;293:153 -158
  25. [33]33. Tang X, Zhong J, Zhang H, et al. Visit-to-visit fasting plasma glucose variability is an important risk factor for long-term changes in left cardiac structure and function in patients with type 2 diabetes. Cardiovasc Diabetol 2019;18:50
  26. [34]34. Gottdiener JS, Arnold AM, Aurigemma GP, et al. Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2000;35:1628 -1637
  27. [35]35. Bangalore S, Fayyad R, Laskey R, DeMicco DA, Messerli FH, Waters DD. Body-weight fl uctuations and outcomes in coronary disease. N Engl J Med 2017;376:1332 -1340
  28. [36]36. Kim MK, Han K, Kim HS, et al. Cholesterol variability and the risk of mortality, myocardial infarction, and stroke: a nationwide populationbased study. Eur Heart J 2017;38:3560 -3566
  29. [37]37. Kim MK, Han K, Park YM, et al. Associations of variability in blood pressure, glucose and cholesterol concentrations, and body mass index with mortality and cardiovascular outcomes in the general population. Circulation 2018;138: 2627 -2637
  30. [38]38. Nishimura R, Osonoi T, Kanada S, et al. Effects of luseogli fl ozin, a sodium-glucose co-transporter 2 inhibitor, on 24-h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, crossover study. Diabetes Obes Metab 2015; 17:800 -804

Cited by

Sorted by citations

Authors
Segar, M. W., Patel, K. V., Vaduganathan, M., Caughey, M. C., Butler, J., Fonarow, G. C., Grodin, J. L., McGuire, D. K., & Pandey, A.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • Brigham and Women's Hospital (US)
  • University of North Carolina at Chapel Hill (US)
  • University of Mississippi Medical Center (US)
  • University of California, Los Angeles (US)
Corresponding author
Pandey, Ambarish
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2020-06-15
Volume
43
Issue
8
Pages
1920-1928
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc19-2541
PMC
PMC7876556
OpenAlex
W3034832116
Cited by
70
References
42
Citations by year
2026: 3 · 2025: 12 · 2024: 18 · 2023: 8 · 2022: 16 · 2021: 12 · 2020: 1
FWCI
6.98
Type
journal article
Language
en
Open access
Licence
www.diabetesjournals.org/content/license (vor, 35 d)
Locations
  • Diabetes Care (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (UL1TR002541)
  • National Heart, Lung, and Blood Institute (T32HL125247)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 2 diabetes, heart failure, glycemic variability, HbA1c, ACCORD trial, coefficient of variation, glycemic control
MeSH terms
Glycemic Control, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Female, Follow-Up Studies, Heart Failure, Glycated Hemoglobin, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Time Factors, Incidence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review