Skip to main content
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes Care

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes Care
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • Special Article Collections
    • ADA Standards of Medical Care
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • Special Article Collections
    • ADA Standards of Medical Care
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Emerging Science and Concepts for Management of Diabetes and Aging

Is HbA1c <7% a Marker of Poor Performance in Individuals >65 Years Old?

  1. Zachary T. Bloomgarden1⇑,
  2. Daniel Einhorn2,3 and
  3. Yehuda Handelsman4
  1. 1Icahn School of Medicine at Mount Sinai, New York, NY
  2. 2University of California, San Diego, San Diego, CA
  3. 3Scripps Whittier Diabetes Institute, San Diego, CA
  4. 4Metabolic Institute of America, Tarzana, CA
  1. Corresponding author: Zachary T. Bloomgarden, zbloom{at}gmail.com.
Diabetes Care 2017 Apr; 40(4): 526-528. https://doi.org/10.2337/dci16-0043
PreviousNext
  • Article
  • Info & Metrics
  • PDF
Loading

In this issue of Diabetes Care, Pogach et al. (1) raise reasonable concepts of the dangers of hypoglycemia as a criterion for assessing glycemic control, but the authors suggest a performance measure pertaining to glycemic control of persons with diabetes with which we disagree. They propose an out-of-range measure of having either HbA1c <7.0% or HbA1c >9.0%, “for patients aged ≥65 years with diabetes and significant comorbid conditions taking antihyperglycemic agents other than metformin alone.” The presence of a “significant comorbid condition” was primarily driven by cardiovascular disease but also included persons with serum creatinine >1.7 mg/dL, cognitive impairment, diabetic retinopathy, major depression, and/or substance abuse. This out-of-range concept certainly merits discussion. Indeed, the notion has recently been put forward that HbA1c <7% is comparable to overuse of anticoagulation for atrial fibrillation, to inappropriate testosterone supplementation, and to opiate use after overdose (2). The strength of the suggested approach might be said to be its appearance of symmetry, given our recognition that excessive glucose lowering may be associated with adverse outcomes. We assert, however, that it is a fundamental error to confound good control with hypoglycemia; the reality, we suggest, is that while hypoglycemia should certainly be considered an adverse outcome, it is not the achievement of glycemic control that is undesirable but rather the excessive use of hypoglycemia-causing treatments. Interestingly, the out-of-range measure showed inverse correlation with what Pogach et al. term the standard measure of HbA1c, <8%. A total of 11.7% of the studied population had HbA1c >9%, but 35.7% had HbA1c <7.0%; those deemed by Pogach et al. to be out of range are, primarily, persons at an HbA1c level currently considered evidence of appropriate treatment.

Is there evidence that better glycemic control is undesirable for older persons with other medical conditions? Are those individuals with HbA1c <7.0% more likely than those with higher HbA1c levels to experience hypoglycemia and adverse outcomes? This idea appears to stem from an interpretation of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veterans Affairs Diabetes Trial (VADT) studies, in which therapies were carried out to improve glycemic control without explicit efforts to avoid hypoglycemia. Although neither trial was restricted to persons ≥65 years of age, in both trials the preponderance of enrollees had cardiovascular disease or were at high risk, with mean ages 62.2 and 60.4 years, respectively. Progression of diabetic retinopathy, explicitly mentioned by Pogach et al. (1) as a significant comorbid condition, was reduced by more than half among participants in ACCORD undergoing intensive rather than standard glycemic treatment (3). Furthermore, allocation to intensive rather than standard glycemic treatment in ACCORD significantly reduced myocardial infarction, coronary revascularization, and unstable angina, an effect explained by the reduction in HbA1c (4). It is noteworthy that a significant increase in mortality was seen only in the intensive intervention arm of ACCORD among persons with baseline HbA1c >8.5% (5); such individuals were less likely to have on-trial mean HbA1c <7%. Those randomized to intensive treatment who achieved lower HbA1c levels actually had lower mortality rates than the control group, while those whose on-trial HbA1c levels were higher were the ones whose mortality rates increased (6). Indeed, epidemiologic evidence suggests that hypoglycemia frequency only increases at relatively low HbA1c (below 6%), and there is also a trend to increased hypoglycemia frequency at HbA1c >9% (7), a pattern similar to that seen in ACCORD (8). The view proposed by Pogach et al. is further contradicted by the findings of recent cardiovascular outcome trials for empagliflozin (9), liraglutide (10), semaglutide (11), and (in an insulin-resistant nondiabetic population) pioglitazone (12). These trials included participants with mean ages 63.1, 64.3, 64.7, and 63.5, respectively, rather than being restricted to those ≥65 years of age. All showed evidence of improvement in coronary disease and/or stroke outcome with glucose-lowering agents having low intrinsic association with hypoglycemia, in persons with or at high risk of cardiovascular disease, for whom the proposed out-of-range measure would lead to less use of glucose-lowering treatments.

Of further importance is the recognition that HbA1c varies with erythrocyte kinetics (13). Conditions that artifactually lower HbA1c levels, such as the more rapid erythrocyte turnover seen in anemia (14), were not taken into account in the analysis reported by Pogach et al. (1). Renal insufficiency, even below the authors’ creatinine cutoff of 1.7 mg/dL, also results in HbA1c levels below those typical of the prevailing blood glucose concentrations (15). By selecting only those persons with diabetes with “high-risk” conditions, the authors may have overselected those who would be expected to have such nonglycemic HbA1c lowering, increasing their inclusion in the “overtreatment” category. Such individuals would also be expected to have increased likelihood of adverse outcomes, leading to the conceptual error that appears to underlie the proposed out-of-range measure. In contrast, HbA1c increases with age for a given level of glycemia (16). We question the supposition by Pogach et al. that age per se represents a suitable marker of risk, given the evidence of increasing population life expectancy (17), even into the ninth decade (18). Comorbidities appear to us to be better predictors for both the risk of and the risk from hypoglycemia for a given individual (19) and should remind us to avoid agents likely to cause hypoglycemia.

The notion that hypoglycemia avoidance should be included in diabetes treatment performance measure initiatives has been advanced (20), and we agree. However, we recommend more nuance and different cutoffs. Based on our reading of the literature, an HbA1c >8% is associated with poorer outcomes, even in populations at high cardiovascular risk such as those participating in the ACCORD (5) and Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) (21) trials, so that would be our upper limit. For the lower limit, the real issue is hypoglycemia. Since ≤6.5% is considered the target in some guidelines (22) and <7% the target for most guidelines, we suggest that a lower cutoff of 6.5% only be used if the individual is taking medication likely to cause hypoglycemia. We do recognize that, in effect, Pogach et al. (1) are arguing that sulfonylureas have an undesirable association with hypoglycemia. This position has been firmly taken in the Comprehensive Type 2 Diabetes Management Algorithm of the American Association of Clinical Endocrinologists and American College of Endocrinology (22), and we would not be averse to considering the use of nonsulfonylurea hypoglycemic treatments as a “good performance” measure. As it stands, however, although it appears superficially attractive to have a “balanced” approach rejecting both low and high HbA1c, we would respectfully suggest that better control using specific approaches to avoid hypoglycemia is indeed better for the vast majority of persons with diabetes, including populations with cardiovascular disease and diabetic retinopathy such as those analyzed by Pogach et al.

Article Information

Duality of Interest. Z.T.B. has been a consultant/advisor for AstraZeneca, Johnson & Johnson, Merck, Intarcia, and Novartis; a speaker for Merck, AstraZeneca, and Johnson & Johnson; and is a stockholder in Allergan, Pfizer, Zimmer Biomet, and Novartis. D.E. has been a consultant for Eli Lilly, Novo Nordisk, Sanofi, Janssen, Adocia, Medtronic, Takeda, Halozyme, Freedom Meditech, Epitracker, Nexus BioPharma, Intarcia, and GlySens; has been involved with research for Eli Lilly, Novo Nordisk, Sanofi, MannKind, Janssen, AstraZeneca, Freedom Meditech, and Adocia; and is a shareholder in Halozyme, GlySens, Epitracker, Nexus BioPharma, and Freedom Meditech. Y.H. has received research grants and consultant and speaker honoraria from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Boehringer Ingelheim–Eli Lilly, Esperion, Grifols, GlaxoSmithKline-Hanmi, Intarcia, Janssen, Lexicon, Eli Lilly, Merck, Novo Nordisk, Pfizer, Regeneron, and Sanofi. No other potential conflicts of interest relevant to this article were reported.

Footnotes

  • See accompanying articles, pp. 440, 444, 453, 461, 468, 476, 485, 494, 502, 509, and 518.

  • © 2017 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

References

  1. ↵
    1. Pogach L,
    2. Tseng C-L,
    3. Soroka O,
    4. Maney M,
    5. Aron D.
    A proposal for an out-of-range glycemic population health safety measure for older adults with diabetes. Diabetes Care 2017;40:518–525
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Morgan DJ,
    2. Dhruva SS,
    3. Wright SM,
    4. Korenstein D
    . 2016 update on medical overuse: a systematic review. JAMA Intern Med 2016;176:1687–1692pmid:27654002
    OpenUrlPubMed
  3. ↵
    1. Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group; Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group
    . Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Follow-On study. Diabetes Care 2016;39:1089–1100pmid:27289122
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Gerstein HC,
    2. Miller ME,
    3. Ismail-Beigi F, et al.; ACCORD Study Group
    . Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet 2014;384:1936–1941pmid:25088437
    OpenUrlCrossRefPubMedWeb of Science
  5. ↵
    1. Calles-Escandón J,
    2. Lovato LC,
    3. Simons-Morton DG, et al
    . Effect of intensive compared with standard glycemia treatment strategies on mortality by baseline subgroup characteristics: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010;33:721–727pmid:20103550
    OpenUrlAbstract/FREE Full Text
  6. ↵
    1. Riddle MC,
    2. Ambrosius WT,
    3. Brillon DJ, et al.; Action to Control Cardiovascular Risk in Diabetes Investigators
    . Epidemiologic relationships between A1C and all-cause mortality during a median 3.4-year follow-up of glycemic treatment in the ACCORD trial. Diabetes Care 2010;33:983–990pmid:20427682
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Lipska KJ,
    2. Warton EM,
    3. Huang ES, et al
    . HbA1c and risk of severe hypoglycemia in type 2 diabetes: the Diabetes and Aging Study. Diabetes Care 2013;36:3535–3542pmid:23900589
    OpenUrlAbstract/FREE Full Text
  8. ↵
    1. Miller ME,
    2. Bonds DE,
    3. Gerstein HC, et al.; ACCORD Investigators
    . 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:b5444pmid:20061360
    OpenUrlAbstract/FREE Full Text
  9. ↵
    1. Zinman B,
    2. Wanner C,
    3. Lachin JM, et al.; EMPA-REG OUTCOME Investigators
    . Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–2128pmid:26378978
    OpenUrlCrossRefPubMed
  10. ↵
    1. Marso SP,
    2. Daniels GH,
    3. Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators
    . Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–322pmid:27295427
    OpenUrlCrossRefPubMed
  11. ↵
    Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834–1844
  12. ↵
    1. Kernan WN,
    2. Viscoli CM,
    3. Furie KL, et al.; IRIS Trial Investigators
    . Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 2016;374:1321–1331pmid:26886418
    OpenUrlCrossRefPubMed
  13. ↵
    1. Malka R,
    2. Nathan DM,
    3. Higgins JM
    . Mechanistic modeling of hemoglobin glycation and red blood cell kinetics enables personalized diabetes monitoring. Sci Transl Med 2016;8:359ra130pmid:27708063
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Ford ES,
    2. Cowie CC,
    3. Li C,
    4. Handelsman Y,
    5. Bloomgarden ZT
    . Iron-deficiency anemia, non-iron-deficiency anemia and HbA1c among adults in the US. J Diabetes 2011;3:67–73pmid:20942846
    OpenUrlCrossRefPubMed
  15. ↵
    1. Lo C,
    2. Lui M,
    3. Ranasinha S, et al
    . Defining the relationship between average glucose and HbA1c in patients with type 2 diabetes and chronic kidney disease. Diabetes Res Clin Pract 2014;104:84–91pmid:24573088
    OpenUrlCrossRefPubMed
  16. ↵
    1. Pani LN,
    2. Korenda L,
    3. Meigs JB, et al
    . Effect of aging on A1C levels in individuals without diabetes: evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001-2004. Diabetes Care 2008;31:1991–1996pmid:18628569
    OpenUrlAbstract/FREE Full Text
  17. ↵
    1. Cao B.
    Future healthy life expectancy among older adults in the US: a forecast based on cohort smoking and obesity history. Popul Health Metr 2016;14:23
  18. ↵
    1. Broad JB,
    2. Dunstan K,
    3. Claridge A,
    4. Harris R
    . Am I too old for this, Doctor? Using population life expectancy to guide clinical decision-making. Australas J Ageing. 27 October 2016 [Epub ahead of print]. DOI: 10.1111/ajag.12355pmid:27785890
    OpenUrlCrossRefPubMed
  19. ↵
    1. Eldor R,
    2. Raz I
    . The individualized target HbA1c: a new method for improving macrovascular risk and glycemia without hypoglycemia and weight gain. Rev Diabet Stud 2009;6:6–12pmid:19557292
    OpenUrlCrossRefPubMed
  20. ↵
    1. Rodriguez-Gutierrez R,
    2. Ospina NS,
    3. McCoy RG,
    4. Lipska KJ,
    5. Shah ND,
    6. Montori VM
    ; Hypoglycemia as a Quality Measure in Diabetes Study Group. Inclusion of hypoglycemia in clinical practice guidelines and performance measures in the care of patients with diabetes. JAMA Intern Med 2016;176:1714–1716pmid:27653613
    OpenUrlPubMed
  21. ↵
    1. Zoungas S,
    2. Chalmers J,
    3. Ninomiya T, et al.; ADVANCE Collaborative Group
    . Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds. Diabetologia 2012;55:636–643pmid:22186981
    OpenUrlCrossRefPubMedWeb of Science
  22. ↵
    1. Garber AJ,
    2. Abrahamson MJ,
    3. Barzilay JI, et al.; American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE)
    . Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm–2016 Executive Summary. Endocr Pract 2016;22:84–113pmid:26731084
    OpenUrlCrossRefPubMed
PreviousNext
Back to top
Diabetes Care: 40 (4)

In this Issue

April 2017, 40(4)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by Author
  • Masthead (PDF)
Sign up to receive current issue alerts
View Selected Citations (0)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about Diabetes Care.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Is HbA1c 65 Years Old?
(Your Name) has forwarded a page to you from Diabetes Care
(Your Name) thought you would like to see this page from the Diabetes Care web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Is HbA1c <7% a Marker of Poor Performance in Individuals >65 Years Old?
Zachary T. Bloomgarden, Daniel Einhorn, Yehuda Handelsman
Diabetes Care Apr 2017, 40 (4) 526-528; DOI: 10.2337/dci16-0043

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Add to Selected Citations
Share

Is HbA1c <7% a Marker of Poor Performance in Individuals >65 Years Old?
Zachary T. Bloomgarden, Daniel Einhorn, Yehuda Handelsman
Diabetes Care Apr 2017, 40 (4) 526-528; DOI: 10.2337/dci16-0043
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Article Information
    • Footnotes
    • References
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations
  • Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006–2013
  • A Proposal for an Out-of-Range Glycemic Population Health Safety Measure for Older Adults With Diabetes
Show more Emerging Science and Concepts for Management of Diabetes and Aging

Similar Articles

Navigate

  • Current Issue
  • Standards of Care Guidelines
  • Online Ahead of Print
  • Archives
  • Submit
  • Subscribe
  • Email Alerts
  • RSS Feeds

More Information

  • About the Journal
  • Instructions for Authors
  • Journal Policies
  • Reprints and Permissions
  • Advertising
  • Privacy Policy: ADA Journals
  • Copyright Notice/Public Access Policy
  • Contact Us

Other ADA Resources

  • Diabetes
  • Clinical Diabetes
  • Diabetes Spectrum
  • Scientific Sessions Abstracts
  • Standards of Medical Care in Diabetes
  • BMJ Open - Diabetes Research & Care
  • Professional Books
  • Diabetes Forecast

 

  • DiabetesJournals.org
  • Diabetes Core Update
  • ADA's DiabetesPro
  • ADA Member Directory
  • Diabetes.org

© 2021 by the American Diabetes Association. Diabetes Care Print ISSN: 0149-5992, Online ISSN: 1935-5548.