The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Death during Intensive Glycemic Therapy of Diabetes: Mechanisms and Implications
Open accessAbstract
Despite its documented microvascular1–3 and potential macrovascular4,5 benefits in both type 1 and type 2 diabetes mellitus, intensive glycemic therapy was not found to produce macrovascular benefits, let alone survival benefits, in three recent randomized clinical trials: Action to Control Cardiovascular Risk in Diabetes (ACCORD),6 Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE),7 and Veterans Affairs Diabetes Trial (VADT).8 Similarly, it was not found to produce a survival benefit in hyperglycemic intensive care unit patients.9–11 Indeed, intensive glycemic therapy resulted in increased mortality in one large trial involving patients with type 2 diabetes6 and in another large trial involving critically ill individuals (Normoglycemia in Intensive Care—Survival Using Glucose Algorithm Regulation (NICE-SUGAR)).9 Regardless of the specific causative mechanisms, the latter findings are of concern. It appears that some aspect of intensive therapy increased the risk of death.
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“The primary cause of hypoglycemia is intensification of antihyperglycemic therapy (almost always using SUs [or to a lesser extent glinides] and/or insulin) aimed at achieving lower A1C targets, as demonstrated by intensive therapy trials.1202,1203”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1203]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“On the other hand, HAAF is clearly maladaptive since defective glucose counterregulation and hypoglycemia unawareness substantially increase the risk of severe hypoglycemia with its morbidity and potential mortality (26).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
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“Hypoglycemia puts patients at risk for injury and death.”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
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“Although profound and prolonged hypoglycemia can cause brain death, most episodes of fatal hypoglycemia are probably the result of other mechanisms, such as ventricular arrhythmias (26).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
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“Although profound and prolonged hypoglycemia can cause brain death, most episodes of fatal hypoglycemia are probably the result of other mechanisms, such as ventricular arrhythmias (26).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
In the citing paper
“There is no doubt that hypoglycemia can be fatal (26).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
In the citing paper
“On the other hand, HAAF is clearly maladaptive since defective glucose counterregulation and hypoglycemia unawareness substantially increase the risk of severe hypoglycemia with its morbidity and potential mortality (26).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
In the citing paper
“Although profound and prolonged hypoglycemia can cause brain death, most episodes of fatal hypoglycemia are probably the result of other mechanisms, such as ventricular arrhythmias (26).”
From Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013) · cites this paper as [26]
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Citations
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Seaquist, E. R., Anderson, J., Childs, B., Cryer, P., Dagogo-Jack, S., Fish, L., Heller, S. R., Rodriguez, H., Rosenzweig, J., & Vigersky, R. (2013) · Diabetes Care · doi:10.2337/dc12-2480 · Cited by 1,389
“Although profound and prolonged hypoglycemia can cause brain death, most episodes of fatal hypoglycemia are probably the result of other mechanisms, such as ventricular arrhythmias (26).”
BackgroundInfluentialSelf-citationGarber, A. J., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bloomgarden, Z. T., Bush, M. A., Dagogo-Jack, S. E., DeFronzo, R. A., EINHORN, D. F., Fonseca, V. A., et al. (2016) · Endocrine Practice · doi:10.4158/ep151126.cs · Cited by 879
Handelsman, Y., Bloomgarden, Z. T., Grunberger, G., Umpierrez, G. E., Zimmerman, R. S., Bailey, T. S., Blonde, L., Bray, G. A., Cohen, A. J., Dagogo-Jack, S. E., et al. (2015) · Endocrine Practice · doi:10.4158/ep15672.gl · Cited by 646
Garber, A. J., Handelsman, Y., Grunberger, G., Einhorn, D., Abrahamson, M. J., Barzilay, J. I., Blonde, L., Bush, M. A., DeFronzo, R. A., Garber, J. R., et al. (2020) · Endocrine Practice · doi:10.4158/cs-2019-0472 · Cited by 598
Handelsman, Y., Bloomgarden, Z. T., Grunberger, G., Umpierrez, G., Zimmerman, R. S., Bailey, T. S., Blonde, L., Bray, G. A., Cohen, A. J., Dagogo-Jack, S., et al. (2015) · Endocrine Practice · doi:10.4158/ep15672.glsuppl · Cited by 559
Metadata
- Authors
- Cryer, P. E.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Cryer, Philip E.
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 124
- Issue
- 11
- Pages
- 993-996
- ISSN
- 0002-9343 (ISSN-L)
- PMC
- PMC3464092
- OpenAlex
- W2044277864
- Semantic Scholar
- bcc2ac94423ef826cfcd974b1f808d52497258e4
- Cited by
- 137
- References
- 68
- Citations by year
- 2025: 5 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 15 · 2018: 8 · 2017: 10 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 18 · 2012: 10
- FWCI
- 10.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Bristol-Myers Squibb
- AstraZeneca
- MannKind Corporation
- Novo Nordisk
- National Institutes of Health (5p60dk020579-35, DK20579, P60-DK-20579, RR‐00036)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK027085, P60-DK20579, R37-DK27085, T32 DK07120, P60-DK-020579, T32DK007120)
- National Center for Research Resources (UL1-RR-24992, M01-RR00036, UL1RR024992, M01RR000036)
- 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 › Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Keywords
- diabetes mortality, type 1 diabetes, type 2 diabetes, cardiovascular risk, tight glycemic control, cardiovascular complications
- MeSH terms
- Female, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Hospital Mortality
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