Glucose Variability; Does It Matter?

Siegelaar, Sarah E.; Holleman, Frits; Hoekstra, Joost B. L.; DeVries, J. Hans

doi:10.1210/er.2009-0021

Cited by 410Diabetes Management and ResearchDiabetes Treatment and ManagementHyperglycemia and glycemic control in critically ill and hospitalized patients

Glucose Variability; Does It Matter?

Siegelaar, Sarah E., Holleman, Frits, Hoekstra, Joost B. L., DeVries, J. Hans·2010·Endocrine Reviews

DOI 10.1210/er.2009-0021

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Abstract

Overall lowering of glucose is of pivotal importance in the treatment of diabetes, with proven beneficial effects on microvascular and macrovascular outcomes. Still, patients with similar glycosylated hemoglobin levels and mean glucose values can have markedly different daily glucose excursions. The role of this glucose variability in pathophysiological pathways is the subject of debate. It is strongly related to oxidative stress in in vitro, animal, and human studies in an experimental setting. However, in real-life human studies including type 1 and type 2 diabetes patients, there is neither a reproducible relation with oxidative stress nor a correlation between short-term glucose variability and retinopathy, nephropathy, or neuropathy. On the other hand, there is some evidence that long-term glycemic variability might be related to microvascular complications in type 1 and type 2 diabetes. Regarding mortality, a convincing relationship with short-term glucose variability has only been demonstrated in nondiabetic, critically ill patients. Also, glucose variability may have a role in the prediction of severe hypoglycemia. In this review, we first provide an overview of the various methods to measure glucose variability. Second, we review current literature regarding glucose variability and its relation to oxidative stress, long-term diabetic complications, and hypoglycemia. Finally, we make recommendations on whether and how to target glucose variability, concluding that at present we lack both the compelling evidence and the means to target glucose variability separately from all efforts to lower mean glucose while avoiding hypoglycemia.

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Glycemic variability is associated with increased risk of hypoglycemia in patients with diabetes, independently of glycated hemoglobin level.
“Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level.”
From Glycemic variability and cardiovascular disease in patients with type 2 diabetes (2021) · cites this paper as [15]

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NLRP3 Inflammasome at the Interface of Inflammation, Endothelial Dysfunction, and Type 2 Diabetes
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Glycemic Variability Is Higher in Type 1 Diabetes Patients with Microvascular Complications Irrespective of Glycemic Control
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Diabetic Complications: Current Challenges and Opportunities
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Glycemic Variability: Risk Factors, Assessment, and Control
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The Roles of Glycated Albumin as Intermediate Glycation Index and Pathogenic Protein
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GDF15 Is a Novel Biomarker for Impaired Fasting Glucose
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Chronic Fatigue in Type 1 Diabetes: Highly Prevalent but Not Explained by Hyperglycemia or Glucose Variability
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A Decrease in Glucose Variability Does Not Reduce Cardiovascular Event Rates in Type 2 Diabetic Patients After Acute Myocardial Infarction
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Ultrafast-Acting Insulins: State of the Art
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Postprandial and Basal Glucose in Type 2 Diabetes: Assessment and Respective Impacts
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Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in Type 2 diabetes
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The Challenges of Measuring Glycemic Variability
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Glycemic Variability and CNS Inflammation: Reviewing the Connection
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Increased Postoperative Glucose Variability Is Associated with Adverse Outcomes Following Total Joint Arthroplasty
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Visit-to-Visit Variations in Fasting Plasma Glucose and HbA1c Associated With an Increased Risk of Alzheimer Disease: Taiwan Diabetes Study
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A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet—A Cross-Over Controlled Inpatient Dietary Study
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Effects of Fluctuating Glucose Levels on Neuronal Cells In Vitro
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High Glucose Variability Increases Mortality Risk in Hospitalized Patients
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Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study)
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HbA1C Variability Is Strongly Associated With the Severity of Peripheral Neuropathy in Patients With Type 2 Diabetes
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Functional and proteomic alterations of plasma high density lipoproteins in type 1 diabetes mellitus
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Assessment of glucose variability in subjects with prediabetes
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Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function
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Hypoglycemia and risk of vascular events and mortality: a systematic review and meta-analysis
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Glycemic Variability: Assessing Glycemia Differently and the Implications for Dietary Management of Diabetes
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Lipid peroxidation is associated with poor control of type-2 diabetes mellitus
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Variability Analysis and the Diagnosis, Management, and Treatment of Sepsis
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The Effects of Glucose Fluctuation on the Severity of Coronary Artery Disease in Type 2 Diabetes Mellitus
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Glucose variability and diabetes complications: Risk factor or biomarker? Can we disentangle the “Gordian Knot”?
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Web-based cognitive behavioural therapy blended with face-to-face sessions for chronic fatigue in type 1 diabetes: a multicentre randomised controlled trial
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Accurate Carbohydrate Counting Is an Important Determinant of Postprandial Glycemia in Children and Adolescents With Type 1 Diabetes on Insulin Pump Therapy
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Exhaled volatile substances in children suffering from type 1 diabetes mellitus: results from a cross-sectional study
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Glucose variability and the risks of stroke, myocardial infarction, and all-cause mortality in individuals with diabetes: retrospective cohort study
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Glycemic Variability in Nondiabetic Morbidly Obese Persons
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Glycemic Variability: Measurement and Utility in Clinical Medicine and Research—One Viewpoint
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No Relevant Relationship between Glucose Variability and Oxidative Stress in Well-Regulated Type 2 Diabetes Patients
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Glycemic Variability and Acute Ischemic Stroke: The Missing Link?
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Glucose control positively influences patient outcome: A retrospective study
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Potentiation of the early-phase insulin response by a prior meal contributes to the second-meal phenomenon in type 2 diabetes
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Association between breakfast skipping and postprandial hyperglycaemia after lunch in healthy young individuals
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Continuous Glucose Monitoring in Insulin-Treated Patients in Non-ICU Settings
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Evaluation of a Minimally Invasive System for Measuring Glucose Area under the Curve during Oral Glucose Tolerance Tests: Usefulness of Sweat Monitoring for Precise Measurement
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Perspectives of glycemic variability in diabetic neuropathy: a comprehensive review
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Insulin Analogs—Is There a Compelling Case to Use Them? No!
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Glucose Variability is an Independent Predictor of Mortality in Hospitalized Patients Treated with Total Parenteral Nutrition
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Data-Driven Personalized Feedback to Patients with Type 1 Diabetes: A Randomized Trial
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Effects of glycemic variability and hyperglycemia in acute ischemic stroke on post-stroke cognitive impairments
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Association between Visit-to-Visit Glucose Variability and Cognitive Function in Aged Type 2 Diabetic Patients: A Cross-Sectional Study
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Mobile Phone-Based Pattern Recognition and Data Analysis for Patients with Type 1 Diabetes
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Effect of Low Carbohydrate Diet on Type 2 Diabetic Patients and Usefulness of M-Value
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Authors: Siegelaar, S. E., Holleman, F., Hoekstra, J. B. L., & DeVries, J. H.
Affiliations: Amsterdam UMC Location University of Amsterdam (NL)
Corresponding author: Siegelaar, Sarah E.
ORCID: Siegelaar, Sarah E.
Holleman, Frits
DeVries, J. Hans
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 2010-04-01
Volume: 31
Issue: 2
Pages: 171-182
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/er.2009-0021
OpenAlex: W2100202103
Cited by: 409
References: 80
Citations by year: 2026: 6 · 2025: 10 · 2024: 11 · 2023: 13 · 2022: 28 · 2021: 25 · 2020: 25 · 2019: 30 · 2018: 30 · 2017: 25 · 2016: 26 · 2015: 33 · 2014: 40 · 2013: 37 · 2012: 30
FWCI: 4.79
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
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: glycemic variability, type 1 diabetes, type 2 diabetes, oxidative stress, microvascular complications, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, hypoglycemia, glycemic control, HbA1c, glycemic excursions, mortality
MeSH terms: Animals, Blood Glucose, Diabetes Mellitus, Humans, Hypoglycemia, Insulin, Blood Glucose Self-Monitoring, Oxidative Stress, Diabetes Complications

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Glucose Variability; Does It Matter?

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