Microvascular complications of impaired glucose tolerance

Singleton, J. Robinson; Smith, A. Gordon; Russell, James W.; Feldman, Eva L.

doi:10.2337/diabetes.52.12.2867

Cited by 373Diabetes, Cardiovascular Risks, and LipoproteinsDiabetes Management and ResearchDiabetes Treatment and Management

Microvascular complications of impaired glucose tolerance

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Singleton, J. Robinson, Smith, A. Gordon, Russell, James W., Feldman, Eva L.·2003·Diabetes

DOI 10.2337/diabetes.52.12.2867

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Abstract

Impaired glucose tolerance (IGT) serves as a marker for the state of insulin resistance and predicts both large- and small-vessel vascular complications, independent of a patient’s progression to diabetes. Patients with IGT are at significantly increased risk for death and morbidity due to myocardial infarction, stroke, and large-vessel occlusive disease. IGT is more predictive of cardiovascular morbidity than impaired fasting glucose, probably because it is a better surrogate for the state of insulin resistance. IGT is also independently associated with traditional microvascular complications of diabetes, including retinopathy, renal disease, and polyneuropathy, which are the topics of this review. Inhibition of nitric oxide-mediated vasodilation, endothelial injury due to increased release of free fatty acids and adipocytokines from adipocytes, and direct metabolic injury of endothelial and end-organ cells contribute to vascular complications. Early detection of IGT allows intensive diet and exercise modification, which has proven significantly more effective than drug therapy in normalizing postprandial glucose and inhibiting progression to diabetes. To what degree intervention will limit recognized complications is not known.

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Hyperglycemia causes nerve toxicity, leading to nerve damage and apoptosis, which causes microvascular damage and loss of perfusion.
“Hyperglycemia causes nerve toxicity, leading to nerve damage and apoptosis ( 242 , 244 ), which causes microvascular damage and loss of perfusion.”
From Exercise and Type 2 Diabetes (2010) · cites this paper as [242]
In “Other metabolic effects of hyperglycemia” (page not available), the paper says hyperglycemia-related ROS and AGEs are neurotoxic and that AGEs can cause axonal degeneration. It does not describe neuronal apoptosis. Its vascular discussion attributes endothelial damage and impaired vasodilation to metabolic and oxidative mechanisms, not to nerve damage causing loss of perfusion. (LLM, conf=0.86)
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Authors: Singleton, J. R., Smith, A. G., Russell, J. W., & Feldman, E. L.
Affiliations: University of Utah (US)
University of Michigan (US)
ORCID: Singleton, J. Robinson
Russell, James W.
Feldman, Eva L.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2003-12-01
Volume: 52
Issue: 12
Pages: 2867-2873
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.52.12.2867
OpenAlex: W2012946594
Cited by: 372
References: 50
Citations by year: 2026: 4 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 13 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 12 · 2017: 15 · 2016: 8 · 2015: 20 · 2014: 21 · 2013: 13 · 2012: 27
FWCI: 2.94
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs (NIH NS38849)
Deutsches Krebsforschungszentrum
National Institutes of Health (1r21ns041634-01)
National Institute of Neurological Disorders and Stroke (NS40458, R01NS038849, NS42065, R01NS036778, R21-NS-41634, R01NS040458, K02NS042056, NS 36778)
National Center for Research Resources (M01-RR00042NS38849, MO1-RR-00064, M01RR000064, M01RR000042)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: impaired glucose tolerance, microvascular complications, insulin resistance, cardiovascular risk, retinopathy, diabetic nephropathy, diabetic polyneuropathy, endothelial dysfunction, nitric oxide, adipokines, free fatty acids, prediabetes, diabetes prevention, diet and exercise intervention
MeSH terms: Diabetic Nephropathies, Diabetic Neuropathies, Diabetic Retinopathy, Humans, Microcirculation, Polyneuropathies, Glucose Intolerance

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Microvascular complications of impaired glucose tolerance

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