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Cited by 193Diabetes, Cardiovascular Risks, and LipoproteinsDiabetes Treatment and ManagementDiabetes Management and Research

The Importance of Hyperglycemia in the Nonfasting State to the Development of Cardiovascular Disease

Haffner, Steven M.·1998·Endocrine Reviews
DOI 10.1210/edrv.19.5.0343
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Abstract

I. Introduction II. Correlation Between Hyperglycemia and CVD A. Type 2 diabetes B. Elevated glucose concentrations in the nondiabetic range C. Atherosclerosis in subjects with asymptomatic hyperglycemia III. Causal Relationship of Postprandial Hyperglycemia to CVD A. Direct effects of hyperglycemia B. Insufficient insulin production C. Insulin resistance and hyperinsulinemia D. Association with risk factors for CVD IV. Therapeutic Interventions for Type 2 Diabetes A. Insulin therapy B. Sulfonylureas C. Biguanides D. Acarbose V. Studies to Prevent Type 2 Diabetes VI. Conclusions CARDIOVASCULAR disease (CVD) is a major cause of morbidity and mortality in patients with diabetes. It is also responsible for significant morbidity and mortality in the nondiabetic population. The development of strategies to recognize individuals with a risk of CVD and of interventions to reduce this risk would therefore be of considerable value both medically and economically. Much research over the last 30–40 yr has investigated risk factors for CVD. A link between glycemia in the nonfasting state (“postprandial hyperglycemia”) and CVD was first suggested in the 1950s and has now been demonstrated, as discussed further in this paper. While postprandial hyperglycemia is probably one of many risk factors, evidence indicating that there is a causal link between elevated blood glucose levels and the development of atherosclerosis suggests that therapeutic interventions to improve glycemic control may reduce the risk of CVD. Much of the data suggesting that glycemia in postprandial hyperglycemia is a risk factor for atherosclerosis, in fact, has derived from studies after glucose challenge rather than after a mixed meal. Strictly speaking, these data might apply most closely to subjects who ingest large amounts of soda (containing sugar), which is common enough in Western society. Few data have been collected on glucose levels following mixed meals although there is a considerable amount of data that postprandial triglyceride levels are consistent risk factors for atherosclerosis (1, 2). One issue that is currently unresolved is what proportion of the elevated HBA1c is due to postprandial glucose levels compared with basal glucose levels. It is clear that in the early phases of diabetes, HBA1c levels show modest elevations of postprandial plasma glucose but basal glucose levels (fasting) are still in the nondiabetic range. This article reviews the evidence for a close association between hyperglycemia (in particular, postprandial hyperglycemia) and the development of CVD. Therapeutic strategies to reduce postprandial hyperglycemia and the risk of CVD are also discussed. Subjects with type 2 diabetes have an increased risk of developing CVD in comparison with nondiabetic subjects. This was initially demonstrated in the results of the Framingham study (3), which reported a 4-fold increase in women and a 2-fold increase in men compared with nondiabetic subjects. Similar results have been obtained in other studies (4, 5). The risk of CVD is increased at the time of diagnosis and is independent of the duration of diabetes in some studies (6–8), thus suggesting that factors before the development of overt diabetes contribute to the risk of CVD. This is also suggested by the finding of increased cardiovascular risk factors before the onset of type 2 diabetes (9). The results of various studies suggest a relationship between hyperglycemia and the development of CVD in patients with type 2 diabetes. For example, the Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR) reported a significant association between glycosylated hemoglobin levels, a measure of long-term blood glucose levels, and mortality from ischemic heart disease (10). This relationship was stronger in younger-onset diabetic subjects (i.e., type 1) rather than in older-onset diabetic subjects (i.e., type 2 diabetic subjects) (10). A 1% rise in glycosylated hemoglobin cardiovascular mortality in younger-onset diabetic subjects was associated with a 20% rise in ischemic heart disease mortality in type 2 diabetic subjects (10). In a group of patients with older-onset diabetes, the hazard ratio for a 1% change in glycosylated hemoglobin was 1.10 (95% confidence interval, 1.04–1.17). Similarly, Standl et al. (11) found in a multivariate analysis that levels of HbA1c, von Willebrand factor protein, and age were the major determinants for CVD-related mortality in a study involving 290 patients with type 2 diabetes (Munich General Practitioner Project). Another study, involving 1059 patients with type 2 diabetes followed for 7 yr, found that high fasting plasma glucose levels (>13.4 mmol/liter) were associated with a 2-fold increase in the risk of coronary heart disease (CHD) mortality and morbidity (12). The risk was further increased to 3-fold in patients who simultaneously had high fasting plasma glucose levels and low high-density lipoprotein (HDL) cholesterol, low HDL-ch

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Authors
Haffner, S. M.
Affiliations
The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Haffner, Steven M.
Venue
Endocrine Reviews
Publisher
The Endocrine Society
Published
1998-10-01
Volume
19
Issue
5
Pages
583-592
ISSN
  • 0163-769X (ISSN-L)
  • 1945-7189
DOI
10.1210/edrv.19.5.0343
OpenAlex
W2158157243
Cited by
193
References
113
Citations by year
2026: 4 · 2024: 1 · 2023: 1 · 2022: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 11 · 2013: 2 · 2012: 11
FWCI
2.19
Type
journal article
Language
en
Open access
closed
Locations
  • Endocrine Reviews (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
cardiovascular disease, type 2 diabetes, atherosclerosis, insulin resistance, hyperinsulinemia, HbA1c, glycemic control, postprandial triglycerides, sulfonylureas, biguanides, acarbose, insulin therapy, type 2 diabetes prevention, cardiovascular risk factors
MeSH terms
Adult, Aged, Aged, 80 and over, Arteriosclerosis, Biguanides, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Fasting, Female, Humans, Hyperglycemia, Hyperinsulinism, Hypoglycemic Agents, Insulin, Male, Middle Aged, Sulfonylurea Compounds, Trisaccharides, Postprandial Period, Acarbose

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