Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: Glucose levels are associated with cardiovascular risk in persons without diabetes mellitus

ACP J Club. 1999 July-Aug;131:23. doi:10.7326/ACPJC-1999-131-1-023

Source Citation

Coutinho M, Wang Y, Gerstein HC, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care. 1999 Feb;22:233-40.



What is the relation between glucose levels and cardiovascular events in persons without diabetes mellitus?

Data sources

Studies were identified by searching MEDLINE (1966 to 1996) using the terms blood glucose, glucose intolerance, coronary artery disease, stroke, cerebrovascular disorders, mortality, heart disease, prospective study, cohort study, and follow-up and by scanning reference lists of relevant studies.

Study selection

Prospective cohort studies were selected if they included persons who did not have diabetes and were not selected because of preexisting disease, analyzed baseline glucose data in ≥ 3 quantiles (i.e., intervals), and reported cardiovascular events (sudden death, stroke, or acute myocardial infarction) per glucose quantile or interval. Studies of persons with a history of diabetes were excluded.

Data extraction

Data were extracted on participant and study characteristics, follow-up duration, method of assessing baseline glucose level, definition of glucose quantiles or intervals, cardiovascular events per quantile or interval, and statistical adjustments.

Main results

29 studies were identified; 20 studies of 95 783 persons (94% men, weighted mean follow-up of 12.4 y) with 3707 cardiovascular events met the selection criteria. Studies reported fasting glucose (n = 6), 2-hour glucose (n = 7), 1-hour glucose (n = 5), and nonfasting glucose levels (n = 4). The highest glucose interval included diabetic glucose levels. When an exponential meta-regression model was used for each of the glucose categories, 9 individual studies showed an association between increased baseline glucose quantile or interval and increased risk for cardiovascular events, including death (P ≤ 0.01). This association existed when all studies were combined for fasting glucose (P = 0.016), 1-hour glucose (P = 0.0013), and 2-hour postprandial glucose levels (P = 0.002). Compared with a fasting glucose level of 4.2 mmol/L (75 mg/dL), the relative risk (RR) for cardiovascular events with a fasting glucose level of 6.1 mmol/L (110 mg/dL) and a 2-hour glucose level of 7.8 mmol/L (140 mg/dL) was 1.33 (95% CI 1.06 to 1.67) and 1.58 (CI 1.19 to 2.10), respectively. When the highest glucose quantile or interval was excluded, there was a trend toward an association between fasting glucose level and cardiovascular risk (P = 0.056) and a definite association between 2-hour glucose level and cardiovascular risk (P < 0.001).


Increased fasting and postprandial glucose levels are associated with increased subsequent 12-year risk for a cardiovascular event in persons without diabetes mellitus.

Sources of funding: Brazilian Conselho Nacional de Desenvolvimento Cientifico e Tecnologico and Medical Research Council (Canada).

For correspondence: Dr. H.C. Gerstein, Department of Medicine, Room 3V38, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada. FAX 905-521-4971.


The results of the recently published United Kingdom Prospective Diabetes Study (UKPDS) 33 clearly showed that blood glucose control reduced the risk for vascular complications in patients with diabetes mellitus (1). The UKPDS 38 also showed that blood pressure control was of even greater relevance in such patients (2). Large-scale clinical studies are under way to evaluate the importance of cholesterol reduction in patients with diabetes mellitus. These studies are attempting to highlight the multiplicative effects of cardiovascular risk factors. In persons who do not have overt diabetes mellitus, the combination of upper-body obesity, glucose intolerance, hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol, and hypertension have been associated with increased risk for cardiovascular disease (3).

In the present meta-analysis, Coutinho and colleagues have shown an association between cardiovascular risk and both fasting and postprandial blood glucose levels in patients without diabetes mellitus. This may be an important finding, but the analysis did not permit assessment of the independence of glucose level from other cardiovascular risk factors.

Because of the emerging epidemic of obesity, more studies are needed to evaluate the role of glucose and glucose reduction on risk for cardiovascular disease. Further data from observational studies—or meta-analysis of individual person-data from such studies—are needed to clarify the age and sex-specific relevance of glucose levels and upper-body obesity to cardiovascular risk in the presence or absence of low HDL cholesterol levels, smoking, and elevated blood pressure.

Robert Clarke, MD
Radcliffe InfirmaryOxford, England, UK


1. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-53.

2. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317:703-13.

3. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37;1595-607.