Clinical Investigation
Diabetes and Metabolism
Fasting glucose levels within the high normal range predict cardiovascular outcome

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Background

Diabetes mellitus and impaired glucose metabolism are associated with increased risk for cardiovascular disease (CVD). However, it is still not clear whether glucose levels can predict CVD risk among patients without diabetes. The primary aim of this study is to assess whether normoglycemic fasting plasma glucose (FPG) is associated with increased risk of CVD outcomes in healthy patients.

Methods

We obtained blood measurements, data from physical examination, and medical and lifestyle information from 10,913 men and women who were evaluated in the Institute for Preventive Medicine of Sheba Medical Center. Enrolled were participants with FPG < 100 mg/dL as well as 100 to 125 mg/dL, who were free of diagnosis of CVD. The participants were actively screened for coronary disease using a stress test. Primary end points were coronary heart disease or self-reported cerebral vascular disease.

Results

A total of 1,119 incident cases of CVD occurred during a mean follow-up of 4.3 years. Subjects with fasting glucose levels in the high normal range (95-99 mg/dL) had an increased CVD risk when compared with levels < 80 mg/dL, (HR 1.53;CI 95% [1.22-1.91], P < .001). A multivariate model, adjusted for age, sex, family history of CVD, blood pressure, body mass index, smoking status, pharmacologic treatment, serum triglycerides, and high-density lipoprotein and low-density lipoprotein cholesterol levels, revealed an independent increased risk of CVD with rising FPG levels in the normal range.

Conclusion

Elevated CVD risk is strongly and independently associated with glucose levels within the normoglycemic range. Fasting plasma glucose may help in identifying apparently healthy persons with early metabolic abnormalities who are at increased risk for CVD before progression to prediabetes and overt diabetes mellitus.

Section snippets

The CARMA study

The CARMA study was designed to investigate cardiometabolic risk factors in healthy male and female adults of white ethnicity. The study has been conducted at the Executive Screening Survey (ESS) at the Sheba Medical Center in Israel. The ESS performs approximately 9,000 screening examinations of adult males and females annually. This population is composed mainly of senior executives referred for periodic health screening by their organizations and so represents a higher-than-average

Results

Data from 10,913 apparently healthy men and woman (mean age 50.4 years, range 34-91), 9,687 with FPG levels of < 100 mg/dL at baseline and 1,226 with IFG values (100-125 mg/dL), were analyzed. Participants were categorized based on glucose levels to 5 groups (50-79, 80-84, 85-89, 90-94, and 95-99 mg/dL). In addition, we have also analyzed the IFG group (100-125 mg/dL). Age, male gender, systolic blood pressure, family history of CVD, TG, and LDL cholesterol levels were more likely to increase

Discussion

In this study, 10,913 men and women without DM or apparent CVD were followed up for a mean of 4.3 years. The risk for coronary disease has linearly increased across FPG levels, already within the normoglycemic range (≤ 100 mg/dL). This increased risk was independent of other traditional risk factors for CVD and was not mediated by the higher risk of DM incidence. Cerebrovascular disease did not follow this pattern, and an increased risk was observed only among participants with IFG. Although the

Acknowledgements

The authors thank Ms Ilana Gelernter from the Department of Statistics and Operations Research, in the School of Mathematical Sciences, at Tel Aviv University, Israel, for statistical analysis and Ms Yael Mintz from the Institute for Preventive Medicine of Sheba Medical Center, Israel, for her administrative and technical support. The study was funded by a grant from the Shlavi foundation for medical research. The authors are solely responsible for the design and conduct of this study, all

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