Fasting Glucose Levels Within the High Normal Range Predict Cardiovascular Outcome

Kivity Shaye, MD; Tirosh Amir, MD, PhD; Segev Shlomo, MD; Sidi Yechezkel,MD


Am Heart J. 2012;164(1):111-116. 

In This Article

Abstract and Introduction


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.


Since the introduction of the concept of impaired fasting glucose (IFG), there has been considerable debate regarding where the lower limit should be set to achieve a reasonable balance between sensitivity and specificity for diabetes mellitus (DM) prediction. In 2003, the American Diabetes Association lowered its threshold for diagnosis of IFG from 110 to 100 mg/dL on the basis of evidence that DM prediction may be optimized at a lower threshold.[1] However, we have previously shown that different populations may require distinct glycemic threshold when DM risk is assessed. In a young adult population, glucose levels already within the normal range independently predicted incident DM during a 6-year follow-up study.[2] Although there is a wealth of epidemiological data on the correlation between fasting plasma glucose (FPG) and DM risk, its association with cardiovascular disease (CVD) risk is less clear.

Diabetes mellitus and impaired glucose metabolism are associated with increased CVD mortality.[3–6] However, most studies have failed to detect evidence of FPG threshold that identifies subgroups at increased CVD risk.[7,8] Cardiovascular disease mortality among individuals with IFG was found to be similar to that of patients with overt DM.[9] Similar to observations with other risk factors such as elevated blood pressure and cholesterol, CVD morbidity and mortality were suggested to progress as a continuum across blood glucose concentration, from levels well below the conventional cutoff values used for the diagnosis of DM.[10–12]

Taken together, it is still not clear whether increased FPG within the normoglycemic range posses a significantly elevated cardiovascular risk.[2,13] Therefore, the aim of this study is to characterize the role of FPG within the entire nondiabetic range (normoglycemia and IFG) in predicting CVD outcomes in nondiabetic patients. Fasting plasma glucose levels from 10,913 healthy adults (mean age 50.4 years, range 34–91 years) from the CArdiovascular Risk and Metabolic Assessment (CARMA) study were obtained at baseline, and CVD outcomes were followed up during a mean follow-up of 4.3 years.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.