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Elevated Fasting Glucose Associated with Cardiovascular Disease and Death

Study from Women’s Health Initiative sought to determine whether low fasting glucose levels are associated with cardiovascular events and/or mortality.

While there is increasing recognition of the risks associated with hypoglycemia in patients with diabetes, few studies have investigated incident cause-specific cardiovascular outcomes with regard to low fasting glucose in the general population.

They started with the hypotheses that low fasting glucose would be associated with cardiovascular disease risk and all-cause mortality in postmenopausal women.

The researchers actually found a neutral effect, whereas in most circumstances hyperglycemia increased the risk. This is in contrast to reports from some larger surveys where lower glucose levels appear to be associated with all-cause mortality. Some feel that, in diabetic cohorts, this reflects the deleterious effects of hypoglycemia on the cardiovascular system. In nondiabetic cohorts, it likely reflects malnutrition, renal or liver disease, or other conditions that may increase the risk of death. In the Mongraw-Chaffin paper, the only event that appeared to be associated with hypoglycemia was heart failure, not an intuitively obvious link. The researchers added that one of the negatives, was that the study was marred by very low numbers of patients at the extremes of blood glucose concentrations, making any conclusions very difficult.

To test the hypothesis, they used both continuous incidence rates and Cox proportional hazards models in 17,287 participants from the Women’s Health Initiative with fasting glucose measured at baseline. Participants were separated into groups based on fasting glucose level: low (<80mg/dL), normal/reference (80-99mg/dL), impaired (100-125mg/dL), and diabetic (≥126mg/dL).

The results showed that the participants were free of cardiovascular disease at enrollment, had a mean age of 62 years, and were 52% Caucasian, 24% African American, 8% Asian, and 12% Hispanic. Median follow-up was 15 years. Graphs of continuous incidence rates compared to fasting glucose distribution exhibited evidence of a weak J-shaped association with heart failure and mortality that was predominantly due to participants with treated diabetes. Impaired and diabetic fasting glucose were positively associated with all outcomes. Associations for low fasting glucose differed, with coronary heart disease (HR=0.64 (0.42, 0.98)) significantly inverse; stroke (0.73 (0.48, 1.13)), combined cardiovascular disease (0.91 (0.73, 1.14)), and all-cause mortality (0.97 (0.79, 1.20)) null or inverse and not significant; and heart failure (1.27 (0.80, 2.02)) positive and not significant.

From the results it was concluded that fasting glucose at the upper range, but not the lower range, was significantly associated with incident cardiovascular disease and all-cause mortality.

Practice Pearls:

  • 17,287 participants from the Women’s Health Initiative with fasting glucose measured at baseline were used.
  • Impaired and diabetic fasting glucose were positively associated with all outcomes.
  • Higher fasting glucose is associated with incident CVD and death.

Metabolism May 2017 DOI: http://dx.doi.org/10.1016/j.metabol.2017.02.010