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J Endocr Soc. 2019 Mar 1;3(5):892-901. doi: 10.1210/js.2019-00033. eCollection 2019 May 1.

Association of Low Fasting Glucose and HbA1c With Cardiovascular Disease and Mortality: The MESA Study.

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Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Medicine, University of California San Diego, La Jolla, California.
Department of Family Medicine and Public Health, University of California San Diego, La Jolla, California.


Trials of intensive glucose control have not improved cardiovascular disease (CVD) risk in populations with type 2 diabetes; however, in the general population, reports are inconsistent about the effects of maintaining lower glucose levels. Some speculate that low glycemic values are associated with increased glycemic variability, which is in turn associated with higher CVD risk. It has also been suggested that fasting glucose and hemoglobin A1c (HbA1c) in the lower ranges have a different relationship with CVD and mortality. In 4990 participants from the Multi-Ethnic Study of Atherosclerosis, we used logistic regression to investigate associations of low fasting glucose (<80 mg/dL) and HbA1c (<5.0%) from baseline and averaged across follow-up with incident CVD and mortality over 13 years. We used normal glycemic ranges (80 to <100 mg/dL and 5.0 to <5.7%) as references and analyzed glycemic levels with visit-matched covariates. We adjusted for potential confounding by age, sex, race/ethnicity, education, income, smoking status, body mass index, total cholesterol level, cholesterol medications, high-density lipoprotein cholesterol, and hypertension. Low baseline glucose and HbA1c were positively, but not significantly, associated with mortality, whereas low average fasting glucose and HbA1c were strongly and significantly associated with incident CVD [glucose OR, 2.04 (95% CI, 1.38-3.00); HbA1c OR, 2.01 (95% CI, 1.58-2.55)] and mortality [glucose OR, 1.93 (95% CI, 1.33-2.79); HbA1c OR, 2.51 (95% CI, 2.00-3.15)]. These results were not due to type 2 diabetes or medication use. Glucose variability did not explain CVD risk beyond average glucose levels. Chronic low fasting glucose and HbA1c may be better indicators of risk than a single low measurement.


HbA1c; cardiovascular disease; epidemiology; fasting glucose; mortality

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