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Effect of fasting glucose levels on
cardiovascular disease and all-cause mortality
Metabolism – Clinical and Experimental
Take-home message
•
In this prospective study, the authors investigated the risk of cardiovascular disease
and all-cause mortality in postmenopausal women with low fasting glucose levels.
In all, 17,287 women from the Women’s Health Initiative were separated into four
groups based on fasting glucose levels: low, normal, impaired, and diabetic. Median
follow-up was 15 years. Impaired and diabetic fasting glucose were positively
associated with all outcomes. Low fasting glucose was significantly and inversely
associated with coronary heart disease. The association was null or inverse and not
significant with stroke, combined cardiovascular disease, and all-cause mortality.
There was a positive but not significant association with heart failure.
•
Higher levels of fasting glucose were significantly associated with cardiovascular
disease and all-cause mortality.
Abstract
BACKGROUND
While there is increasing recogni-
tion of the risks associated with hypoglycemia in
patients with diabetes, few studies have inves-
tigated incident cause-specific cardiovascular
outcomes with regard to low fasting glucose in
the general population.
OBJECTIVE
We hypothesized that low fasting glu-
cose would be associated with cardiovascular
disease risk and all-cause mortality in postmen-
opausal women.
METHODS
To test our hypothesis, we used both
continuous incidence rates and Cox propor-
tional hazards models in 17,287 participants from
the Women’s Health Initiative with fasting glu-
cose measured at baseline. Participants were
separated into groups based on fasting glu-
cose level: low (<80mg/dL), normal/reference
(80–99mg/dL), impaired (100–125mg/dL), and
diabetic (≥126mg/dL).
RESULTS
Participants were free of cardiovas-
cular disease at enrollment, had mean age of
62years, and were 52% Caucasian, 24% African
American, 8% Asian, and 12% Hispanic. Median
follow-up was 15years. Graphs of continuous
incidence rates compared to fasting glucose dis-
tribution 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 fast-
ing 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.
CONCLUSIONS
Fasting glucose at the upper
range, but not the lower range, was significantly
associated with incident cardiovascular disease
and all-cause mortality.
A prospective study of low fasting glucose with
cardiovascular disease events and all-cause
mortality: The Women’s Health Initiative.
Metab
Clin Exp
2017 May 01;70(xx)116-124, M Mon-
graw-Chaffin, AZ LaCroix, DD Sears, et al.
COMMENT
By Silvio E Inzucchi
MD
T
his study from the Women’s
Health Initiative sought to deter-
mine whether low fasting glucose
levels are associated with cardiovas-
cular events and/or mortality. 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 dele-
terious effects of hypoglycemia on the
cardiovascular system. In nondiabetic
cohorts, it likely reflects malnutrition,
renal or liver disease, or other condi-
tions 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 study,
although provocative, is marred by very
low numbers of patients at the extremes
of blood glucose concentrations, mak-
ing any conclusions impossible.
Dr Inzucchi is Professor
of Medicine at Yale
University School of
Medicine, and Clinical
Chief of the Section of
Endocrinology, Program
Director of the
Endocrinology and
Metabolism Fellowship, and Director of
the Yale Diabetes Center, Connecticut.
The study, although
provocative, is marred by
very low numbers of patients
at the extremes of blood
glucose concentrations,
making any conclusions
impossible.
CARDIOVASCULAR COMPLICATIONS
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VOL. 1 • NO. 1 • 2017