Type 2 diabetes, CHD and gender
Original article:
Explaining the sex difference in coronary heart disease mortality among
patients with type 2 diabetes mellitus. A meta-analysis. Kanaya AM,
Grady D, Barrett-Connor E. Arch Intern Med 2002; 162: 173745.
Summary
It has often been suggested that before the menopause female patients with
diabetes lose their protection against heart disease, and following the
menopause heart disease is more common in diabetic women than in diabetic
men. However, some large-scale studies have challenged this view. The
importance of coronary heart disease (CHD) in diabetes cannot be
overestimated and the authors give reference to the many studies which
suggest that the rate of CHD mortality in diabetes may be up to fivefold
that in non-diabetic subjects.
The authors objective was to establish an accurate estimate of the odds
ratio for fatal and non-fatal CHD due to diabetes in both men and women.
This seemed to be a huge task encompassing published articles from January
1966 through February 2000, of which 4578 were ini-tially located. It is
not of course surprising that many articles were duplicated given that
large studies spawn numerous papers, the best example perhaps being the
United Kingdom Prospective Diabetes Study. Only 234 articles contained
primary data. The authors went to the effort of contacting authors twice
to see if they could obtain further data so that the studies could be
included in their analysis and finally ended up with 16 studies fulfilling
all the authors inclusion requirements. Of these, 12 were prospective
cohort studies and four were cross-sectional analyses (Table I).
Table I: Characteristics of studies of CHD risk
in diabetic vs. non-diabetic subjects.
Overall the summary odds ratio for CHD mortality due to diabetes from
eight prospective cohort studies was 2.3 (95% CI 1.92.8) for men and 2.9
(95% CI 2.23.8) for women for all race/ethnic groups combined without
heterogeneity in findings (p = ns) (Fig. 1).
Fig. 1: Odds ratios and 95% confidence intervals
for the risk of CHD mortality for diabetic vs. non-diabetic men (A) and
women (B). Summary odds ratios by random-effects model are presented below
individual study results.
The authors had hoped to study ethnicity, but, as they stated, most of
the studies were performed with white subjects; however, they found that
summary estimates for CHD for white men and women were similar to those
for all ethnicities combined. Examining four population-based studies for
non-fatal myocardial infarction due to diabetes, the odds ratio for men
was 1.6 (95% CI 1.12.2) and for women, 1.7 (95% CI 1.32.3) a
difference that was also not statistically significant. Nor was there any
significant difference when the authors looked at cardiovascular mortality
due to diabetes rather than CHD mortality or non-fatal myocardial
infarction in men compared with women.
Table II: US death rates per 100,000 population
from CHD by sex and age (data from [17]).
The authors final table (Table II) presents the death rates from CHD
by sex and age in the US population in 1998. They used the overall summary
odds ratio for CHD mortality (2.3 for men and 2.9 for women) to calculate
the expected coronary death rate and excess death rate among diabetic men
and women. Since the death rate for coronary artery disease is greater in
men than in women up to the age of 85, Table II demonstrates a higher
excess death rate due to diabetes in men except among the very oldest.
Comment
This is an important article and of interest since it was never clear why
diabetic women should suffer more from heart disease in comparison with
diabetic men and this study clearly shows that indeed there is no evidence
that this concept is correct. The article is also important because it
demonstrates the difficulties in assessing the validity of meta-analyses
and demonstrates how differences in odds ratios can be misleading because
CHD mortality rates are higher in men than in women of the same age. As
with many studies, this study clearly demonstrates that the older one gets
the more likely one is to die and thus in both sexes the influence of
diabetes on death rate becomes less in old age. However, the data suggest
that most of the observed differences in risk between men and women for
CHD mortality from diabetes are mediated by traditional cardiac risk
factors and these of course are modifiable. The paper confirms the
importance of targeting patients with diabetes for cardiovascular risk
intervention because of the increased risk in both men and women with
diabetes.
In conclusion, this is a meta-analysis of CHD mortality among patients
with type 2 diabetes. The study was controlled for age, hypertension,
hypercholesterolemia and smoking, and demonstrates that in both men and
women there is a very important increase in risk of cardiovascular
disease. The study reinforces the view that aggressive treatment of risk
factors in diabetes is necessary if we are to improve the long-term
outcome for people with diabetes.
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Summary and Comment:
Gerald Tomkin, Dublin, Ireland
