Is there a gender difference in diabetes-associated heart failure?

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Risk of cardiovascular disease is known to be higher in women than in men with diabetes. In a new study, published in Diabetologia, researchers examined whether diabetes also confers to women an excess risk of heart failure.

Data on more than 12 million individuals were represented in the systematic review and meta-analysis, by investigators from Australia, Japan, UK and the United States. For the work, they searched PubMed for population-based cohort studies published between January 1966 and November 2018.  

Fourteen studies were included, which reported on sex-specific estimates of relative risks (RRs) for heart failure associated with diabetes and its associated variability, adjusted at least for age. The authors used random-effects meta-analyses with inverse variance weighting to obtain pooled specific RRs and women-to-men ratios of RRs (RRRs) for heart failure associated with diabetes.

More than 250,000 heart failure events were reflected in the data, which showed that both Type 1 and Type 2 diabetes were stronger risk factors for heart failure in women than in men. The pooled multiple-adjusted RR for heart failure associated with Type 1 diabetes was 5.15 (95% CI 3.43-7.74) in women and 3.47 (2.57-4.69) in men, resulting in an RRR of 1.47 (1.44 -1.90). For Type 2 diabetes, the heart failure-associated RRs were 1.95 in men (1.70-2.22) and in women 1.75 (1.55-1.95), with a pooled RRR of 1.09 (1.05-1.13).

The authors said there was evidence of publication bias for the association between Type 2 diabetes and heart failure. No significant differences were found in pooled women-to-men multiple-adjusted RRR in subgroup analyses for study region (P= 0.29), year of baseline study (P= 0.87), ascertainment of diabetes (P= 0.72), study outcomes (p = 0.41), quality of study (P= 0.25) or absolute risk of differences between genders (P= 0.16).

Four possible explanations were offered by the investigators for the sex-linked differences: (1) great risk of coronary heart disease in women than in men; (2) undertreatment of diabetes in women, resulting in development of diabetic cardiomyopathy; (3) prolonged exposure to hyperglycemia during the prediabetic stage; and (4) a mathematical artifact caused by the relatively low absolute risk of heart failure in women versus men. The findings, the authors said, “[highlight] the importance of intensive prevention and treatment of diabetes for women as well as men. Further research is required to understand the mechanisms underpinning the excess risk of heart failure conferred by diabetes (particularly type 1) in women and to reduce the burden associated with diabetes in both sexes.”