Consideration of sex as a biological variable in diabetes research across twenty years

Abstract

Abstract Background Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes. To chart a path toward greater inclusion of biological sex as a variable in diabetes research, we first need a detailed assessment of common practices in the field. Methods We developed a scoring system to evaluate the inclusion of biological sex in manuscripts published in Diabetes, a journal published by the American Diabetes Association. We chose Diabetes as this journal focuses solely on diabetes and diabetes-related research, and includes manuscripts that use both clinical and biomedical approaches. We scored papers published across 3 years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies designed to improve the consideration of biological sex as a variable. Results Our analysis showed fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which > 87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our data highlight significant opportunities for improvement in diabetes research practices. We also present data supporting a positive role for journal policies in promoting better consideration of biological sex in diabetes research. Conclusions Our analysis provides significant insight into common practices in diabetes research related to the consideration of biological sex as a variable. Based on our analysis we recommend ways that diabetes researchers can improve inclusion of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating knowledge to enable the development of sex-informed prevention and treatment strategies.

Keywords

• Biological sex
• Sex-based analysis
• Sex difference
• Diabetes