Glucose control in women versus men: towards sex-specific insulin therapies in type 1 diabetes (DIABETEXX) (2023 – 2026). Reference: PID2022-137723OB-C22. Funded by MICINN & AEI, total: 421.250 € P.I. Josep Vehí. Other participants: Universitat Politècnica de València.
SUMMARY:
There is growing evidence that sex and gender affect the pathophysiology, incidence, prevalence, development and response to therapy in many diseases. This is the case of diabetes, where factors such as differences in lifestyle (diet and exercise), sex hormones and body composition, produce differences in glucose regulation between women and men, leading to poorer glycaemic control in women.
Consequently, women with type 1 diabetes have an additional 37% risk of death, and twice the excess risk of suffering vascular events as compared to men. On the other hand, some studies have shown the influence of menstrual cycle phase in glucose control in fertile women, changes in insulin sensitivity between follicular and luteal phases in women with type 1 diabetes.
Despite technological advancements in the market, such are artificial pancreas or smart insulin pens for multiple insulin dose (MDI) therapies, there is still an unmet need of to improve blood glucose control in people with type 1 diabetes and sex differences are not considered. Women consistently report bigger challenges in controlling their glycemia due to menstrual cycle changes, and differences in glucose regulation between healthy women and men do exist and are not translated into technology. The project hypothesis is that sex-based personalization of insulin therapies will translate into a better blood glucose control, especially among women with a better counteraction of menstrual cycle effects. Then, the overall goal of this project is the personalization of insulin therapy according to physiological differences in women and men for a better blood glucose control. Emphasis will be put in the development of new decision support systems for MDI therapy incorporating real-time monitoring of menstrual cycle phases in women.
Evaluation of the need of sex-specífic control algorithms for the artificial pancreas will also be carried out, as well as proof-of-concept simulation study evaluating a sex-specific version of our artificial pancreas.
To reach the objective and obtain the desired technological results, firstly, beyond-state-of-the-art knowledge will be generated about the influence of the menstrual cycle phase (follicular vs. luteal) on the use of artificial pancreas and on the glycaemic effect of exercise and meals, the two most important disturbances in glucose control, thanks to 3 clinical studies. Secondly, new physiological exercise and meal models, incorporating the new findings will be developed. These models will serve to develop new simulation tools able to describe sex differences in blood glucose control, beyond insulin sensitivity changes among phases. Specific cohorts of virtual patients will be generated incorporating the physiological models developed in the project as well as specific scenarios for each sub-population.
Additionally, new data-driven models based on machine learning techniques will be used for the generation of in silico virtual patients to complement the physiological models. Finally, a new dedicated wearable technology will also be built and validated for real-time monitoring of relevant menstrual cycle phases information. for its integration into decision support systems for MDI users and artificial pancreas systems. Apart from its future integration in decision support systems for MDI users and artificial pancreas systems, the device could be used in many other applications in the future.
Funded by MCIN/ AEI/10.13039/501100011033/ FEDER, UE
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Research Team:
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FUNDACIÓ CLÍNIC PER A LA RECERCA BIOMÈDICA
- Marga Giménez
- Jesús Ignacio Conget Donlo
RESEARCH OUTCOMES:
- Two new exercise and mixed meals physiology-based models of T1D patients considering sexual dimorphism, trained and validated with real data.
- A new T1D simulator with a more faithful representation of variability under meals and exercise. A new wearable device including the sensors, electronics hardware and software, to estimate menstrual cycle phases in women, validated with real data.
- A new system combines MDI control, Decision Support, and personalized features, including specific algorithms for women, using smart pens and CGM with intermittent closed-loop control.
- A new fully-autonomous AP system in-silico evaluated, taking into account the menstrual cycle changes as a new disturbance.
