Objective
The TIMES study aims to understand how insulin needs and blood sugar control change throughout the menstrual cycle in women with type 1 diabetes. We want to analyze how these cycle-related changes affect insulin sensitivity and how these changes are managed by women using AID systems.
The primary study objective is to identify common patterns of insulin sensitivity changes across the menstrual cycle. We will group cycles into clusters with similar changes and fluctuations. Each cluster may require specific adjustments to insulin administration during specific cycle phases. Recognizing these required adjustments is essential for personalizing insulin management according to each woman's unique needs throughout her cycle.
Secondary goals include evaluating differences between the insulin sensitivity clusters, such as the amount of time spent in hypoglycemia, in hyperglycemia, or within the target range, and estimating total insulin needs during different menstrual cycle phases. Additionally, we hope to identify factors that might predict which cluster an individual belongs to, helping us understand and anticipate changes in insulin requirements and blood sugar variability over the cycle. Integrating these insights into AID systems could lead to more precise personalized diabetes care. Beyond the medical aspects, we will examine how cycle-related insulin sensitivity shifts affect daily life, including stress levels, diabetes-related distress, satisfaction with treatment, and overall quality of life. Finally, we will track and evaluate different ways women manually adjust their insulin administration throughout the cycle and compare these modification behaviors across clusters and cycle phases to see how they affect overall trends in insulin sensitivity.
Background Rationale
Managing type 1 diabetes (T1D) in premenopausal women is challenging due to hormone-driven variations in insulin sensitivity throughout the menstrual cycle. Automated insulin delivery (AID) systems are becoming increasingly important in T1D management, yet they struggle to adapt to these menstrual cycle-induced fluctuations. Research and anecdotal reports from the diabetes community indicate that insulin needs can surge by up to 50% during certain cycle phases, which often requires women to manually adjust their AID systems to ensure appropriate insulin delivery. Common manual adjustment strategies include altering carbohydrate intake, skipping bolus doses, or using system features like “boost” or “ease off” modes.
A comprehensive literature review uncovered only a small number of studies examining the effects of the menstrual cycle on diabetes management. Out of 13 studies reviewed, six highlighted a clear connection between menstrual phases and changes in blood sugar control, particularly during the luteal phase occurring just before menstruation. However, seven studies were inconclusive and there was a lack of broad agreement, partially due to differences in study methods, such as how the menstrual cycle was defined and the specific blood sugar measurements used. The variations between the studies were significant, making it impossible to draw a universal conclusion. This variability underlines the complexity of managing T1D for menstruating women; hormone fluctuations are dynamic and current AID systems have no mechanisms to adequately account for them.
A retrospective study with 70 women with T1D who donated their anonymized diabetes and menstrual cycle data was performed in partnership with Tidepool, a non-profit organization supporting diabetes data sharing and research. Analysis of 354 menstrual cycles from these women revealed three distinct patterns of blood sugar control across the menstrual cycle. While the general time-in-range (TIR) was similar across these patterns, the timing of blood sugar highs and lows varied significantly between the patterns and across different cycle phases, typically during the early follicular and late luteal phases, at the beginning and end of the cycle, respectively, and during ovulation. Importantly, women who manually adjusted their AID settings reported better TIR than those who did not, highlighting the limitations of current AID systems to fully automate blood sugar control for these women. Despite AID systems being designed to reduce manual intervention, about 43% of women in the study made regular adjustments to their insulin delivery specifically to counteract hormone-related fluctuations. These adjustments included changing carbohydrate intake, modifying insulin doses, or altering basal rates. While these methods can improve short-term control, they complicate the AID system’s ability to predict insulin needs accurately and can make data interpretation more challenging for health care providers.
To understand how women adjust their insulin needs throughout the menstrual cycle, the study researchers are currently conducting interviews in focus groups to gather insights from women with T1D who use AID systems. These groups are designed to explore what types of manual adjustments women currently use, how these adjustments impact their lives, and what changes they would like to see in future AID technology. The focus groups findings will be used to inform how we collect data on manual adjustment strategies during our proposed study.
By employing a multinational decentralized study design and analyzing real-world data, the TIMES study aims to produce robust scientific evidence on how the menstrual cycle affects insulin requirements and glycemic control in women with T1D.
Description of Project
Premenopausal women with type 1 diabetes (T1D) often experience shifts in blood sugar control related to their menstrual cycles, impacting their diabetes management. As automated insulin delivery (AID) systems play an increasing role in diabetes care, it is important that they can appropriately adapt to various factors affecting blood sugar, such as physical activity, work or leisure schedules, and hormone changes. Current systems are limited in handling menstrual cycle-induced changes, as they lack mechanisms for adapting insulin delivery to hormone fluctuations.
Women in the diabetes community report that their insulin needs can vary by up to 50% during certain phases of the menstrual cycle. However, our review of scientific studies on cycle-related changes in diabetes management revealed mixed results. To deepen our understanding, we partnered with Tidepool to collect data from women with T1D using AID systems. The study confirmed what women in the diabetes community have reported: insulin requirements vary significantly throughout the menstrual cycle, but there is no universal pattern that applies to all women. To manage fluctuations in glycemia, many women make manual adjustments such as logging “fake carbs” for larger insulin doses or using options like “boost” or “ease off” on their insulin pumps. These adjustments are highly individual, and increase the burden of diabetes management.
The TIMES study aims to generate strong scientific evidence on how insulin needs and blood sugar control change across the menstrual cycle, using a multinational, decentralized study design and recruiting 250 women. The decentralized approach facilitates participation of a diverse group of individuals, including those in rural areas. By collecting real-world data, we aim to gain a clearer understanding of how automated insulin delivery systems could better support women with T1D in their daily diabetes management. Our goal is to identify typical variations in insulin requirements and glycemia across the menstrual cycle and their effect on important outcomes such as TIR, hypoglycemia, and hyperglycemia throughout different cycle phases. Additionally, we aim to assess which factors, such as premenstrual symptoms, manual adjustment strategies, and physical activity, significantly affect the different insulin requirements. We also seek to explore how different adjustment strategies impact the perceived burden of diabetes management, psychosocial well-being, diabetes distress, and quality of life.
The TIMES study aims to improve AID systems for women by addressing the fluctuations in insulin needs driven by hormonal changes during the menstrual cycle. Insights from the study could be integrated into AID systems or diabetes management applications in several ways. In an educational module, our findings could help users understand their changing blood sugar levels by providing information on how insulin sensitivity typically changes throughout the menstrual cycle. A real-time adjustment module could offer timely prompts for temporary insulin adjustments, or a “menstrual cycle preset” to dynamically address changing insulin needs. Additionally, a recommendation system could suggest multi-day insulin adjustments during specific phases of the cycle. Finally, the TIMES data could be used to train models that predict individual changes in insulin sensitivity throughout the cycle.
Beyond technological improvements, the TIMES findings will underpin educational resources to empower women with T1D. These resources, shared through apps, blogs, videos, and other digital health platforms, will help women make informed care decisions. By focusing on the menstrual cycle’s impact on T1D, we hope to improve health outcomes, quality of life, and safety in diabetes management for women, enabling personalized, real-time support for better blood sugar control with less effort and more confidence.
This research addresses a significant health gap, as around half of women with T1D experience these cycle-related changes over many years of their lives.
Anticipated Outcome
The TIMES study seeks to fill a crucial data gap in T1D technology by offering validated real-world data on the ways that insulin sensitivity changes throughout the menstrual cycle. We expect to identify several distinct trajectories in insulin requirements and glycemic control that are driven by hormonal changes during the menstrual cycle. By categorizing the effects of these patterns on important outcomes such as TIR, hypoglycemia, and hyperglycemia throughout different cycle phases, we aim to understand effective strategies for managing cycle-related changes in insulin sensitivity as well as why some women experience such changes while others do not. Additionally, we will outline strategies for adjusting insulin administration throughout the menstrual cycle and examine how the effectiveness of these strategies varies across different cycle phases based on the underlying patterns of change in insulin sensitivity.
The TIMES study aims to improve AID systems for women with T1D by addressing variations in insulin needs driven by hormonal changes throughout the menstrual cycle. Insights from the study could be integrated into AID systems or diabetes management apps through various modules. In an educational module, our findings could help users understand patterns in their blood sugar levels by providing information on typical insulin sensitivity changes during the menstrual cycle. A real-time adjustment module could offer timely prompts for temporary insulin adjustments or a “menstrual cycle preset” to dynamically address changing insulin needs. Additionally, a data-driven recommendation system could suggest insulin adjustments over several days during specific phases of the cycle. Finally, the TIMES data could be used to train models that predict individual changes in insulin sensitivity throughout the cycle.
Beyond technological improvements, the TIMES findings will underpin educational resources to empower women with T1D. These resources, shared through apps, blogs, videos, and other digital health platforms, will help women make informed care decisions. In addition, the findings of the TIMES study will contribute to developing clinical guidelines aimed at improving glucose control in menstruating women. Collaboration with diabetes associations and regulatory bodies will support integrating these guidelines into clinical practice. Engaging organizations like the American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) will be essential for advocating policy changes that address menstrual cycle effects in diabetes management. By focusing on the menstrual cycle’s impact on T1D, TIMES hopes to improve health outcomes, quality of life, and safety in diabetes management for women, enabling personalized, real-time support for better blood sugar control with less effort and more confidence.
Relevance to T1D
We anticipate identifying several distinct patterns of insulin sensitivity across the menstrual cycle in women with type 1 diabetes (T1D). Being able to identify these patterns will empower women with T1D to understand how their insulin needs change during their cycle, enabling more precise and effective diabetes management. By understanding how the menstrual cycle affects glucose-insulin regulation, we aim to develop clinical guidelines that can be tailored to each woman's needs.
Menstrual cycle-related changes in insulin requirements affect half of women with T1D at various points throughout their lives, often over the course of many years. Understanding how to identify and compensate for these changes not only helps close the gender health and data gap but also has the potential to improve the quality of life for women managing their diabetes care as well as reduce risks associated with hypoglycemia. Our research offers will offer new insights and tools for diabetes management for women, specifically aiming to improve the effectiveness and reduce the burden of use of automated insulin delivery (AID) systems during the menstrual cycle.
Our innovative study design is decentralized, allowing participants to join remotely and reducing the need for in-person visits. This flexibility can make participation easier, particularly for those in rural or underserved areas, and may lead to greater enrollment and retention. Decentralized studies enable continuous, real-world data collection, offering a more accurate picture of daily diabetes management. This approach also allows us to include a larger, more diverse group from multiple countries, enhancing the applicability of our findings and advancing patient-centered research in T1D.