Menstrual Cycle Mapping While Using Closed-Loop Insulin Delivery (MCM-Loop)

The hypothesis is that menstrual cyclicity affects glucose and energy metabolism in women with type 1 diabetes. The rationale of the hypothesis on cycle effects builds on the assumption that fluctuations of female sex hormones across the menstrual cycle cause changes in physiological parameters of glucose metabolism and energy homeostasis and/or lifestyle aspects involved in the regulation of blood glucose and body weight. It is expected that hormone fluctuations affect insulin sensitivity, gastric emptying, eating behaviour and energy expenditure. It is anticipated that insulin sensitivity is highest in the pre-ovulatory phase and lowest in the mid-luteal phase. It is further expected that gastric emptying peaks in the follicular phase, and highest energy expenditure and dietary intake are expected during the mid-luteal phase.

The primary objective of this study is to characterize glucose and energy metabolism throughout the menstrual cycle in natural cycling women with type 1 diabetes. Further objectives are to assess the impact of the menstrual cycle on glucose control and insulin requirements, investigate how fluctuations in sex hormone levels influence glucose and energy metabolism, and quantify both inter- and intra-individual variability in metabolic changes related to the menstrual cycle. Additionally, the study will evaluate whether changes in key physiological components of glucose metabolism and behavioural factors mediate menstrual cycle-related variations in glucose control and insulin requirements.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 1; Energy Metabolism

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism (UDEM), Inselspital, Bern University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Eligible participants will be women aged 18-45 years, with a natural menstrual cycle (occurring without medical or hormonal interventions), who have Type 1 Diabetes and are willing to follow study-related procedures.

Description

Inclusion Criteria:

• Female sex assigned at birth
• Type 1 diabetes for at least 12 months
• Aged 18-45 years
• Natural menstrual cycle (occurring without medical or hormonal interventions)
• Functional insulin therapy delivered via injection or insulin pump
• Willingness to follow study-related procedures
• Willingness to use mechanical contraception during the time of study participation

Exclusion Criteria:

• Use of contraceptives or medical interventions that interfere with natural hormonal fluctuations of the menstrual cycle or cyclical bleeding
• Interventions interfering with glucose or energy metabolism (other than insulin, thyroid hormone replacement or statins), as judged by the investigator, will be paused for the duration of the study, with an adequate washout duration prior to the start of data collection
• Presence of any physical or psychological condition, or any medical intervention likely to interfere with the conduct of the procedures and/or their evaluation, as judged by the investigator
• Pregnant or breast-feeding
• Participation in another clinical study that interferes with the interpretation of the study results as judged by the investigator

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Women with Type 1 Diabetes; Participants with type 1 diabetes from age 18 to 45 years and a natural menstrual cycle will be followed for 3 consecutive menstrual cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in target glucose range	The primary metric for glucose control is the proportion of time with sensor glucose levels in the target range (3.9-10mmol/L, %). Glucose levels will be measured using a continuous glucose monitoring sensor (Dexcom G6 or an equivalent CGM sensor).	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Substrate oxidation	Substrate oxidation (i.e, quantified by the relative contribution of fat oxidation to resting energy expenditure) will be measured by indirect calorimetry in the fasted state (≥8 hours) to provide additional context as a physiological determinant of glucose and energy metabolism. This outcome is measured only in a subgroup of 15 participants.	Assessed once at each phase-specific assessment (early follicular, pre-ovulatory, and luteal) for one menstrual cycle
Algorithm-directed insulin delivery following a standardized meal	The primary insulin metric is the algorithm-directed insulin dose (units) delivered over a 3 hour period following a standardized meal without a manual bolus. Insulin delivery is recorded using the mylife CamAPS FX automated insulin delivery system.	The outcome will be measured at each standardized meal assessment, performed during the three key menstrual cycle phases (early-follicular, pre-ovulatory, and mid-luteal),across three menstrual cycles, resulting in a total of nine 3-hour assessment times
Insulin sensitivity	Insulin sensitivity will be estimated continuously throughout the study from sensor glucose and insulin pump data, collected via the mylife CamAPS FX automated insulin delivery system, using mathematical modeling.	Continuously over three menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Gastric emptying	This outcome is based in the [13C]-acetate breath test. Breath 13CO2 enrichment is analyzed using infrared spectrometry and kinetics parameters are derived using mathematical modelling. The main parameter of interest is T50 (ie., the time until half of the ingested meal was absorbed). This outcome is measured only in a subgroup of 15 participants.	The outcome is evaluated at each phase-specific assessment (early follicular, pre-ovulatory, and luteal) for one menstrual cycle.
Total energy expenditure	Total energy expenditure will be quantified using the doubly labelled water method. This outcome is measured only in a subgroup of 15 participants.	Continuously over one menstrual cycle. Duration varies depending on individual cycle length, ranging from 20 days to 50 days.
Dietary intake	Total energy intake (kcal/day) will be assessed by recording all meals using an image-based automated food analysis application SNAQ.	Measured for 3 days following each phase-specific assessment (early follicular, pre-ovulatory, and luteal) across three menstrual cycles, totaling 27 days over 3 cycles
Physical activity	The number of steps per day, as a component of physical activity, will be measured using the Garmin Venu 3 smartwatch.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resting energy expenditure	Resting energy expenditure (kcal/day) will be measured by indirect calorimetry in the fasted state (≥8 hours) to provide additional context as a physiological determinant of energy metabolism. This outcome is measured only in a subgroup of 15 participants.	Assessed once at each phase-specific assessment (early follicular, pre-ovulatory, and luteal) for one menstrual cycle.
Patient-reported perceived impact	Perceived impact of the menstrual cycle on diabetes control and management will be captured retrospectively at the end of the study using an experience questionnaire.	At study completion (after three menstrual cycles).
Postprandial mean glucose	Mean postprandial glucose levels measured using continuous glucose monitoring in the 3 hours following meals. Meal timepoints defined as manual carbohydrate entries in the mylife CamAPS FX automated insulin delivery system. This outcome serves as an additional metric within the overall assessment of glucose control. Additionally, mean postprandial glucose levels will be specifically measured in the 3 hours following the standardized meal assessment using continuous glucose monitoring.	The outcome will be evaluated continuously over 3 menstrual cycles (duration varies from 60 days (20-day cycles) to 150 days (50-day cycles)) as well as at each standardized meal assessment, resulting in a total of nine 3-hour assessment times.
Postprandial peak glucose	Peak postprandial glucose levels measured using continuous glucose monitoring in the 3 hours following meals. Meal timepoints defined as manual carbohydrate entries in the mylife CamAPS FX automated insulin delivery system. This outcome serves as an additional metric within the overall assessment of glucose control. Additionally, peak postprandial glucose levels will be specifically measuredin the 3 hours following the standardized meal assessment using continuous glucose monitoring.	The outcome will be evaluated continuously over 3 menstrual cycles (duration varies from 60 days (20-day cycles) to 150 days (50-day cycles)) as well as once for each standardized meal assessment (9 values in total).
Proportion of time spent in the hyperglycaemic range	Glucose levels above 10 mmol/L are classified as hyperglycaemic. Glucose levels will be measured using a continuous glucose monitoring (Dexcom G6 system or an equivalent CGM sensor). This outcome serves as an additional metric within the overall assessment of glucose control.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles)
Proportion of time spent in hypoglycaemic range	Glucose levels below 3.9 mmol/L are classified as hypoglycaemic. Glucose levels will be measured using continuous glucose monitoring (Dexcom G6 system or an equivalent CGM sensor) This outcome serves as an additional metric within the overall assessment of glucose control.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Glucose variability - standard deviation	Glucose variability assessed as the standard deviation (SD) of sensor glucose values measured using continuous glucose monitoring. This outcome provides an additional metric contributing to the assessment of glucose variability and overall glucose control.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Glucose variability - coefficient of variation	Glucose variability assessed as the coefficient of variation (CV) of sensor glucose values measured using continuous glucose monitoring data. This outcome provides an additional metric contributing to the assessment of glucose variability and overall glucose control.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Glucose variability - mean amplitude of glycaemic excursions	Glucose variability assessed as the mean amplitude of glycaemic excursions (MAGE) derived from continuous glucose monitoring data. This outcome provides an additional metric contributing to the assessment of glucose variability and overall glucose control.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Total daily insulin dose	Total daily insulin dose (U/day) will be evaluated using the mylife CamAPS FX automated insulin delivery system, which includes a continuous glucose monitoring sensor (Dexcom G6 or an equivalent CGM sensor for participants already using mylife CamAPS FX with a different sensor), an insulin pump (YpsoPump), and the CamAPS FX application. This outcome serves as an additional measure of individual insulin requirements.	Over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Basal insulin	As an additional measure of insulin requirements, the proportion of basal insulin relative to total insulin delivery (%) will be assessed. It will be measured using the mylife CamAPS FX AID system consisting of a continuous glucose monitoring sensor (Dexcom G6 system or an equivalent CGM sensor if they already use the mylife CamAPS FX AID system with a different sensor), the insuline pump (Ypsopump) and the CamAPS FX app.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Bolus frequency	Units are (n/day). The outcome is the number of manual boluses entered into the mylife CamAPS FX AID system.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Model-estimated energy intake	Daily energy intake (kcal/day) will be estimated using an energy balance model based on frequently measured body weight and physical activity data, and, where available, energy expenditure assessed using the doubly labeled water methodology. This outcome provides a complementary, model-based estimate of energy intake alongside self-reported dietary intake.	Continuously over three menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Proportion of carbohydrate intake	The proportion of carbohydrate intake (% of total energy intake) will be derived from meal records collected using the image-based automated food analysis application (SNAQ), providing complementary information on macronutrient distribution.	Measured over 3 days following each phase-specific assessment (early follicular, pre-ovulatory, and luteal) across three menstrual cycles, totaling 27 days from 9 assessments.
Proportion of fat intake	The proportion of fat intake (% of total energy intake) will be derived from meal records collected using the image-based automated food analysis application (SNAQ), providing complementary information on macronutrient distribution.	Measured over 3 days following each phase-specific assessment (early follicular, pre-ovulatory, and luteal) across three menstrual cycles, totaling 27 days from 9 assessments.
Proportion of protein intake	The proportion of protein intake (% of total energy intake) will be derived from meal records collected using the image-based automated food analysis application (SNAQ), providing complementary information on macronutrient distribution.	Measured over 3 days following each phase-specific assessment (early follicular, pre-ovulatory, and luteal) across three menstrual cycles, totaling 27 days from 9 assessments.
Dietary fiber intake	Dietary fiber intake will be derived from meal records collected using the SNAQ application as an additional component of overall dietary intake assessment.	Total intake over 3 days following each phase-specific assessment (early follicular, pre-ovulatory, and luteal) across three menstrual cycles, totaling 27 days from 9 assessments.
Food category distribution	Food category distribution will be derived from meal records collected using the SNAQ application, providing complementary information on dietary patterns within overall dietary intake.	Measured continuously at every meal for 3 days following each phase-specific assessment (early follicular, pre-ovulatory, and luteal) across three menstrual cycles, totaling 27 days from 9 assessments.
Activity minutes per day	Active minutes per day will be measured using the Garmin Venu 3 smartwatch as a complementary indicator of physical activity.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Body weight	Body weight will be measured using the Garmin Index S2 smart scale to provide additional metabolic context.	Measured daily over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Fat mass	Percentage of body fat mass, as a component of body composition, will be measured using the Garmin Index S2 smart scale to provide additional metabolic context.	Daily over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Fat-free mass	Percentage of fat-free mass, as a component of body composition, will be measured using the Garmin Index S2 smart scale to provide additional metabolic context.	Measured daily over three menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Beta-hydroxybutyrate levels	Beta-hydroxybutyrate levels (mmol/L), will be assessed using the SiBio Ketone Sensor to provide additional metabolic context.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Heart rate	Heart rate (bpm), will be assessed using the Garmin Venu 3 smartwatch to provide a broader metabolic context.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Heart rate variability	Heart rate variability (High and low frequency components or equivalent time domain indices), will be assessed using the Garmin Venu 3 smartwatch to provide a broader metabolic context and as an indicator of autonomic nervous system activity.	Continuously over 3 menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).
Patient-reported perceived impact - real-time electronic logs	Perceived impact of the menstrual cycle on diabetes control and management will be captured additionally in real time using electronic logs in a smartphone app. Data are considered supplementary to the experience questionnaire-based assessment.	Continuously over three menstrual cycles. Duration varies depending on individual cycle length, ranging from 60 days (20-day cycles) to 150 days (50-day cycles).

Collaborators and Investigators

• Sponsor: Lia Bally
• Collaborators: University of Bern; DexCom, Inc.; CSEM Centre Suisse d'Electronique et de Microtechnique SA - Recherche et Developpement; Innosuisse - Swiss Innovation Agency; Insel Gruppe AG, University Hospital Bern; mylife Diabetes Care AG; Gertrud and Walter Siegenthaler Foundation; Burgergemeinde; Bangerter Foundation and Swiss Academy of Medical Science; Fresenius Kabi (Schweiz) AG; Bern Medtech Collaboration Call

Publications and helpful links

General Publications

• Escalante Pulido JM, Alpizar Salazar M. Changes in insulin sensitivity, secretion and glucose effectiveness during menstrual cycle. Arch Med Res. 1999 Jan-Feb;30(1):19-22. doi: 10.1016/s0188-0128(98)00008-6.
• Charkoudian N, Stachenfeld N. Sex hormone effects on autonomic mechanisms of thermoregulation in humans. Auton Neurosci. 2016 Apr;196:75-80. doi: 10.1016/j.autneu.2015.11.004. Epub 2015 Nov 30.
• Hirshoren N, Tzoran I, Makrienko I, Edoute Y, Plawner MM, Itskovitz-Eldor J, Jacob G. Menstrual cycle effects on the neurohumoral and autonomic nervous systems regulating the cardiovascular system. J Clin Endocrinol Metab. 2002 Apr;87(4):1569-75. doi: 10.1210/jcem.87.4.8406.
• Fede C, Albertin G, Petrelli L, Sfriso MM, Biz C, De Caro R, Stecco C. Hormone receptor expression in human fascial tissue. Eur J Histochem. 2016 Nov 2;60(4):2710. doi: 10.4081/ejh.2016.2710.
• McEwen BS, Milner TA. Understanding the broad influence of sex hormones and sex differences in the brain. J Neurosci Res. 2017 Jan 2;95(1-2):24-39. doi: 10.1002/jnr.23809.
• Mayes JS, Watson GH. Direct effects of sex steroid hormones on adipose tissues and obesity. Obes Rev. 2004 Nov;5(4):197-216. doi: 10.1111/j.1467-789X.2004.00152.x.
• Sherman BM, Korenman SG. Hormonal characteristics of the human menstrual cycle throughout reproductive life. J Clin Invest. 1975 Apr;55(4):699-706. doi: 10.1172/JCI107979.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Womens Health; Menstrual Cycle Physiology
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1
• Other Study ID Numbers: MCM-Loop

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) will be made available upon reasonable request to the principal investigator.
• IPD Sharing Time Frame: IPD will be made availabe starting 12 month after publication of trial results.
• IPD Sharing Access Criteria: Ethics approval, as applicable under Swiss legislation, will need to be obtained by those requesting the data. Additionally, a data transfer and processing agreement must be in place to ensure compliance with data protection regulations.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No