Diabetes Mellitus, Type 1, Energy Metabolism
Conditions
Keywords
Womens Health, Menstrual Cycle Physiology
Brief summary
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.
Interventions
None listed
Sponsors
Lia Bally
Gertrud and Walter Siegenthaler Foundation
Bangerter Foundation and Swiss Academy of Medical Science
Innosuisse - Swiss Innovation Agency
CSEM Centre Suisse d'Electronique et de Microtechnique SA - Recherche et Developpement
University of Bern
Insel Gruppe AG, University Hospital Bern
DexCom, Inc.
Fresenius Kabi (Schweiz) AG
Bern Medtech Collaboration Call
mylife Diabetescare AG
Burgergemeinde Bern
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in target glucose range | 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). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Algorithm-directed insulin delivery following a standardized meal | 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 | 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. |
| Insulin sensitivity | 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). | 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. |
| Gastric emptying | The outcome is evaluated at each phase-specific assessment (early follicular, pre-ovulatory, and luteal) for one menstrual cycle. | 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. |
| Total energy expenditure | Continuously over one menstrual cycle. Duration varies depending on individual cycle length, ranging from 20 days to 50 days. | Total energy expenditure will be quantified using the doubly labelled water method. This outcome is measured only in a subgroup of 15 participants. |
| Substrate oxidation | Assessed once at each phase-specific assessment (early follicular, pre-ovulatory, and luteal) for one menstrual cycle | 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. |
| Dietary intake | 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 | Total energy intake (kcal/day) will be assessed by recording all meals using an image-based automated food analysis application SNAQ. |
| 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). | The number of steps per day, as a component of physical activity, will be measured using the Garmin Venu 3 smartwatch. |
Countries
Switzerland
Outcome results
None listed