Glycemic Variations During the Menstrual Cycle in Women With Type 1 Diabetes

Study Overview
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Brief Summary
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In clinical practice, women living with type 1 diabetes frequently report that insulin requirements change across the menstrual cycle. Consequently, glycemic fluctuations are observed. This phenomenon could be explained by a decrease in insulin sensitivity during the second half of the menstrual cycle (luteal phase). Overall, despite an important proportion of women reporting glycemic and/or insulin variations across the menstrual cycle, studies to date have involved small sample sizes, and have had inconsistent results. The objective of this study will be to study glycemic fluctuations across the menstrual cycle using CGM data, alongside insulin data, in a large sample of women.

Official Title
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Glycemic Variations During the Menstrual Cycle in Women With Type 1 Diabetes: the GLYMETY Study

Conditions
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Type1diabetes

Intervention / Treatment
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* Device: Continuous glucose monitoring
* Drug: Insulin
* Other: Premenstrual symptoms
* Other: Ovulation kits
* Device: Fitbit Inspire 2
* Other: Keenoa
* Other: Menstrual cycle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females aged 18 to 50. Clinical diagnosis of type 1 diabetes or latent autoimmune diabetes in adults (LADA) for at least one year. Using insulin pump therapy, multiple daily injections or automated insulin delivery systems for at least 3 months. Using a continuous glucose monitoring (CGM) system. Having at least one menses in the last 40 days. Accepting to share CGM data with the research team and if applicable insulin pump data. Living in the province of Quebec, Canada. Having a smartphone or tablet to follow menstrual cycles. Exclusion Criteria: Using a hormonal contraception method that eliminates menses (Depo Provera, progestin intrauterine device, extented-cycle regimen with birth control pill) Using regular insulin (Entuzity U500, Novolin ge Toronto or Humulin R). Clinically significant nephropathy (eGFR < 30 ml/min/1.73m2, planned or on dialysis) or neuropathy (e.g., known uncontrolled gastroparesis) as judged by the investigator. Recent (< 6 months) acute macrovascular event (e.g., acute coronary syndrome or cardiac surgery). Anticipated therapeutic change (including change of insulin type and/or type of CGM sensor, insulin pump or AID (automated insulin device) system) between admission and end of the study. Anticipated change in contraception method or plan to begin or stop a contraceptive method. Anticipated need to use acetaminophen during the study period at a dose above 1g every 6 hours. Pregnancy (ongoing or current attempt to become pregnant) Breastfeeding Uncontrolled thyroid disease (TSH should be in target range and treatment stable for at least 6 weeks). Severe hypoglycemic episode within two weeks of screening Severe hyperglycemic episodes requiring hospitalization in the last 3 months. Current use of glucocorticoid medication (except low stable dose and inhaled steroids and stable adrenal insufficiency treatment e.g., Cortef®) Agents affecting gastric emptying (Motilium®, Victoza®, Ozempic®, Trulicity®, Byetta® and Symlin®) as well as oral anti-diabetic agents (Metformin, Prandase®, DPP-4 inhibitors) unless at a stable dose for 3 months and without anticipated change during the study. Current use of SGLT-2 inhibitors unless at a stable dose for at least 3 months, without anticipated change during the study and appropriate ketone testing is performed. Other serious medical illnesses which likely interfere with study participation or with the ability to complete the study by the judgment of the investigator. Anticipation of a significant change in exercise or diet regimen between admission and end of the study (i.e., starting or stopping an organized sport; planned significant diet change). Anticipated radiologic examination incompatible with CGM wear for more than 10 days between admission and end of the study (e.g., repeated MRI). In the opinion of the investigator, a participant who is unable or unwilling to complete the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women with type 1 diabetes<br> | Device: Continuous glucose monitoring<br>* Glucose levels will be measured using continuous glucose monitoring<br>Drug: Insulin<br>* Insulin doses will be retrieved from insulin pump reports (for insulin pump users) or journals for (for multiple daily injections users)<br>Other: Premenstrual symptoms<br>* Premenstrual symptoms will be assessed using the Premenstrual symptoms screening tool<br>Other: Ovulation kits<br>* Ovulation testing will be done using ovulation kits<br>Device: Fitbit Inspire 2<br>* Physical activity will be assessed using the Fitbit Inspire 2<br>Other: Keenoa<br>* Food intake will be assessed using the Keenoa phone application<br>Other: Menstrual cycle<br>* The application My Calendar will be used to record information on the menstrual cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean glucose levels during the early follicular phase |  | Day 1 to 5 of the menstrual cycle | 
| Mean glucose levels during the mid-late follicular phase |  | Day 6 until 2 days prior to ovulation | 
| Mean glucose levels during the periovulation phase |  | Ovulation plus/minus 1 day | 
| Mean glucose levels during the early luteal phase |  | Day 2 to 4 after ovulation | 
| Mean glucose levels during the mid-luteal phase |  | Day 5 to 9 after ovulation | 
| Mean glucose levels during the late luteal phase |  | Day 10 after ovulation until the first day of the next menstrual cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time of glucose levels between 3.9 and 7.8 mmol/L |  | Day 1 to 5 of the menstrual cycle | 
| Percentage of time of glucose levels between 3.9 and 7.8 mmol/L |  | Day 6 until 2 days prior to ovulation | 
| Percentage of time of glucose levels between 3.9 and 7.8 mmol/L |  | Ovulation plus/minus 1 day | 
| Percentage of time of glucose levels between 3.9 and 7.8 mmol/L |  | Day 2 to 4 after ovulation | 
| Percentage of time of glucose levels between 3.9 and 7.8 mmol/L |  | Day 5 to 9 after ovulation | 
| Percentage of time of glucose levels between 3.9 and 7.8 mmol/L |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Percentage of time of glucose levels between 3.9 and 10.0 mmol/L |  | Day 1 to 5 of the menstrual cycle | 
| Percentage of time of glucose levels between 3.9 and 10.0 mmol/L |  | Day 6 until 2 days prior to ovulation | 
| Percentage of time of glucose levels between 3.9 and 10.0 mmol/L |  | Ovulation plus/minus 1 day | 
| Percentage of time of glucose levels between 3.9 and 10.0 mmol/L |  | Day 2 to 4 after ovulation | 
| Percentage of time of glucose levels between 3.9 and 10.0 mmol/L |  | Day 5 to 9 after ovulation | 
| Percentage of time of glucose levels between 3.9 and 10.0 mmol/L |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Percentage of time of glucose levels below 3.9 mmol/L |  | Day 1 to 5 of the menstrual cycle | 
| Percentage of time of glucose levels below 3.9 mmol/L |  | Day 6 until 2 days prior to ovulation | 
| Percentage of time of glucose levels below 3.9 mmol/L |  | Ovulation plus/minus 1 day | 
| Percentage of time of glucose levels below 3.9 mmol/L |  | Day 2 to 4 after ovulation | 
| Percentage of time of glucose levels below 3.9 mmol/L |  | Day 5 to 9 after ovulation | 
| Percentage of time of glucose levels below 3.9 mmol/L |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Percentage of time of glucose levels below 3.0 mmol/L |  | Day 1 to 5 of the menstrual cycle | 
| Percentage of time of glucose levels below 3.0 mmol/L |  | Day 6 until 2 days prior to ovulation | 
| Percentage of time of glucose levels below 3.0 mmol/L |  | Ovulation plus/minus 1 day | 
| Percentage of time of glucose levels below 3.0 mmol/L |  | Day 2 to 4 after ovulation | 
| Percentage of time of glucose levels below 3.0 mmol/L |  | Day 5 to 9 after ovulation | 
| Percentage of time of glucose levels below 3.0 mmol/L |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Percentage of time of glucose levels above 10.0 mmol/L |  | Day 1 to 5 of the menstrual cycle | 
| Percentage of time of glucose levels above 10.0 mmol/L |  | Day 6 until 2 days prior to ovulation | 
| Percentage of time of glucose levels above 10.0 mmol/L |  | Ovulation plus/minus 1 day | 
| Percentage of time of glucose levels above 10.0 mmol/L |  | Day 2 to 4 after ovulation | 
| Percentage of time of glucose levels above 10.0 mmol/L |  | Day 5 to 9 after ovulation | 
| Percentage of time of glucose levels above 10.0 mmol/L |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Percentage of time of glucose levels above 13.9 mmol/L |  | Day 1 to 5 of the menstrual cycle | 
| Percentage of time of glucose levels above 13.9 mmol/L |  | Day 6 until 2 days prior to ovulation | 
| Percentage of time of glucose levels above 13.9 mmol/L |  | Ovulation plus/minus 1 day | 
| Percentage of time of glucose levels above 13.9 mmol/L |  | Day 2 to 4 after ovulation | 
| Percentage of time of glucose levels above 13.9 mmol/L |  | Day 5 to 9 after ovulation | 
| Percentage of time of glucose levels above 13.9 mmol/L |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Standard deviation of glucose levels |  | Day 1 to 5 of the menstrual cycle | 
| Standard deviation of glucose levels |  | Day 6 until 2 days prior to ovulation | 
| Standard deviation of glucose levels |  | Ovulation plus/minus 1 day | 
| Standard deviation of glucose levels |  | Day 2 to 4 after ovulation | 
| Standard deviation of glucose levels |  | Day 5 to 9 after ovulation | 
| Standard deviation of glucose levels |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Coefficient of variance of glucose levels |  | Day 1 to 5 of the menstrual cycle | 
| Coefficient of variance of glucose levels |  | Day 6 until 2 days prior to ovulation | 
| Coefficient of variance of glucose levels |  | Ovulation plus/minus 1 day | 
| Coefficient of variance of glucose levels |  | Day 2 to 4 after ovulation | 
| Coefficient of variance of glucose levels |  | Day 5 to 9 after ovulation | 
| Coefficient of variance of glucose levels |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Low blood glucose index |  | Day 1 to 5 of the menstrual cycle | 
| Low blood glucose index |  | Day 6 until 2 days prior to ovulation | 
| Low blood glucose index |  | Ovulation plus/minus 1 day | 
| Low blood glucose index |  | Day 2 to 4 after ovulation | 
| Low blood glucose index |  | Day 5 to 9 after ovulation | 
| Low blood glucose index |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| High blood glucose index |  | Day 1 to 5 of the menstrual cycle | 
| High blood glucose index |  | Day 6 until 2 days prior to ovulation | 
| High blood glucose index |  | Ovulation plus/minus 1 day | 
| High blood glucose index |  | Day 2 to 4 after ovulation | 
| High blood glucose index |  | Day 5 to 9 after ovulation | 
| High blood glucose index |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Standard deviation of insulin delivery |  | Day 1 to 5 of the menstrual cycle | 
| Standard deviation of insulin delivery |  | Day 6 until 2 days prior to ovulation | 
| Standard deviation of insulin delivery |  | Ovulation plus/minus 1 day | 
| Standard deviation of insulin delivery |  | Day 2 to 4 after ovulation | 
| Standard deviation of insulin delivery |  | Day 5 to 9 after ovulation | 
| Standard deviation of insulin delivery |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Coefficient of variance of insulin delivery |  | Day 1 to 5 of the menstrual cycle | 
| Coefficient of variance of insulin delivery |  | Day 6 until 2 days prior to ovulation | 
| Coefficient of variance of insulin delivery |  | Ovulation plus/minus 1 day | 
| Coefficient of variance of insulin delivery |  | Day 2 to 4 after ovulation | 
| Coefficient of variance of insulin delivery |  | Day 5 to 9 after ovulation | 
| Coefficient of variance of insulin delivery |  | Day 10 after ovulation until the first day of the next menstrual cycle | 
| Total insulin delivery |  | Day 1 to 5 of the menstrual cycle | 
| Total insulin delivery |  | Day 6 until 2 days prior to ovulation | 
| Total insulin delivery |  | Ovulation plus/minus 1 day | 
| Total insulin delivery |  | Day 2 to 4 after ovulation | 
| Total insulin delivery |  | Day 5 to 9 after ovulation | 
| Total insulin delivery |  | Day 10 after ovulation until the first day of the next menstrual cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menstrual cycle, Continuous glucose monitoring, Insulin dose, Physical activity, Food intake