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

Official title

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

Overview

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.

Interventions

• Device Continuous glucose monitoring
  Glucose levels will be measured using continuous glucose monitoring
• Drug Insulin
  Insulin doses will be retrieved from insulin pump reports (for insulin pump users) or journals for (for multiple daily injections users)
• Other Premenstrual symptoms
  Premenstrual symptoms will be assessed using the Premenstrual symptoms screening tool
• Other Ovulation kits
  Ovulation testing will be done using ovulation kits
• Device Fitbit Inspire 2
  Physical activity will be assessed using the Fitbit Inspire 2
• Other Keenoa
  Food intake will be assessed using the Keenoa phone application
• Other Menstrual cycle
  The application My Calendar will be used to record information on the menstrual cycle

Primary outcome measures

• Mean glucose levels during the early follicular phase [Time frame: Day 1 to 5 of the menstrual cycle]
• Mean glucose levels during the mid-late follicular phase [Time frame: Day 6 until 2 days prior to ovulation]
• Mean glucose levels during the periovulation phase [Time frame: Ovulation plus/minus 1 day]
• Mean glucose levels during the early luteal phase [Time frame: Day 2 to 4 after ovulation]
• Mean glucose levels during the mid-luteal phase [Time frame: Day 5 to 9 after ovulation]
• Mean glucose levels during the late luteal phase [Time frame: Day 10 after ovulation until the first day of the next menstrual cycle]

Secondary outcome measures (12)

• Percentage of time of glucose levels between 3.9 and 7.8 mmol/L [Time frame: Day 1 to 5 of the menstrual cycle]
• Percentage of time of glucose levels between 3.9 and 7.8 mmol/L [Time frame: Day 6 until 2 days prior to ovulation]
• Percentage of time of glucose levels between 3.9 and 7.8 mmol/L [Time frame: Ovulation plus/minus 1 day]
• Percentage of time of glucose levels between 3.9 and 7.8 mmol/L [Time frame: Day 2 to 4 after ovulation]
• Percentage of time of glucose levels between 3.9 and 7.8 mmol/L [Time frame: Day 5 to 9 after ovulation]
• Percentage of time of glucose levels between 3.9 and 7.8 mmol/L [Time frame: 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 [Time frame: Day 1 to 5 of the menstrual cycle]
• Percentage of time of glucose levels between 3.9 and 10.0 mmol/L [Time frame: Day 6 until 2 days prior to ovulation]
• Percentage of time of glucose levels between 3.9 and 10.0 mmol/L [Time frame: Ovulation plus/minus 1 day]
• Percentage of time of glucose levels between 3.9 and 10.0 mmol/L [Time frame: Day 2 to 4 after ovulation]
• Percentage of time of glucose levels between 3.9 and 10.0 mmol/L [Time frame: Day 5 to 9 after ovulation]
• Percentage of time of glucose levels between 3.9 and 10.0 mmol/L [Time frame: Day 10 after ovulation until the first day of the next menstrual cycle]

Eligibility criteria

Inclusion criteria

• Females aged 18 to 50 living in Canada.
• 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.This access will be limited to the study period.
• Having a smartphone or tablet to follow menstrual cycles.
• Stable weight (less than 5% variation in the last 3 months).

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.
• If taking medication for hypothyroidism, no change of dose (Levothyroxin) in the last 6 weeks.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Canada · 1 center

• Institut de recherches cliniques de Montréal — Montreal

Identifiers

NCT: NCT05258292 · 2022-1165

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗