Blood Glucose Variability and Insulin Action During Menstrual Cycle in Females With Type 1 Diabetes

Investigating Blood Glucose Variability and Insulin Action During Menstrual Cycle in Females With Type 1 Diabetes to Design Innovative Therapies

This research study is designed to look at differences in responsiveness to the subcutaneous injection of a standardized dose of rapid-acting insulin analog and blood glucose variability during different phases of the menstrual cycle in females with type 1 diabetes (T1D).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Luteal Euglycemic clamp; Device: Follicular Euglycemic clamp

Detailed Description

Type 1 Diabetes (T1D) is a chronic disease that leads to disability and premature death if not well treated. While females and males are equally affected by T1D, diabetes places additional burdens of care on females. Characteristically, females with T1D have worse glycemic control, a higher incidence of diabetic ketoacidosis, and a greater risk of cardiovascular complications as compared to their male peers. It has been hypothesized that variations in responsiveness to pre-meal bolus doses of insulin during menstrual cycling is an important underlying cause for increased management problems in females with T1D, but the hypothesis has not been adequately tested. Consequently, insulin treatment of females during the different cycles of menstruation remains a guessing game that often results in major swings in blood glucose from high to low levels. The unfavorable impact of this gap in knowledge extends to the efficiency and accuracy of artificial pancreas closed-loop (CL) system insulin delivery algorithms designed based on insulin action parameters. The proposed study addresses this unmet need in diabetes management for females both in open-loop (OL) and CL therapies.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age 12-35
2. diagnosis of T1D>1year;
3. BMI%<85th;
4. HbA1c <9%.
5. Subjects ages 21-35y on combination oral contraceptive pills (OCP) could be included.

Exclusion Criteria:

1. irregular periods,
2. pregnant, breastfeeding,
3. subjects>20y on progesterone only pills or injections,
4. Likelihood of requiring treatment during the study period with drugs not permitted by the study protocol,
5. mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, including blood glucose monitoring requirements including the documentation of blood glucose data and insulin dosing,and/or inability to return for follow-up visits, and unlikely to complete the study.
6. Subjects on OCP will be excluded in the 12-20y group to capture the physiologic variability in insulin action during pubertal progress.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: luteal phase clamp; Luteal euglycemic clamp administered during luteal phase of menstrual cycle.	Device: Luteal Euglycemic clamp; Luteal Euglycemic clamp during luteal phase
Active Comparator: follicular phase clamp; Follicular euglycemic clamp administered during follicular phase of menstrual cycle.	Device: Follicular Euglycemic clamp; Follicular Euglycemic clamp during follicular phase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in area under the glucose infusion rate (AUCGIR) during different phases of menstrual cycle	The insulin glucodynamic action will be measured by the amount of dextrose infused during the study as previously described by DeFronzo. The primary outcome measure for the euglycemic clamp studies will be area under the glucose infusion rate (AUCGIR) that will be compared between luteal and follicular phases of menstrual cycle.	Up to 30 days
Glucose Infusion Rate	During the luteal phase of the menstrual cycle, subjects will go through an insulin time action (clamp) study. Subjects are injected a bolus dose of insulin and blood sugar levels are kept within a 90-100mg/dL range by intravenous fluid infusion during fasting state. GIR stands for the glucose infusion rate that is measured in mg/kg/minute, indicating the amount of glucose delivered per minute per kilogram of body mass.	Up to 15 days
Glucose Infusion Rate	During the follicular phase of the menstrual cycle, subjects will go through an insulin time action (clamp) study. Subjects are injected a bolus dose of insulin and blood sugar levels are kept within a 90-100mg/dL range by intravenous fluid infusion during fasting state. GIR stands for the glucose infusion rate that is measured in mg/kg/minute, indicating the amount of glucose delivered per minute per kilogram of body mass.	Up to 15 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic variability	Glycemic variability measured by Continuous Glucose Monitor during two different phases of menstrual cycle will be investigated.	Up to 30 days

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: The Leona M. and Harry B. Helmsley Charitable Trust
• Investigators: Principal Investigator: Eda Cengiz, MD, MHS, Yale University

Publications and helpful links

General Publications

• Diaz C JL, Fabris C, Breton MD, Cengiz E. Insulin Replacement Across the Menstrual Cycle in Women with Type 1 Diabetes: An In Silico Assessment of the Need for Ad Hoc Technology. Diabetes Technol Ther. 2022 Nov;24(11):832-841. doi: 10.1089/dia.2022.0154.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): February 7, 2020
• Study Completion (Actual): February 7, 2020

Study Registration Dates

• First Submitted: January 15, 2016
• First Submitted That Met QC Criteria: February 23, 2016
• First Posted (Estimate): February 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 28, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: menstrual cycle; diabetes; insulin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: 1509016531

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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