Type 1 Diabetes Mellitus
Conditions
Keywords
Insulin Pump, Continuous Glucose Monitor, Premenopausal women
Brief summary
This overall research goal will be to develop a mobile-based module to improve glycemic control during the menstrual cycle in women with Type 1 diabetes mellitus (T1DM). This module will run on an Android Operating System (OS) and will be available as: (i) a stand-alone application and (ii) an important additional component to a larger system, the Diabetes Assistant (DiAs) - a mobile-based medical platform for diabetes applications. This proposal aims to build one such application or module targeting the improvement of diabetes control in younger women who experience glucose variation related to their menstrual cycle.
Detailed description
The purpose of this particular protocol is to study the underlying glycemic variability across the menstrual cycle in women with T1DM. A subset of premenopausal women with T1DM experience loss of glucose control during the latter half of the cycle (the luteal phase). Clinical trials are sparse and tools are limited to focus on this aspect of diabetes care which is highly relevant in affected individuals. To obtain data to initialize this mobile-based module, we will enroll premenopausal women for approximately three-month outpatient study designed to characterize at least three complete menstrual cycles. These subjects will wear continuous glucose monitors (CGMs), record self-monitored blood glucoses (SMBGs) and utilize an insulin pump to capture insulin dosing. In-home ovulation kits will be used to determine relevant days for sex-steroid blood measurements to define menstrual cycle phases. Finally, structured at-home meals will be provided during different phases of the menstrual cycle for insulin action parameters assessments. The software module will be developed in parallel with the data collection from study subjects. The software module will not be used with the patients in this study as it is not in existence as would be developed in parallel. The goal of the module functionality will be to 1) assist patients and providers in the identification and management of glycemic variability surrounding the menstrual cycle and 2) add value to and become an integral module within the artificial pancreas.
Interventions
None listed
Sponsors
LifeScan
University of Virginia
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Premenopausal women with menstrual cycles that occur approximately every 20-40 days. 2. T1DM (as defined by the American Diabetes Association criteria or judgment of a physician) for at least 2 years prior to the enrollment in the study 3. Age ≥18 y.o. and ≤55 y.o. 4. Use of an insulin pump to treat their diabetes for at least 6 months. 5. Has an identified healthcare provider who can provide advice about diabetes care. 6. Actively using a current insulin pump with pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity factor. 7. Willingness to do additional fingersticks when requested such as when CGM alarms at low or high end (\<70 mg/dl or \>300 mg/dl), 8. Willingness to come to Center for Diabetes Technology for study visits. 9. Willingness to avoid consumption of acetaminophen-containing products for the duration of the study. 10. Demonstration of proper mental status and cognition for completion of the study. 11. Hemoglobin A1c 5-10%
Exclusion criteria
1. Pregnant or intending to get pregnant during study 2. Active enrollment in another clinical trial 3. Medical requirement for acetaminophen-containing products during the study period for more than 1 week 4. Use of medication or intervention that significantly alters the menstrual cycle such as oral contraceptives, depoprovera, or intrauterine device (IUD). 5. Medical condition that would make operating a CGM or insulin pump difficult (e.g. blindness, severe arthritis, extensive scar tissue at sites where devices are inserted) 6. Anticipated need for Magnetic resonance imaging (MRI)/Magnetic resonance angiography (MRA) during the study. Unplanned MRI/MRA requiring temporary interruption of CGM use would be allowed. 7. Use of prednisone for more than 10 days during the study. 8. Uncontrolled thyroid disease 9. Clinical diagnosis of polycystic ovarian syndrome requiring treatment. 10. Significant elevation in liver function tests (e.g. \>2-3 times normal), known infectious hepatitis or HIV. 11. History of a systemic deep tissue infection with methicillin-resistant staph aureus or Candida albicans 12. Known bleeding diathesis or dyscrasia 13. Active renal dialysis 14. Individuals with cognitive impairment that prevents understanding either consent form or intervention content 15. Psychiatric disorders that would interfere with study tasks (e.g., substance abuse)-self reported List any restrictions on use of other drugs or treatments. 1. Acetaminophen with the use of the CGM. 2. Use of medication or intervention that significantly alters the menstrual cycle such as oral contraceptives, depoprovera, or IUD. 3. Anticipate need for MRI/MRA during the study. Unplanned MRI/MRA requiring temporary interruption of CGM use would be allowed. 4. Use of prednisone for more than 10 days during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| High Blood Glucose Index (HBGI) | Three menstrual cycles (average length of one cycle was 28.7 days) | Measure of Hyperglycemic Risk based on frequency and severity of hyperglycemic events. HBGI \< 4.5 is associated with lower risk of hyperglycemia, 4.5 \< HBGI \< 9 is associated with a moderate risk of hyperglycemia and HBGI \> 9 is associated with high risk of hyperglycemia. Our primary outcome measure is hyperglycemia risk during the luteal phase of the menstrual cycle. The primary hypothesis is there is an increased hyperglycemia risk during the luteal phase when compared to the follicular phase. Subjects will be compared to themselves across the three menstrual cycles captured. Hyperglycemia will be primarily assessed by high blood glucose index which was assessed over 3 menstrual cycles at specific time points in the cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glycemic Changes During Luteal Phase | Three Menstrual Cycles | Changes in estrogen and progesterone will be primary drivers of hyperglycemia risk during the luteal phase. These data will be analyzed as continuous variables. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Female T1DM Premenopausal women with menstrual cycles, 18-55 years of age, who have been diagnosed as type 1 diabetic for at least 2 years. Actively using a current insulin pump for the past 6 months with pre-defined parameters for glucose goal, carbohydrate ratio, and insulin sensitivity factor. Use of medication or intervention that significantly alters the menstrual cycle such as oral contraceptives, depoprovera, or intrauterine device (IUD)is prohibited. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Female T1DM |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 33.1 years STANDARD_DEVIATION 7 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
High Blood Glucose Index (HBGI)
Measure of Hyperglycemic Risk based on frequency and severity of hyperglycemic events. HBGI \< 4.5 is associated with lower risk of hyperglycemia, 4.5 \< HBGI \< 9 is associated with a moderate risk of hyperglycemia and HBGI \> 9 is associated with high risk of hyperglycemia. Our primary outcome measure is hyperglycemia risk during the luteal phase of the menstrual cycle. The primary hypothesis is there is an increased hyperglycemia risk during the luteal phase when compared to the follicular phase. Subjects will be compared to themselves across the three menstrual cycles captured. Hyperglycemia will be primarily assessed by high blood glucose index which was assessed over 3 menstrual cycles at specific time points in the cycle.
Time frame: Three menstrual cycles (average length of one cycle was 28.7 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Female T1DM | High Blood Glucose Index (HBGI) | Early Follicular | 6.87 index score | Standard Error 0.88 |
| Female T1DM | High Blood Glucose Index (HBGI) | Mid-Late Follicular | 8.05 index score | Standard Error 1.08 |
| Female T1DM | High Blood Glucose Index (HBGI) | Peri-Ovulation | 7.92 index score | Standard Error 1.13 |
| Female T1DM | High Blood Glucose Index (HBGI) | Early Luteal | 9.00 index score | Standard Error 1.25 |
| Female T1DM | High Blood Glucose Index (HBGI) | Mid Luteal | 8.02 index score | Standard Error 0.99 |
| Female T1DM | High Blood Glucose Index (HBGI) | Late Luteal | 7.50 index score | Standard Error 0.91 |
p-value: 0.023ANOVA
Secondary
Glycemic Changes During Luteal Phase
Changes in estrogen and progesterone will be primary drivers of hyperglycemia risk during the luteal phase. These data will be analyzed as continuous variables.
Time frame: Three Menstrual Cycles
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Female T1DM | Glycemic Changes During Luteal Phase | Estradiol: Early Follicular | 41.34 pg/mL | Standard Error 3.7 |
| Female T1DM | Glycemic Changes During Luteal Phase | Estradiol: Mid-late Follicular | 91.79 pg/mL | Standard Error 13.77 |
| Female T1DM | Glycemic Changes During Luteal Phase | Estradiol: Periovulation | 225.06 pg/mL | Standard Error 43.69 |
| Female T1DM | Glycemic Changes During Luteal Phase | Estradiol: Mid-Luteal | 213.33 pg/mL | Standard Error 23.15 |
| Female T1DM | Glycemic Changes During Luteal Phase | Estradiol: Late Luteal | 143.81 pg/mL | Standard Error 15.19 |