Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to determine if 2 weeks of nightly exposure (7-12 hours per night) to moderate hypoxia (\ 2,400 meters or 7,500 feet) improves glucose metabolism in people with type 2 diabetes.
Detailed description
Exposure to hypoxia has been advocated as a possible therapeutic aid against obesity. Indeed, our laboratory has provided the first evidence that intermittent, nightly exposure to moderate hypoxia is beneficial in improving insulin sensitivity in healthy obese patients and, therefore, lowers the risk of developing type 2 diabetes. Benefits included reduced fasting glucose levels and improved whole-body (skeletal muscle) and hepatic insulin sensitivity. Whether such intermittent hypoxia improves glucose metabolism in people with type 2 diabetes is unknown.
Interventions
DEVICEHypoxico Altitude Training Systems
Participants will sleep in a tent (which will fit his/her personal mattress) simulating an altitude of \ 2,400 meters for 7-12 hours each night for a period of 14 days. Baseline testing measures will include a oral glucose tolerance test (OGTT) and body composition (iDXA). Post-treatment testing measures will include OGTT only.
Sponsors
Pennington Biomedical Research Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 20-65 yrs * Body mass index (BMI) \< 55 kg/m2 * Body weight 450 lbs or less (to accommodate body composition assessment) * Have either been diagnosed with type 2 diabetes, or fasting blood glucose between 125 and 200 mg/dL, or have a hemoglobin A1c ≥ 6.5% * Non-smokers * Weight stable over the previous 3 months (\<3 kg fluctuation) * Known diagnosis of sleep apnea and ownership of a continuous positive airway pressure (C-PAP) device that must be worn throughout the nights spent in the tent * If no known presence of sleep apnea, be willing to spend one night in a sleep laboratory (Louisiana Sleep Foundation) to assess presence of sleep apnea
Exclusion criteria
* Diagnosed with T2DM ≥ 15 years ago * Pregnant Women * Current insulin treatment * Treatment with sulfonylureas or glitinides * Treatment with a GLP-1 agonist * Any other diabetes medication other than an oral agent is exclusionary unless otherwise cleared by medical investigator. * Chronic Obstructive Pulmonary Disease (COPD) * Congestive heart failure * Prior severe cardiovascular events such as stroke or myocardial infarction * If treated for T2DM with other oral agent, no change in the treatment for 1 month before the study and the duration of the study * Previously known diagnosis of sleep apnea without ownership of a continuous positive airway pressure (C-PAP) device or agreement to use owned CPAP device during the nights spent in the tent * Presence of sleep apnea following a positive home sleep test (HST), or have unsafe oxyhemoglobin saturation levels (less than 78%) during a one night sleep monitoring assessment conducted at the Louisiana Sleep Foundation without ownership of a continuous positive airway pressure (C-PAP) device or agreement to use owned C-PAP device during the nights spent in the tent * History of high altitude sickness * History of altitude sickness * Does not have access to a bed or sleeping surface equivalent to or smaller than a queen size mattress
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Sensitivity | Baseline and Post-Moderate Hypoxia (14 days) | Insulin sensitivity was determined using an oral glucose tolerance test. Insulin sensitivity was estimated using the whole-body insulin sensitivity index (WBISI), also known as the Matsuda Index (unitless): WBISI = 10,000 / \[square root of (Glu0 x Ins0) x (mean glucose x mean insulin during an oral glucose tolerance test)\] where Glu0 and Ins0 denote baseline glucose and insulin concentrations. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Secretion | Baseline and Post-Moderate Hypoxia (14 days) | Insulin secretion was determined using an oral glucose tolerance test. Insulin secretion was estimated using the Insulinogenic Index (IGI), an index of first-phase insulin response, and calculated from the ratio of the increments of serum insulin to glucose measured at 30 minutes: IGI (unitless) = (Ins30 - Ins0)/(Glu30 - Glu0), where insulin and glucose from 0 and 30 minutes are used. |
| Beta-cell Function | Baseline and Post-Moderate Hypoxia (14 days) | Beta-cell function was determined using an oral glucose tolerance test. Beta-cell function was estimated by the Disposition Index, or the product of insulin sensitivity and insulin secretion: DI (unitless) = Matsuda Index (WBISI) x Insulinogenic Index (IGI). |
| 2-hour Glucose Area-under-the-curve | 0, 0.5, 1, 1.5, and 2 hours at Baseline and Post-Moderate Hypoxia (14 days) | 2-hour glucose area-under-the-curve (mg/dL x hour) was determined using an oral glucose tolerance test. |
| 2-hour Insulin Area-under-the-curve Via Oral Glucose Tolerance Test | 0, 0.5, 1, 1.5, and 2 hours at Baseline and Post-Moderate Hypoxia (14 days) | 2-hour insulin area-under-the-curve (μU/mL x hr) was determined using an oral glucose tolerance test. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Moderate Hypoxia 2-weeks of nightly exposure (7-12 hrs per night) to moderate hypoxia (\
2,400 meters) using the Hypoxico Altitude Training Systems device.
Hypoxico Altitude Training Systems: Participants will sleep in a tent (which will fit his/her personal mattress) simulating an altitude of \
2,400 meters for 7-12 hours each night for a period of 14 days. Baseline testing measures will include a oral glucose tolerance test (OGTT) and body composition (iDXA). Post-treatment testing measures will include OGTT only. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Moderate Hypoxia |
|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 10 |
| Body mass index, Continuous | 39.6 kg/m^2 STANDARD_DEVIATION 5.8 |
| Diastolic blood pressure, Continuous | 74 mmHg STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fat-free mass, Continuous | 67.3 kg STANDARD_DEVIATION 14 |
| Fat mass, Continuous | 50.5 kg STANDARD_DEVIATION 12.2 |
| Hemoglobin A1C, Continuous | 6.8 percent STANDARD_DEVIATION 0.7 |
| High-density lipoprotein cholesterol (HDL), Continuous | 55 mg/dL STANDARD_DEVIATION 18 |
| Low-density lipoprotein cholesterol (LDL), Continuous | 95 mg/dL STANDARD_DEVIATION 22 |
| Percent body fat, Continuous | 43 percent STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
| Systolic blood pressure, Continuous | 121 mmHg STANDARD_DEVIATION 13 |
| Total cholesterol (TC), Continuous | 170 mg/dL STANDARD_DEVIATION 36 |
| Triglycerides, Continuous | 100 mg/dL STANDARD_DEVIATION 39 |
| Weight, Continuous | 117.8 kg STANDARD_DEVIATION 18.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Insulin Sensitivity
Insulin sensitivity was determined using an oral glucose tolerance test. Insulin sensitivity was estimated using the whole-body insulin sensitivity index (WBISI), also known as the Matsuda Index (unitless): WBISI = 10,000 / \[square root of (Glu0 x Ins0) x (mean glucose x mean insulin during an oral glucose tolerance test)\] where Glu0 and Ins0 denote baseline glucose and insulin concentrations.
Time frame: Baseline and Post-Moderate Hypoxia (14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moderate Hypoxia | Insulin Sensitivity | Baseline Measure | 1.7 unitless | Standard Deviation 0.7 |
| Moderate Hypoxia | Insulin Sensitivity | Post-Moderate Hypoxia Measure | 2.2 unitless | Standard Deviation 1.7 |
Secondary
2-hour Glucose Area-under-the-curve
2-hour glucose area-under-the-curve (mg/dL x hour) was determined using an oral glucose tolerance test.
Time frame: 0, 0.5, 1, 1.5, and 2 hours at Baseline and Post-Moderate Hypoxia (14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moderate Hypoxia | 2-hour Glucose Area-under-the-curve | Baseline Measure | 501 mg/dL x hour | Standard Deviation 99 |
| Moderate Hypoxia | 2-hour Glucose Area-under-the-curve | Post-Moderate Hypoxia Measure | 439 mg/dL x hour | Standard Deviation 65 |
Secondary
2-hour Insulin Area-under-the-curve Via Oral Glucose Tolerance Test
2-hour insulin area-under-the-curve (μU/mL x hr) was determined using an oral glucose tolerance test.
Time frame: 0, 0.5, 1, 1.5, and 2 hours at Baseline and Post-Moderate Hypoxia (14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moderate Hypoxia | 2-hour Insulin Area-under-the-curve Via Oral Glucose Tolerance Test | Baseline Measure | 180 uU/mL x hour | Standard Deviation 154 |
| Moderate Hypoxia | 2-hour Insulin Area-under-the-curve Via Oral Glucose Tolerance Test | Post-Moderate Hypoxia Measure | 168 uU/mL x hour | Standard Deviation 176 |
Secondary
Beta-cell Function
Beta-cell function was determined using an oral glucose tolerance test. Beta-cell function was estimated by the Disposition Index, or the product of insulin sensitivity and insulin secretion: DI (unitless) = Matsuda Index (WBISI) x Insulinogenic Index (IGI).
Time frame: Baseline and Post-Moderate Hypoxia (14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moderate Hypoxia | Beta-cell Function | Baseline Measure | 0.9 unitless | Standard Deviation 1 |
| Moderate Hypoxia | Beta-cell Function | Post-Moderate Hypoxia Measure | 1.4 unitless | Standard Deviation 1.7 |
Secondary
Insulin Secretion
Insulin secretion was determined using an oral glucose tolerance test. Insulin secretion was estimated using the Insulinogenic Index (IGI), an index of first-phase insulin response, and calculated from the ratio of the increments of serum insulin to glucose measured at 30 minutes: IGI (unitless) = (Ins30 - Ins0)/(Glu30 - Glu0), where insulin and glucose from 0 and 30 minutes are used.
Time frame: Baseline and Post-Moderate Hypoxia (14 days)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Moderate Hypoxia | Insulin Secretion | Baseline Measure | 0.6 unitless | Standard Deviation 0.6 |
| Moderate Hypoxia | Insulin Secretion | Post-Moderate Hypoxia Measure | 0.7 unitless | Standard Deviation 0.7 |