The Influence of Glycemic Control and Obesity on Energy Balance and Metabolic Flexibility in Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to compare the metabolic phenotype of a range of body weights in individuals with and without Type 1 diabetes.

Official Title
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The Influence of Glycemic Control and Obesity on Energy Balance and Metabolic Flexibility in Type 1 Diabetes

Conditions
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Diabetes

Intervention / Treatment
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* Other: DEXA
* Other: MRI
* Other: CGM
* Other: Whole room calorimeters
* Other: Dietary counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 19 to 30 years of age, inclusive. Type 1 Diabetes Cohort: Diagnosis of type 1 diabetes for greater than 1 year at screening. Hemoglobin A1c 6.5-13% or Non-Diabetic Control Cohort: Healthy individuals (non-diabetic) matched to T1D cohort by BMI, and gender 3. Able to provide informed consent. 4. BMI 18-39 Exclusion Criteria: Type 2 diabetes History or presence of cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG, presence of cardiac pacemaker, implanted cardiac defibrillator) Liver disease (AST or ALT >2.5 times the upper limit of normal), history of hepatitis Kidney disease (creatinine >1.6 mg/dl or estimated glomerular filtration rate (GFR)<60 ml/min) Dyslipidemia, including triglycerides >800 mg/dl, LDL >200 mg/dl Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women) Thyroid dysfunction (suppressed thyroid-stimulating hormone (TSH), elevated TSH <10 µIU/ml if symptomatic or elevated TSH >10 µIU/ml if asymptomatic) Uncontrolled hypertension (BP >160 mmHg systolic or > 100mmHg diastolic) History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable). Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to thyroid hormone, birth control or estrogen replacement therapy) History of organ transplant History of HIV, active Hepatitis B or C, or Tuberculosis Pregnancy, lactation or 6 months postpartum from screening visit History of major depression Psychiatric disease prohibiting adherence to study protocol History of eating disorders Cushing's disease or syndrome History of bariatric surgery Tobacco use within the past 3 months History of drug or alcohol abuse (≥3 drinks per day) within the last 5 years Use of oral or injectable anti-hyperglycemic agents (except insulin) Current use of beta-adrenergic blocking agents Use of antibiotics within the past 3 months Weight >450 lbs (This is DEXA table weight limit) Metal implants (pace-maker, aneurysm clips) based on Investigator's judgment at screening Unable to participate in MRI or magnetic resonance spectroscopy (MRS) assessment based on Investigator's judgment at screening Participants with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food allergies, or allergies to food we will provide them during the study) Gastrointestinal disorders including: inflammatory bowel disease or malabsorption, swallowing disorders, suspected or known strictures, fistulas or physiological/mechanical GI obstruction, history of gastrointestinal surgery, Crohn's disease or diverticulitis. Presence of any condition that, in the opinion of the investigator, compromises participant safety or data integrity or the participant's ability to complete study visits

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 39 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lean T1D<br> | Other: DEXA<br>* Measurement of body composition by Dual Energy X-ray Absorptiometry (DEXA)<br>Other: MRI<br>* Whole body magnetic resonance imaging (MRI)<br>Other: CGM<br>* A continuous glucose monitor (CGM) will be placed on the participant and will be used as a safety measure to monitor glucose levels.<br>Other: Whole room calorimeters<br>* Whole room indirect calorimetry allows for the simultaneous measure of total energy expenditure and substrate oxidation in a free living environment with multiple activities.<br>|
| Active Comparator: Obese T1D<br> | Other: Whole room calorimeters<br>* Whole room indirect calorimetry allows for the simultaneous measure of total energy expenditure and substrate oxidation in a free living environment with multiple activities.<br>Other: Dietary counseling<br>* The low carbohydrate diet counseling will be to assist young adult, overweight study participants with Type 1 diabetes in adhering to a lower calorie diet (500 calorie deficit)<br>|
| Active Comparator: Non-diabetic<br> | Other: DEXA<br>* Measurement of body composition by Dual Energy X-ray Absorptiometry (DEXA)<br>Other: MRI<br>* Whole body magnetic resonance imaging (MRI)<br>Other: CGM<br>* A continuous glucose monitor (CGM) will be placed on the participant and will be used as a safety measure to monitor glucose levels.<br>Other: Whole room calorimeters<br>* Whole room indirect calorimetry allows for the simultaneous measure of total energy expenditure and substrate oxidation in a free living environment with multiple activities.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole Room Calorimetry | Compare 24-hour energy expenditure in patients with T1D and healthy normal volunteers that accounts for differences in hyperglycemia and body composition. 24-hour energy expenditure in kcal/24 hours after adjusting for differences in hyperglycemia (CGM) and body composition (DXA). These parameters will be measured by VO2, VC02, and urinary nitrogen. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obesity