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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01DK134398-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
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More than 40% of young adults with type 1 diabetes (T1D) also have overweight or obesity. Each of these diagnoses increase the risk of adverse cardiovascular events. Investigators aim to obtain reference data for individuals with T1D who do not have overweight obesity, to understand how close GLP-1 analogue obesity treatment in those with overweight/obesity brings physiologic markers of cardiometabolic risk to those with BMI in the normal range. Specifically, investigators will describe how drivers of gluconeogenesis and lipemia (specifically measured as visceral fat ratio, insulin resistance, and postprandial lipemia,) that contribute to cardiometabolic risk in T1D change over time.
Primary Objective
The primary objectives of this physiologic study are to:
Secondary Objective
The secondary objective[s] of this study are to determine change in:
Aim 1: Weight and % body fat from baseline to 1 year. Aim 2: Suppression of endogenous glucose production (a measure of insulin resistance), expressed as the change in endogenous glucose rate of appearance (mg/kg/min) at baseline and during the low dose (hepatic) phase, and relationship to VAT/(VAT+SAT) from baseline to 1 year. Glucose rate of appearance, glycerol rate of appearance, glucose oxidation, and fat oxidation will be assessed in all clamp phases baseline to 1 year.
Aim 3: Postprandial rise in other atherogenic lipoproteins baseline to 1 year. The data obtained from this protocol will serve as reference data for a randomized clinical trial of GLP-1 analogue obesity in young adults with T1D and overweight/obesity.
The focus of this registration is the primary objective.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Young adults with T1D who have a body mass index <25 kg/m2 | Experimental | Young adults with T1D who have a body mass index <25 kg/m2 will have: abdominal MRI, hyperinsulinemic-euglycemic clamp wtih stable isotope tracer, DEXA scan and a High Fat Mixed Meal Tolerance Test. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyperinsulinemic-euglycemic clamp | Biological | Hyperinsulinemic-euglycemic clamp will be used to assess insulin resistance. After IVs are placed, participants will be transitioned to intravenous insulin administration for the baseline portion of the study. Stable Isotope Tracer Infusions will assess rates of glucose, lipid metabolism, and beta-hydroxybutyrate turnover during the last 30 minutes of the baseline equilibration period and again during the last 30 minutes of the stepped IV insulin infusion periods. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in VAT/(VAT+SAT) from baseline to 1 year | Measured as VAT/Subcutaneous Adipose Tissue + VAT changes over 1 year in young adults with T1D and body mass index <25kg/m2. | baseline and 1 year |
| Change in hepatic insulin resistance from baseline to 1 year | Hepatic insulin resistance, measured by beta-hydroxybutyrate (surrogate marker of acetyl-CoA, which regulates gluconeogenesis), changes over 1 year in young adults with T1D and body mass index <25kg/m2. | baseline and 1 year |
| Change in triglycerides from baseline to 1 year | Change in triglycerides after a high-fat mixed meal tolerance test, expressed as the total Area Under the Curve (AUCTG) over 6 hours from baseline to 1 year. | baseline and 1 year |
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Inclusion Criteria:
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged 18 to ≤30 years
Diagnosed T1D for at least 12 months and with BMI <25 kg/m2.
HbA1c ≤10%
Clinical use of continuous glucose monitoring (CGM)
Any known laboratory safety parameter consistently outside the below extended laboratory ranges in the past year:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rehema Mtawali | Contact | (475) 414-4035 | rehema.mtawali@yale.edu |
| Name | Affiliation | Role |
|---|---|---|
| Michelle Van Name, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale Pediatric Diabetes Research | Recruiting | New Haven | Connecticut | 06520 | United States |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| High Fat Mixed Meal Tolerance Test | Other | After a 12 hour overnight fast, baseline levels of the lipoproteins will be drawn. The YCCI Bionutrition Service kitchen will prepare the standardized high-fat meal. Participants will administer their bolus insulin per their home regimen for the carbohydrates in the high-fat meal, and then they will consume the meal within a 15-minute timeframe. |
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| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |