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: 1. examine how visceral adipose tissue (VAT), measured as VAT/Subcutaneous Adipose Tissue + VAT changes over 1 year in young adults with T1D and body mass index \<25kg/m2. 2. determine how hepatic insulin resistance changes over 1 year in young adults with T1D and body mass index \<25kg/m2. 3. determine how the area under the curve of triglycerides after a high fat mixed meal tolerance test changes over 1 year in young adults with T1D and body mass index \<25kg/m2. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
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.
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.
Yale Pediatric Diabetes Research
New Haven, Connecticut, United States
RECRUITINGChange 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.
Time frame: 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.
Time frame: 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.
Time frame: baseline and 1 year
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