Physiologic Markers of Cardiometabolic Risk in People With Type 1 Diabetes

Primary Objective

The primary objectives of this physiologic study are to:

• 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.
• determine how hepatic insulin resistance changes over 1 year in young adults with T1D and body mass index <25kg/m2.
• 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.

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:

• Baseline creatinine >1.0mg
• Hypertriglyceridemia (>400 mg/dl)
• ALT ≥3.5 times the upper normal limit (UNL)

Exclusion criteria

• Current use of adjunctive diabetes medication or anti-obesity medication
• Insulin dose <0.5 units/kg/day
• Use of lipid lowering prescription medication other than statins or omega-3 products
• Doesn't meet MRI safety criteria or having claustrophobia
• Known liver disease other than non-alcoholic steatosis or non-alcoholic fatty liver disease
• Known renal impairment
• Pregnancy or lactation, or planning to become pregnant during the study period.
• Anemia or known hematologic condition impacting HbA1c reading, or another medical condition that precludes participation.
• Treatment with another investigational drug within the past 1 month
• Past medical history of or self-reported corn allergy