RecruitingPhase 1NCT06105931

Physiologic Markers of Cardiometabolic Risk in People With Type 1 Diabetes

Sponsor

Yale University

Enrollment

15 participants

Start Date

Dec 13, 2023

Study Type

INTERVENTIONAL

Conditions

Obesity Type1diabetes

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 30 Years

Inclusion Criteria10

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 Criteria10

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

Interventions

BIOLOGICALHyperinsulinemic-euglycemic clamp

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.

OTHERHigh Fat Mixed Meal Tolerance Test

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.