Physiologic Markers of Cardiometabolic Risk in People With Type 1 Diabetes

NCT06105931 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 20000361251R01DK134398-01A1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

type1diabetes; Obesity

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

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.

Biological: Hyperinsulinemic-euglycemic clamp; Other: High Fat Mixed Meal Tolerance Test

Interventions

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.

Young adults with T1D who have a body mass index <25 kg/m2

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.

Young adults with T1D who have a body mass index <25 kg/m2

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Yale Pediatric Diabetes Research

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Michelle Van Name, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rehema Mtawali

CONTACT

(475) 414-4035; rehema.mtawali@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 30, 2023
• Study Start: December 13, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)