Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes

Overview

The purpose of this study is to assess the effects of adiposity on resistance to insulin's ability to suppress hepatic glucose production and to stimulate peripheral glucose metabolism in adolescents with type 1 diabetes. In addition, this study will also examine the role of fatty liver disease on the insulin resistance of obesity in adolescents with type 1 diabetes.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: December 31, 2021

Detailed Description

A major focus of this program of research will be directed at advancing the understanding of the metabolic consequences of obesity and puberty in adolescents with T1D. Thus, an innovative aspect of this research is that it will be the first to use these sophisticated metabolic techniques to examine the effects of obesity and hepatic steatosis on insulin sensitivity in pubertal adolescents with T1D; namely, the 2-step hyperinsulinemic euglycemic clamp with tracer enhancement, which will allow for definition of hepatic and peripheral insulin resistance, glycerol turnover, and glucose and fat oxidation. Further, a second novel aspect is that this will be the first study to utilize gold standard MRI methods to quantify and compare intrahepatic fat content in lean and obese adolescents with T1D. This will allow a global and more detailed understanding of the potential alterations of insulin's effects on key insulin sensitive tissues in youth that are impacted by both T1D and obesity. Furthermore, evaluation of biomarkers for insulin resistance and fatty liver disease in this population will be performed for the first time.

Interventions

  • Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement
    • To characterize the impact of adiposity on metabolism during puberty, adolescents will undergo the euglycemic hyperinsulinemic clamp study with tracer enhancement.
  • Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement
    • A comparison control group of 36 lean young adults with T1D will also be enrolled, since they will be unaffected by the adverse metabolic effects of puberty or obesity.

Arms, Groups and Cohorts

  • Other: Adolescent Overweight
    • The study aims to enroll 36 adolescents with T1D and overweight/obesity, 36 lean adolescents with T1D, and 36 young adults with T1D that will receive a euglycemic hyperinsulinemic clamp with tracer enhancement.
  • Other: Adolescent Typical
    • The study aims to enroll 36 adolescents with T1D and overweight/obesity, 36 lean adolescents with T1D, and 36 young adults with T1D a euglycemic hyperinsulinemic clamp with tracer enhancement.
  • Other: Young Adult
    • The study aims to enroll 36 adolescents with T1D and overweight/obesity, 36 lean adolescents with T1D, and 36 young adults with T1D a euglycemic hyperinsulinemic clamp with tracer enhancement

Clinical Trial Outcome Measures

Primary Measures

  • Rate of Glucose Metabolism
    • Time Frame: 120 minutes
    • euglycemic hyperinsulinemic clamp
  • Rate of Lipid Metabolism
    • Time Frame: 120 minutes
    • euglycemic hyperinsulinemic clamp
  • Hepatic Sensitivity to Low Dose Insulin
    • Time Frame: 120 minutes
    • euglycemic hyperinsulinemic clamp
  • Peripheral Sensitivity to High Dose Insulin
    • Time Frame: 120 minutes
    • euglycemic hyperinsulinemic clamp

Participating in This Clinical Trial

Inclusion Criteria

  • All Participants: 1. Clinical diagnosis of T1D 2. HbA1c ≤9% 3. Diabetes duration of at least 12 months Adolescents with T1D: 1. Age 12-16 years 2. BMI <75th for lean pediatric subjects, > 85th percentile for overweight/obese pediatric subjects; 3. Tanner stage 2-5 4. Parent able to provide written consent and participant able to provide assent 5. Not meeting MRI safety criteria 6. Claustrophobia that will prevent participation in the MRI Lean, young adults with T1D: 1. Age 18-24 years 2. BMI 18.5-24.9 kg/m2 3. Able to provide written consent. Exclusion Criteria:

1. Use of adjunctive diabetes medications 2. Weight loss medications within the past six months 3. Current psychiatric disorders, including eating disorders (DSM-V criteria) 4. Known liver disease other than nonalcoholic hepatic steatosis 5. Females who are pregnant or lactating 6. Anemia or another medical condition that precludes participation in the study

Gender Eligibility: All

Minimum Age: 12 Years

Maximum Age: 24 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Yale University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Michelle Van Name, MD, Principal Investigator, Yale University
  • Overall Contact(s)
    • Michelle Van Name, MD, 475-774-2386, michelle.vanname@yale.edu

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.