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

NCT ID: NCT03582956

Last Updated: 2024-04-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2022-08-12

Brief Summary

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.

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.

Conditions

Type1 Diabetes Mellitus; Adiposity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Adolescent Overweight

Adolescents with T1D and overweight/obesity

Group Type: OTHER

Euglycemic hyperinsulinemic clamp with tracer enhancement

Intervention Type: PROCEDURE

To characterize the impact of adiposity on metabolism during puberty, adolescents will undergo the euglycemic hyperinsulinemic clamp study with tracer enhancement.

Adolescent Typical

Lean adolescents with T1D

Group Type: OTHER

Euglycemic hyperinsulinemic clamp with tracer enhancement

Intervention Type: PROCEDURE

To characterize the impact of adiposity on metabolism during puberty, adolescents will undergo the euglycemic hyperinsulinemic clamp study with tracer enhancement.

Young Adult

Young adults with T1D with a euglycemic hyperinsulinemic clamp with tracer enhancement

Group Type: OTHER

Euglycemic hyperinsulinemic clamp with tracer enhancement

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle Van Name, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale Pediatric Diabetes Research Program

New Haven, Connecticut, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1K23DK115894-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000023149

Identifier Type: -

Identifier Source: org_study_id