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

NCT03582956 | Terminated Results DMC

• 2 other identifiers: 20000231491K23DK115894-01A1
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Type1 Diabetes Mellitus; Adiposity

Outcome Measures

Primary Outcomes (4)

• Rate of Glucose Metabolism

  Insulin function will be measured using a euglycemic hyperinsulinemic clamp procedure. A clamp measures insulin sensitivity. During the low does insulin phase, this reflects hepatic glucose metabolism, which is reported here. A higher glucose infusion rate number indicates more sensitivity to insulin; a lower number means more resistance to insulin.

  120 minutes

• Rate of Lipid Metabolism

  Insulin function will be measured using a euglycemic hyperinsulinemic clamp procedure. A clamp measures insulin sensitivity. During the low dose insulin phase, glycerol turnover (rate of appearance) can reflect adipose specific insulin sensitivity, which is reported here. Insulin should suppress glycerol turnover. A higher number reflects more resistance to insulin; a lower number means more sensitivity to insulin.

  120 minutes

• Hepatic Sensitivity to Low Dose Insulin

  Insulin function will be measured using a euglycemic hyperinsulinemic clamp procedure. A clamp measures insulin sensitivity. Insulin should suppress glucose production. Change of the glucose rate of appearance (which is reported here, and the glucose rate of appearance is measured here utilizing isotopic enrichment) during the low dose insulin phase reflects hepatic sensitivity to insulin. A greater degree of decline reflects more sensitivity to insulin; a smaller number means more resistance to insulin. This is calculated as the low dose insulin phase glucose rate of appearance minus the baseline phase glucose rate of appearance, divided by the basal phase glucose rate of appearance and multiplied x 100.

  120 minutes

• Peripheral Sensitivity to High Dose Insulin

  Insulin function will be measured using a euglycemic hyperinsulinemic clamp procedure. A clamp measures insulin sensitivity. Insulin should suppress glucose production. Change of the glucose rate of appearance (which is reported here, and the glucose rate of appearance is measured here utilizing isotopic enrichment) during the high dose phase reflects peripheral sensitivity to insulin. A greater degree of decline reflects more sensitivity to insulin; a smaller number means more resistance to insulin. This is calculated as the high dose insulin phase glucose rate of appearance minus the baseline phase glucose rate of appearance, divided by the basal phase glucose rate of appearance and multiplied x 100.

  240 minutes

Study Arms (3)

Adolescent Overweight

OTHER

Adolescents with T1D and overweight/obesity

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Adolescent Typical

OTHER

Lean adolescents with T1D

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Young Adult

OTHER

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

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Interventions

Euglycemic hyperinsulinemic clamp with tracer enhancement PROCEDURE

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

Adolescent Overweight; Adolescent Typical

Eligibility Criteria

• Age: 12 Years - 24 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (1)

Yale Pediatric Diabetes Research Program

New Haven, Connecticut, 06511, United States

Location

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

Results Point of Contact

• Title: Michelle Van Name
• Organization: Yale University

michelle.vanname@yale.edu

2037855831

Study Officials

• Michelle Van Name, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 11, 2018
• Study Start: January 1, 2019
• Primary Completion: August 12, 2022
• Study Completion: August 12, 2022
• Last Updated: April 3, 2024
• Results First Posted: April 3, 2024

Record last verified: 2024-03

Locations

US (1)