Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes (T1D)

Yale University

Status: Terminated

Conditions: Type1 Diabetes Mellitus; Adiposity

Treatments: Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03582956

2000023149

1K23DK115894-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: All

Ages: 12 to 24 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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23 participants in 3 patient groups

Adolescent Overweight

Other group

Description:

Adolescents with T1D and overweight/obesity

Treatment:

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Adolescent Typical

Other group

Description:

Lean adolescents with T1D

Treatment:

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Young Adult

Other group

Description:

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

Treatment:

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement

Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement