Clinical trial NCT03582956: Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes
Official title: Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Type1 Diabetes Mellitus
Adiposity
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-07-11
Enrollment: 23
Sex: ALL
Minimum age (years): 12
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Rate of Glucose Metabolism
timeFrame: 120 minutes
measure: Rate of Lipid Metabolism
timeFrame: 120 minutes
measure: Hepatic Sensitivity to Low Dose Insulin
timeFrame: 120 minutes
measure: Peripheral Sensitivity to High Dose Insulin
timeFrame: 240 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Pediatric Diabetes Research Program
state: Connecticut
Study officials:
affiliation: Yale University
name: Michelle Van Name, MD
role: PRINCIPAL_INVESTIGATOR
References: