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

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.

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