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

Adiposity Clinical Trial

— T1D  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03582956
• Other study ID #: 2000023149
• Secondary ID: 1K23DK115894-01A
• Status: Terminated
• Phase: N/A
• Start date: January 1, 2019
• Est. completion date: August 12, 2022

Study information

• Verified date: March 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: August 12, 2022
• Est. primary completion date: August 12, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 12 Years to 24 Years

Eligibility

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

Related Conditions & MeSH terms

• Adiposity
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Insulin Resistance
• Obesity
• Type1 Diabetes Mellitus

Intervention

Procedure:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Yale Pediatric Diabetes Research Program	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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