Trial Outcomes & Findings for Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes (NCT NCT03582956)

Last Updated: 2024-04-03

Results Overview

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.

Recruitment status

TERMINATED

Study phase

Target enrollment

23 participants

Primary outcome timeframe

120 minutes

Results posted on

2024-04-03

Participant Flow

One participant enrolled but did not have any baseline or study data obtained due to scheduling conflicts.

Participant milestones

Participant milestones
Measure	Adolescent Overweight Adolescents with T1D and body mass index ≥85% will undergo a euglycemic hyperinsulinemic clamp with tracer enhancement. 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.	Adolescent Typical Adolescents with T1D and body mass index \<75% will undergo a euglycemic hyperinsulinemic clamp with tracer enhancement. 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.	Young Adult Young Adults with T1D and body mass index 18.5 to \<25 kg/m2 will undergo a euglycemic hyperinsulinemic clamp with tracer enhancement.
Overall Study STARTED	13	7	2
Overall Study COMPLETED	13	7	2
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adolescent Typical Weight n=7 Participants Adolescents with T1D and body mass index \<75% will undergo a euglycemic hyperinsulinemic clamp with tracer enhancement. 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.	Adolescent Overweight/Obese n=13 Participants Adolescents with T1D and body mass index ≥85% will undergo a euglycemic hyperinsulinemic clamp with tracer enhancement. 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.	Young Adult n=2 Participants Young Adults with T1D and body mass index 18.5 to \<25 kg/m2 will undergo a euglycemic hyperinsulinemic clamp with tracer enhancement.	Total n=22 Participants Total of all reporting groups
Age, Continuous	14.3 years STANDARD_DEVIATION 1.11 • n=5 Participants	14.5 years STANDARD_DEVIATION 1.19 • n=7 Participants	20.65 years STANDARD_DEVIATION 2.48 • n=5 Participants	15.57 years STANDARD_DEVIATION 2.03 • n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	8 Participants n=7 Participants	0 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	11 Participants n=7 Participants	2 Participants n=5 Participants	19 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	11 Participants n=7 Participants	2 Participants n=5 Participants	20 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	7 participants n=5 Participants	13 participants n=7 Participants	2 participants n=5 Participants	22 participants n=4 Participants
percentage of glycated hemoglobin	7.32 percentage STANDARD_DEVIATION 0.60 • n=5 Participants	7.74 percentage STANDARD_DEVIATION 0.41 • n=7 Participants	6.35 percentage STANDARD_DEVIATION 0.49 • n=5 Participants	7.48 percentage STANDARD_DEVIATION 0.62 • n=4 Participants

PRIMARY outcome

Timeframe: 120 minutes

Population: Only adolescents were analyzed due to the availability of data in the aftermath of the COVID shutdown- data were not collected on the young adult group.

Outcome measures

Outcome measures
Measure	Adolescent Overweight n=12 Participants Adolescents with T1D and overweight/obesity. 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.	Adolescent Typical n=7 Participants Lean adolescents with T1D. 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.
Rate of Glucose Metabolism	1.74 mg/kg/min Standard Deviation 0.77	1.56 mg/kg/min Standard Deviation 0.41

PRIMARY outcome

Timeframe: 120 minutes

Population: Only adolescents were analyzed due to the availability of data in the aftermath of the COVID shutdown- data were not collected on the young adult group.

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.

Outcome measures

Outcome measures
Measure	Adolescent Overweight n=12 Participants Adolescents with T1D and overweight/obesity. 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.	Adolescent Typical n=7 Participants Lean adolescents with T1D. 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.
Rate of Lipid Metabolism	0.099 mg/kg/min Standard Deviation 0.077	0.12 mg/kg/min Standard Deviation 0.099

PRIMARY outcome

Timeframe: 120 minutes

Population: Only adolescents were analyzed due to the availability of data in the aftermath of the COVID shutdown- data were not collected on the young adult group.

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.

Outcome measures

Outcome measures
Measure	Adolescent Overweight n=12 Participants Adolescents with T1D and overweight/obesity. 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.	Adolescent Typical n=7 Participants Lean adolescents with T1D. 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.
Hepatic Sensitivity to Low Dose Insulin	-27.9 percentage of suppression of Ra glucose Standard Deviation 25.8	-35.8 percentage of suppression of Ra glucose Standard Deviation 15.3

PRIMARY outcome

Timeframe: 240 minutes

Population: Only adolescents were analyzed due to the availability of data in the aftermath of the COVID shutdown- data were not collected on the young adult group.

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.

Outcome measures

Outcome measures
Measure	Adolescent Overweight n=11 Participants Adolescents with T1D and overweight/obesity. 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.	Adolescent Typical n=7 Participants Lean adolescents with T1D. 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.
Peripheral Sensitivity to High Dose Insulin	-75.99 percentage of suppression of Ra glucose Standard Deviation 58.8	-96.48 percentage of suppression of Ra glucose Standard Deviation 32.5

Adverse Events

Adolescent Overweight

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Adolescent Typical

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Young Adult

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Michelle Van Name

Yale University

Phone: 2037855831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place