Type1 Diabetes MellitusT1DNCT03582956
Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes
A study testing Euglycemic hyperinsulinemic clamp with tracer enhancement in people with Type1 Diabetes Mellitus and Adiposity, run by Yale University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 12 to 24 yearsHealthy volunteers can take part
- Conditions the study is for
- Type1 Diabetes Mellitus, Adiposity
- What is being tested?
- Euglycemic hyperinsulinemic clamp with tracer enhancement
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2019to 12 Aug 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 24 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- All Participants:
- Clinical diagnosis of T1D
- HbA1c ≤9%
- Diabetes duration of at least 12 months
- Adolescents with T1D:
- Age 12-16 years
Show all 15Show fewer
- BMI <75th for lean pediatric subjects, > 85th percentile for overweight/obese pediatric subjects;
- Tanner stage 2-5
- Parent able to provide written consent and participant able to provide assent
- Not meeting MRI safety criteria
- Claustrophobia that will prevent participation in the MRI
- Lean, young adults with T1D:
- Age 18-24 years
- BMI 18.5-24.9 kg/m2
- Able to provide written consent.
Who cannot join
- Use of adjunctive diabetes medications
- Weight loss medications within the past six months
- Current psychiatric disorders, including eating disorders (DSM-V criteria)
- Known liver disease other than nonalcoholic hepatic steatosis
- Females who are pregnant or lactating
- Anemia or another medical condition that precludes participation in the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Pediatric Diabetes Research Program
New Haven, Connecticut, 06511
About this study
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.
Read the 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.
- Conditions
- Type1 Diabetes Mellitus, Adiposity
- Being tested
- Euglycemic hyperinsulinemic clamp with tracer enhancement
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Euglycemic hyperinsulinemic clamp with tracer enhancementProcedure or surgery
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 enhancementProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Adolescent Overweight | Other | Adolescents with T1D and overweight/obesity Receives: Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement |
| Adolescent Typical | Other | Lean adolescents with T1D Receives: Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement |
| Young Adult | Other | Young adults with T1D with a euglycemic hyperinsulinemic clamp with tracer enhancement Receives: Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 120 minutes
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.
Measured: 120 minutes
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.
Measured: 120 minutes
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.
Measured: 240 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2018
- Study start1 Jan 2019
- Primary completion12 Aug 2022
- Study completion12 Aug 2022
Why it stopped: Covid
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michelle Van Name, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03582956
- Sponsor's protocol ID
- 2000023149
- Other IDs
- 1K23DK115894-01A1
- Acronym
- T1D
- Status last verified
- Mar 2024
- First submitted
- 15 Jun 2018
- Last updated
- 3 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Adiposity on Hepatic and Peripheral Insulin Resistance in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03582956
- Acronym / sponsor ID
- T1D / 2000023149
- Conditions
- Type1 Diabetes Mellitus, Adiposity
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Covid
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 12 Aug 2022 (actual)
- Study completion
- 12 Aug 2022 (actual)
- First posted
- 11 Jul 2018 (actual)
- Results
- Posted 3 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Adolescent Overweight | Other | Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancementAdolescents with T1D and overweight/obesity |
| Adolescent Typical | Other | Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancementLean adolescents with T1D |
| Young Adult | Other | Procedure: Euglycemic hyperinsulinemic clamp with tracer enhancementYoung adults with T1D with a euglycemic hyperinsulinemic clamp with tracer enhancement |
Who may qualify
- Ages
- 12 to 24 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- All Participants:
- Age 12-16 years
- BMI <75th for lean pediatric subjects, > 85th percentile for overweight/obese pediatric subjects;
- Tanner stage 2-5
- Parent able to provide written consent and participant able to provide assent
Key exclusion criteria (6 listed)
- Use of adjunctive diabetes medications
- Weight loss medications within the past six months
- Current psychiatric disorders, including eating disorders (DSM-V criteria)
- Known liver disease other than nonalcoholic hepatic steatosis
- Females who are pregnant or lactating
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Euglycemic hyperinsulinemic clamp with tracer enhancementTo characterize the impact of adiposity on metabolism during puberty, adolescents will undergo the euglycemic hyperinsulinemic clamp study with tracer enhancement. | Procedure or surgery | Adolescent Overweight, Adolescent Typical |
| Euglycemic hyperinsulinemic clamp with tracer enhancementA 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. | Procedure or surgery | Young Adult |
Primary outcome
Rate of Glucose Metabolism
Time frame: 120 minutes
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.
Rate of Lipid Metabolism
Time frame: 120 minutes
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.
Hepatic Sensitivity to Low Dose Insulin
Time frame: 120 minutes
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.
Peripheral Sensitivity to High Dose Insulin
Time frame: 240 minutes
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Type1 Diabetes Mellitus
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruiting
A Novel Miniature Equine-Assisted Diabetes Education Program for Youth: Evaluating the Diabetes Equine Empowerment Program (DEEP).
Diabetes (Insulin-requiring, Type 1 or Type 2), Pediatric Diabetes
Active, not recruitingPhase 4
Diabetes in African Youth
type1diabetes
RecruitingPhase 3
A Study of Baricitinib (LY3009104) to Preserve Beta Cell Function in Children and Adults Newly Diagnosed With Type 1 Diabetes (BARICADE-PRESERVE)
Diabetes Mellitus, Type 1
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michelle Van Name, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Euglycemic hyperinsulinemic clamp with tracer enhancement in people with Type1 Diabetes Mellitus and Adiposity, run by Yale University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Glucose Metabolism (time frame: 120 minutes). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.