Pathogenesis of the Cardiometabolic Risk in Youth With Type 1 Diabetes
Primary Purpose
Type 1 Diabetes, De Novo Lipogenesis
Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Oral Glucose Tolerance Test
Sponsored by
About this trial
This is an interventional basic science trial for Type 1 Diabetes
Eligibility Criteria
Inclusion Criteria:
- HbA1c >8.5% for the group with poorly controlled diabetes
- HbA1c <7.5% for the well-controlled patients
- T1D for at least 12 months (T1D groups only)
- Negative pregnancy test (all groups)
Exclusion Criteria:
- Baseline creatinine >1
- Being on medications affecting glucose concentrations other than insulin
- Positive pregnancy test
- Endocrinopathies
Sites / Locations
- Yale University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Poorly-controlled T1D
Controlled T1D
Lean controls
Arm Description
Patients in this group will have poorly-controlled T1D (HbA1c >8.5%).
Patients in this group will have T1D and achieve targeted glycemic control (HbA1c <7.5%).
Patients in this group will not have T1D.
Outcomes
Primary Outcome Measures
Fractional hepatic DNL
% Fractional hepatic DNL
Secondary Outcome Measures
Full Information
NCT ID
NCT04101045
First Posted
September 17, 2019
Last Updated
February 8, 2023
Sponsor
Yale University
Collaborators
Juvenile Diabetes Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT04101045
Brief Title
Pathogenesis of the Cardiometabolic Risk in Youth With Type 1 Diabetes
Official Title
Pathogenesis of the Cardiometabolic Risk in Youth With Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
During the pandemic the funding agency stopped funding studies.
Study Start Date
November 21, 2019 (Actual)
Primary Completion Date
March 30, 2022 (Actual)
Study Completion Date
March 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
Juvenile Diabetes Research Foundation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to quantitate hepatic de novo lipogenesis (DNL) in youth with poorly-controlled type 1 diabetes (T1D) (HbA1c >8.5%), youth with T1D who achieve targeted glycemic control (HbA1c <7.5%) and lean controls. Hypothesis: Youth with poor glycemic control experience higher fractional hepatic DNL during the fasting and the postprandial states than youth who achieve targeted glycemic control and lean controls.
Detailed Description
What is not known, is whether hepatic de novo lipogenesis (DNL) contributes to dyslipidemia in this in patients with type 1 diabetes (T1D). The aim of the study is to test the hypothesis that an enhanced rate of DNL largely contributes to dyslipidemia occurring in youth with poorly-controlled T1D. According to this hypothesis, youth with poorly-regulated T1D experience a state of persistent insulin independent, highly variable fluctuations of glucose, and other sugars, through the glycolytic pathway that result in an enhancement of hepatic DNL and an increased production of triglycerides (TG). Newly-formed TG are packaged into large-VLDL that are secreted into the circulation contributing to an increase in plasma TG. When the TG concentration in the hepatocytes exceeds the ability of the liver to secrete TG, the latter start accumulating leading to hepatic steatosis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes, De Novo Lipogenesis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Poorly-controlled T1D
Arm Type
Active Comparator
Arm Description
Patients in this group will have poorly-controlled T1D (HbA1c >8.5%).
Arm Title
Controlled T1D
Arm Type
Active Comparator
Arm Description
Patients in this group will have T1D and achieve targeted glycemic control (HbA1c <7.5%).
Arm Title
Lean controls
Arm Type
Active Comparator
Arm Description
Patients in this group will not have T1D.
Intervention Type
Diagnostic Test
Intervention Name(s)
Oral Glucose Tolerance Test
Intervention Description
Each participant consumes a dinner scaled to his/her energy needs which is prepared by the metabolic kitchen. Dinner will be provided beforehand if patient does this portion at home. The participant consumes the first of three doses of D2O. Two additional doses of D20 are given at on day 1 and on day 2. The total D2O given (3 ml per kg of body water) is designed to raise body deuterium levels to 0.3% and is administered as described above to maintain steady state until the end of the study. At the HRU, an IV catheter will be inserted in order to collect blood to assess DNL. Blood draws begin during the fasting state to assess basal rates of DNL and then for six hours after the consumption of a glucose/fructose beverage (75g glucose and 25g fructose ) to assess postprandial rates of DNL. Blood draws will be taken 15 minutes before ingestion of the sugar beverage, then for every half hour for 6 hours.
Primary Outcome Measure Information:
Title
Fractional hepatic DNL
Description
% Fractional hepatic DNL
Time Frame
Baseline to Six hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
HbA1c >8.5% for the group with poorly controlled diabetes
HbA1c <7.5% for the well-controlled patients
T1D for at least 12 months (T1D groups only)
Negative pregnancy test (all groups)
Exclusion Criteria:
Baseline creatinine >1
Being on medications affecting glucose concentrations other than insulin
Positive pregnancy test
Endocrinopathies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicola Santoro, MD, PhD
Organizational Affiliation
Assistant Professor of Pediatrics (Endocrinology)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32561908
Citation
Monga Kravetz A, Testerman T, Galuppo B, Graf J, Pierpont B, Siebel S, Feinn R, Santoro N. Effect of Gut Microbiota and PNPLA3 rs738409 Variant on Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth. J Clin Endocrinol Metab. 2020 Oct 1;105(10):e3575-85. doi: 10.1210/clinem/dgaa382.
Results Reference
derived
Learn more about this trial
Pathogenesis of the Cardiometabolic Risk in Youth With Type 1 Diabetes
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