Ignite Creation Date:
2025-12-24 @ 2:10 PM
Ignite Modification Date:
2026-01-20 @ 8:50 AM
Study NCT ID:
NCT02193295
Status:
RECRUITING
Last Update Posted:
2025-05-16
First Post:
2014-06-25
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Reversal of Lipid-Induced Insulin Resistance
Sponsor:
Yale University
Organization:
Study Overview
Official Title:
Reversal of Lipid-Induced Insulin Resistance
Status:
RECRUITING
Status Verified Date:
2025-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to examine whether weight reduction decreases intramyocellular (IMCL) and hepatic lipid content, and improves insulin sensitivity of muscle and fat tissue in people who are insulin resistant and have a family history of type 2 diabetes.
Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).
Hepatic mitochondrial oxidation will be assesses using a 3 hour triple tracer study (D7 glucose, 3-13C lactate and 13C4 beta-hydroxybutyrate).
Detailed Description:
In this study, we will examine whether a small weight loss in lean, insulin-resistant offspring of type 2 diabetic patients will improve insulin resistance. The control group will consist of subjects matched for gender, age and body weight with no family history of diabetes. Before and after weight loss, rates of basal and insulin stimulated whole body glucose metabolism will be measured using \[6,6-2H\] glucose during a 3 hour basal period and a 4 hour euglycemic hyperinsulinemic (20 mU/m2-min) clamp. Rates of whole body lipolysis will be determined using \[2H5\] glycerol, localized rates of lipolysis will be measured using the microdialysis technique and muscle PI 3-kinase activity will be assessed in muscle biopsies. FFA metabolites (fatty acyl CoA, ceramides, diacylglycerol) will be measured in fat tissue collected from the abdominal subcutaneous fat cell depot. Body composition will be determined with bioelectrical impedance and whole body MRI; IMCL will be measured with MRS. Before and after weight loss, insulin secretion will be measured with the hyperglycemic clamp (as described under Day 2 Hyperglycemic Clamp).
Hepatic mitochondrial fat oxidation will be assessed in a separate study at baseline. Participants will be admitted to the Yale HRU at 7 AM after an overnight fast. An IV line will be placed in antecubital vein for tracer infusions and a retrograde IV line will be placed in a hand vein for blood collections. The hand will be warmed in a 'hot box' 37°C to approximate collection of 'arterial' blood samples. After collection of a baseline blood samples, infusions of 13C lactate (0.9 mM, 99% 13C, infusion rate: 8.7 micromol/(Kg-min)), D7glucose (25 mg/mL, 99% 13C, infusion rate: 0.84 mg/(m2-min)) and 13C-BHOB (2 mg/mL, 99%rate: 0.01 mg/(Kg-min)) will be started and continued for 180 minutes. During the final 20 minutes of this infusion period blood samples will be collected from the retrograde IV line. The infusion will then be discontinued the IV lines removed, and the participants will be served breakfast/lunch and discharged to home.
Hepatic mitochondrial fat oxidation will be assessed in a separate study at baseline. Participants will be admitted to the Yale HRU at 7 AM after an overnight fast. An IV line will be placed in antecubital vein for tracer infusions and a retrograde IV line will be placed in a hand vein for blood collections. The hand will be warmed in a 'hot box' 37°C to approximate collection of 'arterial' blood samples. After collection of a baseline blood samples, infusions of 13C lactate (0.9 mM, 99% 13C, infusion rate: 8.7 micromol/(Kg-min)), D7glucose (25 mg/mL, 99% 13C, infusion rate: 0.84 mg/(m2-min)) and 13C-BHOB (2 mg/mL, 99%rate: 0.01 mg/(Kg-min)) will be started and continued for 180 minutes. During the final 20 minutes of this infusion period blood samples will be collected from the retrograde IV line. The infusion will then be discontinued the IV lines removed, and the participants will be served breakfast/lunch and discharged to home.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| R01DK135645 | NIH | None | https://reporter.nih.gov/quic… | View |