Effects of Niacin on Intramyocellular Fatty Acid Trafficking in Upper Body Obesity and Type 2 Diabetes Mellitus

Early Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus; Obesity
• Interventions: Drug: Niacin; Drug: Saline

• Registration Number: NCT03867500
• Lead Sponsor: Mayo Clinic

Brief Summary

Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM). It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking is responsible for the abnormal response to insulin. Likewise, the investigators do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. The investigators will measure muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates under both saline control (high overnight FFA) and after an overnight infusion of intravenous niacin (lower/normal FFA) to provide the first integrated examination of the interaction between FFA and muscle insulin action from the whole body to the cellular/molecular level. By identifying which steps in the insulin signaling pathway are most affected, the investigators will determine the site-specific effect of ceramides and/or DG on different degrees of insulin resistance.

Hypothesis 1: Greater trafficking of plasma FFA into intramyocellular DG will impair proximal insulin signaling and reduce muscle glucose uptake.

Hypothesis 2: Lowering FFA in UBO and T2DM by using an intravenous infusion of niacin will alter trafficking of plasma FFA into intramyocellular ceramides in a way that will improve insulin signaling and increase muscle glucose uptake.

Hypothesis 3: Lowering FFA in UBO and T2DM by using an intravenous infusion of niacin will alter trafficking of plasma FFA into intramyocellular DG in a way that will improve insulin signaling and increase muscle glucose uptake.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-11-01
• Study First Submitted: 2019-01-25
• Study First Submitted QC: 2019-03-07
• Study First Posted: 2019-03-08
• Primary Completion: 2021-12-22
• Study Completion: 2021-12-22
• Results First Submitted: 2024-07-11
• Results First Submitted QC: 2024-07-11
• Results First Posted: 2024-08-06
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-15
• Last Update Posted: 2025-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Niacin then saline	Saline	All participants will receive intravenous Niacin overnight on day one and then intravenous saline overnight on the second study day
Niacin then saline	Niacin	All participants will receive intravenous Niacin overnight on day one and then intravenous saline overnight on the second study day

Primary Outcome Measures

Name	Time	Method
Glucose Infusion Rate	18 hours	Glucose infusion rates will be measured in upper body obese and type 2 diabetic volunteers using hyperinsulinemic, euglycemic clamp under saline control conditions and during an intravenous infusion of niacin. The hyperinsulinemic-euglycemic clamp is a method used to measure insulin sensitivity. Plasma insulin concentration is acutely raised and maintained at \~40-80 μU/ml (microunits per milliliter) by continuous insulin infusion. During the clamp, the plasma glucose concentration was held constant at normal blood sugar level. The glucose infusion rate over the last hour of the insulin infusion is the net effect of insulin on whole-body glucose metabolism. This rate serves as a measure of tissue insulin sensitivity. The hyperinsulinemic-euglycemic clamp assesses how sensitive your tissues are to insulin.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States