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

Mayo Clinic

Status and phase

Completed

Early Phase 1

Conditions

Type 2 Diabetes Mellitus

Obesity

Treatments

Drug: Saline

Drug: Niacin

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT03867500

5R01DK045343 (U.S. NIH Grant/Contract)

17-009977

Details and patient eligibility

About

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.

Enrollment

12 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Women and Men (Women premenopausal)
BMI 29-37
Weight stable
Not pregnant/nursing

Exclusion criteria

Ischemic heart disease
Atherosclerotic valvular disease
Smokers (>20 cigarettes per week)
Bilateral oophorectomy
Concomitant use of medications that can alter serum lipid profile:
- High dose fish oil (>3g per day),
- STATINS (if yes hold for 6 weeks and receive PCP's approval),
- Niacin
- Fibrates
- thiazolidinediones
- Beta-blockers
- Atypical antipsychotics
Lidocaine or Niacin/Niaspan allergy
Subjects with 1.5 times upper limit of normal of serum creatinine, Alkaline phosphatase, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) unless participant has fatty liver disease, Total bilirubin (unless the patient has documented Gilbert's syndrome)