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

Overview

About this study

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, we do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. We 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, we 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 6/9/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status	Contact
Rochester, Minn. Mayo Clinic principal investigator Michael Jensen, M.D.	Closed for enrollment	Contact information: Pamela Reich (507) 255-6062 Reich.Pamela@mayo.edu

Mayo Clinic Location

Status

Contact

Rochester, Minn.

Mayo Clinic principal investigator

Michael Jensen, M.D.

Closed for enrollment

Contact information:

Pamela Reich

(507) 255-6062

Reich.Pamela@mayo.edu

More information

Publications

Publications are currently not available

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