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OpenTrials
Completed

NCT Number: NCT03867500

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

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.

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Key information

Conditions

Type 2 Diabetes Mellitus Body Weight Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for 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)

Treatment and study plan

niacin

Drug

Intravenous infusion, a titrated dose starting from 0.6 mg/min to a maximum of 2.8 mg/min (likely needed dose = 1.4 mg/min)

Saline

Drug

Intravenous infusion of 0.9% Sodium chloride (NaCl)

Primary outcomes

  1. Glucose Infusion Rate

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Mayo Clinic

Other

Collaborators

  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Registry information

Important dates

Study start
2018
Primary completion
2021
Study completion
2021
First posted
Mar 8, 2019
Registry last updated
Jan 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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