Muscle Metabolism Characteristics Related to Diabetes-Related Conditions

Overview

About this study

Muscle insulin resistance is a hallmark of upper body obesity (UBO) and Type 2 diabetes (T2DM), whereas lower body obesity (LBO) is characterized by near-normal insulin sensitivity. It is unknown whether muscle free fatty acid (FFA) availability or intramyocellular fatty acid trafficking differs between different obesity phenotypes. Likewise, we do not understand to what extent the incorporation of FFA into ceramides or diacylglycerols (DG) affect insulin signaling and muscle glucose uptake. By measuring muscle FFA storage into intramyocellular triglyceride, intramyocellular fatty acid trafficking, activation of the insulin signaling pathway and glucose disposal rates we will 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: Greater trafficking of plasma FFA into intramyocellular ceramides will impair distal insulin signaling and reduce muscle glucose uptake.
Hypothesis 3: The uptake of plasma FFA destined to intramyocellular triglycerides is increased relative to FFA concentrations in UBO and T2DM compared with LBO.

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

  • Subjects 
    • sedentary, normal weight, premenopausal women and sedentary, age-matched normal weight men
    • healthy LBO (lower body obesity) premenopausal women and healthy, age-matched LBO men will be recruited as the “insulin sensitive” obese group
    • UBO (upper body obesity) premenopausal women and  age-matched UBO men will serve as the insulin resistant, non-diabetic group
    • UBO, T2DM premenopausal women and  age-matched UBO, T2DM men (same BMI) will comprise the most insulin resistant group
  • age range will be 18-55 years
  • In certain cases were premenopausal state is uncertain, serum FSH will be added on screening blood test for further clarification

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

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

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CLS-20307514

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