Potential Impact of Polycystic Ovarian Syndrome on Protein Modifications and Accumulation

A goal of this study is to use a novel methodology to determine whether insulin resistance in women with polycystic ovary syndrome (PCOS) is related to the accumulation of proteins with modifications. This could lead to future research to determine if these modifications interfere with their proper function. Additionally, the investigators will determine how protein quality is affected by exercise training. Aerobic exercise enhances the endogenous oxidant buffering systems which may minimize oxidative damage to proteins. The investigators propose that aerobic exercise minimizes the accrual of modified proteins by increasing the synthesis of new proteins, but also by increasing the degradation and removal of old and damaged proteins. Based on our previous studies the investigators observed that insulin affects plasma protein synthesis and aerobic exercise improves insulin sensitivity not only in muscle but also in liver. The investigators therefore propose that aerobic exercise and related increase in insulin sensitivity (and decline in insulin levels) will reduce accumulation of old and modified skeletal muscle and plasma proteins leading to improved function.

Study Overview

• Status: Completed
• Conditions: Overweight; Insulin Resistance; Obese; Polycystic Ovarian Syndrome (PCOS)
• Intervention / Treatment: Behavioral: Aerobic Exercise Training

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. BMI between 25 kg/m2 and 40 kg/m2
2. Fasting blood glucose < 126 mg/dL
3. Diagnosed with PCOS as outlined by the Rotterdam criteria
4. Insulin resistant as determined by a 3 hour oral glucose tolerance test

Exclusion Criteria:

1. Serum creatinine ≥1.5 mg/ dL.
2. Serum transaminase elevation ≥ 3 times the upper limit of normal range
3. Use of systemic glucocorticoids
4. Use of oral anticoagulation
5. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Sedentary Control; Participants will be randomized to an exercise training program or sedentary control group. The sedentary will not perform any structured physical activity or exercise. Participants will be encouraged to maintain their sedentary lifestyle and will be monitored by an accelerometer to track physical activity.
Experimental: Aerobic Exercise Training; Participants will perform 12-weeks of aerobic exercise training	Behavioral: Aerobic Exercise Training; A progressive increase in duration, frequency and intensity so the last 8 weeks of exercise are performed for 60 min, 5 days per week and at 80% of aerobic capacity. The duration includes a 5 minute warm up and 5 minute cool down. All exercise will be performed on a stationary bicycle (i.e., cycle ergometer).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in insulin sensitivity	To determine the effect of 12 weeks of aerobic exercise training or sedentary behavior on insulin sensitivity measured by a 3 hour hyperinsulinemic-euglycemic clamp and response to a mixed-meal.	Measured before and after 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein modifications and accumulation	Alterations in protein modifications and accumulation will be measured by a novel methodology developed within our laboratory. Infusion of stable amino acid isotopes will be used to measure the accumulation of proteins before and after 12 weeks of aerobic exercise training or sedentary behavior. Plasma and muscle will be resolved using a two dimensional gel electrophoresis which will allow the identification of protein modifications and age.	Before and after 12 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimate): April 7, 2014

Study Record Updates

• Last Update Posted (Estimate): May 17, 2016
• Last Update Submitted That Met QC Criteria: May 16, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Insulin Resistance; Protein Metabolism; Polycystic Ovarian Syndrome (PCOS); Overweight, Obese Women; Post Translational Modifications
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Body Weight; Hyperinsulinism; Polycystic Ovary Syndrome; Syndrome; Insulin Resistance; Overweight
• Other Study ID Numbers: 09-007006