Clinical trial NCT03478046: Fetuin-A Phosphorylation Status in Insulin Resistance and Metabolic Syndrome
Official title: Alterations in Phosphorylated Fetuin-A, a Novel Regulator of Insulin Action in Insulin Resistance and Metabolic Syndrome: Effects of Lifestyle Modification
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Metabolic Syndrome
Lead sponsor: Auburn University
Sponsor class: OTHER
First posted: 2018-03-27
Enrollment: 42
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Fetuin-A has been identified as a novel physiological regulator of insulin action in vitro, in intact cells and in vivo in animals. Previous research has shown that circulating levels of fetuin-A were increased in animal models of insulin resistance and diabetes. Additionally, several human investigation studies demonstrate a correlation of fetuin-A levels with body mass index, insulin resistance, and a fatty liver. Recently, the investigators have elucidated the role of fetuin-A phosphorylation in the regulation of insulin action, demonstrating that phosphorylation is critical for the inhibitory activity of fetuin-A. The objectives of this study are twofold: (1) Quantitate phosphorylated fetuin-A levels in individuals with insulin resistance and metabolic syndrome, and (2) Investigate the effects of lifestyle modifications (acute or chronic exercise and dietary modifications) on fetuin-A phosphorylation and insulin sensitivity.

Detailed description: There are several objectives of this study: (1) Quantitate phosphorylated fetuin-A levels and the daily variation in these levels in individuals with insulin resistance and metabolic syndrome; (2) Investigate the short-term responses of fetuin-A phosphorylation and changes in insulin resistance that occur with a single session of aerobic exercise; (3) Characterize and compare the total and temporal changes in fetuin-A phosphorylation and insulin resistance that occur with an 8 to 10% weight loss induced by chronic exercise training and dietary modification, and; (4) Investigate the influence of weight loss on the short-term responses of fetuin-A phosphorylation and changes in insulin resistance that occur with a single session of aerobic exercise. Our hypothesis is that phosphofetuin-A levels are tightly correlated with insulin resistance and that lifestyle modifications will improve insulin sensitivity and decrease phosphorylated fetuin-A levels.

Eligibility criteria: Inclusion Criteria:

* 30 to 65 years of age
* obese (BMI \> 30 kg⋅m2 or % fat \> 30, and waist girth \> 88 cm)
* weight stable over the previous 6 months

Exclusion Criteria:

* smoker
* documented cardiovascular or metabolic disease
* currently taking medication to alter lipid or glucose metabolism
* practicing regular leisure physical activity over the previous 6 months
* engaged in strenuous vocational activity over the previous 6 months
* signs or symptoms of latent heart disease
* conditions that would preclude treadmill walking

Primary outcomes:
measure: Total plasma fetuin-A and phosphorylated fetuin-A
timeFrame: Total fetuin-A and phosphorylated fetuin-A levels will be measured once every 4 weeks until participant achieves a targeted weight-loss goal of 8-10%. It is anticipated that most participants will achieve their weight-loss goal within 6-10 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Auburn
country: United States
facility: Auburn University
state: Alabama
Study officials:
affiliation: Auburn University
name: Suresh Mathews, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ren G, Bowers RL, Kim T, Mahurin AJ, Grandjean PW, Mathews ST. Serum fetuin-A and Ser312 phosphorylated fetuin-A responses and markers of insulin sensitivity after a single bout of moderate intensity exercise. Physiol Rep. 2021 Mar;9(5):e14773. doi: 10.14814/phy2.14773.