Effects of Caloric Restriction on Fetuin-A and Cardiovascular Risk Factors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01329822
Recruitment Status : Completed
First Posted : April 6, 2011
Last Update Posted : April 6, 2011
Eulji University Hospital
Information provided by:
Korea University

Brief Summary:
The aim of this randomized controlled study was to evaluate the effects of CR on circulating fetuin-A levels in obese humans with type 2 diabetes based on monitoring energy intake and energy expenditure by daily activity. Furthermore, the investigators examined the relationship between the changes of fetuin-A levels induced by CR and cardiovascular risk parameters including atherogenic lipid profile, visceral fat area (VFA), brachial artery endothelial function, and carotid IMT.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Overweight Behavioral: Caloric restriction Not Applicable

Detailed Description:

Rapidly growing aging society augmented the risk of age-associated disorders, such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Dietary interventions that reduce daily energy intake, also known as caloric restriction (CR), has been shown to be the most robust intervention to extend average and maximal lifespan in various experimental animals (1). In addition, CR diminishes the risk of multiple age-associated diseases, such as diabetes, cardiovascular disease, and some forms of cancer in rodents and primates (rhesus monkeys) (1; 2). Moreover, in obese humans, CR improves insulin sensitivity and reduces fasting glucose as well as the other components of metabolic syndrome (3). However, the exact underlying mechanism of CR has not been fully defined yet.

Recently, it is hypothesized that liver may regulate systemic energy metabolism through production of secretory proteins known as hepatokines. Fetuin-A, a circulating glycoprotein almost exclusively secreted by the liver, has been found to inhibit insulin receptor tyrosine kinase activity in animal studies (4). Fetuin-A knockout (KO) mice have enhanced glucose sensitivity, resistance to weight gain, and lower serum free fatty acid levels (5). In humans, high fetuin-A levels are associated with insulin resistance and fat accumulation in the liver (6). Ix et al. reported that higher human fetuin-A concentrations are strongly associated with metabolic syndrome and atherogenic lipid profile in non-diabetic patients with coronary artery disease (7). In addition, fetuin-A levels were associated with surrogate marker of atherosclerosis such as arterial stiffness and intima-media thickness (IMT) (8). Recent studies reported that elevated fetuin-A levels predict increased risk of myocardial infarction and ischemic stroke (9) as well as type 2 diabetes (10). However, there has been no previous report about the effects of CR on fetuin-A comparing with changes of cardiovascular risk indicators in animals or humans.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Effects of Caloric Restriction on Fetuin-A and Cardiovascular Risk Factors in Rats and Humans: A Randomized Controlled Trial
Study Start Date : March 2010
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Caloric restriction group
CR group were educated by a dietitian to reduce their usual energy intake to 1400 kcal/day (-500 kcal/day, -26% from baseline) for weight reduction and the recommended macronutrient composition was the 50-55% of energy intake as carbohydrate, 15-20% as protein and 20-25% as fat. Daily energy intake and nutrient composition were determined using a computer-aided nutritional analysis program (CAN-Pro 3.0; Korean Nutrition Society, Seoul, South Korea).
Behavioral: Caloric restriction
Caloric restriction

No Intervention: Control group
Control group - ad libitum diet

Primary Outcome Measures :
  1. Fetuin-A [ Time Frame: 12 weeks ]
    changes of fetuin-A levels induced by CR

Secondary Outcome Measures :
  1. cardiovascular risk factors [ Time Frame: 12 weeks ]
    atherogenic lipid profile, visceral fat area (VFA), brachial artery endothelial function, and carotid IMT.

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Ages Eligible for Study:   35 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • type 2 diabetes
  • BMI >= 23 kg/m2
  • stable body weight (<2 kg change in weight in the past 6 months)
  • sedentary lifestyle (<20 min of exercise twice a week)

Exclusion Criteria:

  • smoking
  • cardiovascular disease
  • chronic kidney disease
  • chronic liver disease
  • pregnant or breast feeding
  • any major illness
  • taking medications that could affect laboratory test results

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01329822

Korea, Republic of
Eulji University Hospital
Seoul, Korea, Republic of, 139-711
Sponsors and Collaborators
Korea University
Eulji University Hospital
Principal Investigator: Kyung Wan Min Eulji University

Responsible Party: Kyung Wan Min, Eulji University Hospital Identifier: NCT01329822     History of Changes
Other Study ID Numbers: CR-201104
First Posted: April 6, 2011    Key Record Dates
Last Update Posted: April 6, 2011
Last Verified: April 2011

Keywords provided by Korea University:
type 2 diabetes

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Body Weight
Signs and Symptoms