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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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The Effects of Caloric Restriction on Fetuin-A and Cardiovascular Risk Factors in Rats and Humans: A Randomized Controlled Trial

Conditions
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Type 2 Diabetes, Overweight

Intervention / Treatment
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* Behavioral: Caloric restriction


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caloric restriction group<br>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<br>* Caloric restriction<br>|
| No Intervention: Control group<br>Control group - ad libitum diet | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetuin-A | changes of fetuin-A levels induced by CR | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cardiovascular risk factors | atherogenic lipid profile, visceral fat area (VFA), brachial artery endothelial function, and carotid IMT. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes, overweight