Effects of Caloric Restriction on Fetuin-A and Cardiovascular Risk Factors
Condition: Type 2 Diabetes; Overweight
MeSH terms: Diabetes Mellitus, Type 2; Overweight
Study type: Interventional

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.
    

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.
    

Intervention name(s): Caloric restriction
Intervention type(s): Behavioral
Intervention description(s): Caloric restriction
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: type 2 diabetes; overweight