Multi-faceted Evaluations Following Weight Reduction in Subjects With Metabolic Syndrome
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional

Summary: 
      Central obesity, core of metabolic syndrome, has been recognized as one of the rooting
      factors for development of diabetes and cardiovascular disease. Although efforts have been
      devoted to the studies of central obesity and/or metabolic syndrome, much remained unknown as
      to how obesity influences cellular as well as cardiac functions, what is the central
      regulation of one's body weight.

      Weight loss is an undisputed way to improve cardiovascular and metabolic disorders in obese
      individuals. Previous studies have demonstrated that weight loss by 5% of initial weight
      universally provide substantial benefits in these subjects. However, there are little
      integrated research teams, composed of different disciplines, share common weight reduction
      program to look at different aspects of weight reduction in non-diabetic individuals with
      metabolic syndrome. The significances of this proposal we plan to target, namely Rho kinase
      activity from peripheral leukocyte, several cardiac functions measured by noninvasive
      technique (VP-2000) and MRI, circulating brain-derived neurotrophic factors (BDNF) levels,
      are fully explained detailed in each sub-proposal.

      In order to accomplish this integrated proposal, we will form research teams including
      endocrinologists, cardiologists, radiologists, and a coordinating data center. We pan to
      recruit 40 non-diabetic individuals with metabolic syndrome to participate this 12-16 weeks
      weight reduction program. Twenty-five age, sex matched non-diabetes lean will be served as
      controls. Oral glucose tolerance test, fasting blood obtained, noninvasive vascular and MRI
      examinations will be applied before and after weight reduction program in those achieving at
      least 5% loss of initial weight.

      In summary, this study will investigate the effects of weight loss on (1) Rho kinase activity
      obtained from peripheral leukocyte; (2). Aortic stiffness, central aortic pressure and
      hemodynamic by a noninvasive vascular profiling system (VP-2000); (3) Brain function
      specifically reflecting by circulating BDNF; (4). Aortic elastic properties and left
      ventricular function by using MRI examinations, in non-diabetic individuals of metabolic
      syndrome.
    

Detailed description: 
      Obesity, in particular central obesity, has been one of the important documented risk factors
      for development of diabetes and cardiovascular disease. Recent re-delineated various versions
      of definitions of metabolic syndrome, has fueled further the critical involvement of central
      adiposity in these disorders through several facets, including many increased circulating
      pro-inflammatory cytokines, directly or indirectly linking to visceral adipose tissue
      expressions. Although lots of efforts have been devoted to the studies of central obesity
      and/or metabolic syndrome, much remained unknown as to how obesity affect cellular as well as
      cardiac function, what is the central regulation of one's body weight, and how to measure fat
      in visceral organs precisely.

      Weight loss is an undisputed way to improve cardiovascular and metabolic disorders. Both a
      recent review article and data from us demonstrated that only weight loss by 5% of initial
      weight universally delivered benefits on obese individuals. However, there is little
      integrated research teams from different disciplines share common weight reduction protocol
      and look at different aspects of weight reduction in non-diabetic individuals with metabolic
      syndrome. The significances of this proposal we plan to target are explained in detail in
      each sub-proposal. However, we would like to make a briefing description here.

        1. . Rho kinase (ROCK) is a serine/threonine kinase that mediates the downstream signaling
           of the small guanosine triphosphate- binding protein, Rho, on the actin cytoskeleton. In
           mostly animal models, the inhibition of ROCK ameliorates many cardiovascular conditions,
           including hypertension, atherosclerosis, myocardial fibrosis, and stroke. Recent study
           from Taiwan showed that ROCK activity is increased in patients with metabolic syndrome.

        2. . Obese and overweight individuals have increased levels of arterial stiffness which is
           a measure of aortic and large vessel distensibility or compliance. Weight loss could
           induce significant reduction in sympathetic activity and blood pressure. However, little
           is known as whether weight loss can improve arterial stiffness, central aortic blood
           pressure and related hemodynamics.

        3. . Brain-derived neurotrophic factor (BDNF), recently reported related to Alzheimer's
           disease, is present in brain tissues extensively. It is also noted that low circulating
           level of BDNF was associated with impaired glucose metabolism, and might be associated
           higher BMI or body fat. We are interesting in effect of weight reduction on circulating
           BDNF values in non-diabetic subjects with metabolic syndrome.

        4. . Magnetic resonance imaging (MRI) of the heart is frequently used and can provide
           accurate and reproducible measurement of LV mass, volumes, systolic function and aortic
           pulse velocity. Although echo-cardiography has been applied to study effect of weight
           loss on cardiac function, there has been no study by using cardiac MRI to measure cine
           images of cardiac function and related variables before and after weight reduction in
           non-diabetic subjects with metabolic syndrome.

      In order to accomplish this integrated proposal, we will formulate research teams including
      endocrinologists, cardiologists, radiologists, and a data center, coordinated by a PhD
      researcher (infra-structure as described below). We will recruit 40 non-diabetic individuals
      with metabolic syndrome (fulfilled the criteria from IDF, 2006 and DOH of Taiwan).
      Twenty-five age, sex matched non-diabetes lean will be served as controls.

      Written informed consent will be obtained from each subject before being enrolled into the
      study after approval from IRB of Taichung VGH, Taichung, Taiwan. This weight reduction
      program will be assisted by experienced dieticians and sports experts, all of whom we had
      collaborated and published article previously. This program will last for 12-16 weeks with
      every participants join together courses 4 hours per week. Each participant will be
      introduced a dietary plan based on a caloric reduction of 1200 Kcal/day from the values
      thought necessary to maintain their usual weight. Subject will be asked to follow dietary
      advice and their eating habit will be reviewed by dietician at the time of their weekly
      visit. Activity levels will be encouraged to reach 30 min each day and at least 5 days a
      week. During each visit, weight of each participant will be recorded and announced. Meals
      replacement may considered for those did not get much improvement during weekly monitoring
      since recent report indicated that meals replacement may provide certain help in reducing
      body weight. We are confident that adequate weight reduction (at least 5% of initial weight)
      and good compliance will be achieved given our previous experience.

      In aggregate, this study will investigate the effects of weight loss on (1) Rho kinase
      activity obtained from peripheral leukocyte (2). Aortic stiffness, central aortic pressure
      and hemodynamic by a noninvasive technique (3) Brain function specifically reflecting by
      circulating BDNF levels (4). Aortic elastic properties and left ventricular function by using
      MRI examinations, in non-diabetic individuals of metabolic syndrome. Findings from this
      integrated proposal will provide valuable information as mild to moderate weight loss (5% of
      initial body weight) in cellular, cardiac and central nervous system in additional to
      well-known effects on lipids, inflammatory cytokines and insulin resistance in non-diabetic
      subjects with metabolic syndrome.

      Follow up- Subjects received physical check up, fasting blood tests and OGTT 6 and 12 months
      after the end of study.
    

Intervention name(s): Lifestyle Counseling
Intervention type(s): Behavioral
Intervention description(s): Diet control with exercise
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rho kinase; Brain-derived neurotrophic factor