Inflammatory Axis and Sirtuins' in Overweight Pre-diabetics Patients
Condition: Pre-diabetes; Obesity
MeSH terms: Overweight; Prediabetic State
Study type: Interventional

Summary: 
      In obese patients the superficial adipose tissue works as an endocrine active tissue to
      express different cytokines, and multiple molecular pathways implied in the cross talking
      with different part of the human body, such as the cardiovascular system. To date, adipocytes
      and adipose tissue-derived macrophages and adipose tissue synthesize, and secrete several
      cytokines, and sirtuins. In this setting, the excess of body fat is linked to heart
      contractile dysfunction. All these pathways are differently expressed in obese diabetic
      patients as compared to obese non diabetic patients. Intriguingly, in diabetic obese patients
      the hyper-expression of inflammatory cytokines is associated to a hypo-expression of
      sirtuins. Furthermore, microRNAs (miRs) as miR 195 and miR 27 could be implied in the
      regulation of this complex cellular and molecular axis.Therefore, this molecular pattern in
      diabetic obese patients may correlate to altered myocardial performance, and to the
      development of heart failure disease. In this study authors will evaluate at baseline by
      peripheral blood samples and by the abdominal fat tissue, and than at 12 months of follow-up
      by perupheral blood analysis, the expression of cytokines sirtuins and miR 195/27 comparing
      pre-diabetics obese patients vs. non pre-diabetics obese patients.
    

Detailed description: 
      In obese patients the visceral fat, and the superficial adipose tissue work as an endocrine
      active tissue to express different cytokines, and multiple molecular pathways implied in the
      cross talking with different part of the human body, such as the cardiovascular system. To
      date, adipocytes, and adipose tissue-derived macrophages and adipose tissue, synthesize and
      secrete several cytokines, like tumor necrosis factor (TNF)-5 and interleukin (IL)-6, and
      anti-apoptotic proteins, such as sirtuins. Sirtuins are NAD+-dependent deacetylase involved
      in the control of energy metabolism, adipocyte hypertrophy, and of different cardiac
      reparative, and rimodellative functions. Furthermore Sirtuins could cross talk with
      inflammatory/oxidative stress axis, and could be modulated by miR 195/27 expression. In this
      setting, the excess of body fat is linked to heart contractile dysfunction. It is intuitive
      to speculate that, all these pathways are differently expressed in obese diabetic patients as
      compared to obese non diabetic patients. Intriguingly, in diabetic obese patients the
      hyper-expression of inflammatory cytokines is associated to a hypo-expression of sirtuins,
      and over expression of miR 195 and miR 27. Therefore, this molecular pattern in diabetic
      obese patients may correlate to altered myocardial performance, and to the development of
      heart failure disease. Authors' study hypothesis is that, this complex altered bidirectional
      pattern between the inflammatory and apoptotic pathways axis may be due to a progressive
      increase in adipose tissue, produced by long-term alterations in energy balance. However, all
      these alterations may be measured in adipocytes as well as in adipose tissue derived
      macrophages, and by peripheral blood assay. Intriguingly, no data evaluated these pathways in
      pre-diabetics obese patients, and their possible correlation to cardiac function worsening,
      and to the development of heart failure disease. Actually, the pre-diabetic obese subjects
      represent a population of patients associated to higher risk to develop cardiovascular
      disease, myocardial dysfunction, and heart failure. In these patients a not clear indication
      exists about the right dietetic and/or drug treatment to control the hyperglycemia. However,
      there is discussion about the necessity or not to introduce hypoglycemic drug therapy added
      to a hypocaloric diet therapy to control the hyperglycemic overload. Therefore, the aim of
      the present study will be to evaluate at baseline the abdominal fat tissue expression of
      cytokines, sirtuins, miR 195 and miR 27 (by direct tissue biopsy) and by peripheral blood
      samples in pre-diabetics obese patients vs. non pre-diabetics obese patients. As second,
      during six and twelve months of follow up by peripheral blood samples analysis authors will
      evaluate the abdominal fat tissue expression of cytokines, miR 195 and miR 27 in
      pre-diabetics obese patients treated by hypocaloric diet-therapy as compared to pre-diabetics
      obese patients treated by hypocaloric diet-therapy plus metformine. At the end, authors will
      report their correlation to myocardial performance index (MPI) as an index of myocardial
      performance in pre-diabetics obese patients treated by hypocaloric diet-therapy as compared
      to pre-diabetics obese patients treated by hypocaloric diet-therapy plus metformine. Authors
      may speculate to observe a different cytokines, sirtuins, miR 195 and miR 27 expression at
      visceral fat and peripheral blood in pre-diabetics obese patients vs. non pre-diabetics obese
      patients. As second, authors may find that, hypoglycemic drug therapy may induce a down
      regulation of peripheral blood cytokines, a hyper expression of sirtuins, and a down
      regulation of miR 195 and miR 27 involved in the control of energy metabolism, and of
      adipocyte hypertrophy, and secondary implied in a better cardiac function at follow up.
    

Intervention name(s): hypocaloric diet therapy
Intervention type(s): Dietary Supplement
Intervention description(s): all patients will receive an hypocaloric diet, with low carboidrates (<50%) overload.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic