Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03491241 |
| Other study ID # |
22.3.2018 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 1, 2017 |
| Est. completion date |
January 1, 2018 |
Study information
| Verified date |
November 2020 |
| Source |
University of Campania "Luigi Vanvitelli" |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
