Adipose tissue depot-specific differences in adipocyte function and inflammatory mediators in patients with type 2 diabetes mellitus and cardiovascular disease

Type II diabetes mellitus (T2DM) is one of the most common disorder today and
has reached epidemic proportions in many countries. T2DM is characterized by
defects in insulin secretion, failure to suppress hepatic glucose output, and
impaired glucose uptake in peripheral tissue as skeletal muscle and adipose
tissue. Besides insulin resistance, other factors such as hyperglycaemia and
inflammation play a central role in the pathogenesis of this disease.
Eventually, this leads to an 2-4 fold increase in cardiovascular morbidity and
mortality. A significant contributor to the rising prevalence of T2DM and
cardiovascular disease risk in many developed nations is an increase in body
fat. The prevalence of obesity is grown rapidly worldwide and reaching epidemic
proportions in developed countries.
Adipose tissue is a highly metabolic active tissue affecting a lot of tissues
like the liver, skeletal muscle and vasculature. Adipose tissue originates from
visceral and subcutaneous depots, with different metabolic characteristics.
Accumulation of the adipose tissue mass is associated with a disturbed fat
distribution, abnormal secretory functions of enlarged adipocytes, and
increased infiltration of macrophages and lymfocytes into the adipose tissue,
leading to impaired lipid and glucose homeostasis, and inflammation. Therefore,
the adipose tissue associated with a more pro-inflammatory state might play a
central role in the link between obesity, insulin resistance and cardiovascular
disease.

Primary Objective: In this study we investigate the adipose tissue
depot-specific differences in adipocyte function and inflammation in patients
with T2DM and subjects suffering from CVD compared to healthy subjects.

Secondary Objective: Characterize and quantify different cell populations
residing in the two adipose tissue depots from subjects with T2DM, subjects
suffering vascular disease and healthy controls.

In this observational study, the functional and morphological differences in
both visceral and subcutaneous adipose tissue will be compared in subjects
suffering from T2DM, vascular disease and healthy controls without insulin
resistance and vascular disease.
Therefore, paired samples of visceral adipose tissue and subcutaneous adipose
tissue will be obtained from forty five male or female patients (were the ratio
men to women in the three study groups will be similar) recruited at the
department of vascular and abdominal surgery. The surgical procedures includes:
cholecystectomy, abdominal hysterectomy and other routine procedures. During
surgery, adipose tissue biopsies of approximately five grams will be obtained
from both the abdominal subcutaneous and omental visceral depots.

The extra burden for the subjects associated with this study is that blood will
be drawn, without an extra injection (on top of the blood that will
automatically be drawn for the routine surgical procedure). Further, there is a
small change that bleeding might occur at the place were the adipose tissue
biopsies will be obtained, but this could be healed by the present surgeons.
This study is not directly beneficial for the individual subjects, but the
results obtained from this study might increase the understanding of the role
of the different fat depots in relation to the development of CVD.