Physical activity and abdominal subcutaneous adipose tissue biology in middle-aged lean and obese individuals

Insulin therapy is frequently needed to achieve adequate glycaemic control in
type 2 diabetes mellitus (T2DM), but often at the expense of weight gain.
Insulin-associated weight gain is obviously undesirable in an already
overweight population and may negatively affect blood pressure, lipid levels,
inflammatory and fibrinolytic parameters, adipocytokines and also deter further
optimization of insulin therapy. It is unknown what determinants predict
insulin-associated weight gain in type 2 diabetes mellitus.
Recently, a prospective study (CMO study no. 2008/237) started to investigate
determinants of insulin-associated weight gain. One determinant of weight gain
is (change in) physical activity. Fagour et al.1 showed that after short-term
insulin therapy (4 days) resting energy expenditure decreased which might
contribute to weight gain. It is hypothesized that patients who show
(pronounced) weight gain after start of insulin therapy (*gainers*) perform
less total physical activity after initiation of insulin therapy than patients
with less or non weight gain (*non-gainers*). The primary aim of this study is
to detect an association between (change in) total physical activity and
insulin-associated weight gain.
Furthermore, changes in abdominal subcutaneous adipose tissue will occur during
insulin treatment. It is appreciated that fat cell enlargement and increase in
adipocytokines production is associated with obesity/weight gain and insulin
resistance 2,3. To what extent exogenous insulin itself and the concomitant
increase in body weight influences adipocyte size and adipocytokines remains
unknown. The secondary aim of the prospective study is to study changes in
adipose tissue biology after start of insulin therapy and the relationship with
weight gain.
While the prospective study will reveal (changes in) physical activity in
patients with type 2 diabetes, it cannot reveal whether the levels of physical
activity in these patients differ from those of healthy (obese) subjects.
Comparing baseline levels of physical activity and adipose tissue biology in
patients starting insulin to healthy (obese) subjects will provide more insight
in the level of abnormalities between the two groups. Furthermore, after
insulin therapy the change in physical activity and change in metabolic markers
of adipose tissue can be compared to baseline levels of these variables in
healthy (obese) subjects.
Therefore, we would like to investigate the relationship between physical
activity and abdominal subcutaneous adipose tissue biology among men and women
with varying body mass index compared to patients with type 2 diabetes mellitus
at baseline and after start of insulin therapy. This will enable us to compare
patients with diabetes to weight-matched non-diabetic subjects but also with
age-matched lean subjects.

The primary objective of the proposed study is to investigate the level of
physical activity among lean and obese middle-aged individuals. We hypothesize
that the level of physical activity among healthy (obese) subjects is higher
than in patients with type 2 diabetes mellitus.

Case-control study (combining data of prospective study CMO nr. 2008/237)

Except for abdominal adipose tissue biopsy and venapuncture, all the
examinations are non-invasive.