Obesity Insulin Resistance
and Endocrine Complications
Clinical background
Metabolic syndrome
Obesity is associated with a number of
metabolic consequences characterized by insulin resistance and hyperlipidaemia.
These in turn contribute to the increased risk of cardiovascular disease and
diabetes (Fig. 48a and Table 48.1). Metabolic syndrome is the term given to a
range of metabolic disturbances occurring in the same patient, all of which should
be addressed and modified. Patients with metabolic syndrome have insulin
resistance, which precedes the onset of hypertension and Type 2 DM and is
thought to represent the primary pathological disturbance. Metabolic syndrome
thus describes insulin resistance, hyperinsulinaemia, hypertension,
hypertriglyceridaemia, low HDL- cholesterol and obesity. Patients with
metabolic syndrome are at a high risk of macrovascular disease and treatment
should be aimed at improving insulin sensitivity by diet and exercise and
aggressive treatment of hyperlipidaemia.
Polycystic ovary syndrome and
insulin resistance Obesity is
found in around 50% of women with polycystic ovary syndrome (PCOS; see Chapter
26). Furthermore, lean women with PCOS demonstrate lesser degrees of
hyperinsulinaemia and insulin resistance, which play a role in the pathogenesis of PCOS independently of obesity as insulin stimulates ovarian androgen
production. The metabolic consequences of obesity and hyperinsulinaemia are
seen in women with PCOS who have a high risk of developing impaired glucose
tolerance and Type 2 diabetes. Clinical evidence of hyperinsulinaemia may be
seen as acanthosis nigricans, a brown velvety pigmentation usually seen at the
base of the neck and in the axillae in obese women with PCOS.
Other endocrine causes and
implications of obesity
Other endocrine causes and implications
of obesity include Cushing’s syndrome (see Chapter 17) and hypothyroidism (see Chapter
14). Cushing’s syndrome largely reflects the symptoms produced by
excess cortisol secretion
in to the
circulation, although the obesity produced is due to redistribution of
fat to the face, neck and abdominal region. There is also significant fluid
retention with attendant cardiovascular problems due to the mineralocorticoid
action of cortisol when present in the blood in high concentrations. Hypothyroidism
may be associated with weight gain. Obesity distorts results from tests of
hypothalamopituitary function. Provocative tests are often impaired. For
example obesity blunts the response of GH release to a challenge of GHRH. The
cortisol response to CRH is also impaired in obese patients, and these abnormal
responses disappear with a reduction in weight.
Treatment of obesity
Obesity is a chronic disorder
associated with significant morbidity, impaired quality of life and increased
mortality rates. Treatment of obesity is difficult, not only due to the need
for obese individuals to make significant lifestyle changes (Fig. 48b), but
also due to prejudices held by society and doctors towards the condition and
its management. The principle of treating obesity is simple to produce a
negative energy balance that utilizes body stores and is maintained in the long
term. The practice is more complex, requiring education about diet and activity
levels and, where deemed necessary, the intro- duction of pharmacological
agents in addition to lifestyle modification.
Orlistat, inhibits pancreatic lipase
thus reducing gastrointestinal fat absorption has been shown to be effective
and is licensed for use in the UK. Research into a number of other agents
continues, such as leptin and neuropeptide Y antagonists. Surgical therapy such
as gastric banding to reduce gastric size remains an option for patients with
morbid obesity who have failed dietary and medical interventions and is the
most effective treatment for individuals with a BMI >40 kg m2
