Obesity Insulin Resistance and Endocrine Complications
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