clinical benefits.
In any weight management programme, therefore, it is essential that consideration be given to increasing physical activity.
Treatment strategies that combine physical activity with dietary changes are generally much more effective than treatments which are exclusive to one or other strategy (66).
In general, any measure that increases modest daily activity, such as avoiding lifts, or getting off the bus one stop earlier, is beneficial in increasing energy expenditure.
A sedentary obese individual performing 3 h of any activity standing up rather than sitting down will increase his 24-h energy output from 40% to more than 75% above the BMR (67).
However, for the obese individual with Type 2 diabetes, increasing daily activity patterns may not be enough, and more intensive degrees of exercise need to be considered on an individual basis.
Physical activity has a positive effect on insulin action, thus improving glucose control and insulin sensitivity (68).
In addition, exercise improves lipid profiles by reducing serum TG and VLDL and raising HDL concentrations.
Improvements in blood pressure have also been observed, independent of weight loss.
Cardiac fitness is improved, with the risk of myocardial infarction reduced by 35, 50% (69).
Evidence suggests that these benefits are not uniform and that, in general, younger (40, 54 years) individuals with Type 2 diabetes, in the early stage of disease, are more likely to benefit from the effects of exercise (70).
In addition, the greatest benefits from physical activity may be in the weight maintenance phase of obesity management (71).
The psychological benefits of exercise are equally important for the obese individual with Type 2 diabetes.
Reductions in anxiety levels, improved body image and higher self-esteem promote greater self-efficacy and help the individual to cope with stressful situations which often result in overeating and relapses (71,72).
While exercise improves insulin action, the effects of physical training disappear within days when discontinued, so consideration must be given to the nature and duration of the activity.
Programme activities need to be regular and of at least moderate intensity (73).
Aerobic activities, e.g. walking, swimming, cycling, for 20, 60 min at moderate or greater intensity for 3, 4 days/ week will benefit glycaemic control and at least 5 days a week will assist weight loss (74,75).
The value of walking as an exercise strategy for those with Type 2 diabetes should not be overlooked.
Those asked to walk 10 000 steps a day, and maintain a 1000 kcal deficit diet, lost more weight and had greater improvements in insulin sensitivity than those on diet alone (76).
Unfortunately, obese persons with Type 2 diabetes identify more barriers to exercise than to any other aspect of the diabetes self-care regimen, with specific complaints of physical discomfort, fear of hypoglycaemia, being too over- weight to exercise and lack of family support (77).
Physical discomfort as a limiting factor has to be considered from the perspective of both obesity and diabetes.
Obese women report higher degrees of perceived pain and exertion
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when walking than non-obese, suggesting that this moderate intensity activity is actually more intense for the obese due to the greater relative oxygen cost of walking (78).
In addition, the myriad of macrovascular and microvascular complications associated with diabetes may increase discomfort during activity and limit endurance and flexibility (71).
Patients with proliferative retinopathy or hypertension, for example, should avoid resistance training and high- intensity exercises and those with peripheral neuropathy are advised to pursue activities such as swimming, where the ankle and foot are not under stress.
Advice regarding appropriate footwear, foot inspection and adequate hydration should be given and those at risk of hypoglycaemia should take care to adjust insulin doses and consume sufficient carbohydrates (79).
The emergence of exercise referral schemes may be an important development for the treatment of obesity in Type 2 diabetes (1).
BEHAVIOURAL THERAPY Behavioural treatments for obesity originated in the 1960s and were founded on the concept that altering behaviours associated with eating and activity could be central to weight loss.
Specific strategies include self-monitoring of both eating habits and physical activity, stress management, stimulus control, problem solving, contingency management, cognitive restructuring and social support.
Treatments employing cognitive behavioural therapy (CBT) generally achieve levels of between 5, 10% weight loss.
A notable fact with regard to studies which have investigated CBT as a treatment strategy is that drop-out rates are very low.
Over 80% of subjects who enter behavioural treatments complete the programme and are available for follow-up (80).
It is recognised that CBT may produce the best results when combined with other treatments (81).
PHARMACOLOGICAL MANAGEMENT There is incontrovertible evidence to show that early pharmaceutical intervention achieves better glycaemic control and reduces macrovascular and microvascular outcomes for Type 2 diabetic subjects (82).
However, the conflict for obese diabetic patients between the need to achieve glycaemic control whilst minimising weight gain poses a challenging dilemma, as weight gain is an unfortunate consequence of several diabetic medications, a summary of which is provided in Table 8.2 (83).
Despite the undoubted ability of insulin to influence glycaemic control and microvascular outcomes, the mean weight gain by insulin-treated Type 2 obese subjects after 6 years is 10.4 kg.
Sulphonylureas have a similar, but less pronounced effect, with a mean gain of 4.9 kg (84).
For this reason, there is a general reluctance to use insulin in particular with the obese, although there is
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Table 8.2 Anti-diabetic agents and their impact on body weight
Anti-diabetic agent Effect on body weight
Sulphonylureas (e.g. gliclazide) + Biguanides (e.g. metformin) 7 a-Glucosidase inhibitors (e.g. acarbose) 7 Thiazolidinediones (e.g. pioglitazone, rosiglitazone) + Insulin ++ Source: Adapted from Hauner (83).
some evidence that the use of basal insulin as opposed to meal-time insulin will lessen the weight gain effect (85).
Newer agents such as the thiozolidinedione insulin sensitisers remain controversial, as the impact of undesirable subcutaneous weight gain, despite reductions in the more harmful visceral fat, continues to be debated (8). a-Glucosidase inhibitors such as acarbose, although generally less effective hypoglycaemic agents, may have some value in the management of the obese Type 2 diabetic patient.
Although they generally have a neutral effect on weight, some studies suggest they cause modest weight loss and are thought to act by reducing the energy available from carbohydrates by delaying fermentation in the gut (86).
Biguanides such as metformin, on the other hand, have a weak anorectic action, and were shown by the UKPDS to be the treatment of choice for the obese Type 2 diabetic patient, causing no weight gain relative to conventional policy and demonstrating a cardio-protective effect by reducing the rates of mortality and myocardial infarction (87).
Furthermore, there is some evidence that the combination of metformin with intensive insulin therapy can negate the weight gain caused by insulin (88).
However the effects of metformin on microvascular outcomes are less favourable than insulin, and for many patients its side-effects and contra- indications mean that it is not a viable option.
Clearly there is no easy way for an individual with diabetes who is obese to improve glycaemic control, reduce microvascular and macrovascular compli- cations and lose weight at the same time.
A more rational approach may be to address the problem of obesity first, using agents that cause weight loss as a primary effect and achieve reductions in hyperglycaemia as a desirable consequence.
One such agent is orlistat, an intestinal lipase inhibitor, which acts enterically to inhibit the absorption of approximately 30% of dietary fat (89).
Orlistat is recommended for use in those aged 18, 75 years with a BMI 28, 30 kg/m2, in the presence of significant co-morbidities and in those with a BMI>30 kg/m2 with no associated co-morbidities.
Patients are required to demonstrate a weight loss of at least 2.5 kg in the month prior to the drug being prescribed.
The NICE (90) guidelines in the UK have also recently
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recommended that continuation of this therapy beyond three months should be supported by evidence of a loss of at least a further 5% of body weight, and beyond six months by evidence of at least 10% weight loss.
Several clinical trials have been conducted to examine the efficacy of this drug treatment in obese diabetic and non-diabetic patients (89,91).
While over a one-year period, Type 2 diabetic subjects taking sulphonylureas and orlistat lost less weight than non- diabetic subjects taking orlistat (mean 6.2 kg vs 9.5 kg), the subsequent improvements in HbA1c reduced the need for diabetic medication and had favourable effects on lipid profiles and hypertension.
In addition, improvements in the insulin resistance index of obese non-diabetic subjects, proportional to the degree of weight lost, suggest that orlistat may have a valuable role in the delay of onset or perhaps the prevention of Type 2 diabetes in the obese (92).
Sibutramine is a selective serotonin and noradrenaline reuptake inhibitor, which promotes weight loss.
The blocking of serotonin reuptake has a satiety enhancing effect and inhibition of noradrenaline uptake promotes thermogen- esis.
Sibutramine has only recently been licensed in the UK, the drug having been available on prescription in the USA for considerably longer.
The results of the clinical trials show that obese non-diabetic patients are more able to achieve a 5, 10% weight loss with sibutramine than with placebo, although the positive effects are dose-related.
A 10 mg dose results in a mean weight loss of 5.5% and a 15 mg dose a loss of 7.2% (93).
For the Type 2 diabetic patient who loses weight with sibutramine, the ensuing improvements in all modifiable risk factors are proportional to the degree of weight lost, with significant improvements, specifically a reduction in HbA1c of 0.4%, seen in those who lost >5% of body weight (94).
As a word of caution, slight increases in pulse and blood pressure (2, 3 mmHg) are associated with sibutramine, but in the long term, weight loss results in a net decrease in blood pressure.