Thermogenesis-Based Interventions for Obesity and T2DM
Thermogenesis-Based Interventions for Obesity and T2DM
It would be useful to develop parameters for the easy and reliable identification of those with high risk of developing T2DM and CVD. Decreasing abdominal obesity during follow-up clinic visits in a given individual is likely to be more predictive of improving overall CVD risks than improvement in BMI or any single biochemical or radiological measure, no matter how sophisticated. Therefore, in logical terms, targeting reduction of abdominal obesity via focusing and treating its causes can be more effective in CVD risk reduction in this vulnerable group of patients. In this regard, augmenting energy expenditure is a strategic way to address this pathological problem. Irrespective of the BMI, anyone consuming unhealthy meals regularly, in particularly that containing high amounts of refined sugar, saturated- and/or trans-fat, or high calorie fast-food meals on a regular basis would develop unhealthy oxidative stress and a proinflammatory status.
It is important to understand and implement practical weightloss regimens that can be adhered to; these should be combined with improvements in nutritional habits and unhealthy change in lifestyle. Such a regimen would be highly cost effective. Reminders and frequent visits with healthcare workers would also have a significant impact in weightloss and subsequent weight maintenance. In both the Finnish Diabetes Prevention Study and the American Diabetes Prevention Program, those patients who had regular contact with their physicians had sustained beneficial effects on glucose tolerance and reducing abdominal obesity. For instance, in the Diabetes Prevention Program, changing the nutritional and physical activity habits and inducing weightloss in a group of high-risk patients with impaired glucose tolerance was associated with a marked reduction in the probability of developing T2DM over a 3-year period. In fact, the reduction observed was greater than that achieved with the use of pharmacotherapy with metformin.
Evidence substantiates that patients with visceral obesity who lose a moderate amount of bodyweight (e.g., 10–15% or perhaps two inches or more of their abdominal girth) show a selective and significant mobilization of visceral fat. Thus, even in a patient with weightloss of only 5 kg, increased physical activities could induce a substantial loss of visceral adipose tissue. This would have a major beneficial effect on improving insulin sensitivity and decreasing the pro-inflammatory status. Such preferential mobilization of visceral fat could explain the extensive metabolic benefits of moderate weightloss in viscerally obese patients with dyslipidemia or impaired glucose tolerance. Nevertheless, those patients with sub-optimal physiologic compensatory changes of energy handling may experience poor long-term efficacy of treatments for obesity.
Due to a genetically driven set-point in a given individual, it is not surprising that weight-reduction programs are only effective in some individuals but not in others. This adaptive thermogenic effect can clearly influence therapeutic outcomes. Therefore, one should consider the possible role of adaptive thermogenesis in unsuccessful weightloss interventions in a given individual. In addition, many environmental factors can also affect weight regulations including various toxins including endocrine disruptors, tobacco, alcohol, recreational drugs, organochlorine, organophosphorus compounds, bisphenol A, di(2-ethylhexyl)phthalate and phthalates. In addition, there are many medical and metabolic disorders such as obstructive sleep apnea, and climatic adaptations also affects thermogenesis and thus the bodyweight. Figure 1 illustrates practical yet simple algorithm for managing overweight and obese patients based on two simple easily measurable variables: the combination of WC and the BMI.
(Enlarge Image)
Figure 1.
The management of overweight and obese patients. BMI does not take into account the quantity of visceral fat, body frame size or the muscularity. Therefore, clinically, other measurements such as WC, waist-to-hip ratio, skinfold thickness or bioimpedance may be used as surrogate markers to assess body fat.
WC: Waist circumference.
There is considerable evidence that physical activity and exercise can improve the mobilization of glycogen and fat stores, creating a glucose storage space that improves insulin sensitivity. Sedentary patients with visceral obesity, insulin resistance and the features of metabolic syndrome should benefit from any regular physical activity such as cycling or brisk walking of 30–45 min daily. In addition to regular physical activity, positive transformation of nutritional habits, changing sedentary lifestyles, and losing a moderate amount of weight, leading to a selective loss of visceral fat would improve the cardiometabolic risk profile of such patients.
While the bariatric surgical approaches can decrease bodyweight by more than 20%, medical management can induce 5–10% weightloss; both methods improve health in obese individuals and improve the long-term outcomes, including cardiometabolic benefits. Bariatric surgery procedures are indicated for patients with severe obesity; many of which have comorbidities. These procedures cause weightloss but have variable success in weightloss maintenance over time.
Although the rates of being overweight or obese have plateaued in the USA and a few other countries, rates of severe obesity continue to increase. In the USA, approximately 15 million people have BMI of 40 kg/m or greater. Appropriate patient selection is an important part of successful bariatric surgery. There a few bariatric surgical options that offer different mechanisms for weight reductions: gastric restriction, malabsorption and changes in gut peptides and hormones. Beneficial effects of surgical options include alleviation of T2DM, sleep apnea, CVD and decreased risk in some cancers. However, surgery is also associated with intraoperative and postoperative complications including dumping syndrome, and significant nutritional deficiencies.
A simple and focused clinical approach for identifying individuals with excess visceral fat, as indicated by higher abdominal girth, or WHR, together with elevated serum triglycerides, would be cost effective. Physicians should be able to recognize the presence of excess abdominal fat in their patients, and the measurement of WC should be considered as a routine essential vital sign. Individuals with high risk for metabolic syndrome may need additional biochemical studies. Measurement of the WC is a simple and easy method and a reliable marker for identifying those who are at a higher risk, which is a strong predictor of morbidity and mortality, independent of BMI. This phenotype, which is referred to as 'hypertriglyceridemic' waist, is a predictor of increased risks of coronary artery disease. This simple, cost-effective measurement should be used worldwide to identify those who are at risk and for appropriate behavioral modifications.
Clinical Perspectives
It would be useful to develop parameters for the easy and reliable identification of those with high risk of developing T2DM and CVD. Decreasing abdominal obesity during follow-up clinic visits in a given individual is likely to be more predictive of improving overall CVD risks than improvement in BMI or any single biochemical or radiological measure, no matter how sophisticated. Therefore, in logical terms, targeting reduction of abdominal obesity via focusing and treating its causes can be more effective in CVD risk reduction in this vulnerable group of patients. In this regard, augmenting energy expenditure is a strategic way to address this pathological problem. Irrespective of the BMI, anyone consuming unhealthy meals regularly, in particularly that containing high amounts of refined sugar, saturated- and/or trans-fat, or high calorie fast-food meals on a regular basis would develop unhealthy oxidative stress and a proinflammatory status.
It is important to understand and implement practical weightloss regimens that can be adhered to; these should be combined with improvements in nutritional habits and unhealthy change in lifestyle. Such a regimen would be highly cost effective. Reminders and frequent visits with healthcare workers would also have a significant impact in weightloss and subsequent weight maintenance. In both the Finnish Diabetes Prevention Study and the American Diabetes Prevention Program, those patients who had regular contact with their physicians had sustained beneficial effects on glucose tolerance and reducing abdominal obesity. For instance, in the Diabetes Prevention Program, changing the nutritional and physical activity habits and inducing weightloss in a group of high-risk patients with impaired glucose tolerance was associated with a marked reduction in the probability of developing T2DM over a 3-year period. In fact, the reduction observed was greater than that achieved with the use of pharmacotherapy with metformin.
Evidence substantiates that patients with visceral obesity who lose a moderate amount of bodyweight (e.g., 10–15% or perhaps two inches or more of their abdominal girth) show a selective and significant mobilization of visceral fat. Thus, even in a patient with weightloss of only 5 kg, increased physical activities could induce a substantial loss of visceral adipose tissue. This would have a major beneficial effect on improving insulin sensitivity and decreasing the pro-inflammatory status. Such preferential mobilization of visceral fat could explain the extensive metabolic benefits of moderate weightloss in viscerally obese patients with dyslipidemia or impaired glucose tolerance. Nevertheless, those patients with sub-optimal physiologic compensatory changes of energy handling may experience poor long-term efficacy of treatments for obesity.
Due to a genetically driven set-point in a given individual, it is not surprising that weight-reduction programs are only effective in some individuals but not in others. This adaptive thermogenic effect can clearly influence therapeutic outcomes. Therefore, one should consider the possible role of adaptive thermogenesis in unsuccessful weightloss interventions in a given individual. In addition, many environmental factors can also affect weight regulations including various toxins including endocrine disruptors, tobacco, alcohol, recreational drugs, organochlorine, organophosphorus compounds, bisphenol A, di(2-ethylhexyl)phthalate and phthalates. In addition, there are many medical and metabolic disorders such as obstructive sleep apnea, and climatic adaptations also affects thermogenesis and thus the bodyweight. Figure 1 illustrates practical yet simple algorithm for managing overweight and obese patients based on two simple easily measurable variables: the combination of WC and the BMI.
(Enlarge Image)
Figure 1.
The management of overweight and obese patients. BMI does not take into account the quantity of visceral fat, body frame size or the muscularity. Therefore, clinically, other measurements such as WC, waist-to-hip ratio, skinfold thickness or bioimpedance may be used as surrogate markers to assess body fat.
WC: Waist circumference.
There is considerable evidence that physical activity and exercise can improve the mobilization of glycogen and fat stores, creating a glucose storage space that improves insulin sensitivity. Sedentary patients with visceral obesity, insulin resistance and the features of metabolic syndrome should benefit from any regular physical activity such as cycling or brisk walking of 30–45 min daily. In addition to regular physical activity, positive transformation of nutritional habits, changing sedentary lifestyles, and losing a moderate amount of weight, leading to a selective loss of visceral fat would improve the cardiometabolic risk profile of such patients.
While the bariatric surgical approaches can decrease bodyweight by more than 20%, medical management can induce 5–10% weightloss; both methods improve health in obese individuals and improve the long-term outcomes, including cardiometabolic benefits. Bariatric surgery procedures are indicated for patients with severe obesity; many of which have comorbidities. These procedures cause weightloss but have variable success in weightloss maintenance over time.
Although the rates of being overweight or obese have plateaued in the USA and a few other countries, rates of severe obesity continue to increase. In the USA, approximately 15 million people have BMI of 40 kg/m or greater. Appropriate patient selection is an important part of successful bariatric surgery. There a few bariatric surgical options that offer different mechanisms for weight reductions: gastric restriction, malabsorption and changes in gut peptides and hormones. Beneficial effects of surgical options include alleviation of T2DM, sleep apnea, CVD and decreased risk in some cancers. However, surgery is also associated with intraoperative and postoperative complications including dumping syndrome, and significant nutritional deficiencies.
A simple and focused clinical approach for identifying individuals with excess visceral fat, as indicated by higher abdominal girth, or WHR, together with elevated serum triglycerides, would be cost effective. Physicians should be able to recognize the presence of excess abdominal fat in their patients, and the measurement of WC should be considered as a routine essential vital sign. Individuals with high risk for metabolic syndrome may need additional biochemical studies. Measurement of the WC is a simple and easy method and a reliable marker for identifying those who are at a higher risk, which is a strong predictor of morbidity and mortality, independent of BMI. This phenotype, which is referred to as 'hypertriglyceridemic' waist, is a predictor of increased risks of coronary artery disease. This simple, cost-effective measurement should be used worldwide to identify those who are at risk and for appropriate behavioral modifications.