Thermogenesis-Based Interventions for Obesity and Type 2 Diabetes Mellitus

Sunil J Wimalawansa


Expert Rev Endocrinol Metab. 2013;8(3):275-288. 

In This Article

Abstract and Introduction


Obesity is one of the key noncommunicable diseases leading to significant comorbidities. In recent years, obesity has become a major public health issue and has threatened the wellbeing of millions of patients. Although there are multiple reasons for people becoming obese, sustained positive energy balance – energy intake is greater than energy expenditure – is the key for accumulating excess bodyfat. Prevention of obesity by lifestyle changes, healthy eating and increased physical activity are more cost effective than pharmacotherapy, bariatric surgery or ultimately treating complications of Type 2 diabetes mellitus (T2DM). Not all patients with obesity experience complications such as T2DM. The distribution of bodyfat is important in determining whether a person is obese and healthy or needs medical attention; however, the use of BMI alone will not differentiate this. Obesity patients with excess abdominal fat have the highest risk for T2DM, insulin resistance and thus, higher incidence of cardiovascular diseases. Obesity-associated complications can be reversed through healthy eating habits and increased duration and intensity of physical activity. Increasing work- and leisure-related physical activities increase the energy expenditure, having salutary effects on weightloss programs. Although treating symptoms of obesity and related disorders is important, it is not a solution for the obesity epidemic. Causes that lead to weight-gain need to be identified in individual patients, who should be educated about the causes of weight gain and ways to prevent it, and be provided with simple and practical interventions to lose weight.


More than 60 million Americans are obese. Of the more than 25 million adults with Type 2 diabetes mellitus (T2DM), most are obese.[1,2] More than half of patients who are overweight and obese have at least one comorbid condition,[3] a situation that is associated with poor quality of life and premature death.[4–8] Obesity continues to be a major public health problem worldwide. In the USA, between 2009 and 2010, more than a third of US adults were considered to be obese, as defined by a BMI of 30 kg/m2 or greater.[9,10]

In the USA in the mid-1970s, the prevalence of obesity was approximately 15%.[11] Whereas, between 2007–2008, the prevalence of overweight or obese adults was 68%, and 34% were considered to have severe obesity.[12,13] Obesity has been associated with an increased hazard ratio for all-cause mortality,[14] as well as significant medical and psychological comorbidities. Therefore, obesity should be regarded as a bona fide disease state.[15]

The health risks associated with obesity and being overweight can contribute substantially to morbidity and premature mortality.[16,17] Assessment tools, including BMI and waist circumference (WC) thresholds,[18] have been developed to identify those who are at risk.[19] However, these tools are not applicable to all ethnic groups equally. Moreover, these tools are frequently underused, and even when their utility is recognized, patients may not receive appropriate early interventions needed to reduce their current and future health risks. Public awareness of the health risks associated with being overweight and obesity should be heightened, so that healthy weight management programs garner the attention they deserve in mainstream medical care.[3]

BMI can be used in clinical practice to assess potential health risks but has been inconsistent in its ability to predict the risk of cardiovascular disease (CVD) or mortality.[20] BMI correlates with mortality risk in middle-aged individuals,[21] but has been less accurate in predicting mortality risk in the young or in the elderly. Abdominal obesity, as measured by WC or waist-to-hip ratio (WHR), reflects increased health risks. In some ethnic groups,[20] WC and WHR are the strongest obesity-related parameters associated with cardiometabolic risk. The information obtained from WHR seems similar to that from the WC, but is a somewhat complicated measurement that needs calculation. Consequently, WC has been recognized as a practical and a more useful component in the routine assessment of metabolic and CVD risks.[18,22,23] However, none of these anthropometric measurements can distinguish visceral fat from subcutaneous fat around the waist, which can be achieved with costly technologies such as MRI or computed tomography.[24] Alternatively, the use of dual energy x-ray absorptiometry body composition analysis is an office-based tool that is relatively inexpensive and accurate. Dual energy x-ray absorptiometry allows the measurement of total fat and visceral adipose tissue mass, and calculates fat mass and lean mass indexes.[25,26] Although BMI or total bodyweight would not capture the weight and fat redistributions, particularly the visceral fat accumulation during the early postmenopausal periods, weight gain or during weightloss programs, WC and WHR, would capture such.

The Healthy People 2010 document from the US federal government includes targets related to weight, nutrition and physical activity that provide the nation's target goals for key health measures.[27] During the past decade alone, the prevalence of obesity among adults has increased from 23 to 34%.[28–30] Thus, the US population has made little progress in meeting its health targets related to obesity or minimizing health disparities.[28,29]

Visceral adiposity is an important factor for cardiometabolic risks.[31,32] Several studies have confirmed that visceral adiposity, but not subcutaneous adiposity, is associated with the excess CVD mortality,[33] even in the absence of T2DM.[34] However, patients with T2DM have more abdominal fat.[35,36] The loss of abdominal fat content – indicated by decreasing abdominal girth, by consuming less calories and increasing physical activity – is an important goal for those who have obesity, to improve their health.

Energy homeostasis is regulated by a complex system that integrates a series of varied biochemical signals. These signals influence satiety, food intake and the energy metabolism. These metabolic and hormonal signals that control neurohormonal feedback also affect the adiposity. In addition to the centrally-mediated biochemical signals that control hunger and satiety, a complex interplay of neuroendocrine signals that control bodyweight through appetite and metabolism is recognized.[23] These neurohormones and cytokines are generated from various organs; some arise from visceral fat deposits that drain directly into the liver via the portal vein.[37] In addition, the signals generated from the gut and CNS interact via cytokines and hormones on key brain areas and on the GI tract.

The basal metabolic rate (BMR) is the energy required for the functioning of core body activities involved in energy expenditure. The rate is determined primarily by genetics.[38] The BMI accounts for most of the BMR, and it also accounts for approximately 60% of daily energy expenditure in a sedentary person.[3] In addition, the endocannabinoid system also plays an important part in the physiological mechanisms by which the body regulates energy homeostasis.[39,40,41] Activation of the endocannabinoid system is associated with hedonic eating habits; excessive eating and accumulation of visceral fat, leading to additional increases in cardiometabolic risks.[42,43]

Patients who are overweight and obese who have excessive visceral adiposity have a higher risk of developing T2DM, insulin resistance and CVD.[3,44] For any given BMI, the level of physical activity is inversely correlated with CVD risk.[45,46] Evidence also suggests that those who are overweight but are fit have little excess risk of CVD.[47,48] For the majority of these overweight and fit people, the adipose tissue is located outside the visceral region.[49] They have relatively low intra-abdominal fat content and thus, lower levels of circulatory inflammatory markers.[33,50,51] Current evidence suggests that metabolically-healthy obese individuals, despite being obese as defined by higher BMI, have no increased risk of CVD.[52–54] Therefore, it is not surprising that the measurement of abdominal girth, albeit not an ideal as it cannot distinguish between intra-abdominal and extra-abdominal fat, is superior to the calculated BMI in assessing the metabolic risks of obesity.[18,32,55] Thus, those with higher metabolic risks cannot be accurately assessed using the BMI alone.[53] Considering these, the use of BMI to identify and manage cardiometabolic risks (and to measure physicians performance by Medicare and other agencies) can be misleading.[56]