Review
Obesity, risk of diabetes and role of physical activity, exercise training and cardiorespiratory fitness

https://doi.org/10.1016/j.pcad.2019.08.004Get rights and content

Abstract

The epidemic of obesity contributes to the burden of type 2 diabetes mellitus (T2DM) in the United States and worldwide. Importantly, obesity is not only preventable but can be treated, particularly with lifestyle modifications to forestall T2DM in those with excess adiposity. The mechanisms linking obesity to T2DM are numerous and involve adipose tissue remodeling as a result of unhealthy behaviors, including unhealthy diet, reduced physical activity (PA) and exercise training (ET), and increased sedentary behaviors. Taken together, these factors markedly reduce cardiorespiratory fitness (CRF), one of the strongest predictors for cardiovascular outcomes and all-cause mortality in the general population, but also in those with T2DM.

In this review we describe the mechanisms leading to adipose tissue remodeling resulting in obesity, as well as the mechanisms linking excess adiposity to insulin resistance and, in turn, T2DM. We then present the therapeutic strategies that can be implemented in obesity to prevent T2DM, with a brief discussion on weight loss, and greater emphasis on PA and ET. We finally present the evidence to support the beneficial effects of such strategies in patients with established T2DM and discuss the importance of achieving improvements in CRF in this population to potentially improve clinical outcomes.

Section snippets

Obesity and adipose tissue remodeling

Obesity is a multifactorial chronic disease, in which environmental and genetic factors, as well as abnormalities of energy metabolism regulation, which may be caused by the use of medications that induce weight gain as a side effect, contribute to weight gain. Monogenic forms of obesity, mainly resulting from dysregulation of energy homeostasis, also exist.12 Although environmental factors (i.e., unhealthy diet, physical inactivity and SB) are considered the major causes for obesity, the fact

Mechanisms leading obesity to T2DM: contributions of insulin resistance and chronic low-grade systemic inflammation

With respect to the risk of metabolic diseases, obesity remains perhaps the strongest modifiable risk factor for the development of insulin resistance, ultimately resulting in T2DM.33 Hyperplasia and hypertrophy of the adipocytes can, in fact, occur in different locations within the body, including insulin-dependent tissues, like skeletal muscle, liver, and the adipose tissue itself.34 In addition to accumulation of excess fat within the adipose tissue, skeletal muscle and liver, ectopic fat

PA and ET to improve body weight and CRF to prevent T2DM

As discussed at length elsewhere, intentional weight loss induced by caloric restriction, but also pharmacologic and surgical interventions, in the setting of a comprehensive lifestyle modification program, remains the cornerstone therapy to improve insulin sensitivity and in some circumstances to prevent the incidence of T2DM in individuals with obesity and prediabetes.64 The amount of weight loss required to result in clinically significant improvements can vary, but even small improvements

PA and ET to increase CRF in T2DM

In addition to the strong association between improved CRF and reduced risk for T2DM, the role of CRF has been also investigated in those with established disease. In a recent analysis of 150 patients with T2DM, CRF (i.e., peak VO2) was found to be markedly reduced, even after adjustments for fat-free mass,8 which has been proposed to be a better assessment of CRF,82 particularly in individuals with overweight and obesity, in which the use of CRF adjusted by total body weight may result in an

Conclusions

Chronic positive caloric balance from unhealthy dietary habits, reduced PA and increased SB result in increased adiposity, eventually leading to adipose tissue remodeling and obesity. This excess adiposity, in turn, markedly increases the risk for cardiometabolic disease, particularly T2DM. Importantly, in patients with obesity, T2DM can be prevented by implementing lifestyle behavior modifications, including improvements in diet, increased PA, ET and perhaps SB, ultimately leading to improved

Funding support

Salvatore Carbone is supported by a Career Development Award 19CDA34660318 from the American Heart Association.

Declaration of competing interest

None.

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