Dynamic Analysis of the Possible Effects of Leptin in Some Metabolic Disorders in Obesity

Dynamic Analysis of the Possible Effects of Leptin in Some Metabolic Disorders in Obesity

Alejandro Talaminos (Biomedical Engineering Group, School of Engineering, University of Seville, Seville, Spain) and Laura M. Roa Romero (Biomedical Engineering Group, School of Engineering, University of Seville, Seville, Spain)
DOI: 10.4018/ijsbbt.2012100101
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Obesity and metabolic syndrome represent an increasing epidemiological challenge for society given the associated social and health implications. Obesity is related to different metabolic disorders, like diabetes mellitus type 2, which has been subject to study in the last decades. Nowadays, most of the related research focuses on endocrine aspects, especially related to adipose tissue. This is due to the fact that some adipocytokines are proven to be of great relevance as therapeutic agents both for obesity and mellitus type 2 diabetes. This work integrates some aspects of the knowledge generated under these research studies. In this context, it is proposed the design and development of a computational model that provides a better dynamic view of the existing interactions between endocrine aspects of the adipose tissue and glucose control mechanisms in people with obesity. The model behaves as an observer that estimates the dynamics of internal state variables, not easy to be measured in the clinical practice, and which helps to understand the dynamic behaviour of measurable variables. The work analyses the effects of the external energy intake and exercises over the obesity control and glycemia. The model has been validated by using other authors’ data. Predictions of the influence over the measurable variables of the behaviours considered when the virtual patient follows different diets and physical exercise are shown as results.
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Diabetes mellitus is a group of metabolic diseases divided into two main types: type-1 and type-2 diabetes. In type-1 diabetes, or insulin-dependent (IDDM), the body is unable to produce insulin in the pancreas. On the other hand, type-2 diabetes, or non-insulin-dependent (NIDDM), is characterized by a disturbance in glucose homeostasis and the resistance to insulin (Sengupta et al., 2009).

World Health Organization estimates that about 300 million people will be affected by diabetes mellitus in 2025. Diabetes mellitus complications, such as vascular diseases or neuropathies, will also increase (Jacobson et al., 2011). These risks explain the general concern about the micro and macro-vascular associated incidence, as well as for its health cost (Alter et al., 2012). Several studies highlight that overweight and obesity at an early age are behind the increase of diabetes in children and youngsters (Brauchla et al., 2012) and middle-aged women.

Nowadays, the identification of patients with a higher risk of contracting these complications and the elaboration of prevention and treatment plans become aspects of high social and economical interest.

Currently, the overall results concerning obesity, metabolic syndrome and its associated complications with pharmacological agents have been overcome by a healthy lifestyle (a regular aerobic physical activity, healthy diet and the elimination of toxic habits) (Rankin et al., 2012).

Concerning obesity, recent studies (Conroy et al., 2011) focus on endocrine aspects, particularly on the adipose tissue (AT), which secretes a group of regulating hormones called adipocytokines. Among these hormones are the leptin and the adiponectin, which have proved to have a high significance in the regulation of several aspects related to the endocrine system, both for obesity and type-2 diabetes mellitus.

However, the physiological mechanisms associated to these hormones concerning insulin resistance has not been completely understood yet (Rasmussen-Torvik et al., 2012). The immune system is also involved in obesity. This system is represented in some works by the study of the C-reactive protein (CRP), closely related to leptin and the metabolic syndrome (Hepgul et al., 2012).

C-reactive protein also acts as an independent predictor of progressive myocardial functional deterioration associated with development of heart failures (Choi et al., 2012). Mechanisms such as sympathetic nervous activity (Harlan & Rahmouni, 2012), endothelial dysfunction (Wang et al., 2012) or oxidative stress (Boşnak et al., 2010) mediate leptin and adiponectin regulation. Leptin concentration levels as well as adiponectin, also vary dependending on the individual's ethnic group (Khan et al., 2012). However, important issues are still to be studied in depth, e.g., leptin hypertrophic or antihypertrophic effects in myocardium, whether resistance to leptin exists or not, and how it acts in order to regulate glucose utilization (Hou & Luo, 2011).

Daily physical exercise also improves to have a high impact on leptin and adiponectin; an experiment is presented in Yan (2011) where it is shown that levels of adiponectin are significantly increased after 10 weeks of aerobic exercise. Similarly, positive effects are obtained in order to prevent arteriosclerosis. These same results are analysed in Hou and Luo (2011), where a study with 47 middle-aged women is carried out. They followed an aerobic exercise routine for 15 minutes in the first session, which was gradually increased to 30 minutes in the 8 following weeks. Leptin levels decreased after those 8 weeks. Other similar experiments also checked these results in children (Kamal & Ragy, 2012) and middle-aged men (Dimitrow et al., 2011).

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