Preface

Cellular metabolism is the process within the cells by which food and nutrients are converted into energy. Metabolic processes in the cells must be under strict regulation to maintain homeostasis in the body. There are multiple levels of metabolic regulation in the body. For effective metabolism, different enzymes, coenzymes, and hormones are required.

Any disorder of metabolism, either due to imbalance of the regulating enzymes or the hormones, is characterized by the inability to properly utilize and/or store energy. Metabolic disorders affect the ability of the cells to perform critical biochemical reactions that involve the processing or transport of carbohydrates (sugars and starches), proteins (amino acids), or lipids (fatty acids). Disorders of metabolism can be either congenital or acquired. Congenital metabolic disorders are usually due to mutation of genes resulting in deficiency or absence of particular enzymes. Acquired disorders are usually complex and both genes as well as environmental factors are responsible for them.

The objective of this book was to collect and compile articles on the metabolism of fuels in the brown adipose tissue and brain as well as updates on several disorders of metabolism ranging from diabetes mellitus, insulin resistance, hypothyroidism, and metabolic syndrome to some congenital disorders such as glycogen storage disease and urea cycle disorder.

This book is divided into nine sections. The Introductory section includes the prologue entitled energy metabolism and weight control by Prof. Hsieh Po-Shiuan.

The second section, 'Energy Metabolism', includes two chapters. The first chapter, 'Brown Adipose Tissue Energy Metabolism', is written by Prof. Lu Yuan. This chapter describes the mechanism underlying brown fat energy metabolism and the therapeutic potential in metabolic disorders, especially obesity-related metabolic diseases.

The second chapter, 'Cerebral Energy Metabolism: Measuring and Understanding its Rate', by Avital Schurr summarizes the history of the science behind the current knowledge of the biochemical processes responsible for the production of adenosine triphosphate (ATP) in the brain. It also briefly reviews the various techniques used to measure cerebral metabolic rates of oxygen and glucose, two of the substrates involved in ATP production and elaborates on the potential of measuring the cerebral metabolic rate of lactate to improve understanding of brain energy metabolism.

The third section, 'Diabetes Mellitus', includes the chapter entitled 'Diabetes Mellitus: A Group of Genetic-based Metabolic Diseases' written by Lilian Sanhueza. This chapter discusses the overall picture of different types of diabetes mellitus including the main clinical presentations with the proven genetic basis. In this chapter, emphasis is given to the candidate genes for Diabetes Mellitus type 1

**II**

**Section 5**

**Section 6**

**Section 7**

**Section 8**

**Section 9**

*by Ágnes Kinyó*

Hypothyroidism

Lipid Disorders in Uremia

Danger or Therapy? *by Georg Bollig*

Is Ammonia Control Enough? *by Andrea L. Gropman*

Hypothyroidism **127**

**Chapter 8 129**

Uremia and Lipid Disorders **141**

**Chapter 9 143**

Glycogen Storage Disease **165**

**Chapter 10 167**

Imaging Studies **179**

**Chapter 11 181**

Toxicity of Associated Drug **201**

**Chapter 12 203**

Sports and McArdle Disease (Glycogen Storage Disease Type V):

Emerging Knowledge From Noninvasive Imaging Studies:

Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid

*by Mauricio Alvarez Andrade and Oscar Rosero Olarte*

*by Valdete Topçiu-Shufta and Valdete Haxhibeqiri*

(DM1), Diabetes Mellitus type 2 (DM2), and Monogenic Diabetes and Latent Autoimmune Diabetes in Adults (LADA). Subtypes of maturity onset diabetes in the young (MODY) and their genetic basis is also elaborated in this chapter.

The next chapter, 'Pathogenesis of Insulin Resistance', written by Dr. Zaman Gaffar discusses the risk factors, pathogenesis, and molecular mechanism of insulin resistance in muscle and adipose tissue and the methods for diagnosis of insulin resistance. Understanding the cellular mechanisms might help the researchers to develop novel targets for various treatment modalities in the future.

The fourth section, 'Metabolic Syndrome', includes the chapter 'Metabolic Syndrome', which reviews the pathophysiology of metabolic syndrome (MS) and the relationship between its different components. This chapter mainly discusses the historical evolution, prevalence, relationship of MS with obesity, insulin resistance, and its effects on the body.

The next chapter of this section is 'Metabolic Syndrome: Impact of Dietary Therapy' by Suzanne Fouad. In addition to the general features of MS, this chapter discusses the management of MS through lifestyle modification and the role of different diets in the management of MS.

Thyroid hormones regulate the basal metabolic rate in the body. A low level of thyroid hormones in hypothyroidism leads to reduced metabolism and related effects in the body. The next section contains the chapter 'Hypothyroidism' written by Mauricio Alvarez Andrade and Oscar Rosero Olarte. In this chapter, the authors discuss the physiology and regulation of thyroid hormone production, different types, manifestations, diagnosis, differential diagnosis, and treatment of hypothyroidism.

Chronic uremia causes profound alteration in lipoprotein metabolism, promoting the development of atherosclerosis and cardiovascular disease. The next section contains the chapter 'Lipid Disorders in Uremia' by Valdete Topçiu-Shufta and Valdete Haxhibeqiri, and discusses lipid disorders in chronic uremia.

McArdle disease (glycogen storage disease type V) is an inborn error of energy metabolism in the muscle. Usually the patients regard physical activity as painful and possibly dangerous. The next section contains the chapter 'Sports and McArdle Disease (Glycogen Storage Disease Type V) - Danger or Therapy?' by Georg Bollig, who provided an overview of this disease and the advantages and possible risks of sports for patients with McArdle disease.

The next section contains the chapter 'Emerging Knowledge from Noninvasive Imaging Studies: Is Ammonia Control Enough?' written by Prof. Gropman Andrea, which focuses on the use of noninvasive neuroimaging coupled with neuropsychological tests to understand the complex relationship between ammonia, glutamine, cognitive function, seizures, and specifically the impact on development of working memory in patients with urea cycle disorders (UCD), one of the most common groups of inborn errors of metabolism.

The last section, 'Toxicity of Associated Drug', contains the chapter 'Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid' by Ágnes Kinyó, which discusses the side effects of Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors,

**V**

in this chapter.

also called gliptins). They are widely used drugs in the treatment of type 2 diabetes mellitus. There is an increased risk of bullous pemphigoid (BP) in patients during DPP-4 inhibitor treatment. An overview of BP during gliptin treatment is provided

> **Jasmine Khan** Faculty of Medicine,

Selengor, Malaysia

**Po-Shiuan Hsieh**

Taiwan

Universiti Teknologi MARA (UiTM),

Institute of Preventive Medicine, National Defense Medical Center, also called gliptins). They are widely used drugs in the treatment of type 2 diabetes mellitus. There is an increased risk of bullous pemphigoid (BP) in patients during DPP-4 inhibitor treatment. An overview of BP during gliptin treatment is provided in this chapter.

**Jasmine Khan**

Faculty of Medicine, Universiti Teknologi MARA (UiTM), Selengor, Malaysia

#### **Po-Shiuan Hsieh**

Institute of Preventive Medicine, National Defense Medical Center, Taiwan

**IV**

(DM1), Diabetes Mellitus type 2 (DM2), and Monogenic Diabetes and Latent Autoimmune Diabetes in Adults (LADA). Subtypes of maturity onset diabetes in the young (MODY) and their genetic basis is also elaborated in this chapter.

develop novel targets for various treatment modalities in the future.

resistance, and its effects on the body.

sports for patients with McArdle disease.

in the management of MS.

hypothyroidism.

The fourth section, 'Metabolic Syndrome', includes the chapter 'Metabolic Syndrome', which reviews the pathophysiology of metabolic syndrome (MS) and the relationship between its different components. This chapter mainly discusses the historical evolution, prevalence, relationship of MS with obesity, insulin

The next chapter, 'Pathogenesis of Insulin Resistance', written by Dr. Zaman Gaffar discusses the risk factors, pathogenesis, and molecular mechanism of insulin resistance in muscle and adipose tissue and the methods for diagnosis of insulin resistance. Understanding the cellular mechanisms might help the researchers to

The next chapter of this section is 'Metabolic Syndrome: Impact of Dietary Therapy' by Suzanne Fouad. In addition to the general features of MS, this chapter discusses the management of MS through lifestyle modification and the role of different diets

Thyroid hormones regulate the basal metabolic rate in the body. A low level of thyroid hormones in hypothyroidism leads to reduced metabolism and related effects in the body. The next section contains the chapter 'Hypothyroidism' written by Mauricio Alvarez Andrade and Oscar Rosero Olarte. In this chapter, the authors discuss the physiology and regulation of thyroid hormone production, different types, manifestations, diagnosis, differential diagnosis, and treatment of

Chronic uremia causes profound alteration in lipoprotein metabolism, promoting the development of atherosclerosis and cardiovascular disease. The next section contains the chapter 'Lipid Disorders in Uremia' by Valdete Topçiu-Shufta and

McArdle disease (glycogen storage disease type V) is an inborn error of energy metabolism in the muscle. Usually the patients regard physical activity as painful and possibly dangerous. The next section contains the chapter 'Sports and McArdle Disease (Glycogen Storage Disease Type V) - Danger or Therapy?' by Georg Bollig, who provided an overview of this disease and the advantages and possible risks of

The next section contains the chapter 'Emerging Knowledge from Noninvasive Imaging Studies: Is Ammonia Control Enough?' written by Prof. Gropman Andrea, which focuses on the use of noninvasive neuroimaging coupled with neuropsychological tests to understand the complex relationship between

ammonia, glutamine, cognitive function, seizures, and specifically the impact on development of working memory in patients with urea cycle disorders (UCD), one

The last section, 'Toxicity of Associated Drug', contains the chapter 'Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid' by Ágnes Kinyó, which discusses the side effects of Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors,

of the most common groups of inborn errors of metabolism.

Valdete Haxhibeqiri, and discusses lipid disorders in chronic uremia.

**1**

Section 1

Introductory Section
