Metabolism In Metabolic Disorders Proteins


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 Metabolism In Metabolic Disorders Proteins Background

What is a metabolic disorders?

Metabolism is a broadly defined term that encompasses the various chemical reactions in living cells that allow life to exist. To put it simply, metabolism is both the breakdown of food and nutrients into energy and the use of that energy to build up various components (like fat and muscle). Colloquially, many individuals talk about having a “high” or “low” metabolism from anecdotes about how much food they eat compared to how quickly they gain weight.

Metabolic disorders manifest themselves in many different forms, from the inability of individuals to regular blood glucose properly to the wasting of muscle tissue with overall body inflammation. The following section describes several metabolic disorders (diabetes, metabolic syndrome, sarcopenia, and protein energy wasting) that are highly prevalent in the United States or represent a major global health care cost.

The extent of metabolic disorders observed worldwide is a serious global crisis and warrants collaborative efforts to curtail the pandemic. Metabolic disorders are associated with lifelong effects, particularly increased morbidity and mortality due to lifestyle-related diseases such as type 2 diabetes, kidney disease, and cardiovascular disease.

Obesity was first recognized as a medical condition in which excess body fat leads to many comorbidities and premature death in the 18th century. Many of the co-morbid related to overweight and obesity are lifelong and fatal, including cardiovascular disease, type 2 diabetes, respiratory illnesses, cancer, and other abnormalities. Obesity at the age of 40 years has also been shown to decrease life expectancy by 7 years. The global obesity pandemic is now a phenomenon that transcends geographic, socioeconomic, and demographic factors. Worldwide, the age-standardized prevalence of obesity doubled between 1980 and 2008. By these estimates, one in nine individuals (508 million) was classified as obese in 2008. Furthermore, an estimated 170 million children, ages 2 to 18 years, are classified as overweight or obese. Although the prevalence of obesity in the U.S. is higher than any other developed country, the epidemic has spread to other countries as a result of the increased adoption to a Western lifestyle involving decreased physical activity levels and the overconsumption of readily available, energy-dense food.

Hyperglycemia is defined as having high blood glucose, a required metabolic fuel for the brain under physiologic conditions. Hyperglycemia is related to insulin resistance, a condition in which defects in the action of insulin are such that normal levels of insulin do not trigger the signal for glucose absorption. Insulin is a hormone produced by beta cells in the pancreas which regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose. Hyperglycemia has many adverse health effects. Glucose induces vascular inflammation, which impairs the immune status of an individual by inhibiting leukocyte function. Additionally, hyperglycemia increases the production of oxygen-derived free radicals, which induces endothelial dysfunction. Moreover, hyperglycemia is causally related to many chronic illnesses, including diabetes, metabolic syndrome, and cardiovascular disease.

Type 2 diabetes, previously known as noninsulin-dependent diabetes mellitus or adult onset diabetes, is an illness marked by chronic hyperglycemia and requiring continuous medical care with risk reduction strategies to manage glycemic control and other comorbidities. Type 2 diabetes was first recognized as a serious and fatal medical condition in 1812. In 1910, Edward Albert Sharpey-Schafer, MD, performed a study of the pancreas, which led to the discovery of insulin. Insulin was first used to treat diabetes in 1922 and, after one year of clinical testing, became commercially available in 1923. In 1970, research established an association between obesity and type 2 diabetes. Type 2 diabetes is often observed among individuals with marked obesity associated with insulin resistance. Furthermore, around 60% of type 2 diabetes cases could be prevented if individuals maintained a normal weight. Due the risk of progression to type 2 diabetes, there has been increasing awareness of prediabetes, an intermediate medical condition that is an important risk factor for both type 2 diabetes and coronary heart disease. Similar to type 2 diabetes, prediabetes is often observed among overweight and obese individuals.

Sarcopenia is the term used to describe the gradual loss of skeletal muscle mass over time. Derived from the Greek term meaning “poverty of the flesh”, sarcopenia is associated highly with aging. Protein-energy wasting is a total decrease in whole body protein and fat mass and is commonly associated with chronic kidney disease. Between 5-13% of elders aged 60- to 70-years old and 11-50% aged 80 or older suffer from sarcopenia in the US. Nearly 10% of HIV/AIDS patients suffer from significant weight loss and wasting. Chronic kidney disease, commonly complicated with protein-energy wasting, has increased in prevalence by 43% from 1991-2001. Cachexia, a term describing the complex disorder relating total weight loss, functional mass reduction, and inflammation, is prevalent in more than 30 million Americans

Muscle wasting, found in all of these conditions, is a loss of functional mass, resulting in decreased strength and reduced bone mass. Currently, there is no technique that directly measures functional muscle mass. Because most protein is found in muscle, it could be argued that total body protein is a surrogate for functional mass. Unfortunately, there is no clinically useful measure for the quantity of or change in distribution of total body protein.