Co-Evolution of Disease and Living Conditions

CASE 1
Diabetes: Genes, Metabolism, and Evolutionary Selection

Diabetes is a disease arising from a disruption of the metabolic balance in the body's digestion of sugar. Diabetes Mellitus is an ancient disease in humans; its incidence is increasing, and there are now very high rates in many countries. Today, the World Health Organization estimates that there are about 150 million cases worldwide, and that this number could double by 2025.

To understand the disease, one must first have a basic understanding of the normal process of digestion. In normal digestion, the body breaks down sugars in the food we consume and forms a very simple sugar, called glucose. Glucose is absorbed from the intestines into the bloodstream, where it is distributed to cells throughout the body for use as fuel.

Once a certain amount of glucose has been absorbed into the bloodstream, the pancreas begins to release insulin, a hormone that alerts the cells of the arrival/availability of the glucose. Glucose cannot pass into the cells without this alert by insulin. Diabetes occurs when either little/no insulin is produced, or when the cells become insensitive to insulin. Excess glucose builds up in the blood (hyperglycemia), and overflows into the urine. The word "mellitus" means honey-like, referring to the sugar and hence sweetness in the urine of diabetic patients.

There are two types of diabetes. Type I diabetes occurs when the insulin-producing beta cells in the pancreas are damaged, either by the body’s own immune system (making it an autoimmune disease), or by a viral infection. The pancreas ceases to produce sufficient insulin for the cells to metabolize glucose. This type of diabetes, also known as IDDM (Insulin Dependant Diabetes Mellitus), usually develops during childhood, and accounts for 5-10% of diabetes cases in the U.S.. This type of diabetes can be regulated through daily injections of insulin.

Type II diabetes (NIDDM, Non-Insulin Dependant Diabetes Mellitus) is the result of cells becoming resistant, or insensitive, to insulin. Because it often develops in people over age 40, it is commonly referred to as “adult onset diabetes.” Type II diabetes is most common in people who are overweight (especially abdominal obesity), and is occurring more frequently in children because of the increase in childhood obesity. Lower sensitivity to insulin can also arise as a side effect of taking certain drugs for long periods of time.

Although medical researchers are as yet uncertain of the specific cause of Type II Diabetes, a team of researchers at University of Pennsylvania (led by Dr. Mitchell Lazar) recently has discovered a protein secreted by fat cells in lab mice that causes tissues to be less sensitive to insulin. The larger fat cells of obese mice produced more of this protein (dubbed Resistin, for “resist insulin”), leading to much higher insulin insensitivity in obese mice. Today there are about 140 million cases of Type II diabetes, about 91% of which are preventable through monitored weight and diet.

Insulin regulates the metabolism of glucose and fatty acids, which store energy and fuels our activities. It also has various other functions. Insulin has been conserved in evolution over millions of years. (Certain molecules have not changed or have been "conserved" over long periods of time in evolution, insulin, melatonin, and cytochromes are among these.)

The interaction between genes and environment for diabetes has been studied extensively. One overall conclusion is that while there is a genetic component, diabetes manifests itself when the way of life is out of balance. Thus in people in Yanomanni Indians of South America, and several Native American groups, who are known to be genetically at high risk of diabetes, do not show the disease unless they become obese. So it appears that tehse populations hage a genetic susceptibility but certain external conditions (obesity) are needed for the disease to be actually manifested. Other factors such as malnutrition of the mother, can lead to metabolic imbalances in a fetus that leads to diabetes. This is because the fetus develops greater insulin insensitivity so that other development that is vital such as that of the brain is enabled. These low birth-weight babies are likely to develop Type II Diabetes later in life.

Population groups that started farming early seem to have developed a greater capability to digest sugar. Agriculture is believed to have started early in the Middle East, and the European populations that descended from them have low rates of diabetes. This is because of natural selection. Individuals who had high insulin sensitivity and could digest starch and sugar properly survived and reproduced, and over generations, the rate of diabetes became low. That is, individuals who tended to develop diabetes died out. Populations have developed insulin sensitivity following genetic adaptation to diets with different fractions of sugar (termed "glycemic load"). Thus Native Americans and Polynesians show least insulin sensitivity with high prevalence of diabetes and Europeans are most sensitive (they can digest sugar better) and show least rates of diabetes. This type of information has been pieced together from various studies and is still being completed. The bottom line is that diabetes is a disease that manifests itself when human ecology has deviated from conditions for its healthy living. Other intolerances, such as lactose or wheat intolerance, also have evolutionary origins.

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