of Disease and Living Conditions
Diabetes: Genes, Metabolism, and Evolutionary Selection
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.
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.
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.
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.
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.
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.
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.)
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.
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