International Biopharmaceutical Association Publication
Diabetes Mellitus, a rich man's disease
Dr. J. Bryant
joy.osafo@mail.mcgill.ca
Abstract
Diabetes,
a metabolic disease characterised by hyperglycaemia is now a worldwide endemic. Epidemiological studies have estimated that
by the year 2025 about 350 million people in the world will be affected by
diabetes, predominantly type 2 diabetes which is non-insulin dependent.
Defective
beta cell production of insulin (type 1 diabetes) and tissue insensitivity to
insulin (type 2 diabetes) lead to abnormally high levels of glucose in the
bloodstream. Depending on the levels of
glucose in the bloodstream and the degree of tissue responsiveness to insulin,
affected persons may or may not experience symptoms of the disease. Most common presentations include increased
thirst, lethargy, blurred vision and polyuria.
Obesity, diets
rich in carbohydrates and fats, and physical inactivity are risk factors for
developing the disease. However genetic
factors also play a role as diabetes seems to exist in families.
Diabetes has
always been considered to be a rich man's disease as it was observed in well
nourished persons. Global studies have
shown that it is now prevalent across the world, India being named the
'diabetic capital of the world'.
Developing countries are showing increases in the incidence of diabetes.
Urbanisation, obesity and physical inactivity have been the major contributing
factors. Persons of lower socioeconomic status (SES) have a higher incidence of
diabetes than do persons of higher SES.
In this paper,
I explore whether diabetes is indeed a rich man's disease by defining 'rich
man' in terms of country development and SES.
Introduction
Metabolism of sugars
Carbohydrate
metabolism is regulated by two endocrine hormones: insulin and glucagon. Following a meal, carbohydrates are digested
in the stomach and glucose is absorbed from the small intestine and transported
to the bloodstream. Glucose is then
absorbed by hepatocytes and muscle cells and
converted into glycogen for storage, an action regulated by insulin. This process is known as glycogenesis. Insulin, produced by the beta cells found in
the islets of langerhans of the pancreas, is secreted
in response to increased blood concentrations of glucose (10). The process of glucose absorption by liver and
muscle cells is an active process whereas other cells such as fat cells require
glucose transporters. In such cases,
insulin facilitates the absorption of glucose by glucose uptake by activating
the GLUT4 glucose transporter (10).
During periods of fasting or where the levels of glucose in the blood
are low, glycogen is catabolised into glucose by a process known as glycogenolysis and is controlled by glucagon.
Diabetes
The earliest
known description of diabetes was by the Indian surgeon, Sushrata,
about 600 BC. He named it 'Medhumeha'. He associated the disease with obesity and
physical inactivity, suggesting exercise as a way of managing the disease
(1). In the 2nd century, it
was described as 'siphon' by the Greek physician Arateus
because of the great thirst and excessive urine production of patients. Later in the 17th century, mellitus
meaning 'honey' was added by Thomas Willis as patients presented with sweet
urine (3).
Diabetes
mellitus is a chronic metabolic disorder in which the patient's body
poorly regulates sugar. This leads to an
increase in blood glucose levels as a result of defective insulin production
and/or action and diabetics present with hyperglycaemia. (Figure 1)
Types of diabetes
There are two
main classes of diabetes mellitus:
type 1 and type 2 diabetes (Figure 1).
Type 1 diabetes is also known as maturity onset diabetes of the young
(MODY), juvenile diabetes and insulin dependent diabetes mellitus (IDDM). In general the onset of IDDM occurs during
childhood and youth, but it can also occur in adult life.
In patients with
type 1 diabetes, the beta cells in the pancreas are destroyed by the body's own
antibodies (autoimmune) or unknown causes (1, 8). Autoimmunity is the most common cause of
IDDM, where antibodies produced include anti-insulin antibodies, anti-islet
cell antibodies and anti-glutamic decarboxylase
antibodies (2). It is not really known
why the body would attack its own pancreas but it has been suggested that the
production of antibodies that destroy the pancreas happens after a viral
infection. The insulin producing beta
cells are found in the islets of langerhan and their
destruction will lead to a decrease in insulin production (1,2,
8). 10% of all diabetic cases in the
North America and Europe are type 1.
In
type 2 diabetes, the cells of the body are less sensitive to insulin and are
therefore insulin resistant. Cell
surface insulin receptors are down regulated and in order for the body to
compensate for the insensitivity, the secretion of insulin is increased
resulting in high levels of it in the bloodstream. Central obesity is a predisposing factor to
type 2 diabetes, 55% of patients diagnosed with type 2 diabetes having central
obesity and 20% of all diagnoses being in elderly patients in North America
(1). Type 2 diabetes is also referred to
as non-insulin dependent diabetes (NIDDM) or late onset diabetes.
Figure
1: Diabetes results from an imbalance between the insulin-producing
capacity of the islet β cell and the requirement for insulin action in
insulin target tissues such as liver, adipose tissue and skeletal muscle. Some
of the many genes that have been shown or could possibly contribute to the
imbalance are illustrated. T1D (type 1 diabetes), T2D (type 2
diabetes). (16). 
Gestational
diabetes is another type of diabetes that occurs specifically in pregnant
women. Normally, pregnant women in the
first and early part of their second trimester have lower fasting glucose
levels than normal, non-pregnant women.
When maternal plasma glucose levels are elevated in early pregnancy,
this is a cause for concern as it could cause complications in pregnancy such
as a miscarriage or stillbirth, as well as putting the fetus at high risk for
diabetes. If a first time diagnosis of
diabetes is done during pregnancy then it is termed gestational diabetes and is
different from a diabetic woman who becomes pregnant. Gestational diabetes
could resolve with the end of pregnancy or it could predispose the mother to
type 2 diabetes.
Diabetes
can be caused by genetic or environmental factors or a combination of
both. Diabetes appears to run within
families, if one or more parents have the disease, chances of the offspring
also developing the disease are increased.
Now whether this is based on genetic factors or the fact that they are
exposed to the same environmental and physical backgrounds has not yet been
determined. It is possible that both
contribute to the prevalence in families (14).
Women that develop gestational diabetes during pregnancy and type 2 diabetes thereafter are said to be genetically predisposed
to diabetes with pregnancy being the environmental trigger. Genetic factors play a role in 10% of all
type 1 diabetic cases whereas in type 2 diabetics, it is 30% of all cases. Single mutations in certain genes have been
mapped and identified as causes of MODY . Mutations in the two liver enriched transcription
factors, human nuclear factor 1 alpha (HNF-1α) and HNF-4α cause MODY
1 and 3 respectively, MODY 2 by a mutation in the gene encoding glucokinase and MODY 4, a mutation in the gene encoding the
transcription factor IPF-1 (17). These
transcription factors and enzymes are involved in the expression of liver genes
involved in glucose metabolism.
Clinical presentations
Hyperglycaemia is
a common symptom as inadequate insulin production and function are incapable of
maintaining blood sugar levels within the normal range.
Most type 1
diabetic patients develop symptoms within days to weeks following the
malfunction of insulin production. In
contrast, type 2 diabetic patients may be asymptomatic for years and are
usually diagnosed during routine medical check-ups.. Symptoms are more severe in children although
they can also present severely in adults.
Clinical presentations of diabetes mellitus include increased
urine production, glycosuria, increased thirst,
increased fluid intake, blurred vision, weight loss, muscle loss and lethargy
(1, 7).
When blood levels
of glucose exceed the normal limit, it reduces the ability of the kidney to
reabsorb glucose and thus large amounts are excreted in the urine. This is known as glycosuria. Glucose increases the osmotic pressure of
urine causing water molecules to flow into the urine and reduce the amount
reabsorbed the kidney tubules, producing large quantities of urine (polyuria). The loss
of large amounts of water in urine causes the body to replace blood volume by
drawing water from cells and causing dehydration which is compensated for by an
increased need to take in more fluids (thirst). Insulin facilitates glucose storage and
conversion to energy and therefore improper processing of carbohydrates after a
meal, as exists in diabetics, will make the individual feel tired.
Type 1 diabetics
may present with ketoacidosis (1).
Diagnosis
There
are two glucose involving tests used to diagnose diabetes: the fasting blood
glucose test and the oral glucose tolerance test (OGTT). For the fasting blood glucose test, the
patient is required to fast overnight for at least 8 hours. A glucose test is done the next day.
Normal
fasting plasma glucose levels are less than 100 mg/dl and levels for a diabetic
are over 126 mg/dl on two or more tests.
The
OGTT is in two parts: following an overnight fast for 8-16 hours, the patient
first takes a regular plasma glucose test.
The second test involves the patient taking 75 g of glucose and blood
being sampled regularly (5 times in 3hrs).
If the patient is normal, blood glucose levels will rise following the
ingestion of the glucose bolus and fall rapidly. If the patient is diabetic, blood glucose
levels will rise and fall at a much slower rate than normal (2).
The glycated hemoglobin HbA1c is not used to diagnose diabetes
but is used to track the efficacy of treatment.
It measures blood glucose levels over the previous two to three
months. Glucose will irreversibly bind
to hemoglobin when the levels in the blood are above the normal range.
Gestational
diabetes is diagnosed using the same tests as for the other types of
diabetes. However after six or more
weeks, mothers must be retested (OGTT) to determine whether they have diabetes,
impaired glucose tolerance (IGT) or normal glucose tolerance (17).
High
glucose levels in the blood causes the glucose to form complexes with proteins,
thickening the blood and damaging the blood vessels. If diabetes is left untreated, blood vessel
damage in various organs can lead to renal failure (diabetic nephropathy),
vascular disease, loss of vision (diabetic retinopathy), numbness and pain in
the extremities (diabetic neuropathy), liver damage (non-alcoholic steatohepatitis), erectile dysfunction, poor wound healing
and heart failure (diabetic cardiomyopathy) (8).
Management and treatment
It is
most important to monitor blood glucose levels and maintain within the normal
range. Due to modern advancement in
medical devices, patients can now monitor their own sugar levels several times
a day using home kits produced by pharmaceutical companies. Patients have regular checkups with their
doctor or at a diabetic clinic to monitor their status. Routine assessments include the evaluation of
glucose home readings, glucose tests, HbA1c test, blood pressure and weight
checks, lipid profile tests, foot assessments and discussion of lifestyle
(exercise, alcohol, smoking etc).
The
first step treatment to diabetes is exercise, losing weight (in overweight and
obese patients), and dietary intervention (eg.
decreasing carbohydrate intake) (1).
This is useful for all diabetic patients. The second line of treatment
for diabetes is the administration of insulin via a syringe, a pump or a
pen. The insulin can be given once a day
(long acting) or several times a day (shorter acting). This is most effective in type 1 and some
cases of type 2 diabetes.
Oral antidiabetic drugs act to suppress glucagon action,
increase insulin secretion and action, and delay intestinal absorption of
glucose (19). These include biguanides, sulfonylureas and glitazones.
Metformin
belongs to the biguanide class of antidiabetic
drugs and is a common drug of choice for diabetic patients because of the few
side effects. It is a chemical
derivative of guanidine, the active ingredient in the french
lilac (Galega officinalis)
used to treat diabetes in the Middle Ages and works in two ways. Firstly it increases the activity of the
liver enzyme AMP activated protein kinase
(AMPK). AMPK acts by increasing the
activity of the transcriptional repressor, small heterodimer
protein (SHP) which in turn downregulates the
expression of key liver enzymes involved in hepatic gluconeogenesis
(8), thereby decreasing the production of
glucose. It also increases binding of
insulin to the insulin receptor, thereby increasing the sensitivity of cells to
insulin and insulin action (8).
Rich man's disease
For
many years, diabetes has been viewed as a rich man's disease, a disease of
developed countries and over nourished peoples (3, 10). However in recent times, it can no longer be
described as such. Diabetes is now
global and the widespread presence can be attributed to urbanisation,
changing lifestyles and an increase in obesity and average body weight (4,5). In 2005, 80% of
all diabetes related deaths in the world were from developing countries
(4). This can be attributed to poor
education for patients and inadequate medical care.
In
the US, 16 million people suffer with diabetes mellitus, stretching
across different socioeconomic groups.
No longer is over nourishment the cause of diabetes but also a poor diet
that is imbalanced and rich in refined foods can cause the disease (7).
In
order to address whether diabetes is a rich man's disease, I have chosen to
define the 'rich man' in two ways: globally (developed versus developing
countries) and, socioeconomic status within a country.
Developed countries, developing
countries and diabetes
Globally,
the incidence of diabetes has increased (6, 8). WHO predicts that by 2025 about
350 million people, 75% of the whom will be living in developing countries, will
have diabetes. In the US alone, diabetes cost the country
approximately $98 million in 1997 (2).
The disease is not restricted to race or age. In the US, 20% of all diagnosed cases are in
the elderly (ages 65-74 years), 6% in Caucasians, 10% in Asian and African
Americans, 15% in Hispanics and 20-50% in Native Americans (2).
The increasing incidence of diabetes has been
attributed mainly to changes in lifestyle.
In developing countries, people are moving out of rural areas into
cities to find jobs and earn a better living (16). The change in location is accompanied by them
adopting a Western lifestyle: changing diets and physical activities. This is also true for migrants that come from
developing countries and settle in developed countries such as the US, Canada
and countries in Western Europe (15).
Globally,
people are spending more time sitting in front of computers and television
sets, and less time staying physically fit (8).
Diets have changed to include foods more rich in fats. Traditional home cooked meals which are
viewed in general to provide a balanced diet are now being rapidly replaced by
fast foods (9). A combination of these factors
leads to an unhealthy lifestyle.
Then
there is what is described as the metabolic syndrome which includes
hypertension, increased levels of triglycerides in the body, low levels of good
cholesterol (HDL) and insulin resistance (8).
This predisposes a person to diabetes.
A worldwide study was conducted in 1999 to
assess the global impact of diabetes over three time points: 1995, 2000 and 2025. It was noted that there was a high prevalence
of diabetes in developed countries compared to developing countries for all
three time points. However the
percentage increase in developing countries for 2025 was greater than in
developed countries. In general, a high
increase in prevalence of diabetes is expected from 1995 (4%) to 2025 (5.4%) (15). The
three top countries that will have the highest incidence of diabetes by 2025 are
India, China and the USA (Table 1) (4,15).
Table 1: List of countries with the highest numbers of
estimate cases of diabetes for 2000 and 2030 (Wild et al, 2004) (4)
|
Ranking |
2000 |
2030 |
|||
|
|
Country |
People with diabetes (million) |
Country |
People with diabetes (million) |
|
|
1 |
India |
3.7 |
India |
79.4 |
|
|
2 |
China |
20.8 |
China |
42.3 |
|
|
3 |
US |
17.7 |
US |
30.3 |
|
|
4 |
Indonesia |
8.4 |
Indonesia |
21.3 |
|
|
5 |
Japan |
6.8 |
Pakistan |
13.9 |
|
|
6 |
Pakistan |
5.2 |
Brazil |
11.3 |
|
|
7 |
Russian Federation |
4.6 |
Bangladesh |
11.1 |
|
|
8 |
Brazil |
4.6 |
Japan |
8.9 |
|
|
9 |
Italy |
4.3 |
Philippines |
7.8 |
|
|
10 |
Bangladesh |
3.2 |
Egypt |
6.7 |
|
The
high increase in diabetes is attributed to increasing obesity in the world's
population. In the US, obesity is said
to account for 2.2% of the increase in the incidence of diabetes. Obesity is not the sole contributor to this
increase. If rising education lowers the
prevalence of diabetes by 1.2% then it can be inferred that diminishing or lack
of education will contribute to the rise in the incidence of diabetes (14). Public health strategies to educate persons
will improve early detection rates, individual management of the disease and
reduce the progression and mortality rates of the disease.
Migration
to developed countries and urbanization will increase in the years to come. These are factors that may not be
changeable. However educating people on
healthy diets, the importance and benefits of physical activity and healthy
lifestyles will allow them to make informed choices in preventing the
progression from glucose intolerance to diabetes.
Socioeconomic status and diabetes
Socioeconomic
status (SES) is defined as a combined economic and sociological measure of a
person's education, income and occupation relative to other persons (19). SES affects various parts of our lives including
literacy, health, motivation and self-esteem.
The
incidence of diabetes is increasing among people of low socioeconomic
status. In most countries, the
prevalence of diabetes (3%) among persons of higher socioeconomic status is
lower than that among persons of lower socioeconomic status (5%) (18). In India, the incidence of diabetes has not
just increased among the rich, but also among peoples of low income. There is evidence to suggest that Asian
Indians are more resistant to actions of insulin than Caucasians, suggesting an
as yet unidentified genetic predisposition to diabetes (4). 11% of all diabetic cases are among people of
low income groups (6). Findings from
the study conducted between October 2002 and April 2003 in a rural a community in India, indicate
that poorer people had inadequate access to health education and health care
and thus their conditions deteriorated at stages when it could have been well
managed with proper health care (6). In
a study conducted in the US on the socioeconomic status of women with diabetes,
women with a household income of less than $25,000 were twice as likely to have
diabetes (11).
In
2000, a Canadian study of 140 neighbourhoods in the
Greater Toronto Region (GTA) was conducted to investigate links between
socioeconomic status (SES) and health.
Findings show that there was a strong correlation between lower
socioeconomic status (lower household incomes per annum, higher unemployment,
lower formal education) and high incidences of diabetes (12). Persons of lower SES had poor diets and
understandably so as healthy foods such as fresh fruits and vegetables are more
expensive than processed and less nutritious foods. They were also less physically active leading
to poor health and increased mortality from the disease. There was a 50% increase in the rate of
diabetes in low income neighbourhoods (12).
Another
study conducted in Middleborough and East Cleveland in the UK investigated the
prevalence of types 1 and 2 diabetes in deprived areas. Their findings show that socioeconomic status
is inversely related to prevalence of diabetes type 2 rather than type1
(13). The high incidence of type 2
diabetes among person of lower socioeconomic status is due to physical
inactivity, adult obesity and low birth weight, factors which are associated
with poverty in the UK (13).
In
countries where better health care is costly, persons of low socioeconomic
status do not have adequate health care and thus have poorer health. Persons of
higher socioeconomic standing have access to better health care and plans
thereby having better access to information on healthy lifestyles and diabetes
prevention. They also have better access
to treatment, preventing the progression and fatality of the disease.
People
generally feel safer in affluent neighbourhoods and
are more likely to take walks whereas in less affluent areas, the sense of
community may be weak and residents may not feel comfortable walking around the
neighbourhood.
Affluent neighbourhoods are also said to have
more park space than their less affluent counterparts.
Gyms
and social clubs that encourage physical activity will be frequented by persons
of a higher income as opposed to those with a lower income. These factors
contribute to the physical fitness of the people living in the areas.
The
'thrifty genotype hypothesis' suggests that fetal malnutrition leads to impaired development of the
pancreatic beta cell and insulin resistance thereby predisposing
the child to diabetes and the metabolic syndrome when they are exposed
to better nutrition later in life. Fetal
malnutrition can be seen in women of lower socioeconomic status regardless of
whether they are from developed or developing countries. A change in the socioeconomic status of the
parents or the offspring (in adult life) and/or migration will lead to a change
in lifestyle and therefore change the nutritional input. Epidemiological studies have proved the
validity of the 'thrift genotype hypothesis' (4, 16).
Dealing with the global diabetic
endemic
In
1985, 20 million were affected by diabetes.
The drastic increase in the incidence of diabetes between then, now and
the predicted values for 2025 cannot only be attributed to risk factors. Medical science is constantly advancing and the
methods of diabetes detection and rate of diagnosis have vastly improved since
1985. This means that more cases than
before are also detected because of more sensitive tests and the general
education of the public.
Attempts
to manage the disease by encouraging changes in lifestyle have had very modest
results. Educating the general public on
screening, prevention, management and treatment of diabetes will increase
awareness. Accessible diabetic clinics staffed with educated
personal such as nutritionists, health and exercise trainers and health
educators will ensure that individuals have access to health information and
care regardless of socioeconomic status (of individuals and countries).
At
present, developed countries have better access to home tests kits and
medicines (eg. Insulin, antidiabetic drugs, analgesics) than developing countries. The lack of adequate treatment in developing
countries due to costs will contribute to the increasing incidence. Cooperation between developed and developing countries
to supply the necessary medical equipment and supplies will be beneficial in
preventing the explosive increase that has been predicted for 2025.
Conclusion
It is
a known fact that the rate of diabetes in the world is rapidly rising both in
developed and developing countries. Many
of the cases that were previously undetected due to the limits of medical
technology are now being diagnosed with improving technology, adding to the
increasing incidence. More sensitive
methods of detection are a welcome factor as they allow for earlier
intervention of the disease and therefore a better prognosis.
Urbanization,
obesity among all social class, health care access and changing lifestyles that
include physical inactivity all contribute to the increasing rate of diabetes
in the world. The disease is no longer
restricted to the rich (develop countries and persons of higher SES).
Public
education, affordable access to health care and healthy lifestyles will
contribute to better management of diabetes.