Re: My published research on diabates
- From: ray <ray@xxxxxxxxxx>
- Date: Sat, 13 Oct 2007 09:24:19 -0600
On Sat, 13 Oct 2007 00:20:16 -0700, Earl Evleth wrote:
I have a PhD and this peer reviewed article appeared in the NE Journal
of Medicine in October 1996. Most of you I'm sure have no scientific
training like I do, however try to understand the article, it most
certainly will help you.
IMHO - you have an over inflated sense of your own importance. Many here
would have 'scientific training' whether it might be medical or not. For
example, I have advanced degrees in Mathematics and worked as a
mathematician and computer scientist for 30 years doing scientific
software support and development. Don't be such a snob.
Gestational diabetes typically resolves with delivery of the child,
however types 1 and 2 diabetes are chronic conditions.[1] All types
have been treatable since insulin became medically available in 1921.
Type 1 diabetes, in which insulin is not secreted by the pancreas, is
directly treatable only with injected or inhaled insulin, although
dietary and other lifestyle adjustments are part of management. Type 2
may be managed with a combination of dietary treatment, tablets and
injections and, frequently, insulin supplementation. While insulin was
originally produced from natural sources such as porcine pancreas,
most insulin used today is produced through genetic engineering,
either as a direct copy of human insulin, or human insulin with
modified molecules that provide different onset and duration of
action. Insulin can also be delivered continuously by a pump
surgically embedded under the skin.
Diabetes can cause many complications. Acute complications
(hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur
if the disease is not adequately controlled. Serious long-term
complications include cardiovascular disease (doubled risk), chronic
renal failure, retinal damage (which can lead to blindness), nerve
damage (of several kinds), and microvascular damage, which may cause
impotence and poor healing. Poor healing of wounds, particularly of
the feet, can lead to gangrene, which may require amputation. Adequate
treatment of diabetes, as well as increased emphasis on blood pressure
control and lifestyle factors (such as not smoking and keeping a
healthy body weight), may improve the risk profile of most
aforementioned complications. In the developed world, diabetes is the
most significant cause of adult blindness in the non-elderly, the
leading cause of non-traumatic amputation in adults, and diabetic
nephropathy is the main illness requiring renal dialysis.
Diabetes mellitus
The term diabetes, without qualification, usually refers to diabetes
mellitus, which is associated with excessive sweet urine, (known as
'glycosuria') but there are several rarer conditions also named
diabetes. The most common of these is diabetes insipidus in which the
urine is not sweet (insipidus meaning "without taste" in Latin); it
can be caused by either kidney (nephrogenic DI) or pituitary gland
(central DI) damage.
The principal two idiopathic forms of diabetes mellitus are known as
types 1 and 2. The term "type 1 diabetes" has universally replaced
several former terms, including childhood-onset diabetes, juvenile
diabetes, and insulin-dependent diabetes (IDDM). Likewise, the term
"type 2 diabetes" has replaced several former terms, including adult-
onset diabetes, obesity-related diabetes, and non-insulin-dependent
diabetes (NIDDM). Beyond these two types, there is no agreed-upon
standard nomenclature. Various sources have defined "type 3 diabetes"
as, among others, gestational diabetes,[4] insulin-resistant type 1
diabetes (or "double diabetes"), type 2 diabetes which has progressed
to require injected insulin, and latent autoimmune diabetes of adults
(or LADA or "type 1.5" diabetes[5]). There is also maturity onset
diabetes of the young (MODY) which is a single gene disorder with
strong family history that presents as type 2 diabetes before 30 years
of age.
[edit] Type 1 diabetes mellitus
Main article: Diabetes mellitus type 1
Type 1 diabetes mellitus is characterized by loss of the insulin-
producing beta cells of the islets of Langerhans in the pancreas,
leading to a deficiency of insulin. The main cause of this beta cell
loss is a T-cell mediated autoimmune attack.[3] There is no known
preventative measure that can be taken against type 1 diabetes, which
comprises up to 10% of diabetes mellitus cases in North America and
Europe (though this varies by geographical location). Most affected
people are otherwise healthy and of a healthy weight when onset
occurs. Sensitivity and responsiveness to insulin are usually normal,
especially in the early stages. Type 1 diabetes can affect children or
adults but was traditionally termed "juvenile diabetes" because it
represents a majority of cases of diabetes affecting children.
The principal treatment of type 1 diabetes, even from the earliest
stages, is replacement of insulin combined with careful monitoring of
blood glucose levels using blood testing monitors. Without insulin,
ketosis and diabetic ketoacidosis can develop and coma or death will
result. Emphasis is also placed on lifestyle adjustments (diet and
exercise) though these cannot reverse the loss. Apart from the common
subcutaneous injections, it is also possible to deliver insulin by a
pump, which allows continuous infusion of insulin 24 hours a day at
preset levels, and the ability to program doses (a bolus) of insulin
as needed at meal times. An inhaled form of insulin, Exubera, was
approved by the FDA in January 2006.[6]
Type 1 treatment must be continued indefinitely. Treatment does not
impair normal activities, if sufficient awareness, appropriate care,
and discipline in testing and medication is taken. The average glucose
level for the type 1 patient should be as close to normal (80–120 mg/
dl, 4–6 mmol/l) as possible. Some physicians suggest up to 140–150 mg/
dl (7-7.5 mmol/l) for those having trouble with lower values, such as
frequent hypoglycemic events. Values above 200 mg/dl (10 mmol/l) are
often accompanied by discomfort and frequent urination leading to
dehydration. Values above 300 mg/dl (15 mmol/l) usually require
immediate treatment and may lead to ketoacidosis. Low levels of blood
glucose, called hypoglycemia, may lead to seizures or episodes of
unconsciousness.
[edit] Type 2 diabetes mellitus
Main article: Diabetes mellitus type 2
Type 2 diabetes mellitus is due to insulin resistance or reduced
insulin sensitivity, combined with reduced insulin secretion. The
defective responsiveness of body tissues to insulin almost certainly
involves the insulin receptor in cell membranes. In the early stage
the predominant abnormality is reduced insulin sensitivity,
characterized by elevated levels of insulin in the blood. At this
stage hyperglycemia can be reversed by a variety of measures and
medications that improve insulin sensitivity or reduce glucose
production by the liver. As the disease progresses the impairment of
insulin secretion worsens, and therapeutic replacement of insulin
often becomes necessary.
There are numerous theories as to the exact cause and mechanism in
type 2 diabetes. Central obesity (fat concentrated around the waist in
relation to abdominal organs, but not subcutaneous fat) is known to
predispose individuals for insulin resistance. Abdominal fat is
especially active hormonally, secreting a group of hormones called
adipokines that may possibly impair glucose tolerance. Obesity is
found in approximately 55% of patients diagnosed with type 2 diabetes.
[7] Other factors include aging (about 20% of elderly patients in
North America have diabetes) and family history (type 2 is much more
common in those with close relatives who have had it). In the last
decade, type 2 diabetes has increasingly begun to affect children and
adolescents, likely in connection with the increased prevalence of
childhood obesity seen in recent decades in some places.[8]
Type 2 diabetes may go unnoticed for years because visible symptoms
are typically mild, non-existent or sporadic, and usually there are no
ketoacidotic episodes. However, severe long-term complications can
result from unnoticed type 2 diabetes, including renal failure due to
diabetic nephropathy, vascular disease (including coronary artery
disease), vision damage due to diabetic retinopathy, loss of sensation
or pain due to diabetes neuropathy, and liver damage from non-
alcoholic steatohepatitis.
Type 2 diabetes is usually first treated by increasing physical
activity, decreasing carbohydrate intake, and losing weight. These can
restore insulin sensitivity even when the weight loss is modest, for
example around 5 kg (10 to 15 lb), most especially when it is in
abdominal fat deposits. It is sometimes possible to achieve long-term,
satisfactory glucose control with these measures alone. However, the
underlying tendency to insulin resistance is not lost, and so
attention to diet, exercise, and weight loss must continue. The usual
next step, if necessary, is treatment with oral antidiabetic drugs.
Insulin production is initially only moderately impaired in type 2
diabetes, so oral medication (often used in various combinations) can
be used to improve insulin production (e.g., sulfonylureas), to
regulate inappropriate release of glucose by the liver and attenuate
insulin resistance to some extent (e.g., metformin), and to
substantially attenuate insulin resistance (e.g., thiazolidinediones).
According to one study, overweight patients treated with metformin
compared with diet alone, had relative risk reductions of 32% for any
diabetes endpoint, 42% for diabetes related death and 36% for all
cause mortality and stroke.[9] Oral medication may eventually fail due
to further impairment of beta cell insulin secretion. At this point,
insulin therapy is necessary to maintain normal or near normal glucose
levels.
[edit] Gestational diabetes
Main article: Gestational diabetes
Gestational diabetes mellitus (GDM) resembles type 2 diabetes in
several respects, involving a combination of inadequate insulin
secretion and responsiveness. It occurs in about 2%–5% of all
pregnancies and may improve or disappear after delivery. Gestational
diabetes is fully treatable but requires careful medical supervision
throughout the pregnancy. About 20%–50% of affected women develop type
2 diabetes later in life.
Even though it may be transient, untreated gestational diabetes can
damage the health of the fetus or mother. Risks to the baby include
macrosomia (high birth weight), congenital cardiac and central nervous
system anomalies, and skeletal muscle malformations. Increased fetal
insulin may inhibit fetal surfactant production and cause respiratory
distress syndrome. Hyperbilirubinemia may result from red blood cell
destruction. In severe cases, perinatal death may occur, most commonly
as a result of poor placental profusion due to vascular impairment.
Induction may be indicated with decreased placental function. A
cesarean section may be performed if there is marked fetal distress or
an increased risk of injury associated with macrosomia, such as
shoulder dystocia.
[edit] Other types
There are several rare causes of diabetes mellitus that do not fit
into type 1, type 2, or gestational diabetes; attempts to classify
them remain controversial. Genetic mutations (autosomal or
mitochondrial) can lead to defects in beta cell function. Abnormal
insulin action may also been genetically determined in some cases. Any
disease that causes extensive damage to the pancreas may lead to
diabetes (for example, chronic pancreatitis and cystic fibrosis).
Diseases associated with excessive secretion of insulin-antagonistic
hormones can cause diabetes (which is typically resolved once the
hormone excess is removed). Many drugs impair insulin secretion and
some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic
entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10
code E12), was deprecated by the World Health Organization when the
current taxonomy was introduced in 1999.[2]
[edit] Signs and symptoms
The classical triad of diabetes symptoms is polyuria, polydipsia and
polyphagia, which are, respectively, frequent urination; increased
thirst and consequent increased fluid intake; and increased appetite.
Symptoms may develop quite rapidly (weeks or months) in type 1
diabetes, particularly in children. However, in type 2 diabetes the
symptoms develop much more slowly and may be subtle or completely
absent. Type 1 diabetes may also cause weight loss (despite normal or
increased eating) and irreducible fatigue. These symptoms can also
manifest in type 2 diabetes in patients whose diabetes is poorly
controlled.
When the glucose concentration in the blood is raised beyond the renal
threshold, reabsorption of glucose in the proximal renal tubuli is
incomplete, and part of the glucose remains in the urine (glycosuria).
This increases the osmotic pressure of the urine and inhibits the
resorption of water by the kidney, resulting in increased urine
production (polyuria) and increased fluid loss. Lost blood volume will
be replaced osmotically from water held in body cells, causing
dehydration and increased thirst.
Prolonged high blood glucose causes glucose absorption, which leads to
changes in the shape of the lenses of the eyes, resulting in vision
changes. Blurred vision is a common complaint leading to a diabetes
diagnosis; type 1 should always be suspected in cases of rapid vision
change whereas type 2 is generally more gradual, but should still be
suspected.
Patients (usually with type 1 diabetes) may also present with diabetic
ketoacidosis (DKA), an extreme state of metabolic dysregulation
characterized by the smell of acetone on the patient's breath; a
rapid, deep breathing known as Kussmaul breathing; polyuria; nausea;
vomiting and abdominal pain; and any of many altered states of
consciousness or arousal (such as hostility and mania or, equally,
confusion and lethargy). In severe DKA, coma may follow, progressing
to death. Diabetic ketoacidosis is a medical emergency and requires
hospital admission.
A rarer but equally severe possibility is hyperosmolar nonketotic
state, which is more common in type 2 diabetes and is mainly the
result of dehydration due to loss of body water. Often, the patient
has been drinking extreme amounts of sugar-containing drinks, leading
to a vicious circle in regard to the water loss.
[edit] Genetics
Both type 1 and type 2 diabetes are at least partly inherited. Type 1
diabetes appears to be triggered by some (mainly viral) infections, or
in a less common group, by stress or environmental exposure (such as
exposure to certain chemicals or drugs). There is a genetic element in
individual susceptibility to some of these triggers which has been
traced to particular HLA genotypes (i.e., the genetic "self"
identifiers relied upon by the immune system). However, even in those
who have inherited the susceptibility, type 1 diabetes mellitus seems
to require an environmental trigger. A small proportion of people with
type 1 diabetes carry a mutated gene that causes maturity onset
diabetes of the young (MODY).
There is a stronger inheritance pattern for type 2 diabetes. Those
with first-degree relatives with type 2 have a much higher risk of
developing type 2, increasing with the number of those relatives.
Concordance among monozygotic twins is close to 100%, and about 25% of
those with the disease have a family history of diabetes. Candidate
genes include KCNJ11 (potassium inwardly rectifying channel, subfamily
J, member 11), which encodes the islet ATP-sensitive potassium channel
Kir6.2, and TCF7L2 (transcription factor 7–like 2), which regulates
proglucagon gene expression and thus the production of glucagon-like
peptide-1.[3] Moreover, obesity (which is an independent risk factor
for type 2 diabetes) is strongly inherited.[10]
Various hereditary conditions may feature diabetes, for example
myotonic dystrophy and Friedreich's ataxia. Wolfram's syndrome is an
autosomal recessive neurodegenerative disorder that first becomes
evident in childhood. It consists of diabetes insipidus, diabetes
mellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.[11]
[edit] Pathophysiology
Mechanism of insulin release in normal pancreatic beta cells. Insulin
production is more or less constant within the beta cells,
irrespective of blood glucose levels. It is stored within vacuoles
pending release, via exocytosis, which is triggered by increased blood
glucose levels.Insulin is the principal hormone that regulates uptake
of glucose from the blood into most cells (primarily muscle and fat
cells, but not central nervous system cells). Therefore deficiency of
insulin or the insensitivity of its receptors plays a central role in
all forms of diabetes mellitus.
Much of the carbohydrate in food is converted within a few hours to
the monosaccharide glucose, the principal carbohydrate found in blood
and used by the body as fuel. Some carbohydrates are not so converted.
Notable examples include fruit sugar (fructose), usable as cellular
fuel but it is not converted to glucose, and which therefore does not
participate in the insulin/glucose metabolic regulatory mechanism.
Additionally, the carbohydrate cellulose (though it is actually many
glucose molecules in long chains) is not converted to glucose, as
humans and many animals have no digestive pathway capable of breaking
up cellulose.
Insulin is released into the blood by beta cells (β-cells), found in
the Islets of Langerhans in the pancreas, in response to rising levels
of blood glucose after eating. Insulin is used by about two-thirds of
the body's cells to absorb glucose from the blood for use as fuel, for
conversion to other needed molecules, or for storage. Insulin is also
the principal control signal for conversion of glucose to glycogen for
internal storage in liver and muscle cells. Lowered glucose levels
result both in the reduced release of insulin from the beta cells and
in the reverse conversion of glycogen to glucose when glucose levels
fall. Glucose thus recovered by the liver re-enters the bloodstream;
muscle cells lack the necessary export mechanism.
Higher insulin levels increase many anabolic ("building up") processes
such as cell growth and duplication, protein synthesis, and fat
storage. Insulin (or its lack) is the principal signal in converting
many of the bidirectional processes of metabolism from a catabolic to
an anabolic direction, and vice versa. In particular, a low insulin
level is the trigger for entering or leaving ketosis (the fat burning
metabolic phase).
If the amount of insulin available is insufficient, if cells respond
poorly to the effects of insulin (insulin insensitivity or
resistance), or if the insulin itself is defective, then glucose will
not be absorbed properly by those body cells that require it or it
will be stored appropriately in the liver and muscles. The net effect
is persistent high levels of blood glucose, poor protein synthesis,
and other metabolic derangements, such as acidosis.
[edit] Diagnosis
The diagnosis of type 1 diabetes, and many cases of type 2, is usually
prompted by recent-onset symptoms of excessive urination (polyuria)
and excessive thirst (polydipsia), often accompanied by weight loss.
These symptoms typically worsen over days to weeks; about a quarter of
people with new type 1 diabetes have developed some degree of diabetic
ketoacidosis by the time the diabetes is recognized. The diagnosis of
other types of diabetes is usually made in other ways. These include
ordinary health screening; detection of hyperglycemia during other
medical investigations; and secondary symptoms such as vision changes
or unexplainable fatigue. Diabetes is often detected when a person
suffers a problem that is frequently caused by diabetes, such as a
heart attack, stroke, neuropathy, poor wound healing or a foot ulcer,
certain eye problems, certain fungal infections, or delivering a baby
with macrosomia or hypoglycemia.
Diabetes mellitus is characterized by recurrent or persistent
hyperglycemia, and is diagnosed by demonstrating any one of the
following:[2]
fasting plasma glucose level at or above 126 mg/dL (7.0 mmol/l).
plasma glucose at or above 200 mg/dL (11.1 mmol/l) two hours after a
75 g oral glucose load as in a glucose tolerance test.
random plasma glucose at or above 200 mg/dL (11.1 mmol/l).
A positive result, in the absence of clinical symptoms of diabetes,
should be confirmed by another of the above-listed methods on a
different day. Most physicians prefer to measure a fasting glucose
level because of the ease of measurement and the considerable time
commitment of formal glucose tolerance testing, which takes two hours
to complete. According to the current definition, two fasting glucose
measurements above 126 mg/dL (7.0 mmol/l) is considered diagnostic for
diabetes mellitus.
Patients with fasting glucose levels between 110 and 125 mg/dL (6.1
and 7.0 mmol/l) are considered to have impaired fasting glycemia.
Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/l two
hours after a 75 g oral glucose load are considered to have impaired
glucose tolerance. Of these two pre-diabetic states, the latter in
particular is a major risk factor for progression to full-blown
diabetes mellitus as well as cardiovascular disease.
While not used for diagnosis, an elevated level of glucose
irreversibly bound to hemoglobin (termed glycosylated hemoglobin or
HbA1c) of 6.0% or higher (the 2003 revised U.S. standard) is
considered abnormal by most labs; HbA1c is primarily used as a
treatment-tracking test reflecting average blood glucose levels over
the preceding 90 days (approximately). However, some physicians may
order this test at the time of diagnosis to track changes over time.
The current recommended goal for HbA1c in patients with diabetes is
<7.0%, which is considered good glycemic control, although some
guidelines are stricter (<6.5%). People with diabetes who have HbA1c
levels within this range have a significantly lower incidence of
complications from diabetes, including retinopathy and diabetic
nephropathy.[12][13]
[edit] Screening
Diabetes screening is recommended for many people at various stages of
life, and for those with any of several risk factors. The screening
test varies according to circumstances and local policy, and may be a
random blood glucose test, a fasting blood glucose test, a blood
glucose test two hours after 75 g of glucose, or an even more formal
glucose tolerance test. Many healthcare providers recommend universal
screening for adults at age 40 or 50, and often periodically
thereafter. Earlier screening is typically recommended for those with
risk factors such as obesity, family history of diabetes, high-risk
ethnicity (Mestizo/Hispanic, Native American, Afro-Caribbean, Pacific
Island, and South Asian ancestry)[14][15].
Many medical conditions are associated with diabetes and warrant
screening. A partial list includes: high blood pressure, elevated
cholesterol levels, coronary artery disease, past gestational
diabetes, polycystic ovary syndrome, chronic pancreatitis, fatty
liver, hemochromatosis, cystic fibrosis, several mitochondrial
neuropathies and myopathies, myotonic dystrophy, Friedreich's ataxia,
some of the inherited forms of neonatal hyperinsulinism. The risk of
diabetes is higher with chronic use of several medications, including
high-dose glucocorticoids, some chemotherapy agents (especially L-
asparaginase), as well as some of the antipsychotics and mood
stabilizers (especially phenothiazines and some atypical
antipsychotics).
[edit] Prevention
Type 1 diabetes risk is known to depend upon a genetic predisposition
based on HLA types (particularly types DR3 and DR4), an unknown
environmental trigger (suspected to an infection in most cases), and
an uncontrolled autoimmune response that attacks the insulin producing
beta cells.[16] Research from the 1980s suggested that breastfeeding
decreased the risk;[17] various other nutritional risk factors are
being studied, but no firm evidence has been found.[18]
Type 2 diabetes risk can be reduced in many cases by making changes in
diet and increasing physical activity.[19][20] The American Diabetes
Association (ADA) recommends maintaining a healthy weight, getting at
least 2½ hours of exercise per week (a brisk sustained walk appears
sufficient), having a modest fat intake, and eating a good amount of
fiber and whole grains. The ADA does not recommend alcohol consumption
as a preventative, but it is interesting to note that moderate alcohol
intake may reduce the risk (though heavy consumption clearly increases
damage to body systems significantly). There is inadequate evidence
that eating foods of low glycemic index is clinically helpful.[21]
Some studies have shown delayed progression to diabetes in predisposed
patients through prophylactic use of metformin,[20] rosiglitazone,[22]
or valsartan.[23] In patients on hydroxychloroquine for rheumatoid
arthritis, incidence of diabetes was reduced by 77%.[24] Breastfeeding
might also be correlated with the prevention of type 2 of the disease
in mothers.[25]
[edit] Treatment and management
Main article: Diabetes management
Diabetes mellitus is currently a chronic disease, without a cure, and
medical emphasis must necessarily be on managing/avoiding possible
short-term as well as long-term diabetes-related problems. There is an
exceptionally important role for patient education, dietetic support,
sensible exercise, self glucose monitoring, with the goal of keeping
both short-term blood glucose levels, and long term levels as well,
within acceptable bounds. Careful control is needed to reduce the risk
of long term complications. This can be achieved with combinations of
diet, exercise and weight loss (type 2), various oral diabetic drugs
(type 2 only), and insulin use (type 1 and increasingly for type 2 not
responding to oral medication). In addition, given the associated
higher risks of cardiovascular disease, lifestyle modifications should
be undertaken to control blood pressure[26] and cholesterol by
exercising more, smoking cessation, consuming an appropriate diet,
wearing diabetic socks, and if necessary, taking any of several drugs
to reduce pressure.
In countries using a general practitioner system, such as the United
Kingdom, care may take place mainly outside hospitals, with hospital-
based specialist care used only in case of complications, difficult
blood sugar control, or research projects. In other circumstances,
general practitioners and specialists share care of a patient in a
team approach. Optometrists, podiatrists/chiropodists, dietitians,
physiotherapists, clinical nurse specialists (eg, Certified Diabetes
Educators and DSNs (Diabetic Specialist Nurse)), or nurse
practitioners may jointly provide multidisciplinary expertise. In
countries where patients must provide their own health care, the
impact of out-of-pocket costs of diabetic care can be high. In
addition to the medications and supplies needed, patients are often
advised to receive regular consultation from a physician (eg, at least
every three months).
[edit] Curing type 1 diabetes
Main article: Cure for diabetes mellitus type 1
There is no practical cure now for type 1 diabetes. The fact that type
1 diabetes is due to the failure of one of the cell types of a single
organ with a relatively simple function (i.e. the failure of the
islets of Langerhans) has led to the study of several possible schemes
to cure this form diabetes mostly by replacing the pancreas or just
the beta cells.[27] Only those type 1 diabetics who have received a
kidney-pancreas transplant (when they have developed diabetic
nephropathy) and become insulin-independent may now be considered
"cured" from their diabetes. Still, they generally remain on long-term
immunosuppressive drugs and there is a possibility that the immune
system will mount a host versus graft response against the
transplanted organ.[27]
Transplants of exogenous beta cells have been performed experimentally
in both mice and humans, but this measure is not yet practical in
regular clinical practice. Thus far, like any such transplant, it has
provoked an immune reaction and long-term immunosuppressive drugs will
be needed to protect the transplanted tissue.[28] An alternative
technique has been proposed to place transplanted beta cells in a semi-
permeable container, isolating and protecting them from the immune
system. Stem cell research has also been suggested as a potential
avenue for a cure since it may permit regrowth of Islet cells which
are genetically part of the treated individual, thus perhaps
eliminating the need for immuno-suppressants.[27] A 2007 trial of 15
newly diagnosed patients with type 1 diabetes treated with stem cells
raised from their own bone marrow after immune suppression showed that
the majority did not require any insulin treatment for prolonged
periods of time.[29]
Microscopic or nanotechnological approaches are under investigation as
well, in one proposed case with implanted stores of insulin metered
out by a rapid response valve sensitive to blood glucose levels. At
least two approaches have been demonstrated in vitro. These are, in
some sense, closed-loop insulin pumps.
[edit] Curing type 2 diabetes
Type 2 diabetes can be cured by one type of gastric bypass surgery in
80-100% of severely obese patients. The effect is not due to weight
loss since it usually occurs within days of surgery, which is before
significant weight loss occurs. The pattern of secretion of
gastrointestinal hormones is changed by the bypass and removal of the
duodenum and proximal jejunum, which together form the upper
(proximal) part of the small intestine.[30] One hypothesis is that the
proximal small intestine is dysfunctional in type 2 diabetes; its
removal eliminates the source of an unknown hormone that contributes
to insulin resistance.[31] This surgery has been widely performed on
morbidly obese patients and has the benefit of reducing the death rate
from all causes by up to 40%.[32] A small number of normal to
moderately obese patients with type 2 diabetes have successfully
undergone similar operations.[33][34]
[edit] Prognosis
Patient education, understanding, and participation is vital since the
complications of diabetes are far less common and less severe in
people who have well-controlled blood sugar levels.[35][36] Wider
health issues accelerate the deleterious effects of diabetes. These
include smoking, elevated cholesterol levels, obesity, high blood
pressure, and lack of regular exercise. According to a study, women
with high blood pressure has three-fold risk of developing diabetes.
[37]
The way diabetes is managed changes with age. Insulin production
decreases due to age-related impairment of pancreatic beta cells.
Additionally, insulin resistance increases due to the loss of lean
tissue and the accumulation of fat, particularly intra-abdominal fat,
and the decreased tissue sensitivity to insulin. Glucose tolerance
progressively declines with age, leading to a high prevalence of type
2 diabetes and postchallenge hyperglycemia in the older population.
[38] Age-related glucose intolerance in humans is often accompanied by
insulin resistance, but circulating insulin levels are similar to
those of younger people. [39] Treatment goals for older patients with
diabetes vary with the individual, and take into account health
status, as well as life expectancy, level of dependence, and
willingness to adhere to a treatment regimen.[40]
[edit] Acute complications
Main articles: Diabetic ketoacidosis , Nonketotic hyperosmolar coma ,
Hypoglycemia , and Diabetic coma
Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is an acute and dangerous complication
that is always a medical emergency. Lack of insulin causes the liver
to turn fat into ketone bodies, a fuel mainly used by the brain.
Elevated levels of ketone bodies in the blood decrease the blood's pH,
leading to most of the symptoms of DKA. On presentation at hospital,
the patient in DKA is typically dehydrated and is breathing rapidly
and deeply. Abdominal pain is common and may be severe. The level of
consciousness is typically normal until late in the process, when
lethargy may progress to coma. Ketoacidosis can become severe enough
to cause hypotension, shock, and death. Prompt proper treatment
usually results in full recovery, though death can result from
inadequate or delayed treatment, or from complications. Ketoacidosis
is much more common in type 1 diabetes than type 2.
Nonketotic hyperosmolar coma
The hyperosmolar nonketotic state (HNS) is an acute complication with
many symptoms in common with DKA, but an entirely different cause and
different treatment. In a person with very high blood glucose levels
(usually considered to be above 300 mg/dl (16 mmol/l)), water is drawn
out of cells into the blood by osmosis and the kidneys dump glucose
into the urine. This results in loss of water and an increase in blood
osmolality. If fluid is not replaced (by mouth or intravenously), the
osmotic effect of high glucose levels combined with the loss of water
will eventually lead to dehydration. The body's cells become
progressively dehydrated as water is taken from them and excreted.
Electrolyte imbalances are also common and dangerous. As with DKA,
urgent medical treatment is necessary, especially volume replacement.
Lethargy may ultimately progress to a coma, which is more common in
type 2 diabetes than type 1.
Hypoglycemia
Hypoglycemia, or abnormally low blood glucose, is a complication of
several diabetes treatments. It may develop if the glucose intake does
not cover the treatment. The patient may become agitated, sweaty, and
have many symptoms of sympathetic activation of the autonomic nervous
system resulting in feelings similar to dread and immobilized panic.
Consciousness can be altered or even lost in extreme cases, leading to
coma, seizures, or even brain damage and death. In patients with
diabetes, this can be caused by several factors, such as too much or
incorrectly timed insulin, too much or incorrectly timed exercise
(exercise decreases insulin requirements) or not enough food
(specifically glucose-producing carbohydrates). In most cases,
hypoglycemia is treated with sugary drinks or food. In severe cases,
an injection of glucagon (a hormone with the opposite effects of
insulin) or an intravenous infusion of glucose is used for treatment,
but usually only if the person is unconscious. In hospital,
intravenous dextrose is often used.
[edit] Chronic complications
Vascular disease
Chronic elevation of blood glucose level leads to damage of blood
vessels (angiopathy). The endothelial cells lining the blood vessels
take in more glucose than normal, since they don't depend on insulin.
They then form more surface glycoproteins than normal, and cause the
basement membrane to grow thicker and weaker. In diabetes, the
resulting problems are grouped under "microvascular disease" (due to
damage to small blood vessels) and "macrovascular disease" (due to
damage to the arteries).
Image of fundus showing scatter laser surgery for diabetic
retinopathyThe damage to small blood vessels leads to a
microangiopathy, which can cause one or more of the following:
Diabetic retinopathy, growth of friable and poor-quality new blood
vessels in the retina as well as macular edema (swelling of the
macula), which can lead to severe vision loss or blindness. Retinal
damage (from microangiopathy) makes it the most common cause of
blindness among non-elderly adults in the US.
Diabetic neuropathy, abnormal and decreased sensation, usually in a
'glove and stocking' distribution starting with the feet but
potentially in other nerves, later often fingers and hands. When
combined with damaged blood vessels this can lead to diabetic foot
(see below). Other forms of diabetic neuropathy may present as
mononeuritis or autonomic neuropathy. Diabetic amyotrophy is muscle
weakness due to neuropathy.
Diabetic nephropathy, damage to the kidney which can lead to chronic
renal failure, eventually requiring dialysis. Diabetes mellitus is the
most common cause of adult kidney failure worldwide in the developed
world.
Macrovascular disease leads to cardiovascular disease, to which
accelerated atherosclerosis is a contributor:
Coronary artery disease, leading to angina or myocardial infarction
("heart attack")
Stroke (mainly the ischemic type)
Peripheral vascular disease, which contributes to intermittent
claudication (exertion-related leg and foot pain) as well as diabetic
foot.
Diabetic myonecrosis ('muscle wasting')
Diabetic foot, often due to a combination of neuropathy and arterial
disease, may cause skin ulcer and infection and, in serious cases,
necrosis and gangrene. It is the most common cause of adult
amputation, usually of toes and or feet, in the developed world.
Carotid artery stenosis does not occur more often in diabetes, and
there appears to be a lower prevalence of abdominal aortic aneurysm.
However, diabetes does cause higher morbidity, mortality and operative
risks with these conditions.[41]
[edit] Epidemiology
In 2006, according to the World Health Organization, at least 171
million people worldwide suffer from diabetes. Its incidence is
increasing rapidly, and it is estimated that by the year 2030, this
number will double. Diabetes mellitus occurs throughout the world, but
is more common (especially type 2) in the more developed countries.
The greatest increase in prevalence is, however, expected to occur in
Asia and Africa, where most patients will likely be found by 2030. The
increase in incidence of diabetes in developing countries follows the
trend of urbanization and lifestyle changes, perhaps most importantly
a "Western-style" diet. This has suggested an environmental (i.e.,
dietary) effect, but there is little understanding of the mechanism(s)
at present, though there is much speculation, some of it most
compellingly presented.
Diabetes is in the top 10, and perhaps the top 5, of the most
significant diseases in the developed world, and is gaining in
significance there and elsewhere (see big killers).
For at least 20 years, diabetes rates in North America have been
increasing substantially. In 2005 there are about 20.8 million people
with diabetes in the United States alone. According to the American
Diabetes Association, there are about 6.2 million people undiagnosed
and about 41 million people that would be considered prediabetic.[42]
However, the criteria for diagnosing diabetes in the USA means that it
is more readily diagnosed than in some other countries. The Centers
for Disease Control has termed the change an epidemic. The National
Diabetes Information Clearinghouse estimates that diabetes costs $132
billion in the United States alone every year. About 5%–10% of
diabetes cases in North America are type 1, with the rest being type
2. The fraction of type 1 in other parts of the world differs; this is
likely due to both differences in the rate of type 1 and differences
in the rate of other types, most prominently type 2. Most of this
difference is not currently understood. The American Diabetes
Association point out the 2003 assessment of the National Center for
Chronic Disease Prevention and Health Promotion (Centers for Disease
Control and Prevention) that 1 in 3 Americans born after 2000 will
develop diabetes in their lifetime.[43][42]
According to the American Diabetes Association, approximately 18.3%
(8.6 million) of Americans age 60 and older have diabetes. [44]
Diabetes mellitus prevalence increases with age, and the numbers of
older persons with diabetes are expected to grow as the elderly
population increases in number. The National Health and Nutrition
Examination Survey (NHANES III) demonstrated that, in the population
over 65 years old, 18% to 20% have diabetes, with 40% having either
diabetes or its precursor form of impaired glucose tolerance.[38]
[edit] History
The term diabetes (Greek: διαβήτης) was coined by Aretaeus of
Cappadocia. It is derived from the Greek word διαβαίνειν, diabaínein
that literally means "passing through," or "siphon", a reference to
one of diabetes' major symptoms—excessive urine production. In 1675,
Thomas Willis added the word mellitus, from the Latin meaning "honey",
a reference to the sweet taste of the urine. This sweet taste had been
noticed in urine by the ancient Greeks, Chinese, Egyptians, and
Indians. In 1776, Matthew Dobson confirmed that the sweet taste was
because of an excess of a kind of sugar in the urine and blood of
people with diabetes.[45]
The ancient Indians tested for diabetes by observing whether ants were
attracted to a person's urine, and called the ailment "sweet urine
disease" (Madhumeha). The Korean, Chinese, and Japanese words for
diabetes are based on the same ideographs (糖尿病) which mean "sugar
urine disease".
Although diabetes has been recognized since antiquity, and treatments
of various efficacy have been known in various regions since the
Middle Ages, and in legend for much longer, pathogenesis of diabetes
has only been understood experimentally since about 1900.[46] The
discovery of a role for the pancreas in diabetes is generally ascribed
to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs
whose pancreas was removed developed all the signs and symptoms of
diabetes and died shortly afterwards.[47] In 1910, Sir Edward Albert
Sharpey-Schafer suggested that people with diabetes were deficient in
a single chemical that was normally produced by the pancreas—he
proposed calling this substance insulin, from the Latin insula,
meaning island, in reference to the insulin-producing islets of
Langerhans in the pancreas.[46]
The endocrine role of the pancreas in metabolism, and indeed the
existence of insulin, was not further clarified until 1921, when Sir
Frederick Grant Banting and Charles Herbert Best repeated the work of
Von Mering and Minkowski, and went further to demonstrate they could
reverse induced diabetes in dogs by giving them an extract from the
pancreatic islets of Langerhans of healthy dogs.[48] Banting, Best,
and colleagues (especially the chemist Collip) went on to purify the
hormone insulin from bovine pancreases at the University of Toronto.
This led to the availability of an effective treatment—insulin
injections—and the first patient was treated in 1922. For this,
Banting and laboratory director MacLeod received the Nobel Prize in
Physiology or Medicine in 1923; both shared their Prize money with
others in the team who were not recognized, in particular Best and
Collip. Banting and Best made the patent available without charge and
did not attempt to control commercial production. Insulin production
and therapy rapidly spread around the world, largely as a result of
this decision.
The distinction between what is now known as type 1 diabetes and type
2 diabetes was first clearly made by Sir Harold Percival (Harry)
Himsworth, and published in January 1936.[49]
Despite the availability of treatment, diabetes has remained a major
cause of death. For instance, statistics reveal that the cause-
specific mortality rate during 1927 amounted to about 47.7 per 100,000
population in Malta.[50]
Other landmark discoveries include:[46]
identification of the first of the sulfonylureas in 1942
reintroduction of the use of biguanides for Type 2 diabetes in the
late 1950s.
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