Transcript Diabetes Mellitus

Epidemiology
 The worldwide prevalence of diabetes mellitus (DM) has risen
dramatically over the past two decades, from an estimated 30 million
cases in 1985 to 177 million in 2000.
 Based on current trends, >360 million individuals will have diabetes by
the year 2030.
 Although the prevalence of both type 1 and type 2 DM is increasing
worldwide, the prevalence of type 2 DM is rising much more rapidly
because of increasing obesity and reduced activity levels as
countries become more industrialized. This is true in most countries,
and 6 of the top 10 countries with the highest rates are in Asia.
 In the United States, the Centers for Disease Control and Prevention
(CDC) estimated that 20.8 million persons, or 7% of the population,
had diabetes in 2005 (~30% of individuals with diabetes were
undiagnosed).1
Epidemiology
 Approximately 1.5 million individuals (>20 years) were
newly diagnosed with diabetes in 2005. DM increases
with aging. In 2005, the prevalence of DM in the United
States was estimated to be 0.22% in those <20 years and
9.6% in those >20 years. In individuals >60 years, the
prevalence of DM was 20.9%.
 The prevalence is similar in men and women throughout
most age ranges (10.5% and 8.8% in individuals >20 years)
but is slightly greater in men >60 years. Worldwide
estimates project that in 2030 the greatest number of
individuals with diabetes will be 45–64 years of age. 1
Epidemiology
 There is considerable geographic variation in the incidence of
both type 1 and type 2 DM. Scandinavia has the highest
incidence of type 1 DM (e.g., in Finland, the incidence is
35/100,000 per year). The Pacific Rim has a much lower rate (in
Japan and China, the incidence is 1–3/100,000 per year) of
type 1 DM; Northern Europe and the United States have an
intermediate rate (8–17/100,000 per year).
 Much of the increased risk of type 1 DM is believed to reflect
the frequency of high-risk HLA alleles among ethnic groups in
different geographic locations. The prevalence of type 2 DM
and its harbinger, impaired glucose tolerance (IGT) is highest in
certain Pacific islands, intermediate in countries such as India
and the United States, and relatively low in Russia. This
variability is likely due to1 genetic, behavioral, and
environmental factors.
Epidemiology
Epidemiology
 DM prevalence also varies among different ethnic populations within
a given country. In 2005, the CDC estimated that the prevalence of
DM in the United States (age > 20 years) was:
 13.3% in African Americans, 9.5% in Latinos
 15.1% in Native Americans (American Indians and Alaska natives)
 8.7% in non-Hispanic whites
 Individuals belonging to Asian-American or Pacific-Islander ethnic
groups in Hawaii are twice as likely to have diabetes compared to
non-Hispanic whites. The onset of type 2 DM occurs, on average,
at an earlier age in ethnic groups other than non-Hispanic whites.
 Diabetes is a major cause of mortality, but several studies indicate
that diabetes is likely underreported as a cause of death.
 In the United States, diabetes was listed as the sixth-leading cause of
death in 2002; a recent estimate suggested that diabetes was the
fifth leading cause of death worldwide and was responsible
for almost
1
3 million deaths annually (1.7–5.2% of deaths worldwide).
Types of Diabetes
 Currently, DM is classified by the pathogenesis that leads to
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hyperglycemia.
Pre-diabetes is characterized by:
Plasma glucose levels elevated (2-hour postprandial >140 mg/dL),
but not diagnostic of DM
Type 1 Diabetes is characterized by:
Complete or near-total insulin deficiency
Type 2 Diabetes is characterized by:
Variable degrees of insulin resistance, impaired insulin secretion,
and increased glucose production
Gestational Diabetes is characterized by:
Development during pregnancy
Insulin resistance related to the metabolic changes of late
pregnancy
Increased insulin requirements that may lead to IGT
Reversion to normal glucose tolerance post-partum for most
women, but with a substantial risk (30–60%) for development of DM
later in life
Anatomy and Physiology
 Diabetes (DM) is a disease of the endocrine system that alters the
metabolism of all of the energy nutrients in the body and whose
sequelae impacts most organ systems in the body.
 The pancreas is an organ that has both endocrine and exocrine
functions. We will concern ourselves here with the endocrine function
of the pancreas.
 The videos should have given you an idea of how the absolute insulin
deficiency of type one DM and the insulin resistance of type two DM
affects the level of serum glucose in the body. We will now discuss
how this elevation in serum glucose impacts the various organ
systems of the body.
 The chronic complications of DM are responsible for the majority of
morbidity and mortality associated with the disease.
Chronic Complications
 Two types of complications:
1. Vascular
2. Nonvascular
 Subdivisions of the two types of complications
1. Vascular
a. Microvascular (retinopathy, neuropathy,
nephropathy)
b. Macrovascular [coronary vascular
disease (CAD), peripheral vascular
disease (PVD), cerebrovascular disease]
Chronic Complications
2. Nonvascular
a. Gastroparesis
b. Infections
c. Skin changes
d. Possible hearing loss
 The risk of chronic complications increases as a
function of the duration of hyperglycemia; they
usually become apparent in the second decade of
hyperglycemia. Since type 2 DM often has a long
asymptomatic period of hyperglycemia, many
individuals with type 2 DM have complications at
the time of diagnosis.
Chronic Complications
 Before we consider each of these complications
in detail, let’s explore the underlying reasons for
these complications. In other words, what is it
about hyperglycemia that causes these
complications?
 In order to answer this question, we need to go
back and refresh our memories about the
anatomy of capillary walls.
 In particular, let us consider the structure and
function of the basement membrane of the
blood vessels and nerves.
Anatomy and Physiology of Chronic
Complications
Anatomy and Physiology of Chronic
Complications
Anatomy and Physiology of Chronic
Complications
Chronic Complications
So, in order to answer our
earlier question regarding
why hyperglycemia
causes vascular and nonvascular complications:
Sustained hyperglycemia
creates an imbalance of
substances used for
making the extracellular
matrix. Enzyme systems
normally convert glucose
to other sugars, such as
sorbitol and fructose to
decrease serum glucose.
Sorbitol, fructose, and
glucose accumulate in
the basement membrane
of the cell and between
the cells, causing
intracellular edema and
affecting function.
This “clogging up”
of the basement
membrane by
sugars, restricts the
free flow of
oxygen, nutrients,
and wastes across
the cell membrane
and alters the
structure of the
membranes
themselves.
Remember:
Structure equals
function!
Cells are
impeded in
ridding
themselves of
their waste
material and in
taking up
oxygen and
nutrients—
therefore, cells
malfunction
and die.
Chronic Complications
Vascular
MICROVASCULAR: Retinopathy
• DM is the leading cause of blindness between the ages of 20 and 74
in the United States, and individuals with DM are 25 times more likely
to become legally blind than individuals without D.
• Blindness is primarily the result of progressive diabetic retinopathy and
clinically significant macular edema.
• Diabetic retinopathy is classified into two stages: nonproliferative and
proliferative.
• Nonproliferative diabetic retinopathy usually appears late in the first
decade or early in the second decade of the disease and is marked
by retinal vascular microaneurysms, blot hemorrhages, and cotton
wool spots. The pathophysiologic mechanisms invoked in
nonproliferative retinopathy include loss of retinal pericytes, increased
retinal vascular permeability, alterations in retinal blood flow, and
abnormal retinal microvasculature, all of which lead to retinal
ischemia. Remember the basement membrane??
Chronic Complications
Vascular
MICROVASCULAR: Retinopathy
 The appearance of neovascularization in response
to retinal hypoxia is the hallmark of proliferative
diabetic retinopathy. These newly formed vessels
appear near the optic nerve and/or macula and
rupture easily, leading to vitreous hemorrhage,
fibrosis, and ultimately retinal detachment. Not all
individuals with nonproliferative retinopathy develop
proliferative retinopathy, but the more severe the
nonproliferative disease, the greater the chance of
evolution to proliferative retinopathy within 5 years.
Chronic Complications Vascular
Diabetic retinopathy
results in scattered
hemorrhages, yellow
exudates, and
neovascularization.
This patient has
neovascular vessels
proliferating from the
optic disc, requiring
urgent pan retinal
laser
photocoagulation.
Chronic Complications
Vascular
MICROVASCULAR: Retinopathy: TREATMENT
 The most effective therapy for diabetic retinopathy is prevention.
 Intensive glycemic and blood pressure control will delay the development or
slow the progression of retinopathy in individuals with either type 1 or type 2
DM.
 Individuals with known retinopathy are candidates for prophylactic
photocoagulation when initiating intensive therapy.
 Once advanced retinopathy is present, improved glycemic control imparts
less benefit, though adequate ophthalmologic care can prevent most
blindness.
 Regular, comprehensive eye examinations are essential for all individuals with
DM.
 Most diabetic eye disease can be successfully treated if detected early.
 Routine, nondilated eye examinations by the primary care provider or
diabetes specialist are inadequate to detect diabetic eye disease, which
requires an ophthalmologist for optimal care of these disorders.
 Laser photocoagulation is very successful in preserving vision. Proliferative
retinopathy is usually treated with panretinal laser photocoagulation, whereas
macular edema is treated with focal laser photocoagulation.
Chronic Complications
Neurological
MICROVASCULAR: Neuropathy
 Diabetic neuropathy occurs in ~50% of individuals with long-standing
type 1 and type 2 DM. As with other complications of DM, the
development of neuropathy correlates with the duration of diabetes
and glycemic control.
 Additional risk factors are BMI (the greater the BMI, the greater the risk
of neuropathy) and smoking.
 The presence of cardiovascular disease, elevated triglycerides, and
hypertension is also associated with diabetic peripheral neuropathy.
 Both myelinated and unmyelinated nerve fibers are lost.
 The American Diabetic Association (ADA) recommends screening for
distal symmetric neuropathy beginning with the initial diagnosis of
diabetes and screening for autonomic neuropathy 5 years after
diagnosis of type 1 DM and at the time of diagnosis of type 2 DM. All
individuals with diabetes should then be screened annually for both
forms of neuropathy.
Chronic Complications
Neurological
MICROVASCULAR: Neuropathy
 The most common form of diabetic neuropathy is distal symmetric
polyneuropathy.
 It most frequently presents with distal sensory loss, but up to 50% of
patients do not have symptoms of neuropathy. Hyperesthesia,
paresthesia, and dysesthesia also may occur.
 Symptoms may include a sensation of numbness, tingling, sharpness,
or burning that begins in the feet and spreads proximally.
 Neuropathic pain typically involving the lower extremities, is usually
present at rest, and worsens at night.
 Both an acute (lasting <12 months) and a chronic form of painful
diabetic neuropathy have been described.
 As diabetic neuropathy progresses, the pain subsides and eventually
disappears, but a sensory deficit in the lower extremities persists.
 Physical examination reveals sensory loss, loss of ankle reflexes, and
abnormal position sense.
Work in Progress
 New slides will appear here.