Diabetes mellitus
Dr. Rajaa Ali Hussein
College of pharmacy-Third stage
[ 20-12-2010]
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Introduction
Diabetes mellitus is the most common endocrine disorder.
Approximately 800,000 new cases of diabetes are diagnosed each year.
The prevalence of diabetes is 8.2% among all men and women in the
United States. The frequency of the disease increases to 18.4% in
individuals 65 years of age or older. Diabetes is a disease of the
endocrine pancreas . Some risk factors for diabetes mellitus are presented
in Table 19.1.
Endocrine pancreas
Throughout the pancreas there are endocrine cells found in scattered
clusters called islets of Langerhans . These endocrine cells can be
classified into three distinct types: Cells that produce the hormone
glucagon,
Cells that produce insulin and Cells that produce
somatostatin (see Table 19.2). The major regulator of insulin and
glucagon release from the pancreas is the blood glucose level. An
increase in blood glucose (as occurs after a meal) will stimulate the
release of insulin and inhibit the release of glucagon. Conversely,
decreases in blood glucose (during fasting, for example) will stimulate
the release of glucagon and inhibit the release of insulin. When released,
the main effect of insulin is to lower blood glucose levels by enhancing
the utilization and uptake of insulin. Glucagon directly counters the
effects of insulin by decreasing glucose utilization and uptake as well as
by stimulating the formation of new glucose from glycogen and amino
acids. The major target tissues for insulin and glucagon are liver, skeletal
muscle and fat.
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Types of diabetes mellitus
Type I diabetes (insulin-dependent diabetes)
• Cause appears to be a progressive autoimmune destruction of the
Pancreatic cells.
• Most instances of autoimmune pancreatic destruction are idiopathic, but
some may occur following viral infections.
• Little or no insulin secretion occurs.
Manifestations
• Hyperglycemia
• Weight loss
• The three “polys” — polydypsia (increased thirst), polyphagia
(increased appetite), polyuria (increased urine output)
• Weakness and fatigue due to poor energy utilization and skeletal muscle
catabolism
• Diabetic ketoacidosis — Accumulation of acidic ketone bodies in the
blood due to a lack of insulin-stimulated fatty acid utilization (see Tables
19.3 and 19.4).
•Hyperglycemic hyperosmolar syndrome(see Table 19.5).
Why do the three “polys” occur?
• Polyuria — Excess blood glucose filtered by the kidneys cannot be
reabsorbed and is eliminated at the expense of water.
• Polydyspsia — Excessive thirst caused by the osmotic diuresis of
glucose and subsequent tissue dehydration. The thirst response is
mediated by the hypothalamus.
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• Polyphagia — Poor utilization of carbohydrates (due to the lack of
insulin) results in depletion of stored fats, proteins and carbohydrates
Treatment
• Insulin replacement therapy (see Table 19.6)
• Dietary management
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Type II diabetes mellitus (non-insulin-dependent diabetes)
• Greater prevalence than type I diabetes.
• The primary manifestation is “insulin resistance,” which is a lack of
responsiveness by tissues and the pancreas itself to insulin. The exact
etiology of the insulin resistance is unknown but may be linked to
abnormalities of insulin receptors, intracellular signaling pathways or
glucose transporters.
• Insulin resistance may be related to increased levels of free fatty acids
(FFA) that stimulate insulin secretions and inhibit glucose uptake by
tissues (Figure 19.1). FFAs are elevated in obese individuals with a
predisposition to type II diabetes.
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• Obesity appears to be an important contributing factor to development
of type II diabetes.
Tissues (liver, fat and muscle) in obese individuals have an altered
responsiveness to the effects of insulin.
• A strong genetic component is also present.
• Insulin secretion may be normal or even elevated at the time of
diagnosis.
• The continued overproduction of insulin by the cells can eventually
lead to -cell “burnout” and destruction.
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'''Manifestations
Manifestations of type II diabetes may include many of those seen in type
I diabetes including polyuria, polydypsia, polyphagia, fatigue and
weakness.
Other manifestations of type II diabetes tend to be more generalized:
• Hyperinsulinemia
• Visual changes
• Parasthesias
(abnormal sensations such as tingling or burning, often occur in the
extremities)
• Recurrent infections
• Ketoacidosis is rare with type II diabetes
Treatment
• Weight loss has been reported to improve insulin sensitivity in obese
individuals with type II diabetes.
• Exercise may enhance glucose utilization and improve glucose control
in patients with type II diabetes, thus reducing the risk of diabetic
complications.
• Dietary management.
• Oral hypoglycemic drugs (see Table 19.7).
• Insulin-replacement may be necessary during later stages of the disease
When cells are destroyed in order to maintain normal metabolic
function (see Table 19.6).
Long-term complications of diabetes mellitus
There are a number of long-term complications of diabetes mellitus that
contribute significantly to the mortality and morbidity that is seen with
this disease. The etiology of the complications is likely multifactorial and
involves tissue injury related to chronically elevated blood glucose levels.
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Some possible causes of tissue injury in chronic diabetes mellitus are
listed in Table 19.8. The occurrence of these long-term complications can
be greatly reduced by proper management of blood glucose levels.
Chronic diabetes mellitus can lead to injury in a number of different
target organs including the kidney, eye, blood vessels and nervous
system.
1. Diabetic neuropathy
• Most common cause of neuropathy in the United States.
• Abnormality of nerve conduction and function.
• Often affects peripheral nerves.
• Can involve sensory or motor neurons.
• May manifest as numbness, pain or sensory/motor impairment.
• Often progressive and irreversible.
• Although the exact cause is unknown, the neuropathy may be related to
ischemia or altered nerve cell metabolism.
2. Diabetic nephropathy
• Diabetes is the leading cause of end-stage renal disease in the United
States.
• Glomerular injury is the key feature of diabetic nephropathy. The
glomerular injury is characterized by thickening of the glomerular
basement membrane and glomerulosclerosis.
• Although the exact etiology is unclear, trapping of glycosylated proteins
in the glomeruli appears to be a key contributing factor.
• The appearance of protein (albumin) in the urine is an early indicator of
altered glomerular permeability.
• Renal function may continue to deteriorate as glomerular filtration
decreases. Signs and symptoms of renal insufficiency will appear as renal
function continues to decline.
3. Vascular disease
• Chronic diabetes mellitus is associated with significant increases in the
incidence of coronary artery disease, cerebrovascular disease and
peripheral vascular disease.
• May be due to a number of factors including elevated serum lipid levels,
vascular injury, and enhanced atherogenesis (formation of atherosclerotic
lesions).
• Coronary artery disease and stroke are significant sources of mortality
and morbidity in patients with diabetes. Peripheral vascular disease can
lead to gangrene and amputations (particularly of the toes and feet) in
people suffering from diabetes.
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4. Impaired healing and increased infections risk
• As a result of peripheral vascular disease, injuries in patients with
diabetes do not heal properly. Poor blood flow limits the delivery of
leukocytes and oxygen to the injured area while impairing removal of
debris and infectious organisms.
• The high glucose levels serve as a nutrient to support the growth of
microorganisms.
• Patients with diabetes might also be more susceptible to physical
injuries as a result of impaired vision and sensory perception.
5. Diabetic retinopathy
• Diabetes mellitus is the leading cause of acquired blindness in the
United States.
• The most serious consequence of long-term diabetes in terms of the eye
is retinal damage. The retina is a highly metabolic tissue that is especially
vulnerable to the effects of chronic hypoxia and diabetes. Hemorrhage of
eye capillaries and chronic inflammation is common and can lead to
increases in intraocular pressure that scar the retina and impair vision.
This phenomenon is usually progressive and can lead to blindness.
• Diabetes is also associated with an increased incidence of glaucoma
and cataract formation.
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Gestational diabetes
• Glucose intolerance in about 1 to 6% of pregnancies.
• May present with variable severity.
• Most commonly seen during the third trimester of pregnancy.
• Resolves itself in most patients after birth but a certain percentage (50 to
60%) will go on to develop diabetes mellitus in the years following the
pregnancy.
• May be associated with an increased risk of fetal abnormalities.
• Currently recommended that all pregnant women be screened for the
presence of gestational diabetes.
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