Integrating Seminar 3 - Diabetes Mellitus
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What is diabetes mellitus?
A group of chronic metabolic diseases
characterized by high blood sugar (glucose)
levels that result from defects in insulin
secretion, or action, or both.
Normally, blood glucose levels are tightly
controlled by insulin, an anabolic hormone
produced by the beta cells of the Islets of
Langerhans of the pancreas.
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mg/dl or mmol/l ?
There are two main methods of describing
concentrations: by weight, and by molecular count.
Weights are in grams, molecular counts in moles.
mg/dl (milligrams/deciliter) is the traditional unit formeasuring bG (blood glucose). All scientific journals are
moving quickly toward using mmol/L exclusively.
mmol/l (millimoles/liter) is the world standard unit for
measuring glucose in blood. Specifically, it is thedesignated SI (Systeme International) unit.
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Conversion formulas
To convert mg/dl of glucose to mmol/l, divide
by 18 or multiply by 0.055.
To convert mmol/l of glucose to mg/dl,multiply by 18.
e.g., convert 110 mg/dl to mmol/l
= 110/18 = 6.1 mmol/le.g., convert 5.5 mmol/l to mg/dl
= 5.5 x 18 = 99 mg/dl
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Manifestations of diabetes
Classic signs - polyuria, polydipsia,
polyphagia, weight loss
Hyperglycemia, glycosuria (glucosuria)
Non-specific malaise, fatigue, nausea, and
vomiting
Blurred vision, lethargy, and coma if severe
Predisposition to bladder, skin, and vaginal
infections
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IDDM versus NIDDM
IDDM Autoimmune attack on beta cells of
pancreas: type 1, juvenile onset, thin, prone
to ketosis
NIDDM combination of insulin resistance
and insulin deficiency: type 2, adult onset,
obese, more familial, 90% of diabetics
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Pathophysiology of IDDM
IDDM is an autoimmune disease where antibodies
destroy the insulin-producing beta cells of the
pancreatic Islets of Langerhans
Theory- damage to pancreatic beta cells from aninfectious or environmental agent triggers an
autoimmune response against altered pancreatic beta
cell antigens or beta cell molecules that resemble a viral
protein 85% of patients have circulating islet cell antibodies and
majority also have detectable anti-insulin antibodies
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Pathophysiology of NIDDM
Polygenic inheritance - Type 2 diabetes is genetically
determined. Having one or both parents with type 2
diabetes carries a 40% to 70% life risk of developing the
disease, versus about 15% in subjects with no family
history.
A combination of insulin resistance and pancreatic beta
cell failure
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Metabolic defects of type 2 diabetes
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How is diabetes diagnosed?
Classic manifestations: polyuria, polydipsia, polyphagia, andweight loss
Fasting plasma glucose levels of more than 126 mg/dl on two or
more tests on different days indicate diabetes.
A random blood glucose test can also be used to diagnose
diabetes. A blood glucose level of200 mg/dl or higher indicates
diabetes.
Oral glucose tolerance test (OGTT)-values greater than 200 mg/dl
and 140 mg/dl at 1 hour and 2 hours after intake of 75 g of
glucose, respectively
When fasting blood glucose stays above 100mg/dl, but in the
range of 100-126mg/dl, this is known as impaired fasting glucose
(IFG). While patients with IFG do not have the diagnosis of
diabetes, this condition carries with it its own risks and concerns.
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Acute complications of diabetes
Diabetic ketoacidosis for type 1 diabetics
Hyperosmolar nonketogenic coma for type 2
diabetics
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Diabetic ketoacidosis (DKA)
Diabetic ketoacidosis is due to a marked deficiency of insulin in
the face of high levels of hormones that oppose the effects of
insulin, particularly glucagon. Even small amounts of insulin can
turn off ketoacid formation.
In the fasted state, glycolysis is diminished, the flow of substrate
into the citric acid cycle drops, and ketone manufacture is turned
on. This is unfortunately just what happens in diabetic
ketoacidosis.
In the midst of plenty, the liver cell in DKA cries 'starvation' and
produces ketones! Both absence of insulin and excess glucagon
result in inhibition of glycolysis. Such inhibition not only raises
glucose levels, but stimulates ketone formation.
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Chronic Complications of Diabetes
Microvascular disease small vessel disease
such as those involving the eyes, kidneys, and
nerves
Macrovascular disease large vessel disease
such as those that lead to hardening of the
the arteries as in coronary artery disease,
strokes, and claudication
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Chronic complications of diabetes
Coronary artery disease (CAD)
Diabetic retinopathy, cataracts, and glaucoma
Retina detachment
Diabetic nephropathy possibly leading to
ESRD
Diabetic neuropathy and vasculopathy Erectile dysfunction (ED)
Other organs
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Treatment Diabetes Type 1
Insulin
Regular exercise and maintaining IBW
Eating healthy foods
Regular blood sugar monitoring
Other medications: Pramlintide (slows movement of
food through the stomach), low-dose aspirin therapy,
antihypertensive agents, cholesterol-lowering drugs
Investigational treatments e.g., pancreas transplant,
islet cell transplant, stem cell transplant
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Treatment of Diabetes Type 2
Sulfonylureas (oral hypoglycemic agents) e.g.,
Diamicron
Meglitinides
Biguanides Alpha-glucosidase inhibitors
Thiazolidinediones (glitazones)
Incretin-mimetic Dipeptidyl peptidase IV inhibitors
Insulin
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Glycosylated Hemoglobin Test or HbA1c Test
A glycosylated hemoglobin test (HbA1c) is a blood test that measures
the amount of glycosylated hemoglobin in the blood
Based on the attachment of blood glucose to hemoglobin. This
process is called glycosylation. Once attached to the hgb, it remains
there for the life of the RBC
. The higher the level of blood sugar, themore sugar attaches to red blood cells.
The best test available for determining if a persons blood sugar is
under control. HbA1c shows how high your blood sugar levels have
been during the past three months.
Results are given in percentages. An HbA1c of 6% or less is normal.Diabetics should try to keep their HbA1c values at 7% or less.
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P th h i l f Di b t M llit
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Pathophysiology of DiabetesMellitus
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Dialysis
Diabetes sometimes leads to ESRD,necessitating dialysis or transplantation
Dialysis, the more common form of kidney-
replacement therapy, is a way of cleaning theblood with an artificial kidney
There are two types of dialysis: hemodialysisand peritoneal dialysis.
di l i
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Hemodialysis
In hemodialysis, an artificial kidney removes wastefrom the blood
A surgeon must first create an "access," a placewhere blood can easily be taken from the body and
sent to the artificial kidney for cleaning. The access,usually in the forearm, can be made from thepatient's own blood vessels or from a piece ofimplanted tubing. The access is inside the body andcannot be seen from the outside. Usually, this
surgery is done 2 to 3 months before dialysis startsso the body has time to heal.
H di l i 2
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Hemodialysis 2
Hemodialysis must be done 2 to 3 days per
week, and lasts 3 to 5 hours each time. Blood
travels through the artificial kidney, where
waste products are filtered out, and the cleanblood returns to the body. Only about 120 ml
of blood is out of your body at any one time.
H di l i 3
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Hemodialysis 3
Usually, hemodialysis is done in a clinic, with
many people receiving dialysis at the same
time. Hemodialysis can also be done at
home, but it requires a partner, such as arelative or friend, and special training.
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Hemodialysis 3
Hemodialysis is not perfect for everyone. Duringtreatments, people can have high or low bloodpressure, an upset stomach or muscle cramps. Aspecial diet is needed to stay healthy. Other
problems can develop over time, such as nerveproblems, anemia, bone disease, poor nutrition,problems with infection, problems with the access,and difficulty regulating insulin doses. Sometimes,
these complications are the result of diabetes, notof hemodialysis.
P it l Di l i
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Peritoneal Dialysis
The lining inside your abdomen (theperitoneum) becomes the filter. A soft plastictube is put into the abdomen by a surgeon.
When the body heals, cleansing fluid(dialysate) is put into the abdomen throughthis tube. Waste products in the bloodstreampass through the peritoneum into the
dialysate. Then the dialysate, along with thewaste products is drained off.
F i f Di l
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Function of Dialysate
Dialysate is one of the two fluids used in dialysis.The other fluid being blood. The term dialysate isborrowed from physical chemistry and refers tofluids and solutes which have crossed a membrane.
The main function of the dialysate, is to removewaste material from the blood and to keep usefulmaterial from leaving the blood. Electrolytes andwater are some materials included in the dialysate
so that their level in the blood can be controlled.
C iti f Di l t
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Composition of Dialysate
Sodium chloride
Sodium bicarbonate
Sodium acetate
Calcium chloride
Potassium chloride
M
agnesium chloride Glucose is sometimes included
P it l Di l i
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Peritoneal Dialysis
The two main types of peritoneal dialysis are
continuous ambulatory peritoneal dialysis
(CAPD) and continuous cycling peritoneal
dialysis (CCPD).
CAPD
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CAPD
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Continuous Ambulatory Peritoneal Dialysis
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y y
(CAPD)
People perform CAPD themselves by attaching a plastic bagfilled with cleansing fluid to the tube in the abdomen andraising it to shoulder level. This causes the fluid to run intothe abdomen. The bag is then unhooked or rolled up aroundthe waist. In several hours, the fluid is drained out and
thrown away. A fresh bag of fluid is then put into theabdomen to begin cleansing again. This is called an"exchange" and takes about 30-45 minutes. It is done 4 or 5times a day. Between exchanges, the person can movearound and perform daily activities.
Continuous Cycling Peritoneal Dialysis
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(CCPD)
In CCPD, a machine puts the cleansing
fluid into the abdomen and drains itautomatically. This is usually done at
night during sleep.
Peritoneal Dialysis
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Peritoneal Dialysis
CAPD and CCPD may be better treatments
than hemodialysis for some people. With
daily dialysis, the body does not build up too
much fluid. This reduces the stress on theheart and blood vessels. A person is able to
eat a more normal diet and have more time
for work and travel.
Peritoneal Dialysis
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Peritoneal Dialysis
Peritoneal dialysis is not for everyone,
however. A person must be able to see
well and do each step correctly to
prevent infection in the abdomen.
Anemia, bone disease, and poor
nutrition can occur, just like in
hemodialysis.
Kidney Transplantation
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Kidney Transplantation
One option for the person with ESRD is a new
kidney. Transplants are most successful when
the kidney comes from a living relative.
Another option is a cadaver kidney (a kidneyfrom an unrelated person who has just died).
Success Rate for Kidney Transplantation
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Success Rate for Kidney Transplantation
One year after getting a kidney from a living
relative, about 97% of people with diabetes
are still alive. After 5 years, the number is
approximately 83%. For people who getcadaver kidneys, about 93% are still alive
after 1 year, and 75% are alive after 5 years.
Grim Statistics?
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Grim Statistics?
Statistical studies show that up to 40% of
dialysis patients die within 2 years of
commencement of dialysis
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