integrating seminar 3 - diabetes mellitus

8/7/2019 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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(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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integrating seminar 3 - diabetes mellitus

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