Download to DIABETES MELLITUS ppt

Question
Make a scenario of an MCQ. Outline the
signs and symptoms that you would expect
in a Diabetic patient keeping in mind the
actions of Insulin. Remember, Diabetes
would have the same symptoms as that of
Insulin deficiency. Give 4 options for the
MCQ question.
PATHOPHYSIOLOGY OF
DIABETES MELLITUS
(EFFECTS OF INSULIN
DEFICIENCY)
1. Hyperglycemia
EFFECTS OF INSULIN
DEFICIENCY:
2. Glucosuria
EFFECTS OF INSULIN
DEFICIENCY:
3. Polyuria
EFFECTS OF INSULIN
DEFICIENCY:
4. Polydipsia & Polyphagia
(There is an extracellular glucose excess
& an intracellular glucose deficiency“starvation in the midst of plenty”)
EFFECTS OF INSULIN
DEFICIENCY:
5. Weight Loss
(For every gram of glucose excreted, 4.1
kcal is lost from the body. Increasing the
caloric intake to cover this loss simply
raises the plasma glucose further.)
EFFECTS OF INSULIN
DEFICIENCY:
6. Increase in plasma Cholesterol &
Phospholipid conc.
(Role in the accelerated development of
atherosclerosis that is a major
complication)
COMPLICATIONS
When Diabetes continues for a long time period (15-20
years) chronic complications occur.
1. Neuropathies
2. Peripheral vascular disease
3. Gangrene
4. Atherosclerosis
5. Ischemic heart disease
6. Renal disease
7. Early cataract
8. Retinopathy
9. Skin infections
10. Neuropathies affecting the ANS
Diabetic foot showing ulcer
Gangrene that must be treated with
an amputation
KETOSIS AND COMA
• In severe form of Insulin deficiency, plasma levels of FFA is more
than doubled.
↓
• In the liver and other tissues, the fatty acids are catabolized to acetyl
Co-A.
↓
• Some of the acetyl-CoA enters into the citric acid cycle.
↓
• When the supply exceeds the capacity of the citric acid cycle, the
excess are converted into acetoacetate and β-hydroxybutyrate.
↓
These are ketone bodies that lead to progressive metabolic acidosis.
↓
Acidosis can depress the brain and if severe enough can lead to coma
and death.
CHO, Fat &
Protein
Metabolism
Disturbed
Diabetes
Mellitus
Fluid and
Acid- Base
Balance
Disturbed
DIABETES MELLTIUS
DIABETES MELLITUS
Def:
Diabetes mellitus is a syndrome of impaired
carbohydrate, protein & fat metabolism caused by
either lack of insulin secretion or decreased
sensitivity of the tissues to insulin.
The word “Diabetes Mellitus” literally means
“excessive secretion of sweet urine”.
• Third leading cause of death
• Leading cause of blindness
• Diabetes is a very prevalent disease, has a huge
economic toll, forces individuals to change their
lifestyle thus affecting their quality of life &
predisposes the affected to a variety of
troublesome & even life threatening conditions.
Diabetes Mellitus
Type I
Juvenile onset/
Insulin Dependant
10%
Lack of Insulin
secretion
Type II
Adult onset/
Insulin Independent
90%
Reduced sensitivity of
target cells to insulin
TYPE I/ Juvenile Onset/ Insulin
Dependent
It is the more severe from of diabetes and more prevalent in
children.
DEFINITION:
It is a catabolic disorder in which the circulating insulin is virtually
absent, plasma glucose is elevated & the pancreatic beta
cells fail to produce any insulin in response to all insulinogenic
stimuli.
Cause: Lack of insulin secretion from the beta cells of the
islets of langerhans.
• It is an autoimmune disorder in which there is selective
destruction of the pancreatic beta cells by T lymphocytes.
• Mostly it seems to have an immunological basis & circulating
islet cell antibodies & anti-insulin antibodies may be
demonstrated.
• Usually there is a genetic predisposition to this type of
diabetes which may be triggered off by:
- Viral infections e.g. rota virus, coxsackie virus
- Environmental triggers.
TYPE II DIABETES/ Non-Insulin
Dependant/ Adult Onset Diabetes
It is further classified into:
•
It is the most common type of diabetes, accounting for
about 90% of all cases of diabetes mellitus.
•
The age of onset is usually after 30, often b/w 50 & 60
years of age.
•
It develops gradually & is the less severe form of
diabetes.
1.
2.
Non-obese type II
Obese type II
•
Cause: Decreased sensitivity of target tissues to the
metabolic effects of insulin. This reduced sensitivity to
insulin is often called INSULIN RESISTANCE.
TYPE II DIABETES
Factors that can lead to Insulin resistance include:
1. Anti-insulin antibodies
2. Autoantibodies to the insulin receptor
3. Mutation of insulin receptor
4. Down-regulation of insulin receptors by sustained
hyperinsulinism.
5. Primary hyperinsulinism (Beta cell adenoma).
6. Secondary hyperinsulinism (Cushing’s syndrome,
acromegaly, pregnancy or diabetes mellitus)
7. Obesity/overweight especially excess fat deposits
around the abdomen
8. Insulin resistance in peripheral tissues such as skeletal
muscle, brain and liver.
PATHOPHYSIOLOGY
• Diabetes type I is far more rapid in onset
occurring over a few days as compared to type II
which has a more gradual onset.
• Type I also shows far more complications as
compared to Type II which rarely shows
complications
• Type I requires Insulin while Type II can usually
be controlled by simple changes in lifestyle as
diet, exercise & weight control
• Type I insulin is more prone to Ketoacidosis
while Type II is not!
DIAGNOSIS OF DIABETES
1. Blood sugar random ( 80-120 mg/100ml)
2. Blood sugar fasting (80-90 mg/100ml)
3. GTT or Glucose Tolerance Test:
When a normal fasting person is given 1g of glucose /kg
body weight, his plasma glucose levels rise to 120-140
but fall back to normal within 2 hours
In a prediabetic or diabetic, not only is the fasting plasma
glucose on the higher side but also the post meal
plasma glucose rises to as high as 140-200 & fails to
come back to normal within 2 hours of giving conc.
glucose solution. Even after 4-6 hours it rarely comes
back to the normal range!
NORMAL MEAN BLOOD GLUCOSE IS APP. 110 !
Glucose Tolerance Test
POINT TO REMEMBER!
WHY IS ORAL GLUCOSE A MORE
POWERFUL STIMULANT THAN
INJECTABLE GLUCOSE FOR INSULIN
SECRETION?
DIAGNOSIS OF DIABETES
4. Presence of glucose in urine (glucosuria)
5. Acetone breath
6. Lab test for assessing control of diabetes:
HbA1c is a minor component of Hb A & is normally present
in small amounts .i.e. up to 6% of normal Hb. In the
presence of long standing hyperglycemia, its
concentration rises. When plasma glucose is
episodically elevated over time, small amounts of Hb A
are non-enzymatically glycated to form HbA1c
Careful control of diabetes with insulin reduces the amount
formed and thus, HbA1c levels give an index of diabetic
control for past 4-6 weeks.
TREATMENT for Type I DIABETES
WHY CANNOT INSULIN BE GIVEN BY MOUTH?
WHY IS ONLY CHO RESTRICTION NOT VERY EFFECTIVE?
Administer enough insulin so that metabolism of fat, proteins & CHO proceed
as normally as possible!
Insulin is available in various forms:
1.
Insulin preparations are available with rapid (regular), intermediate & long
durations of action:
- regular: duration of action is 3-8 hours.
- Intermediate (NPH): not used during
- Long: duration of action is 10-48 hours
Individualized insulin schedules which consist of one injection of longer acting
insulin followed by regular insulin when the glucose level is expected to
rise .i.e. at meals.
Insulin is administered subcutaneously (s/c) except in the case of
emergencies when it is given intravenously (i/v).
The less soluble an insulin preparation is, the longer it acts!
INSULIN SYRINGES
Insulin
Human insulin is absorbed
more quickly from its site of
action than are beef or pork
insulins. Thus, duration of
action of human Insulin is
shorter & doses must be
adjusted.
Hypoglycemia is the most
serious & common side
effect of Insulin therapy!
B/C long term diabetics do
not produce counteracting
hormones of Glucagon, EN,
cortisol etc. that normally
provide defense against
Hypoglycemia!
TREATMENT for Type II DIABETES
• Diet
• Exercise: is useful in managing both types of Diabetes,
because working muscles are not Insulin dependent.
Exercising muscles take up some of the excess blood
glucose, reducing the overall need for insulin.
• Weight loss
• Oral Hypoglycemic Drugs.
Oral Hypoglycemic Drugs
There are many types of oral Hypoglycemic drugs, some of
which are:
• Sulfonylureas: act by stimulating the β- cells to secrete more
insulin than they do on their own. E.g: Glucotrol.
• Metformin: acts by suppressing liver output of glucose. E.g:
Glucophage.
• Alpha-glycosidase Inhibitors: act by slowing CHO digestion
and absorption from the digestive tract into the blood, thus
reducing the glucose surge seen after a meal. E.g: Precose.
• Byetta (Glucagon-like peptide 1 mimic) mimics the incretin
GLP-1. It suppresses glucagon secretion and slows gastric
emptying. By promoting satiety, it decreases food intake and
in the long term leads to weight loss.
Because none of the drugs deliver new insulin to the body, they
cannot replace insulin therapy for people with Type I Diabetes
and later in Type II Diabetics as well.
SULFONYLUREAS!
NIDDM patients above the age of 40 years & having h/o
diabetes of less than 5 years are given Oral
Hypoglycemics!
Mechanism of Action:
1. Stimulate release of Insulin from beta cells of
pancreas.
2. Reduction of serum Glucagon!
3. Increased binding of Insulin to target tissues &
receptors.
E.g. Tolbutamide
Glyburide
Glipizide
WHO NEEDS INSULIN?
•
•
•
•
•
•
•
•
•
􀂄 Type 1
􀂄 Type 2 uncontrolled w/meds
􀂄 DKA
􀂄 Hyperosmolar hyperglycemic state (HHS)
􀂄 Surgery
􀂄 Illness/Infection
􀂄 Stress
􀂄 Those receiving parental/ enteral nutrition
􀂄 Pancreatitis /diseases that ↓ beta cell function
WHAT HAPPENS WHEN
THERE IS INSULIN EXCESS?
Insulin Excess
Insulin Shock
When a diabetic
takes an overdose
of Insulin
Reactive
Hypoglycemia
When there is a βcell tumour or
overresponsiveness
Symptoms
• Decreased blood supply to the brain, as
the brain literally starves.
• Tremors
• Fatigue
• Sleepiness
• Inability to concentrate
• Unconsciousness
• Death
NOTE
A diabetic can lose consciousness and die
from either diabetic ketoacidotic coma
caused by prolonged Insulin deficiency or
acute hypoglycemia caused by Insulin
excess.
How do you differentiate between the two if
a diabetic patient is brought to you
unconscious?