Professional Documents
Culture Documents
Metabolism
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Postprandial state Fasting state
1.Glycogen in the
live sufficient up
Liver removes 70% of glc load brain Liver brain
to 24hr
Glycogen Glycogen
E+ Fat 100gm
glc Blood glc glc Blood glc
TG TG
Adipose Adipose
E+ Tissue E+ Tissue
reabsorbed reabsorbed
glycogen Glycogen
400gm
BS>180 BS>180
Muscle Muscle
Urine Urine
Fasting state-cont
Urine
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Insulin
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IRS which act as a second messenger to
Insulin Receptor (IR)
produce a wide variety of cellular effects such as
increase the transport of glucose into cells
throw movement glucose transporter protein
(GLUT-4) from the intracellular vesicles to the
When insulin binds to cell membrane
-subunit the - subunit GLUT-4 found in adipose tissue and muscles
autophosphorylated
which intern GLUT-4
phosphorylate proteins
called insulin receptor
substrate (IRS)
Glucagon Epinephrine
Growth hormone
Secreted by anterior pituitary
antagonizes glucose uptake by cells
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Measurement of glucose concentration
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Arterial
> capillary > venous
Due to peripheral clearance
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Prevalence of Types 1 & 2 Classification
1-2% 0f western world
Primary DM
Type 1
In 2002, the U.S was 6.3% (18.2 million people Type 2 Type 1 <10%
Third leading cause of death-- United States
Alarming incidence of type 2 DM Secondary DM
18 yr old and younger type 2 DM sky rocking Gestational diabetes
200 million world wide by the year of 2010 Chronic pancretitis
Cushing syndrome
Acromegaly Type 2 >90%
in Jordan? Drugs- thiazides in high dose, other
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Type 1-Insulin dependent DM (IDDM)-conti
Types of Diabetes mellitus
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What is Insulin Resistance (IR)-conti
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2. Diabetic Ketoacidosis (DKA)
Definition
Hyperglycemia causes osmotic diuresis A complex disordered metabolic state
decrease plasma volume characterized by hyperglycemia, acidosis,
ketonemia
increases plasma osmolality which stimulates
A medical emergency requiring intensive therapy
thirst center.
Osmotic diuresis and thirst causes the It may be be precipitated by omitting insulin dose
classical symptom of polyuria and or insulin become an adequate due increase H
polydipsia with opposing action
decrease plasma volume - pre-renal uremia infection, trauma or psychological stress.
Pathophysiology of KA
Lack of insulin
KB are substances related to
Increase of glycogenolysis, gluconeogenesis, and
lipolysis acetone ( 3 compounds)
Produced in the liver when
Increase of glucagon, cortisol, growth hormone, large amount of Acetyl-CoA
epinephrine
glucagon / insulin ratio are produced by beta
oxidation
Increase mobilization of fat from adipose tissue
to liver ( H S Lipase)
1.Diabetes mellitus
NOTE Insulin and glucose inhibit the mobilization of fat 2.Starvation
3.High fat low carbohydrate diet
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Pathophysiology of KA-cont.
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Microvascular complications:
Microvascular Complications
(Proposed mechanisms)
The risk of the complications increases with It appears to be directly related to Hyperglycemias
poor glycemic control
Narrowing of the lumen of small vessels which
directly related to prolong exposure to high BS
Nephropathy
Neuropathy
Retinopathy
Microvascular complications (Proposed mechanisms)-conti Why the damage by sorbitol occur in retina, kidney
and nerve cells and not in other cells?
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Retinopathy: Neuropathy Diabetic
Diabetic retinopathy (damage to the Diabetic neuropathy is a peripheral nerve
retina) is caused by complications of disorder caused by diabetes.
diabetes mellitus, neuropathy are often slight at first.
which could eventually lead to
blindness. Numbness, pain, or tingling in the feet, or
legs may, after several years, lead to
affects up to 80% of all diabetics weakness in the muscles of the feet.
who have had diabetes for 15 years
or more May affect specific nerves
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Diabetic long-term complications Diabetic Macrovascular Disease
Pathophysiology
Macrovascular
Due to multiple metabolic changes
Related to atherosclerosis Lipid changes in DM
Clinical
Manifestations: Coronary Artery
Disease (Angina, MI) and Peripheral
Vascular Disease
Lipoprotein metabolism in DM
p.223
Exercise
Weight reduction
can reduce insulin
resistance, and
reduce the need
for medication.
Eat less!
Drugs
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DIAGNOSIS Criteria for DIAGNOSIS of
Criteria for the DIAGNOSIS OF D M-
DM
WHO-1997
P.212 fig. 11.7
symptoms symptoms
polyuria, polydipsia, polyphagia and weight polyuria, polydipsia, polyphagia and weight
loss & loss &
random venous plasma glucose level >200
random venous plasma glucose level >200
mg/dl(11.1mmol/l)
mg/dl(11.1mmol/l)
or
or
fasting venous plasma glucose >126 mg/dL
fasting venous plasma glucose >126 (>7.0mmol/L N <6.1)
mg/dL;(>7.0mmol/L N <6.1) ((Venous or capillary blood glc>or=110mg/dl
or 6.1mmol/L (N 5.6) ))
Impaired Fasting Glucose (IFG): fasting venous in the absence of symptoms venous
plasma glucose between 110 and 125 mg/dL plasma glucose in the diabetic range
(>6.1-<7.0) and 2-hour post glc load glucose < should be detected on at least two
140 (<7.8)
separate occasions
Impaired Glucose Tolerance:
fasting venous plasma glucose <126 mg/dL;
and
2-hour post glc load glucose between 140 and
199 mg/dL (>7.8-<11.1)
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Oral Glucose Tolerance Test
perform OGTT after at least 3 days of
(OGTT) unrestricted diet (> 250gm CHO daily)
Indication fast patient overnight (10-16 hours)
vague Fast/Random BS rest during the test.
Unexplained glycosuria take fating blood sample
Clinical feature of DM with normal BS give 75 gm glc in water orally
take blood at 1 hr & 2 hr
Some lab consider blood sample other
than 0 and 2 hours are not necessary for
diagnosis
Management of DM
Education of patients
Regular follow- up
- blood sugar
- urine sugar
- HbA1c
Normal fasting plasma sugar < 6.1mmol/l Diet, physical activity
IFG - <6.8 mmol/l
IGT 2h post glucose load >=7.8<=11.1
Drugs
DM fasting >=7.0 or 2h post glucose load>=11.1
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Glycated Hb (HbA1c)
HbA1c is a test that measures the amount of
glycosylated hemoglobin in your blood. Plasma Fructoseamine
-measure glycated plasma albumin
Glucose binds slowly spontaneously to hemoglobin
-index of glycemic control for 10-15 days
A, forming the HbA1c subtype.
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Causes of hypoglycemia
Reactive hypoglycemia
Fasting hypoglycemia
Drug induced
Insulin induced:
Insulinoma,
-dietary noncompliance,
Hyperthyroidism, Adrenal insufficiency
- increased exercise, pituitary failure
- excessive insulin Drugs ethanol
Sulphonyluria glycogen storage diseases
inherited metabolic carbohydrate disorders
galactosemia
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