diabetes mellitus part one resident chemical pathology thanks to my supervisor & all concern sources

1. Dr.Ghulam Murtaza
Resident Chemical Pathology -R1
1

2.  Introduction
o Definition
o Classification of DM
o Pathogenesis of diabetes mellitus
o Diagnostic criteria
part one 2

3.  Insulin
 INSULIN
Protein in nature, anabolic hormones (
stimulates uptake of glucose into fat ,&
muscle
secreted by β cells pf pancreas
 First substance to be measured by
radioimmune assay & first compound
produced by recombinant DNA technology
part one 3

4. part one 4
Human insulin consist of 51 amino acid in
in two chains (A & B) joined by disulfide
bond
& third sulfide bond within A

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 Main stimuli for insulin release is glucose
 insulin respond within minutes –in pulsatile
fashion
 First phase begin with 1 to 2 minutes after
I/V load of glucose & ends within 10 minutes
(rapid release of stored insulin )
 Second phase within 60 to 120 minutes until
normoglycemia restored .

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In DM first phase & pulsatile
manner of insulin release
impaired while second phase
is preserved

7.  50 % of insulin is extracted by the liver
additional insulin is degradation occurs in
kidney
 The basal insulin secretory rate is
1U/(43µg)/h with total daily secretion of 40
U.
 Half life of Insulin is between 4 & 5 minutes
part one 7

8.  Evaluation of fasting hypoglycemia
 Evaluation of polycystic ovarian syndrome
 Classification of diabetes
 Assessment of beta-cell activity
 Investigation for insulin resistance
part one 8

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Has low biological activity (approx.10% of insulin )
Major storage form of insulin.
Only 3% of of Proinsulin enter in circulation
25 % is hepatic clearance rate
Half life of proinsulin is 30 minutes
In fasting state circulating proinsulin concentration are approx.
10 to 15% of insulin concentration

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Diagnosis of
β-cell tumors
Familial
hyper-
insulinoma
Cross-
reactivity
of insulin
assays

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 31 amino acid polypeptide
 C-peptide is measure of endogenous insulin
 Insulin & c-peptide are secreted into the
portal circulation in equimolar amounts .
 Longer half line 35 minutes ( fasting level are
higher than insulin 5 to 10 folds)
 Degraded in almost kidney

12.  Evaluation of fasting hypoglycemia
β cell tumors & factitious
 Classification of DM
 Assessment of β cell activity
 Monitoring therapy
 Pancreatectomy
 Transplant & immunomodulation of type 1
part one 12

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Glucogan,cortisol
,growth hormones &
epinephrine

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15.  DM is state of “ Chronic hyperglycemia .
 Group of metabolic disorder characterized by
hyper glycemia due to defect in insulin
secretion or insulin action , or both
 Deficiency of insulin is NOT an essential
feature of DM
part one 15

16. a. Type 1 diabetes
A. immune mediated
B. idiopathic
b. Type 2 diabetes
c. Other specified types :
( genetics defects of beta cells , defects in
insulin action ,drug or chemical induced &
infection )
d. Gestational diabetes mellitus
part one 16

17.  Normoglycemic
 Impaired glucose regulation :
impaired fasting glycemia (IFG)
impaired glucose tolerance test (IGT)
• Diabetes mellitus
• required insulin
required insulin for control
required insulin for survival
part one 17

18.  5 to 10 % cases included in this category
 Insulinopenia ( deficiency of insulin )
 Autoimmune process
 75% acquire before the age of 18 years
part one 18

19.  Cellular mediated autoimmune destruction of
insulin secreting cells of pancreatic Beta
cells other cells remain normal alpha &
gamma .
 Immune mediated diabetes Insulitis
80-90% reduction in volume of beta cells is
required to induce clinical symptoms
part one 19

20.  Islets cell antibodies (ICAs)
 Autoantibodies to insulin
 Auto antibodies to glutamic acid
decarboxylase (GAD65)
 Autoantibodies to tyrosine t phosphatase IA-2
& IA-2β
part one 20

21.  HLA: DQ & DR genetic factor are by far the
most important determinants for risk type of
type 1 diabetes
 Environmental factor are
 Virus including rubella ,mumps ,entero &
coxsackie b
 cow milk
part one 21

22.  Islets cell cytoplasmic antibodies :
 70 to 80 % in newly diagnosed type one DM
 are detected by immuno fluorescence
microscopy
on frozen section of human pancreatic tails
 Insulin auto antibodies (IAA) :
 are present in > 90 % of children in before
age 5
& less than 40% after 12 years
continue :
part one 22

23.  Its type I DM of adults
 Family history of Autoimmune
 Positive Anti-GAD (glutamic acid
decarboxylase or islets cell antibodies
 Do not require insulin at diagnosis but
progress to insulin dependence after several
months to years
part one 23

24.  > 90 % of all case
 Insulin independent
 Patient have minimal symptoms are prone to
ketosis
 Most patient acquire the disease after 40
years but it may occur in younger people .
part one 24

25.  Studies shows that first degree relatives of
individual with T2DM are about 3 times more
than likely to develop the disease than
individual without a positive family history of
DM
 It also has been shown that concordance
rates of Monozygotic twins have ranged from
60-90 % are significantly higher than type 1
DM 30-40 %
part one 25

26.  Two major identifiable pathological factors
 One is decrease ability of insulin to act on
peripheral tissue this is called
Insulin resistance
 Second is inability of pancreas to produce
sufficient insulin to compensate for insulin
resistance
beta cell dysfunction
part one 26

27.  any of following is diagnosis
 HbA1c > 6.5 %
 Fasting plasma glucose level is > 126 mg/dl
repeat at interval at least one week or stress free
 Symptoms of hyperglycemia & random
plasma glucose level is 200mg/dl
 OGTT > 200mg
part one 27

28.  If one of these is higher than the cut off
value repeat the same
if FPG is greater than 126mh/dl & Hba1c is
less than 6.5 % repeat FPG to confirm.
 If both of these tests are above these levels
no need to repeat –
part one 28

29.  Categorized for risk of diabetes
 Impaired fasting glucose(IFG) 100-126mg/dl
 Impaired glucose tolerance test (IGT-2 hrs.)
140-200mg/dl
 HbA1c – 5.7-6.4%
part one 29

30.  Provocation test to examine the efficiency of
the body to metabolise glucose
 Differentiate between metabolically healthy
individuals from people with impaired
glucose tolerance & those with diabetes
 More sensitive than FPG for diagnosis of
diabetes
 Used mainly by IGT & in epidemiological
population study
part one 30

31.  Three days unrestricted carbohydrate rich
diet & activity
 No medication on the day of test
 No smoking
 Fasting (12hours to 16 hours )
part one 31

32.  Should be begin between 7:00 am to 9;00 am
 For non pregnant adult recommended dose is
75mg & for children 1.75g/kg up to 75 g
max: is given
 The glucose solution should be dissolved in
300ml of water & ingested over 5 minutes
 Glucose sampling
10minutes before glucose load
120minutes after glucose load
part one 32

33.  Fasting
Normal - < 100mg/dl ,
impaired – 100-125 mg/dl
diabetes – >126 mg/dl
 2hours
normal – 140mg/dl
impaired- 140-199 mg/dl
diabetes - > 200mg /dl
part one 33

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35.  Tietz book of clinical chemistry
volume -3 chapter 57 edition 6
 laboratory Diagnosis & monitoring of DM
(WHO-2002 )

part one 35

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37.  Role of medical laboratory in Diabetes
mellitus
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