DIABETES MELLITUS
Definition
Diabetes is a group of metabolic disorders
characterized by abnormal metabolism,
which results most notably in
hyperglycemia
, due to defects in insulin secretion,
insulin action, or both.
Etiology –
•Genetics
• Environmental factors
•Life style
Pathogenesis of DM –
• Reduced Insulin secretion
• Decreased glucose utilization
• Increased glucose production
Classification –
1. Type 1 DM
2. Type 2 DM
Other specific types of DM –
o MODY-Maturity Onset Diabetes of the
Young
o Endocrinopathies (Acromegaly,
Cushing syndrome)
o Genetic syndromes (Down’s
syndrome
Turner’s
syndrome )
o Pancreatic exocrine diseases
(Chronic pancreatitis, Pancreatic tumor)
o Gestational DM
TYPE 1 DM
• Pancreatic β-cell destruction
• Absolute deficiency of insulin secretion
• 2 Types – Type 1 A – immune-
mediated
Type 1 B – idiopathic
• Age – mostly develops in childhood,
manifest at puberty, progressive
with age.
ETIOLOGY
:
• Synergistic* effects of Genetic,
Environmental & Immunological factors
1. Genetic factors –
• Major susceptibility gene –
Class 2 MHC HLA locus
CLASS 2 MHC HLA Locus
Present Beta- cell Antigen to CD4+ Cells
Activation of Macrophages
Destruction of Cell
Sever Lack Of Insulin
Type 1 DM
2. Environmental Factors –
a) Viruses b) Dietary
factors
Viral agents
Produce protein that mimic self-
antigens
Immune response to viral protein cross
reacts with self-tissue
2 b . Dietary factors
*Bovine milk proteins *Nitrosamines
compounds *Coffee
Bovine serum albumin (BSA) –
resembles β cells
Antibodies cross-react with β cells
Destruction of β cells
3. AUTOIMMUNITY:
• Triggered by infectious / environmental factor
• Presence of Islet cell autoantibodies (ICA) –
against GAD65-Glutamic acid decarboxylase
enzyme and insulin
• Occurrence of Lymphocytic infiltrate in &
around islets – Insulitis
• Selective destruction of β cells.
TYPE 2 DM
• A hetrogenous group of disorders
• 3 main pathophysiologic defects –
* Peripheral Insulin resistance
* β cell dysfunction
* Increased hepatic glucose production
• Greater role for Genetic susceptibility
INSULIN RESISTANCE:
• Decreased ability of peripheral tissues to
respond to insulin.
• Influenced by Genetic & Environmental
factors.
• Genetic factor – a mystery
• Environmental factor – Mainly Obesity
Obesity
High circulating &
intracellular
Cytokines released by
levels of free fatty
acids adipocytes
(lipotoxicity)
modulation of insulin secretion & action
Insulin
resistance
Insulin resistance
Impaired peripheral glucose intake
(PPBS)
Hyperglycemia
INCREASED HEPATIC GLUCOSE OUTPUT
( FBS)
Maturity onset diabetes of the young
(MODY)
• Autosomal dominant inheritance
• Present as type 2 DM
• Age - before 30 years.
• Impaired insulin secretion
GESTATIONAL
DM
• Cause – metabolic changes during
pregnancy
• Often revert back to normalcy after
delivery
• Prone to develop DM later
Diff. b/w Type 1 & Type 2 DM
Frequency 10 – 20 % 80 – 90 %
Age Early ( <30 yrs ) Late ( >40yrs )
Onset Abrupt & severe Gradual & insidious
Family history < 20% About 60%
Genetic loci Chromosome 6 Unknown
pathogenesis Autoimmune destruction β cell dysfunction
of β cells
ICA Present Absent
Blood insulin Decreased Normal / increased
level
Islet cell change β cell destruction,insulitis Fibrosis of islets
Signs & Symptoms
Classical triad of diabetes symptoms
o Polyuria-Excessive urination
Polydipsia-Intense thirst
o Polyphagia-Increased
appetite
o Other
symptoms:
o Weight loss
o Fatigue
[Glucose] in the blood beyond renal threshold
Reabsorpt’n of glucose is incomplete
Part of the glucose remains in urine – Glycosuria
Osmotic pressure of urine
Inhibits reabsorption of water by kidney
Polyuria & fluid loss
Dehydration and Polydipsia.
Symptoms of
Diabetes
• Blurred vision
Prolonged high blood glucose
fluid loss from lens
changes in the shape of the lenses
vision changes
• Unexplained fatigue, weakness
• Weight gain / Weight loss
• Gingival recession
Diagnostic Tests
• DM is characterized by recurrent or persistent
hyperglycemia
• Diagnosed by demonstrating any one of the
following:
o Fasting blood sugar
o Post prandial blood sugar
o HbA1C
o Lipid Profile – To diagnose dyslipidaemia
o RBS
RBS can be done only if the patient follows up for
the diagnostic tests after a meal
FASTINGBLOODSUG
•Person to be tested should be on a normal diet for at least 3 days
AR
prior to testing.
•The test should be done after an overnight fast of 8 – 10 hours (no
beverages including tea or coffee should be consumed),
•Draw a sample of blood after confirming fasting state of the
patient.
Fasting Serum Diagnosis
Glucose
(mg/dl)
Below 110 Normal
Between 110and 126 Pre-diabetes
Above 126 Diabetes (Must be confirmed with a
second fasting test)
Post prandial blood
sugar
Following the collection of the fasting blood sample
for analysis of fasting serum glucose (FSG). Patient is
advised to have a normal meal and return to the clinic
after 2 hours following the meal.
Draw a sample of blood after confirming the time
of meal.
Post prandial blood Diagnosis
sugar
< 140mg/dl Normal
140-200mg/dl Pre -diabetic
>200mg/dl Diabetic
HbA1
Person to be tested should be on a normal diet for at
C
least 3 days prior to testing.
The test should be done after an overnight fast of 8 –
10 hours
Draw a sample of blood after confirming fasting state
of the patient.
HbA1C Levels Diagnosis
4-6 Normal for those without
diabetes
6.1-7 Target range for diabetics
>7 Poor control
To be
continued………………..
