Strength, it is that we want so much
in this life, for what we call sin &
sorrow have all one cause, and that
is our weakness. With weakness
comes ignorance, and with
ignorance comes misery.
- - Swamy Vivekananda
Most likely .. What type of DM ?
1. 56 year male obese
2. 30 year female following pregnancy
3. 8 year old boy, poor growth, DKA.
4. 24 year female Cushing‟s sy
5. 68 Year male following Ca. pancreas.
6. 32 male, DM, BMI 18, Anti-GAD +ve.
7. 34 year male, extensive tuberculosis.
8. 12 year old female following viral fever
9. 41y DM2, BMI 17.1, HbA1c 14.1, DKA
10.15y male, BMI 16.2, recurrent infect.
Definition? types common? Diagnosis?
Primary & Sec? Congenital? Gestational?
Monogenic? MODY, LADA, drugs?
List functions of Insulin? Antagonists?
Etiology & Pathogenesis of Type 1 & 2.
Stages of DM & their pathological basis?
Obesity & Insulin resistance *
• FFAs, PKC, Adipkines, PPARγ
• Inflammation & Insulin resistance.
Mechanism of β cell destruction type 1, 2.
Islet Amyloid PolyPeptide (IAPP)?
“Nothing great in the world has
ever been accomplished without
- - CHRISTIAN FRIEDRICH HEBBEL
Dr. Venkatesh M. Shashidhar
Assoc. Prof. & Head of Pathology
“….a wonderful but not very frequent
affection among men, being a melting down of
the flesh and limbs into urine…Life is short,
offensive, and distressing, thirst
unquenchable, death inevitable…”
-- Aretaeus of Cappadocia (AD 81-3)
• 150 AD – Aretaeus, named "diabetes“ Greek for "siphon” “Sweet”
• 1788 – Cawley – damaged pancreas in DM.
• 1921 – Banting & Best, Insulin
unite for diabetes
world diabetes day
Most Common non communicable disease (3%)
Incidence increasing alarmingly (259m 2025)
Asia Pacific – maximum Increasing incidence.
High Morbidity & mortality.
Shortens life (15y) – HTPN, MI, Stroke, CRF.
7th top cause of death, 50% unaware (Au)
Diabetes Mellitus - Definition
2nd Century, Greek physician, Aretus named
Diabetes from diabainein, “to flow through or
siphon & Mellitus meaning sweet/Honey.
• * insipidus tasteless – dilute urine.
Disorder of metabolism (Carb, Prot & Fat)
Absolute/Relative deficiency of insulin.
Characterized by hyperglycemia.
Polyuria, Polydypsia, Polyphagia.
Criteria for the Diagnosis of Diabetes
1. Random blood glucose - 11.1mmol/L or high,
2. Fasting glucose - 7mmol/L or high
3. HbA1C of > 6.5%
• On more than one occasion + classical signs & symp.
4. OGTT for borderline cases (5.5 - 6.9 mmol/L),
>11mmol/L at 2 hours after a 75 gm of oral glucose.
Why Oral GTT - not IV..? *
What is normal blood glucose..? <7..?
Why glucose needs tight control..?
MODY: Maturity Onset Diabetes of Young.
5% of DM in Young*, non obese, insulin release defect*
Like DM2, non-ketotic hyperglycemia, no DM Antibodies.
Auto. Dom. - Monogenic – Genetic testing*.
Treatment is specific to type. Unlike type 1 or 2
Subtypes: 1,2,3,4,5,6 – type 3 & 2 common.
1,3,4,5,6 – Insulin transcription defect HNF.
Type 2 – Enzyme glucokinase, defective β cell response.
Type 2 in children
LADA: Late onset Autoimmune DM
Rapid onset & progression to insulin dependency.
Immune markers like type 1 diabetes,
May lack ketoacidosis symptoms.
Incidence: 6-10% (UK).
Diagnosis: Elevated pancreatic autoantibodies
Risk factors: Metabolic Syndrome
LADA + Metabolic syndrome = DM Type 1.5.
Features & complications of both type 1 & 2.
Type 1 in Adults
One machine can do the work of
fifty ordinary men. No machine
can do the work of one
- - Elbert Hubbard
Pathogenesis of Type I DM
Ab to ß cells/insulin
Islet cell Ab - ICA
Insulin Auto Ab - IAA
Glut. Acid Decarb - GAD65
DM2 Islets: Normal early amyloid
Loss of ß cells (only in late stage) replaced
by Amyloid protein deposit (hyalinization).
Less common (10%)
Children < 25 Years
Acute Metabolic complications
Family History: No
Insulin levels: low
50% in twins
More common (90%)
Adult >25 Years
Months to years
Normal or high *
Normal / Exhaustion
~100% in twins
Lymphocytic infiltrate within islets.
Central hyaline deposits replacing
dead beta cells
(only in late stage…!)
Being a good human is maintaining complete
harmony between thought, word and deed.
Divergence between thought, word and deed
is the cause of all our problems…!
DM Complications: Glucose is like burning coal*
Glucose is highly reactive - damages proteins,
cells & tissues.
Insulin - safely uses & stores glucose. – mom..!*
Diabetes is state of insulin deficiency.
Hyperglycemia PPP Tissue damage
Clinical symptoms & signs are mainly due to
Acute: metabolic - DKA / HONK.
Chronic: BV - Kidney, CNS & immune system.
Short term Complications: (metabolic)
• Diabetic Ketoacidosis DKA
• Hyper Osmolar Non Ketotic coma HONK
Long term Complications: (Angiopathy)
• Microngiopathy -
Retinopathy, Nephropathy, Neurophathy, der
• Macroangiopathy – Atherosclerosis.
Cataract – Sorbitol.. Polyol..osmotic..
Lens epithelium (Insulin independent) is exposed to Hyperglycaemia,
excessive flux of glucose to sorbitol by the polyol pathway. The
accumulation of intracellular sorbitol exerts osmoprotection and prevents
cell shrinkage. The excessive accumulation of sorbitol, causes an
increased osmotic load within the lens causing swelling, fibre breakdown,
and opacification (the osmotic hypothesis). Other mechanisms, including
glycation and oxidative stress, may also be responsible for lens
"Decision and determination are the
engineer and fireman of
our train to opportunity and success."
-- Burt Lawlor
Urine glucose - dip-stick –Screening
Fasting > 7mmol, Random >11mmol
If Fasting level is 5.5 to 7 OGTT
HbA1c - for follow-up, not for diagnosis
Fructosamine – similar to HbA1c - long
Antibodies – Type-1
Gene testing: MODY
Points to remember/review:
Diabetes is a state of hyper ketabolism.
Increased fat & protein breakdown, wt loss.
Blood vessel damage – arteriosclerosis is central to
Increased Infections – why?.
Glucose control is critical * why?
Hypoglycemia is more dangerous. Not hyper
FBS, GTT & HbA1C – interpretation.
56y woman, nocturia
56y Fem, 3/12 nocturia excessive thirst and
polyuria(1-4 times) disturbing her sleep.
Recently noticed blurring of vision, & tingling
sensation in her toes on both sides.
Weight 94kg & height 1.71m. BMI 32. Hypertensive
for several years. Mother diabetic type2.
Glucometer capillary BS is 15mmol/L.
What further Investigations?
Ans: Twice..Lab RBS/FBS, GTT.
Why not HbA1c for diagnosis?
60% of new diabetics have normal HbA1c.
What other investigations should be done?
Retina, urine, Lipid profile, Cardiac exam.
Endocrinology Other : (Brief notes)
Tumours – adenomas of endocrine gl.
Zollinger Ellison syndrome.
MEN Syndromes – MEN type 1 & 2.