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"Never offer the devil a

ride. He will always want to

be in the driving seat…!"
Pathology of
Dr. Venkatesh M. Shashidhar
Associate Professor of Pathology
Fiji School of Medicine
Diabetes Mellitus
z Disorder of metabolism (Carb, Prot & Fat)
z Due to Absolute/relative deficiency of insulin.
z Characterized by hyperglycemia.

z Clinically : Polyuria, Polydypsia, Polyphagia.

z Diabetes mellitus (sweet urine)
z 3% of world population, 100 million people
z Incidence is increasing alarmingly (40% in the
past decade, more in future. 259 m by 2025.
z Most Common non communicable disease
z High Morbidity & mortality.
z DM shortens life span by 15 years.
z Leading cause of blindness and Kidney dis.
z Pacific Islands – leaders in DM & Obesity…!
World Statistics:
Normal Pancreatic Islet:
ß α

ß cells (Insulin) α cells (Glucagon)

δ cells (Somatostatin) pp Cells (pan prot)
Insulin - Anabolic Steroid
z Transmembrane transport of glucose
z Liver, muscle & fat Æ ↓ blood glucose
z Liver & skeletal muscle - ↑ glycogen
z Converts glucose to triglycerides
z Nucleic acid & Protein synthesis
z Diabetes Æ Increased catabolism.
z Hyperglycemia, ↓ protein synthesis, Liplysis,
wasting, weight loss.
Blood Glucose & Hormones
Hormone Action
z Insulin z ↓ Glucose

z Glucortocoids z ↑ Glucose

z Glucagon z ↑ Glucose

z Growth Hormone z ↑ Glucose

z Epinephrine z ↑ Glucose
Cellular Glucose Uptake
Insulin Requiring Non-Insulin Requiring
z Striated Muscle z Blood Vessels

z Cardiac Muscle z Nerves

z Fibroblasts z Kidney

z FAT z Eye Lens

Pathology in Diabetes:

z Low glucose inside cell

z decreased cell metabolism (muscle,
z High glucose outside
z Glycosylation damage (BV)
z Polyol products – osmotic damage*
z Primary DM – (primary - no other disease)
z Type I – IDDM / Juvenile – 10%.
z Type II – NIDDM /Adult onset – 80%.
z MODY – 5% maturity onset - Genetic
z Gestational Diabetes
z Secondary DM – (secondary to other dis.)
z Pancreatitis/tumors/Hemochromatosis.
z Infectious – congenital rubella, CMV.
z Endocrinopathy, downs.
z Drugs – Corticosteroids.
Pathogenesis of Type I DM
HLA-DR3/4 Environment
Viral infe..? Autoimmune Insulitis
• PS Glomerulonephritis Ab to ß cells/insulin
• Graves, Hashimoto thyroiditis.
• Rheumatic heart disease
• SLE, Collagen vascular disease
• Rheumatoid arthritis.
ß cell

Type I / IDDM Insulin deficiency

Progression of Type I
Pathogenesis of Type II DM
Genetic / Obesity /
ß cell defect Life style ?

Abnor. Secretion
Insulin Resistance

IDDM Insulin Def.
ß cell
“Things may come to those who
wait, but only the things left by
those who hustle.”
– Abraham Lincoln
What type?
1. 56 year male obese II NIDDM

2. 30 year female following II GDM

3. 8 year old boy.
4. 24 year female with Cushing’s Sec IDDM
5. 68 Year male following Sec IDDM
Carcinoma of pancreas.
6. 34 year male with extensive Sec IDDM
Type-I Type-II
z Less common z More common
z Children < 25 Years z Adult >25 Years
z Insulin- Dependent z Insulin Independent *
z Duration: Weeks z Months to years
z Acute Metabolic z Chronic Vascular
complications complications.
z Autoantibody: Yes z No
z Family History: No z Yes
z Insulin levels: very low z Normal or high *
z Islets: Insulitis z Normal / Exhaustion
z 50% in twins z 60-80% in twins
Insulitis – Type I

Islets in Type II Diabetes:
Loss of ß cells, replaced by Amyloid deposits (hyalinization)
Islets in Type II Diabetes:
Loss of ß cells, replaced by Amyloid deposits (hyalinization)
z Short term Complications: (metabolic)
z Hypoglycemia
z Diabetic Ketoacidosis
z Non Ketotic hyperosmolar diabetic coma
z Lactic acidosis
z Long term Complications:(Angiopathy)
z Microngiopathy - Retinopathy,
Nephropathy, Neurophathy, dermatopathy.
z Macroangiopathy – Atherosclerosis.
Microangiopathy Pathogenesis:

¾ Hyperglycemia chronic.
¾ Glycosylation of basement membrane
proteins Æ Leaky blood vessels.
¾ Excess deposition of proteins –
glycosylation cycle.
¾ Thick and Leaky blood vessels.
¾ Narrow lumen
¾ Ischemic Organ damage...
Diabetic Microangiopathy

¾ Glucose
¾ Glycosylation
¾ BM damage leak
¾ ‘AGE’ deposition Diabetic
z Sensory Æ Motor (myelin)
z Peripheral Neuropathy
z Bilateral, symmetric
z Progressive, irreversible
z Paraesthesia, pain, muscle
z Visceral neuropathy
z Cranial nerve – diplopia, Bell palsy
z GIT- constipation, diarrhoea
z CVS – orthostatic hypotension

Myelin loss in nerve

Chronic Polyneuropathy

Claw foot – Dermopathy & Neuropathy

Diabetic Amyotrophy

Painful muscle wasting

Diabetic Neuropathic ulcer
Neuropathic ulcer

¾ peripheral sensory
neuropathy, Trauma &
¾ Ischemia, callus
formation, and edema.
Neuropathic ulcers

Painless, surrounded by callus
At pressure points.
associated with good foot pulses
May not be associated with gangrene
z Nodular Glomerulo
z Common morbidity &
z Deposition of ‘AGE’
Advanced Glycosylation
End-products as nodules.
z Nephrotic syndrome
z Pyelonephritis
z End stage renal failure
Diabetic Nephropathy
Microangiopathy, atherosclerosis & infections:
z Diffuse or nodular diabetic
glomerulosclerosis (Kimmelstiel Wilson Sy)
z Renal arteriolosclerosis & atherosclerosis

z Necrotizing renal papillitis.

z Pyelonephritis.

z End stage kidney.

Nodular Glomerulosclerosis –
KW lesion.
Diabetic Glomerulosclerosis

Hyaline nodules
Diabetic Glomerulosclerosis
z Non Proliferative
z Microaneurysms,
z Dot blot hemorrhages
z Hard and soft exudates
z Cotton wool – infarcts
z Macular edema.
z Proliferative.
z Neovascularization
z Retinal detachment.
Normal Retina
Diabetic Retinopathy

Cotton wool spots

Diabetic Retinopathy

Dot blot – Hemorrhages / Microaneurysms

Diabetic Retinopathy

Pre retinal Hemorrhage - detachment

Diabetic Retinopathy

Advanced fibrous plaques

“The past cannot be changed, but the
future can.. by actions in the present
time.” --BK

Past is history,
Future is mystery
Present is the gift…!
Label the diagram.
1. Hard dep.
2. Optic disc
3. Macula
4. Blot hem
5. Cotton wool
Macroangiopathy Atherosclerosis

z Dyslipidemia
z ↓ HDL
z Non-Enzymatic Glycosylation
z ↑ Platelet Adhesiveness
z ↑ Thromboxane A2
z ↓ Prostacyclin
z Endothelial damage Æ Atherosclerosis
z MI, CVA, Gangrene of Leg (PVD), Renal
Slide Show
Diabetic Gangrene
Fungal infections: Candidiasis

With Polycythemia
Blood vessel calcification:

Amputated thumb
Acanthosis Nigricans

¾Insulin resistance…
Acanthosis Nigricans

¾Insulin resistance…
Label the diagram.
1. Capillary
2. Nodule – AGE
3. Bowman caps
4. Hyaline arteriolo
sclerosis in
Infections in Diabetes:
z Decreased metabolism – low immunity.
z Decreased function of lymphocytes &
neutrophils – glycosylation.
z Glycosylation of immune mediators. Ab
z Capillary thickening – impaired inflammation.
z Ischemia & infarctions.
z Increased glucose (alone is not the cause*)

z Diabetes Æ State of immunosuppression.

Laboratory Diagnosis:
z Urine glucose - dip-stick –Screening
z Random or fasting blood glucose (<11)
z Fasting > 7mmol, Random >11mmol
z If Fasting level is between 7-11 then OGTT

z HbA1c - for follow-up, not for diagnosis

z Fructosamine - for long term maintenance.
Points to remember:
z Disorder of metabolism – Insulin
z Type-I Children, Acute, Metabolic compl.
z Type-II Adults, Chronic, Vascular compl.
z Angiopathy (micro/macro),
z Heart, Brain, Kidney, Retina, Skin, BV.
z Increased Infections – know reasons.
z Hypoglycemia is more dangerous. Not hyper
z Glucose control is critical *
z FBS, GTT & HbA1C.
z How – Ketoacidosis?
z How – hypoglycemia ?
z Angiopathy – Macro & Micro ?
z Infections in
z Types of retinopathy ?
z Diabetes insipidus ?
z Nephrotic / Nephritic syndrome ?
z Kidney damage in Diabetes ?
“It's not that I'm so smart,
it's just that I stay with
problems longer”
--Albert Einstein