"Never offer the devil a

ride. He will always want to

be in the driving seat…!"
BK.
Pathology of
Diabetes
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.

 Introduction
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,
liver)
z High glucose outside
z Glycosylation damage (BV)
z Polyol products – osmotic damage*
 Classification
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
Genetic
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
Destruction

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

Relative
IDDM Insulin Def.
ß cell
exhaustion
Type II NIDDM
“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

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

Insulinitis
 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)
 Complications:
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
Normal

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

Myelin loss in nerve

Chronic Polyneuropathy

Claw foot – Dermopathy & Neuropathy

Diabetic Amyotrophy

Painful muscle wasting

Diabetic Neuropathic ulcer
 Neuropathic ulcer

Etiology:
¾ peripheral sensory
neuropathy, Trauma &
deformity.
Factors:
¾ Ischemia, callus
formation, and edema.
Neuropathic ulcers

FEATURES:
Painless, surrounded by callus
At pressure points.
associated with good foot pulses
May not be associated with gangrene
 Nephropathy
z Nodular Glomerulo
Sclerosis.
z Common morbidity &
mortality.
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
 Retinopathy
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
Insufficiency
Atherosclerosis:
Slide Show
Diabetic Gangrene
Fungal infections: Candidiasis
Macrosomia

With Polycythemia
 Blood vessel calcification:

Amputated thumb
Cataract
Acanthosis Nigricans

¾Insulin resistance…
Acanthosis Nigricans

¾Insulin resistance…
Label the diagram.
1. Capillary
2. Nodule – AGE
3. Bowman caps
4. Hyaline arteriolo
sclerosis in
arteriole.
 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.
 Questions..
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