“Age is an issue of mind over matter.
If you don't mind… it doesn't matter…!”
- Mark Twain
Pathology of Diabetes
Dr. Venkatesh M. Shashidhar Senior Lecturer in Pathology Fiji School of Medicine
Diabetes Mellitus
Disorder of metabolism (Carb, Prot & Fat) Due to Absolute or relative deficiency of insulin. Characterized by hyperglycemia.
Clinically : Polyuria, Polydypsia, Polyphagia.
Classification
Primary DM.
o Type I – IDDM / Juvenile – 10%. o Type II – NIDDM /Adult onset – 80%. o MODY – 5% maturity onset - young - Genetic
Secondary DM – islet destruction.
o o o o Infectious – congenital rubella, CMV. Pancreatitis/tumors/Hemochromatosis. Endocrinopathy, gestational DM, downs. Drugs – Corticosteroids.
Normal Pancreatic Islets:
ß cells Glucagon cells
Pathogenesis of Type I DM
Genetic HLA-DR3/DR4 Environment ? Viral infe..??
Autoimmune Insulitis
ß cell Destruction
Severe Insulin deficiency
Type I DM
Pathogenesis of Type II DM
ß cell defect Genetic Abnormal Secretion Environment Obesity ??? Insulin resistance
Relative Insulin Def.
ß cell exhaustion
Type II DM
IDDM
Insulitis – Type I
Insulinitis
Islets in Type II Diabetes:
Loss of ß cells Amyloid deposits Hyalinization
Complications:
Short term Complications: (metabolic)
o Hypoglycemia o Diabetic Ketoacidosis o Non Ketotic hyperosmolar diabetic coma o Lactic acidosis
Long term Complications:(microangiopathy)
o Angiopathy, Retinopathy, Nephropathy, Neurophathy
Long term Complications:
Angiopathy
o Atherosclerosis o Hyaline arteriolosclerosis o Diabetic microangiopathy
Nephropathy
o Nodular glomerulosclerosis
Retinopathy
o Non Proliferative & Proliferative
Neuropathy
o Peripheral axonal neuropathy
Pathogenesis of Microangiopathy:
1. Long standing diabetes
2. Glycosylation of BV proteins. 3. Protein deposits in the BM. 4. Thick and Leaky blood vessels 5. Exudation & Ischemia
6. End Organ damage...
“Diabetic Micro-angiopathy is the primary cause of diabetic …pathies” (hyaline arteriolosclerosis)
Microangiopathy
Pathogenesis of Complications
Neuropathy
Angiopathy Atherosclerosis
Atheroma Coronary Artery:
Diabetic Gangrene
Diabetic Gangrene – Amp.
Candidiasis
Pathogenesis of Retinopathy
Normal Retina
Diabetic Retinopathy
Cotton wool spots
Proliferative Retinitis:
Neovascularization Haemorrhagia Fibroplasia Retinal detachment Laser cauterization
Cataract
Pathogenesis of Nephropathy
Diabetic Glomerulosclerosis
Hyaline nodules
Diabetic Glomerulosclerosis
Laboratory Diagnosis:
Urine glucose - dip-stick –Screening Random or fasting blood glucose (<11) Fasting > 7mmol, Random >11mmol If Fasting level is between 7-11 then OGTT
HbA1c - for follow-up, not for diagnosis Fructosamine - for long term maintenance.
Take home points:
Type-I – Young, Acute Metabolic complications - Ketoacidosis. Type-II - Chronic Vascular complications
o Microangiopathy – Kidney,Retina,Brain, BV.
Hypoglycemia is more dangerous.
Take home points:
Duration & level of hyperglycemia are directly proportional to Chronic (Vascular) complications. Infections are due to microangiopathy and ischemia, immuno suppression and lastly hyperglycemia.