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z Glucortocoids z ↑ Glucose
z Glucagon z ↑ Glucose
z Epinephrine z ↑ Glucose
Cellular Glucose Uptake
Insulin Requiring Non-Insulin Requiring
z Striated Muscle z Blood Vessels
z Fibroblasts z Kidney
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
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
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 Pyelonephritis.
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
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*)