Basic mechanism . inclusive of pathophysiology. Mbbs level.

1. Complications of Diabetes

2. What is Diabetes Mellitus?
Chronic metabolic disorder characterized-
persistent hyperglycemia, altered metabolism of
lipids, carbohydrates and proteins.

3. Etiological Classification
I. Type 1 diabetes - previously known as juvenile diabetes
insulin-dependent diabetes mellitus (IDDM)
II. Type 2 diabetes - previously known as adult-onset diabetes
non-insulin-dependent diabetes mellitus (NIDDM)
III. Gestational diabetes mellitus (GDM)
American Diabetes Association

4. Complications of diabetes mellitus
Acute (Metabolic) Chronic (Angiopathy)
Macro Vascular
Complications
Micro Vascular
Complications

32. Mechanism of
Complications of Diabetes

33. Mechanisms causing diabetic complications-1
Accumulation of Sorbitol
Polyol (Polyhydroxy alcohols) Pathway
 Sorbitol is formed from glucose catalyzed by aldose
reductase
 This pathway is activated in hyperglycemia
 Sorbitol does not cross cell membranes, accumulates
intracellularly and produces osmotic stress.
 Sorbitol normally helps in osmoregulation

34. Consequences of high Sorbitol concentration
• Osmotic damage to cells: caused by impermeable Sorbitol
intracellularly
• Reduction in nerve myoinositol: causes decrease activity of
Na/K ATP Pump- causes decreased nerve conduction
velocity
• Inhibition of nitric oxide (NO) production: results in
vasoconstriction and hypertension
• Increased production of free radicals: which cause oxidative
damage to tissue

35. Mechanisms causing diabetic complications-2
Glycation of Proteins
 Sugars in the blood and inside cells form chemical bonds to proteins and
to DNA by glycation or nonenzymatic glycosylation.
 Over time, the glycated proteins are chemically modified to become
molecular structures called Advanced Glycation Endproducts (AGEs).

36. Pathological Consequences
of Glycation of Proteins in Diabetics
 Crosslinking reduces the flexibility, elasticity and functionality of the
proteins.
 The chemical modifications of glycation and crosslinking can initiate
harmful inflammatory and autoimmune responses.
 Glycation has been found in connective tissue collagen, arterial collagen,
kidney glomerular basement membrane, eye lens crystallins, nerve myelin
proteins and in the circulating low-density lipoprotein (LDL) of the blood.

37. Metabolic injury to large vessels
Heart Brain Extremities
Coronary artery
disease
– Coronary
syndrome
– MI
– CHF
Cerebrovascular
disease
Peripheral vascular
disease
– Ulceration
– Gangrene
– Amputation
Biology of Macrovascular Injury

38. Hyperglycemia
Neuropathy
– Peripheral
– Autonomic
Kidney Nerves
Retinopathy
- Cataract
- Glaucoma
Nephropathy
– Microalbuminuria
– Gross albuminuria
Blindness Kidney failure Amputation
Death and/or disability
Eye
Biology of Microvascular Injury

39. Microvascular Complications of Diabetes-1
Retinopathy: Damage to blood vessels in and around the
retina. It could occur with varying degrees of severity.
Normal ------------- Small hemorrhages --------- Large hemorrhage

40. Nephropathy:
 Glomeruli are damaged in the
kidneys.
 Results in loss of protein
 DIAGNOSTIC VALUE-Normal
microalbumin level is 30mg/24 hours.
 May lead to kidney failure
Microvascular Complications of Diabetes-2

41. Microvascular Complications of Diabetes-3
Neuropathy
 Nerve fibres degenerate
 Blood vessels supplying the nerves are ‘grossly diseased’