Complications of Diabetes

What is Diabetes Mellitus?

Chronic metabolic disorder characterized- persistent hyperglycemia, altered metabolism of lipids, carbohydrates and proteins.

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

diabetesnon-insulin-dependent diabetes mellitus (NIDDM)

III. Gestational diabetes mellitus (GDM)

American Diabetes Association

Complications of diabetes mellitus

Acute (Metabolic) Chronic (Angiopathy)

Macro Vascular Complications

Micro Vascular Complications

Mechanism of Complications of Diabetes

Mechanisms causing diabetic complications-1

Accumulation of SorbitolPolyol (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

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

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).

Pathological Consequencesof 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.

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

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

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

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

Microvascular Complications of Diabetes-3

Neuropathy

Nerve fibres degenerate Blood vessels supplying the nerves are ‘grossly

diseased’