UNDERSTANDING DIABETES MELLITUS COMPLICATION

here are complications of diabetes mellitus:

Diabetic retinopathy

Damage of of pericyte covering endothelium causing weakening of blood vessels and cause microaneurysm and increase permeability resulting in protein and lipid leakage

Hyperglycemia also increase proliferative processes cause formation of abnormal vessels resulting in haemorrhage and finally cause visual problems up to blindness.

Diabetic nephropathy

Complication of diabetes mellitus :

1.   Non nephrotic  proteinuria(microalbuminemia)
2.  Nephrotic syndrome
3. Renal failure

Proteinuria:

Formation of microalbuminemia results fromm loss of negative charge of basement membrane in glomeruli because AGE(advance glycated endproduct) decrease of heparin sulphate(negative charge)

Nephrotic syndrome:

Which is loss of negative charge and increase of basement membrane pore size due to :

1.       Increase of intraglomerular pressure because of glycosuria, increase glomerular filtration rate and cause hyperfiltration

2.       Imbalance between several growth factors

3.       Non enzymatic glycation of basement membrane constituents

Chronic renal insufficiency:

Diabetes mellitus causing deposition of glucose to extracellular space causing thickening of basement membrane and diffuse proliferation of mesangial cells eventually nodular deposition of hyaline to mesangium.

Gradually mesangial cells infringe on capillary lumen casue decrease glomerular filtration up to complete obliteration result in renal insufficiency.

Diabetic neuropathy

Diabetes mellitus effect nervous system in our bodies.

It cause microangiopathy of small artery that supply nerve fibers. This is because hyperglycemia .

It also cause distal neuropathy where it cause symmetric loss of skin sensitivity resulting in diabetic foot and motor problems.

DM also cause wegetative nerve dysfunction :

1.       Impotention and urine incontenetia

2.       Stomach dystonia and diarhoeas

3.       Anhidrosis(can not sweat properly) or profuse sweating

Macroangiopathy

A disease of the large blood vessels in which fat and blood clots build up and stick to the vessel walls, blocking the flow of blood. Types of macroangiopathy include coronary artery disease (macroangiopathy in the heart), cerebrovascular disease (macroangiopathy in the brain), and peripheral vascular disease (macroangiopathy that affects, for example, vessels in the legs).when formation of artherosclerosis increases, this cause arterial hypertension, coronary heart disease, infarctions, decrease perfusion of the legs result in ischemic changes and neuropathy finally diabetic foot with ulceration and formation of gangrene(black foot)

DM accelerated atherosclerosis by formation of:

1.   Advanced glycated end products(AGE)
2.     Dyslipoproteinemia-increase VLDL, cholesterol,LDL, and decrease HDL

AGE:

Formation of AGE is non receptor mediated mechanisms which effect extracellular matrix especially collagen cross linking. Its also enhanced synthesis of extracellular matrix components, trapping of LDJ in the subendothelium and this cause quenches nitric oxide.

Hyperglycemia also modified lipoprotein by glycosylation. Glycosylated LDL has lower recognition by cellular LDL receptor and cause high concentration of LDL in blood and increase susceptibility of LDL to oxidative modification

Its also cause endothelial dysfunction by increasing permeability of endothelial cell monolayers, procoagulant activity, expression of adhesion molecules and intracellular oxidative stress.

Dyslipoproteinemia:

 DM type 1

When there is lack of insulin, reduced inactivation of lipoprotein lipase and increased activity of hormone sensitive lipase causing hyperlipoproyeinemia resulting rapid formation of artherosclerosis.

DM type 2

Concentration of insulin normal at the beginning , when there are certain factor that cause insulin resistance for example inflammation, hyperglycemia or increased free fatty acids in blood, this cause muscle and adipose tissue decrease uptake of glucose resulting in hyperglycemia. When high glucose in blood, this glucose must be converted to glycogen in liver, but when the capacity of liver to store glycogen reached maximum, liver must convert glucose tto lipoproteinemia resulting in hyperlipoproteinemia. Hyperlipoproteinemia increase activity of lipoprotein lipase and decrease activity of hormone sensitive lipase resulting in fat depositon causing obesity. Hyperlipoproteinemia also increase formation of artherosclerosis.