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Metabolic changes and complications of Diabetes Mellitus with diagrams

This is a review of the metabolic changes that occurs in patients with D.M .
This changes are similar to that occur during fasting or starvation with the exception of hyperglycemia.
The changes are mainly due to decreased insulin action.

I- Changes in Carbohydrate metabolism :

- Decreased glucose uptake and oxidation by tissues, which produce decrease in ATP production espicially in muscles leading to muscle weakness .
Diabetes-Mellitus

- Decreased glucose utilization ( -- Glycogenesis and lipogenesis )

- Increased glucose formation ( Glycogenolysis and gluconeogenesis )
The net result is Hyperglycemia .
- Glucosuria occurs when blood glucose level exceeds 180 mg/dl (renal threshold) .

II- Changes in Lipid metabolism 

- Decreased lipogenesis and increased lipolysis in adipose tissues produce loss of weight and increase the release of free fatty acids .

- Over mobilization of depot fat may cause Fatty liver .

- Hypercholesterolemia and hypertriacylglycerolemia (Hyperlipidemia) may result from increased synthesis and decreased clearance of plasma lipoproteins (Insulin induces synthesis of plasma lipoprotein lipase in adipose tissue) .

- Increased oxidation of free fatty acids increases ketogenesis in liver which may lead to ketosis and acidosis in severe cases (Diabetic Keto-Acidosis) which may be fatal .

III- Changes in Protein metabolism 

- Increased protein catabolism and decreased protein synthesis (Negative Nitrogen balance) produce increase in non-protein nitrogenous (NPN) compounds in urine .

-Decreased protein synthesis leads to increased sensitivity to infection and delayed healing of wounds .

IV- Vascular complications

-These include atherosclerosis, hypertension, kidney failure, myocardial infarction and neuropathy .
- Most of these complications are due to damage of the vascular system.
- It is now believed that most of that damage is initiated by hyperglycemia as follows:
- High blood glucose levels promotes glycosylation of protein molecules .glycosylated proteins produce complex products (aggregates) with cross linkages that cause extensive damage to CVS and promote atherosclerosis which decrease the efficiency of vascular system.
-Hypercholesterolemia and hypertriacylglycerolemia add another risk factor for atherosclerosis .

V- Diabetic cataract 

Due to accumulation of Sorbitol, which produces osmotic damage of the lens .

VI- Diabetic retinopathy, nephropathy and neuropathy 

These complications are due to both vascular damage and  accumulation of Sorbitol .

VII- Other changes

- Glucosuria produces polyurea, dehydration and polydipsia (excessive water drinking) .
- Polyphagia due to decreased glucose utilization by brain centers .
- Polyurea leads to loss of Electrolytes (sodium and potassium) .
- Proteinuria in case of renal failure .
Summary of important changes in D.M
Diabetes-Mellitus
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Tamer Mobarak

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