Download Diabetes Mellitus

Diabetes Mellitus
Lec.10
• Glucose is a major energy substrate.
• The body’s source of glucose are:
a) dietary carbohydrate b) glycogenolysis
c) gluconeogenesis
• Physiologically there are two important
hormones control glucose homostasis:
I) Insulin II) glucagon
• Disordered glucose homostasis can lead to
hyperglycemia or hypoglycemia.
Insulin
• Insulin secretion is stimulated by various
gut hormones.
• Insulin promotes the removal of glucose
from the blood by stimulating glucose
transporter from the cytoplasm to the cell
membrane (adipose tissue and skeletal
muscle).
• It stimulate glucose uptake in the liver.
• It stimulate glycogen synthesis.
• Binding of insulin to its receptor leads to:
-activation of protein phosphatase
- dephosphorylate glycogen synthase and
phosphorylase kinase.
• Insulin exerts controle over glycolysis and
gluconeogenesis.
glucagon
• It secreted by the α cells of pancreas.
• Its secretion is ↓ by rise in the blood
glucose conc.
• Its action is oppose of insulin
• It stimulates hepatic glycogenolysis,
lipolysis and ketogenesis.
Aetiology and pathogenesis of DM
• Diabetes mellitus is a metabolic disorder.
• Defect of insulin → disturbances in
carbohydrate,fat,protein metabolism
→chronic hyperglycemia.
• DM can occur secondary to other diseases
e.g.chronic pancreatitis and conditions of
increased secretion of hormones opposed
to insulin.(cushing’ssyndrome,Acromegaly)
• Most cases of DM are primary, not
associated with other conditions.
• Type I DM→ damage of pancreatic cells
• Type I DM usually in younger people
→developing over days or weeks
• Type II DM → insufficient insulin is
secreted or resistant to its actions.
• Type II DM → in the middle aged (40y), in
obese young people.
• It increase by increasing age (over 75y).
• Used terms: insulin dependent, juvenile
onset, non- insulin dependent are obsolete.
Pathophysiology and clinical features
• Related directly to the metabolic
disturbance
• Related to the long term complication.
Hyperglycaemia
• It is the increase of production of glucose
by the liver and decrease the removal of
glucose from blood.
• In the kidneys, filtered glucose is normally
completely reabsorbed in tubules.
• Glucose conc. must be above 10mmol/L
(the renal threshold).
• Reabsorption becomes saturated and
glucose appear in the urine.
• Glycosuria results in an osmotic diuresis
i.e increasing water excretion and raising
plasma osmolality.
• Symptoms of polyuria.
Long term complications of diabetes
These complications occur in both typeI and
type II
Microvascular complications
• Nephropathy
• Neuropathy
• Retinopathy
Macrovascular complications
• Atherosclerosis and polydipsia.
The common pathological feature in
microvascular disease is narrowing of the
lumens of small blood vessels due to the
prolonged exposure to ↑↑ glucose conc.
How?
1. ↑↑ formation of sorbitol → accumulation
of sorbitol in the cell → osmotic damage.
2. Formation of advanced glycation end
products.
•
• Glycation (sometimes called nonenzymatic glycosylation) is the result of a
sugar molecule, such as fructose or
glucose, bonding to a protein or lipid
molecule without the controlling action of
an enzyme.
• Glucose can react with amino groups in
proteins to form glycated plasma and
tissue proteins.
• These can undergo cross-linking and
accumulate in vessel walls and tissues lead
to structural and functional damage.
• Diabetes → Abnormalities of lipids and
glycation of lipoproteins.
• Oxidtive stress.