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Diabetes Mellitus

Metabolically DM is a multiorgan catabolic


response caused by an insufficiency of insulin.
Type I DM (5-10% of all diabetics western)
Insulin-dependent diabetes mellitus (IDDM) /
juvenile onset DM
Type II DM (90-95% of all diabetics western)
Insulin-independent DM / Non-insulin
dependent DM (NIDDM) / adult onset DM.

Diabetes Mellitus
Type I Diabetes Mellitus / IDDM
Autoimmune disorder that destroys the pancreatic beta cells
Insulin deficit hyperglycemia
Favored by genetic predisposition
1st degree children of diabetic parents: 5-10% risk
Risk is 5x higher for children of a diabetic father than of a
diabetic mother
Insulin deficit decreased glucose uptake by pancreatic cells
increased glucagon level:
hepatic glycogenolysis & gluconeogenesis
hepatic glucose output hyperglycemia
lypolisis FFA A-CoA TCA
ketone bodies
Hyperglycemia osmotic diuresis
glucosuria
Treated by insulin replacement

Diabetes Mellitus
Type II DM (90-95% of all diabetics western)
Insulin-independent DM / Non-insulin dependent DM (NIDDM) / adult
onset DM.
Resistance to insulin, rather than lack of insulin, or both (late stage)
Insulin levels may be normal, lowered or elevated
Strongly favored by genetic predisposition
Environment
Excessive caloric intake, obesity
Metabolic alterations are less pronounced than type I
Resistance to insulin
decreased glucose uptake by pancreatic cells increased
glucagon level
hepatic glucose output hyperglycemia
lipolysis increased FFA
decreased glucose uptake by insulin-sensitive cells hyperglycemia
Corrected by diet, weight loss

Exercise
Decreases insulin secretion (sympathetic effect on

pancreatic B cells alpha adrenergic receptors


predominance)
Increases the number of GLUT-4 molecules
Recruits GLUT-4 molecules to cell membrane
Increases the sensitivity of insulin receptors

Exercise for diabetic patients, particularly type II diabetes


mellitus (Non Insulin Dependent Diabetes Mellitus / NIDDM)

Metabolic Consequencies of Insulin Insufficiency


Insulin insufficiency
Hyperglycemia
Glycosuria

Polyuria

Catabolism of macromulecules
Protein degradation
(muscle wasting)
Amino acids
Carbon skeletons

Polydipsia

Triglyceride degradation
(reduction of fat stores)
Fatty acid oxidation
ATP

Excess acetyl Co-A

Hepatic
glucose synthesis

Ketone synthesis
Ketonuria

Ketonemia

C.J. Coffee: Integrated Medical Sciences: Metabolism 1 st ed 1998

Effects of Insulin Deficiency


Insulin deficiency (and glucagon excess)

Decreased
glucose uptake

Hyperglycemia,
glycosuria,
osmotic diuresis,
electrolyte depletion

Increased
protein catabolism

Increased plasma
amino acids,
nitrogen loss in urine

Dehydration,
acidosis,
Coma,
death

Increased
lipolysis

Increased plasma FFA,


ketogenesis,
ketonuria,
ketonemia

Glucose toxicity in Diabetes Mellitus

Hyperglycemia excess glucose uptake by insulin-independent cells:


peripheral nerves, retina, lens, basement membrane of kidneys, small blood
vessels chronic complications of DM that caused by glycosylated protein
and polyol formation

Glycosylation of protein:
Glucose + Protein Schiffs base Glycosylated protein
Lens of the eyes, peripheral nerves, basement membrane of kidneys

Polyol formation:
Glucose sorbitol
Peripheral nerves, lens, renal glomeruli, seminal vesicles