Dr.

Farrukh Majeed
Department of Physiology
Diabetes Mellitus
 Learning objectives
At the end of this lecture student should be able
to:
• Analyze pathophysiology of type 1 and 2
Diabetes mellitus
 Definition
Diabetes mellitus is by far the most common of
all endocrine disorders.
Diabetes mellitus is a syndrome of impaired
carbohydrate, fat, and protein metabolism
caused by either lack of insulin secretion or
decreased sensitivity of the tissues to insulin.
 DM: Types
There are two general types of diabetes mellitus:
1. Type I diabetes or insulin-dependent diabetes mellitus
(IDDM),  lack of insulin secretion.
2. Type II diabetes or non–insulin-dependent diabetes mellitus
(NIDDM), decreased sensitivity of target tissues to the
metabolic effect of insulin. This reduced sensitivity to insulin
is often called insulin resistance.
 Type I diabetes/ IDDM
• Injury to the beta cells of the pancreas or
diseases that destruction of beta cells
absolute deficiency of insulin.
• occurs more in children juvenile diabetes
mellitus
• may develop very abruptly, over a period of a
few days or weeks,
DM-1: pathogenesis
 Type II DM/NIDDM
• more common than type I 90 per cent of all
cases of DM.
• In most cases, the onset occurs after age 30,
often between the ages of 50 and 60 years
adult-onset diabetes mellitus
• disease develops gradually
• increased plasma insulin concentration
hyperinsulinemia
• Type ll DM  Insulin resistance.
Insulin resistance: diminished sensitivity of target tissues to the metabolic effects of insulin
consequences of diabetes mellitus
• The acute consequences of diabetes mellitus
can be grouped according to the effects of
inadequate insulin action on carbohydrate, fat,
and protein metabolism
 Consequences Related to Effects on
Carbohydrate Metabolism
• Hyperglycemia  from reduced glucose uptake by cells &
increased output of glucose from the liver.
• Glycogenolysis and gluconeogenesis proceed unchecked in
the absence of insulin  hepatic output of glucose increases.
• many of the body’s cells cannot use glucose without the help
of insulin  insulin deficiency glucose unable to move
inside the cell intracellular glucose deficiency “starvation
in the midst of plenty”
• In intracellular glucose deficiency ↑appetite (polyphagia)
• When blood glucose rises  exceeds the tubular
cells’ capacity for reabsorption glucose appears in
the urine glucosuria
• Glucose in the urine exerts an osmotic effect that
draws H2O with it producing an osmotic diuresis 
polyuria (frequent urination).
• The excess fluid lost from the body dehydration,
polydipsia.
• reduction in blood volume  peripheral circulatory
failure
• ↓ cerebral blood flow, ↓ renal perfusion  death
 Consequences Related to Effects on Fat
Metabolism
• ↓Triglyceride synthesis, ↑lipolysis  mobilization of
fatty acids from triglyceride stores  cells largely use
the ↑ blood fatty acids as an alternative energy source.
• ↑ liver use of fatty acids release of excessive ketone
bodies into the blood, causing ketosis., metabolic
acidosis.
• A compensatory measure for metabolic acidosis 
increased ventilation
• Acidosis depresses the brain  diabetic coma and
death
 Consequences Related to Effects on
Protein Metabolism
• shift toward protein catabolism.
• Breakdown of muscle proteins muscle
wasting and weakness, weight loss
• Diabetic child reduction in overall growth
• The increased circulating amino acids 
gluconeogenesis  hyperglycemia
 Long-Term Complications
occur after 15 to 20 years hyperglycemia degenerative
disorders of the blood vessels and nervous system.
• Cardiovascular lesions Heart disease and strokes
• vascular lesions develop in the kidneys  kidney failure
and retinas of the eyes  blindness
• Impaired delivery of blood to the extremities  gangrene,
and toes or even whole limbs may have to be amputated.
• degenerative lesions in nerves  neuropathies that result
in dysfunction of the brain, spinal cord, and peripheral
nerves  pain, numbness, and tingling, especially in the
extremities.
Diagnosis: Diabetes Mellitus
 Treatment: Type 1 DM
• T1DM is a controlled balance of regular insulin
injections timed around meals,
• management of the amounts and types of
food consumed, and
• Exercise
• Cure:
– Pancreases/ Islets cell transplant
– Artificial pancreas device
 Treatment: Type ll DM
• T2DM in conjunction with a dietary and exercise regime.
• Medicine: help the patient’s body use its own insulin more
effectively
– By suppressing liver output of glucose  metformin 
first line therapy.
– By stimulating the beta cells to secrete more insulin
sulfonylureas.
– By blocking enzymes that digest complex carbohydrates,
slowing glucose absorption from the digestive tract
alpha glycosidase inhibitors
 Reading material
• Guyton 11th edition, chapter 78, page 961-976.
• Sherwood 9th edition, page 685- 701