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Chapter 32
Diabetes Mellitus and the
Metabolic Syndrome
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Anabolism and Catabolism
available foodstuffs
(in blood)
glucose
amino acids
free fatty acids
Anabolism
insulin,
anabolic
steroids
stored foodstuffs
(in cells)
Catabolism
glucagon,
epinephrine,
cortisol
liver can convert amino acids
and free fatty acids into
ketones
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
glycogen
proteins
triglycerides
Insulin and Glucagon Are the Main
Controls
available foodstuffs
(in blood)
glucose
Anabolism
insulin ,
stored foodstuffs
(in cells)
anabolic
steroids
glycogen
amino acids
Catabolism
glucagon ,
proteins
free fatty acids
epinephrine,
cortisol
triglycerides
liver can convert amino acids
and free fatty acids into
ketones
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
Tell whether the following statement is true or false.
Anabolic reactions release energy.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
False
Rationale: Anabolic reactions use energy to
build/produce/synthesize (like building proteins from
amino acids). Catabolic reactions break down
substances, releasing energy in the process (like
digestion).
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Scenario
Two women have benign pancreatic tumors.
• In one, the tumor is an insulinoma that secretes insulin
• In the other, the tumor is a glucagonoma that secretes
glucagon
Questions:
• What differences do you expect to see between these
two women? Why?
• Both of the women have arthritis, but only one is being
treated with corticosteroids. Which one? Why is the
other not receiving corticosteroids?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
The Pancreas
pancreas
exocrine
pancreas
endocrine
pancreas
releases digestive
juices through a
duct
releases hormones
into the blood
to the
duodenum
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
endocrine
pancreas:
islets of
Langerhans
alpha
cells
glucagon
beta cells
delta cells
PP cells
insulin
and amylin
somatostatin
pancreatic
polypeptide
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Functions of Pancreatic Hormones
• Glucagon: causes cells to release stored food
into the blood
• Insulin: allows cells to take up glucose from the
blood
• Amylin: slows glucose absorption in small
intestine; suppresses glucagon secretion
• Somatostatin: decreases GI activity; suppresses
glucagon and insulin secretion
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
Which pancreatic hormone decreases blood glucose levels?
a. Glucagon
b. Insulin
c. Amylin
d. Somatostatin
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
b. Insulin
Rationale: Insulin allows cells to take glucose from the
blood and use it for energy/to make ATP. Because it
stimulates movement of glucose out of the blood and
into the cells, blood glucose levels decrease when insulin
is released.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Discussion
Think back on your day so far.
• When do you think you had your highest insulin
levels?
• When do you think you had your lowest insulin
levels?
• When did you have your highest glucagon
levels?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Discussion
Review the figure on insulin’s actions.
• If someone lacks insulin, what happens to his:
–
Blood glucose levels?
–
Blood amino acid levels?
–
Blood pH?
–
Intracellular fat levels?
–
Intracellular protein levels?
–
Cell growth?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Discussion
Review the following diagrams on
anabolism/catabolism and insulin’s mechanism of
action.
Questions:
• Identify five things that could go wrong to cause
increased blood glucose
• Which of the cases you identified would be least
likely to respond to insulin?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Anabolism and Catabolism
available foodstuffs
(in blood)
glucose
amino acids
free fatty acids
Anabolism
insulin,
anabolic
steroids
stored foodstuffs
(in cells)
Catabolism
glucagon,
epinephrine,
cortisol
liver can convert amino acids
and free fatty acids into
ketones
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
glycogen
proteins
triglycerides
Types of Diabetes Mellitus
• Type 1: pancreatic beta cell destruction predominantly
by an autoimmune process
• Type 2: a combination of beta cell dysfunction and
insulin resistance
• Other
– Genetic defects in insulin production
– Genetic defects in insulin action
– Diabetes secondary to other diseases
– Drug interactions
• Gestational diabetes mellitus
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Pathogenesis of Type 2 Diabetes
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
Tell whether the following statement is true or false.
Type 2 DM is more common than type 1 DM.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
True
Rationale: Type 1 DM is autoimmune (juvenile diabetes is
type 1), and affects only 5–10% of the diabetic
population. Type 2 DM is associated with risk factors like
obesity, poor diet, and sedentary lifestyle; 90–95% of
diabetics suffer from this type.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Metabolic Syndrome
• Abdominal obesity
• Increased blood triglyceride levels
• Decreased HDL levels
• Increased blood pressure
• Increased fasting plasma glucose
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Treatments for Type 2 diabetes
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Acute Complications of Diabetes
• Diabetic ketoacidosis
• Hyperglycemic hyperosmolar nonketotic coma
• Hypoglycemia
• Somogyi effect
• Dawn phenomenon
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Acute Complications of Diabetes (cont.)
Discussion
• How would hyperglycemia with ketoacidosis cause:
– Heavy breathing?
– Polyuria?
– Dehydration?
• Which of these would you not see in hyperglycemia
without ketoacidosis?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Scenario
You find a man collapsed on the sidewalk.
• He is wearing a diabetic alert bracelet and has an
insulin syringe in his briefcase
Questions:
• Does he need insulin?
• Why or why not?
• What signs might help you tell whether he has a
hyperglycemic or hypoglycemic problem?
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Chronic Complications of Diabetes
Mellitus
• Increased glucose levels allow glucose to bind to
proteins in:
– Hemoglobin  Hb A1C has higher O2 affinity
– Basement membranes of blood vessels
º Nephropathy
º Retinopathy
º May cause increased risk of atherosclerosis
– Lens  cataracts
(Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams & Wilkins and
Greenspan, F. & Gardner, D. G. [2004]. Basic and clinical endocrinology [7th ed.]. McGraw-Hill.)
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Osmolarity in Diabetes Mellitus
• When blood glucose is
high, increased blood
osmolarity can cause
cells to shrink
• Nerve cells produce
intracellular osmoles to
keep their osmolarity
balanced with the blood
A
Hypotonic
cell A
shrinks
Cell B is in
osmotic
balance
(Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams &
Wilkins.)
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
B
Osmolarity in Diabetes Mellitus (cont.)
• When the client brings
blood glucose back to
normal, the nerve cells
are hyperosmolar to the
blood and gain water,
swelling
• Nerve damage may be
caused by swelling,
demyelination, and lack
of O2 secondary to
vascular disease
A
Hypertonic
cell B
swells
Cell A is in
osmotic
balance
B
(Porth, C. M. [2005]. Pathophysiology [7th ed.]. Lippincott Williams &
Wilkins.)
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Diabetic Neuropathy
• Somatic neuropathy
– Diminished perception of vibration, pain, and
temperature
– Hypersensitivity to light touch; occasionally,
severe “burning” pain
• Autonomic neuropathy
– Defects in vasomotor and cardiac responses
– Impaired motility of the gastrointestinal tract
– Inability to empty the bladder
– Sexual dysfunction
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Question
Which of the following is not a complication of diabetes
mellitus?
a. Nephropathy
b. Retinopathy
c. Neuropathy
d. All of the above are complications of DM.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Answer
d. All of the above are complications of DM.
Rationale: Nephropathy and retinopathy are caused by
increased blood glucose levels that cause binding of
excess glucose to the basement membranes of the
blood vessels of the kidneys and eyes. Neuropathy is
due to swelling and demyelination of nervous tissue.
Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins