Download Pre-test for Glucose Metabolism

UNIT 15
Disorders of Glucose Metabolism
Originally developed by:
Frank MacDonald RN, MN,
Former Clinical Nurse Specialist, Diabetes Clinic,
Foothills Hospital
Revised (2000) by:
Lorraine Anderson, PhD
in consultation with Alison Husband RN, MN
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
1
Unit 15 Table of Contents
Overview ...................................................................................................................... 4
Aim ............................................................................................................................. 4
Objectives .................................................................................................................. 4
Resources ................................................................................................................... 4
Web Links.................................................................................................................. 5
Pre-test for Glucose Metabolism.............................................................................. 6
Section 1: Type 1 Diabetes ...................................................................................... 10
Learning Activity #1 .............................................................................................. 10
Pathophysiology .................................................................................................... 11
Clinical Manifestations .......................................................................................... 12
Evaluation and Treatment .................................................................................... 12
Section 2: Type 2 diabetes ....................................................................................... 16
Pathophysiology .................................................................................................... 16
Etiology.................................................................................................................... 16
Clinical Manifestations .......................................................................................... 17
Evaluation and Treatment .................................................................................... 17
Learning Activity #2 .............................................................................................. 17
Section 3: Acute Complications of Diabetes Mellitus ....................................... 19
Hypoglycemia ........................................................................................................ 19
Diabetic Ketoacidosis ............................................................................................ 20
Hyperosmolar Hyperglycemic NonKetotic Syndrome (HHNKS) ................. 20
Section 4: Chronic Complications of Diabetes Mellitus ................................... 21
Microvascular Disease ........................................................................................... 21
Macrovascular Disease .......................................................................................... 21
Preventing Long Term Complications—The Diabetes Control and
Complications Trial (DCCT)................................................................................. 22
Learning Activity #3 .............................................................................................. 23
Section 5: Gestational Diabetes Mellitus (GDM) ............................................... 24
Final Thoughts........................................................................................................... 25
References .................................................................................................................. 26
Glossary ...................................................................................................................... 27
Acronym List .............................................................................................................. 27
Checklist of Requirements ...................................................................................... 28
Required Readings ................................................................................................. 28
Learning Activities ................................................................................................. 28
Answers to Learning Activities .............................................................................. 29
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Answers to the Pretest ........................................................................................... 29
Answers to Learning Activity #1......................................................................... 29
Answers to Learning Activity #2......................................................................... 30
Answers to Learning Activity #3......................................................................... 31
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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UNIT 15
Disorders of Glucose Metabolism
Diabetes mellitus is a metabolic disease characterized by the presence of
hyperglycemia due to defective insulin secretion, insulin action or both.
Diabetes mellitus is a serious health problem affecting 5% of Canadians.
American data indicates that diagnosis of diabetes may be underestimated
by almost half, which may mean that up to 10% of Canadians are diabetic. In
the United States, in 1995, diabetes mellitus was the seventh leading cause of
death. There is no available data on the cost of the disease in Canada, but
American costs per year are about $98.2 billion—$44.1 billion in direct costs
and approximately $54.1 in indirect costs such as work loss, disability and
premature mortality.
For further statistical information on diabetes mellitus statistics go to:
Intelihealth.com
http://www.intelihealth.com/IH/ihtIH?d=dmtContent&c=203032&p=~br,IHW
|~st,21054|~r,WSIHW000|~b,| - cost
Although the means for controlling the primary metabolic derangement,
hyperglycemia, are available, the continual balancing of blood glucose levels
by patients over a lifetime is problematic.
Nurses are part of the multidisciplinary team who care for people with
diabetes. An understanding of the pathophysiologic mechanisms and
therapeutic interventions will enhance your ability to help people with
diabetes to learn techniques and problem-solving that will improve their
health outcomes.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Overview
This unit contains five parts:
1.
2.
3.
4.
5.
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Acute complications of diabetes mellitus
Chronic complications of diabetes mellitus
Gestational diabetes
Note: Insulin dependent diabetes mellitus (IDDM) is now referred to as
Type 1 diabetes and non-insulin dependent diabetes (NIDDM) is now
referred to as Type 2 diabetes.
Aim
The general aim of this unit is to facilitate your understanding of the
pathophysiology of the different types of diabetes mellitus, as well as the
clinical manifestations, treatment, and complications.
Objectives
On completion of this unit, you will be able to:
1. Classify diabetes mellitus according to type.
2. For Type 1 and 2 diabetes mellitus:
 explain the underlying pathophysiological processes.
 describe the clinical manifestations.
 describe the evaluation and treatment.
 identify the acute complications which may develop.
 identify the long-term complications which may develop,
including the value of intensive treatment
3. Define gestational diabetes mellitus and describe the clinical
manifestations, evaluation and treatment.
Resources
Required
Harris, S.B., & Lank C.N., (1998). 1998 Clinical Practice Guidelines for
the Management of Diabetes in Canada. Canadian Diabetes, 12(1), 3-10.
Canadian Diabetes Association, Guidelines for the Nutritional
Management of Diabetes Mellitus in the Millennium. Retrieved October 26, 2000
from the World Wide Web http://www.diabetes.ca/prof/index.html, pages
3-6.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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Porth, C. M. (2005). Pathophysiology-Concepts of Altered
Health States (7th ed). Philadelphia: Lippincott. Chapter 43.
Print Companion: Disorders of Glucose Metabolism
Learning Activities
Activities for this unit include:
1. Pre-test
2. Learning Activities 1, 2, and 3
Supplemental Materials
Supplemental materials include:
Canadian Diabetes Association, Clinical practice guidelines for the
management of diabetes in Canada. 1998. Retrieved October 26, 2000 from the
World Wide Web http://www.diabetes.ca/prof/publications/cpg98eng.pdf
(Note that this is a more complete version of the guidelines than the
publication indicated in the required reading section.)
Canadian Diabetes Association, CDA Position Statement Regarding the
UKPDS and Revision of Diabetes Clinical Practice Guidelines Accounting for the
UKPDS Results, Retrieved October 26, 2000 from the World Wide Web
http://www.diabetes.ca/prof/cpg_ukpdsposition.html
Web Links
All web links in this unit can be accessed through the Web CT system.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Pre-test for Glucose Metabolism
This unit presumes that you have a basic understanding of the normal
physiology of insulin secretion and blood glucose regulation. Please take the
following PRE-TEST. This test is NOT consistent with the content or style of
the course exams and is a pretest only. If you have difficulty with the pretest, you should review a standard physiology text before commencing the
unit.
The pre-test answers are at the end of this unit.
1. Glycogenolysis is stimulated by
a. human growth hormone
b. steroids and glucagon
c. glucagon and epinephrine
d. insulin and norepinephrine
e. none of the above
2. Which of the following hormones increases the heart rate and raises
blood sugar levels?
a. epinephrine
b. aldosterone
c. oxytocin
d. prolactin
e. none of the above
3. Which one of the following statements about glucagon is NOT true?
It
a. is a polypeptide
b. stimulates glycogenolysis
c. promotes hypoglycemia
d. stimulates gluconeogenesis
4. The hormone insulin promotes
a. the formation of glucose from glycogen
b. the formation of glycogen from glucose
c. the actions of epinephrine
d. the deamination of amino acids
5. The major action of the hormone glucagon is to
a. evoke vasoconstriction
b. cause uterine contractions
c. lower blood calcium ion levels
d. decrease liver glycogen levels
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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6. When blood sugar levels are high
a. alpha islet cells release insulin
b. beta islet cells release insulin
c. alpha islet cells release glucagon
d. beta islet cells release glucagon
e. none of the above
7. Glucagon is produced by the ______ cells in the pancreatic islets
a. beta
b. delta
c. alpha
d. chromaffin
e. oxyphilic
8. Which of the following metabolic processes would result in lowered
blood sugar levels?
a. glycolysis
b. gluconeogenesis
c. glycogenesis
d. glycogenolysis
9. After all of the different kinds of cells have stored all the glucose they
can, any excess glucose present is converted into
a. fat
b. glycogen
c. keto acids
d. amino acids
e. urea
10. During the post-absorptive state, nerve cells utilize __________ as
their major energy source
a. glucose
b. amino acids
c. glycerol
d. keto acids
e. fatty acids
11. Which one of the following metabolic processes will DECREASE
when insulin is present in the blood?
a. glycogen formation
b. amino acid transport
c. keto acid formation
d. lipogenesis
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
12. Which one of the following hormones is NOT secreted in response to
stress?
a. cortisol
b. epinephrine
c. vasopressin
d. renin-angiotensin-aldosterone
e. insulin
13. The actions of insulin include
a. the insertion of additional glucose transporters onto the plasma
membrane of insulin-dependent cells
b. the stimulation of glycogenesis and the inhibition of
glycogenolysis
c. increased insulin secretion in response to a drop in the blood
glucose concentration
d. both A and B are correct
e. all of the above are correct
14. Which one of the following is a metabolic effect of insulin?
a. increased glucose uptake by the cells
b. increased breakdown of fat by the cells
c. decreased uptake of amino acids by the cells
d. both A and B are correct
15. Which one of the following does NOT stimulate insulin secretion?
a. elevated blood amino acid concentration
b. gastrointestinal hormones
c. starvation
d. elevated blood glucose concentration
16. Increased levels of which of the following hormones will NOT result
in increased blood fatty acid levels?
a. glucagon
b. human growth hormone
c. insulin
d. epinephrine
17. The actions of glucagon include
a. decreased blood glucose levels
b. increased breakdown of fat
c. increased hepatic glucose production
d. increased amino acid uptake by the cells
e. increased calcium ion reabsorption by the renal tubules
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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18. Excessive growth hormone levels could cause hyperglycemia
a. TRUE
b. FALSE
19. The formation of glycogen from glucose is known as gluconeogenesis
a. TRUE
b. FALSE
20. Both glucagon and epinephrine will increase lipolysis and
ketogenesis
a. TRUE
b. FALSE
21. The effects of insulin, together with epinephrine, produce a “stress
hyperglycemia” when the sympathoadrenal axis is activated
a. TRUE
b. FALSE
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Section 1: Type 1 Diabetes
. Read Porth – pp. 987- 994.
Type 1 diabetes is diabetes that is primarily a result of pancreatic beta-cell
destruction and thus these patients are prone to ketoacidosis. It is due to an
autoimmune process. The etiology of beta cell destruction is under active
investigation.
Future Possibilities: Santamaria and his colleagues found that treating
mice predisposed to diabetes with a small protein reduced the
production of the problematic T-cells, and halted the progression from
inflammation to diabetes. This means that a VACCINE against Type 1
diabetes may be possible in the future. For more information, go to
University of Calgary Website
http://www.ucalgary.ca/unicomm/newsrelease/diatype1.htm
Note: The fasting plasma glucose diagnostic level for the standard oral glucose
tolerance test OGTT has been lowered from 7.8 mmol/L (140 mg/dl) to 7 mmol/L
Note: First Nation people are three to five times more likely than the
general population to have or develop diabetes. Two thirds of First
Nation people with diabetes are women. For more information, go to
The Canadian Diabetes Association Website
http://www.diabetes.ca/about_diabetes/globe/aboriginal.html
Learning Activity #1
Answers are at the back of this unit.
1. Which of the following lab results are diagnostic of diabetes mellitus:
a. Serial fasting blood glucose values of 6.7, 7.9, 5.4, and 8.1 mmol/L
in one individual.
b. A random blood glucose of 15.3 mmol/L with symptoms of
polydipsia, polyuria, and fatigue.
c. A random blood glucose of 11.1 mmol/L with no symptoms.
2. Which of the following glucose tolerance test results are diagnostic of
diabetes?
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
Fasting
30 min.
60 min.
90 min.
120 min.
11
A
5.7
mmol/L
8.9
11.0
10.2
9.1
B
7.4
mmol/L
10.7
12.2
12.9
11.3
C
4.3
mmol/l
7.9
10.0
12.6
15.9
Pathophysiology
.
Note: There is strong evidence suggesting that genetic susceptibility is
not a sufficient condition for the development of IDDM; only 50% of
genetically identical twins of Type 1 siblings will develop diabetes.
Breaking News: Another note of Canadian pride is some exciting
research being done here at the University of Calgary by Pere
Santamaria. For further information please go to
University of Calgary Website
http://www.ucalgary.ca/unicomm/NewsReleases/diabtype1.htm
The white blood cells referred to here are T lymphocytes specific for beta
pancreatic cells. The reference for the complete article is:
Amrani, A., Verdguer, J., Serra, P. et al 2000. Progression of
autoimmune diabetes driven by avidity maturation of a T-cell population.
Nature. 406(6796), 739-42.
Controversy: The cow milk controversy. Some studies suggest that
exposure to cow's milk at an early age may predispose a susceptible
individual to Type 1 diabetes. This remains controversial.
For a website that supports the cow milk controversy see:
Science News Online
http://www.sciencenews.org/sn_arc99/6_26_99/fob2.htm
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Controversy: Another, possibly more serious controversy, is the view
that vaccinations are an environmental trigger for Type 1 diabetes. Some
parents are resisting vaccinating their children for fear it may trigger
diabetes. For a website that examines this controversy go to
Science News Online
http://www.sciam.com/2000/0300issue/0300infocus.html
Future Possibilities: As discussed above it is possible a vaccine for Type
1 diabetes may be developed. This group is looking at EDIBLE vaccines:
Scientific American Magazine
http://www.sciam.com/2000/0900issue/0900langridge.html
Clinical Manifestations
Note: The main and most important clinical manifestation of Type 1 diabetes
is hyperglycemia which occurs whenever normal blood glucose levels are
exceeded. However osmotic fluid shifting and diuresis are not common until
blood glucose levels typically exceed 12 –16 mmol/L.
Evaluation and Treatment
Know what is meant by glycated hemoglobin – see page 1000.
Harris, SB, & Lank, C.N. (1998). 1998 Clinical Practice Guidelines for
the Management of Diabetes in Canada. Canadian Diabetes, 12(1), 4-8.
Canadian Diabetes Association, Guidelines for the Nutritional
Management of Diabetes Mellitus in the Millennium (pages 3-6). Retrieved
October 26, 2000 from the World Wide Web
http://www.diabetes.ca/prof/index.html
Insulin
Note: Insulin effectiveness depends on:




Location of injection site.
Consistency of timing of injection.
Age or temperature of insulin.
Vascular dilation/constriction.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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Insulin action times vary. Rapid-acting insulin (Lispro) reaches the blood
within 15 minutes after injection. It peaks 30 to 90 minutes later and may last
as long as 5 hours.
Short-acting (regular) insulin usually reaches the blood within 30 minutes
after injection. It peaks 2 to 4 hours later and stays in the blood for about 4 to
8 hours.
Intermediate-acting (NPH and lente) insulins reach the blood 2 to 6 hours
after injection. They peak 4 to 14 hours later and stay in the blood for about
14 to 20 hours.
Long-acting (ultralente) insulin takes 6 to 14 hours to start working. It has no
peak or a very small peak 10 to 16 hours after injection. It stays in the blood
between 20 and 24 hours.
History: Our American textbook has left out an important historical
matter and one of great Canadian pride, namely the discovery of insulin
in 1922 at the University of Toronto by Banting and Best. Banting and the
supervisor of the laboratory MacLeod were awarded the Nobel Prize for
the critical discovery. Banting shared his prize with his assistant Best. See
the web page on Banting and Best by going to
The Public Broadcasting System Website
http://www.pbs.org/wgbh/aso/databank/entries/dm22in.html
Note: Since the publication of the textbook a large study on the intensive
blood glucose control and/or blood pressure control, called the United
Kingdom Prospective Diabetes Study or UKPDS. This study was
published in September 1998, after the Canadian Clinical Practice
Guidelines were developed. To see more information about this study
and how it lead to slight revisions in the 1998 CPG please go to
The Canadian Diabetes Association Website
http://www.diabetes.ca/prof/cpg_ukpdsposition.html
Note: The textbook discusses animal insulin. Most physicians prescribe
human recombinant insulin. This is not human insulin but a form of
insulin produced using recombinant DNA technology. Recombinant
DNA is created when DNA is synthesized in a test tube and transferred
into cells where it can be replicated and expressed as a protein. Here the
gene for human insulin was transferred into microorganisms. These
organisms produce human insulin.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Meal Planning
Note: For your reference the Guidelines for the Nutritional Management
of Diabetes Mellitus in the Millennium may be accessed at
The Canadian Diabetes Association Website
http://www.diabetes.ca/prof/index.html
Exercise
Note: Physical activity can make balancing insulin dosage and food intake
more complicated. The true benefits of exercise in Type 1 diabetes seem to
be in the reduction of other cardiovascular risks that work synergistically
with diabetes. Exercise has many other benefits including increased energy
reserve and an improved outlook on life which are the same with or without
diabetes. Exercise is not recommended for insulin dependent individuals
when their blood glucose is 16 mmol/L or greater and they are ketonuric.
Under these conditions due to inadequate availability of circulating insulin
exercise will exacerbate the ketosis.
Transplantation
Breaking News: Improvements in the isolation and transplantation of beta
islet cells has led to the development of a non surgical transplantation
procedure which is in clinical trials. The procedure was refined at the
University of Alberta and is known as the Edmonton Protocol. For web
access go to
Alberta Foundation for Diabetes Research Website
http://www.afdr.ab.ca/press/100005/main.htm
For more information on beta cell transplantation go to
Diabetes Research Institute Website
http://www.drinet.org/html/islet_cell_transplantation.htm
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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Future Possibilities: Genetic engineering may be able to cure Type 1
diabetes by introducing genes for insulin production. Very recently at the
University of Calgary researchers have developed a gene that is
introduced into diabetic rats via a genetically engineered virus. The gene
is for an insulin regulator that will produce insulin when blood glucose
levels are too high, normalizing the glucose levels. This will be tested in
higher organisms and possibly humans. For further information click
here:
University of Calgary
http://www.ucalgary.ca/unicomm/NewsReleases/diabet4.htm
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Section 2: Type 2 diabetes
Type 2 diabetes is a form of diabetes mellitus that may range from insulin
resistance with relative insulin deficiency to a predominant secretory defect
with insulin resistance. Peripheral insulin resistance may be related to a
defective insulin receptor and/or post-receptor defects, and/or hepatic overproduction of glucose. These defects combine to cause hyperglycemia
without the ketosis of Type 1 diabetes.
Pathophysiology
Read: Porth, pp. 995-997
Etiology
Note: A clear indication of the importance of genetics in the etiology of Type 2
diabetes is the fact that nearly 100% of monozygotic twins are concordant for
the disease. Environmental factors are also important. Obesity is strongly
correlated with Type 2 diabetes, particularly truncal obesity. Obesity and a
sedentary lifestyle are the major modifiable and independent risk factors for
Type 2 diabetes according to the 1998 Clinical Practice Guidelines. The role of
environmental factors is demonstrated most clearly by research done with
aboriginal peoples throughout the world who have moved from traditional
lifestyles to modern urban lifestyles. The incidence of Type 2 diabetes is
significantly higher (25 times) in the urban subgroups than in the traditional
setting and lifestyle.
Breaking News: On the rapid increase in the number of children diagnosed
with Type 2 diabetes, go to
Intelihealth.com
http://www.intelihealth.com/IH/ihtIH/WSIHW000/333/21142/296067.html
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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Note: The actual percentage of Type 2 diabetics that are obese varies
considerably from 60 to 90 percent depending on the source. This
probably reflects different definitions of obesity.
Clinical Manifestations
Read Porth – pp. 998-999
Note: Type 2 diabetes may be asymptomatic.
Evaluation and Treatment
Read: Porth – pp.1000 - 1005
Learning Activity #2
Answers are at the back of this unit.
1. For the following, identify each as being characteristic of Type 1 or
Type 2 diabetes.
a.
b.
c.
d.
e.
f.
Ketosis prone
Onset usually over 40 years of age
Strong familial pattern
Insulin required for survival
Occurs in younger people usually
Non-ketosis prone
Type 1
______
______
______
______
______
______
Type 2
______
______
______
______
______
______
2. Identify which of the following statements are false, and then rewrite
the statement so that it is true.
a. Familial inheritance is a bigger risk factor in Type 1 than in Type 2
diabetes.
b. Obesity of the legs and hips is closely associated with Type 2
diabetes.
c. Nearly 100% of genetically identical twins of a Type 2 sibling will
get diabetes.
d. Viral destruction of beta cells is the primary cause of Type 1
diabetes
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
3. Identify which of the following statements are false then rewrite the
statement so that it is true.
a. Type 2 persons often develop much higher blood glucose levels
than Type 1 before they are severely ill.
b. The symptoms of hyperglycemia are different in Type 1 and Type
2 diabetes.
c. Weight loss is the usual treatment of choice in Type 1 diabetes.
d. Exercise is important in blood glucose control in both types of
diabetes.
e. Urine testing is of no use in monitoring either type of diabetes.
4. Which of the following metabolic processes occur due to insulin
deficiency? (Answer all that apply)
a. glycogenolysis
b. gluconeogenesis
c. lipogenesis
d. increased glucose uptake by muscle cells
e. glycogenesis
f. lipolysis
5. List the following treatment measures for Type 2 diabetes in the usual
order of usage:
a. dietary intervention
b. oral hypoglycemic agents
c. exercise
d. human recombinant insulin
6. What is the major pathophysiologic factor in Type 2 diabetes?
7. List the main treatment measures used for Type 1 diabetes.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
19
Section 3: Acute Complications of Diabetes Mellitus
Hypoglycemia
Read: Porth – pp. 1007 - 1008
Note: that the textbook gives the glucose values here in mg/dl.
Note: Hypoglycemia can be defined as a plasma glucose level less than
3.6 mmol/L. It may occur due to a number of factors including more
physical activity and/or less food than usual, resulting in excess insulin
availability. Variability in insulin absorption and action as mentioned
previously can be responsible for hypoglycemia. As blood glucose
drops, counter regulatory hormones are produced to raise the blood
glucose. This is not fast enough however, to correct the falling glucose
level before symptoms are apparent. In addition, the counter regulation
(particularly glucagon secretion) can be impaired in diabetes,
particularly diabetes of long duration. Hypoglycemia may lead to
insulin shock and eventually to coma if untreated.
Point of Interest: The electroencephalogram will indicate isoelectricity
at a blood glucose of 1.0 to 0.8 mmol/L. If isoelectricity is longer than 30
minutes permanent brain damage will result, particularly in the
hippocampus and caudate (Auer, R.N., Olsson Y., & Siesjo, B.K. (1984).
Hypoglycemic brain injury in the rat.. Correlation of density of brain
damage with the EEG isoelectric time: A quantitative study. Diabetes 33,
1090 1098). It may result in death if untreated. It has been used in
suicides and murder.
History: Insulin shock was used as a THERAPY in the last century,
primarily in treating the mentally ill. It was also used to ‘treat’ morphine
addiction and even acne (Baker, A.B. 1938. Cerebral lesions in
hypoglycemia. II. Some possibilities of irrevocable damage from insulin
shock. Arch. Pathol. 26, 765-776.).
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Diabetic Ketoacidosis
Read: Porth – pp.1006 -1007
The textbook is a little unclear about ketogenesis. Here is a quick review:
1. As insulin levels drop, more fatty acids are converted to ketones
(acetoacetate and beta-hydroxybutyrate), and there is decreased
ketone use in the periphery.
3. Increasing glucagon levels results in increasing ketone formation.
4. Ketones lose hydrogen ion (H+) as they circulate in the blood, that is
they act as an acid in blood. The pH of the blood drops.
5. This contributes to metabolic acidosis.
Note: Untreated diabetic ketoacidosis (DKA) eventually causes changes
to mentation with eventual stupor and coma. Central nervous system
depression seems to be mainly correlated with the level of serum
osmolarity. Mortality occurs in 7-8% of cases.
Hyperosmolar Hyperglycemic NonKetotic Syndrome
(HHNKS)
Read: Porth – p. 1007.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
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Section 4: Chronic Complications of Diabetes
Mellitus
Read: Porth – 1008 – 1013.
Harris and Lank, pp. 5-6 and 8-9.
Microvascular Disease
Retinopathy
Note: According to the 1998 Clinical Practice Guidelines for the
Management of Diabetes in Canada, diabetic retinopathy is THE major
cause of adult blindness in North America and is the most feared
complication. They recommend that screening and evaluation for
retinopathy should be performed annually 5 years after the onset of
diabetes in postpubertal patients (age 15 years or over) with Type 1
diabetes and in everyone with Type 2 diabetes at the time of diagnosis.
The interval for follow up assessments should be tailored to the severity
of the retinopathy. In those with Type 2 diabetes who have no or
minimal retinopathy, the recommended interval is 2 years and should
not exceed 4 years.
Macrovascular Disease
Note: Diabetic macrovascular disease is essentially an accelerated form
of the atherosclerotic vascular disease found in the non-diabetic
population. Uncontrolled hyperglycemia associated with dyslipidemia
is thought to be the primary etiologic factor. Review the new target
levels for lipids in Table 5 of Harris, S.B., and C.N. Lank, 1998. Also
review carefully their recommendations for the control of blood
pressure and lipid control on page 5.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Preventing Long Term Complications—The Diabetes
Control and Complications Trial (DCCT).
The Diabetes Control and Complications Trial Research Group: The
effect of intensive treatment of diabetes on the development and progression
of long-term complications in insulin-dependent diabetes mellitus. 1993.
New England Journal of Medicine 329:977.
Point of Interest: The DCCT was a prospective, randomized, clinical
trial. The general objective was to determine whether tight glycemic
control resulting in near euglycemia, that is normal glucose levels,
would slow down or prevent long term complications (retinopathy,
nephropathy and neuropathy). The DCCT enrolled 1,400 people in
1983-1993 with insulin dependent diabetes (13-39 years old) and was
comprised of two cohorts with no complications or minor
complications.
The study design consisted of two randomized groups. The
conventional treatment group received one to two insulin injections
and blood glucose tests per day with no predefined target blood
glucose values. The intensive treatment group received three or more
injections per day, or an insulin pump with frequent blood glucose
monitoring. Treatment goals were aimed at achieving near normal
glycemia. The results showed that the intensive treatment group had
much tighter blood glucose control, and also had a statistically
significant reduction in long term complications.
Retinopathy
63% reduction
Nephropathy
41% reduction
Neuropathy
60% reduction
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
23
Learning Activity #3
Answers are at the back of this unit.
1. Briefly list measures thought to aid in preventing diabetic
retinopathy.
2. What are three mechanisms by which the person with diabetes may
be more susceptible to infection?
3. Why is someone with long duration diabetes more likely to have a
‘silent heart attack’?
4. True or False:
a. It is now known that tight blood glucose control will prevent the
long-term complications of diabetes.
b. Patient education and knowledgeable medical care can ensure
early detection and prompt treatment of long-term complications.
c. Having diabetes presents continual challenges in controlling the
disease and may require repeated adjustments to new losses
associated with long-term complications.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Section 5: Gestational Diabetes Mellitus (GDM)
Read: Porth – p. 998
Gestational diabetes mellitus is defined as diabetes that is diagnosed during
pregnancy. Because pregnancy itself causes a lower range of ‘normal’ blood
glucose, the diagnostic criteria for gestational diabetes are correspondingly
lower than for other types of diabetes, i.e., a blood glucose of 7.8 mmol/L or
higher one hour after a 50 g glucose drink is considered a positive screen
indicating the need for an oral glucose tolerance test.
Any two plasma glucose levels exceeding the following during a 100 g oral
glucose tolerance test (GTT) are diagnostic of GDM:
Fasting
60 min.
120 min.
180 min.
5.8 mmol/L (venous plasma glucose)
10.6 mmol/L
9.2 mmol/L
8.1 mmol/L
A screening test for GDM is recommended for all women between 24 and 28
weeks gestation. The third trimester of pregnancy is the usual time of onset
due to the diabetogenic effects of increasing placental hormone production.
Controversy: There is some controversy over the diagnosis of GDM. Many
physicians identify pregnant women with a 2 hour GTT result of 6.7 mmol/L
or greater as glucose intolerant and treat them with dietary intervention and
surveillance. Parameters for prescribing insulin in GDM vary but typically 2
hours after a meal blood glucose levels in excess of 6.5 mmol/L will be
treated with insulin. Oral hypoglycemic medications are contraindicated in
pregnancy.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
25
Final Thoughts
The study of glucose metabolism is not only fascinating and important, but
an excellent model of the consequences of the deregulation of hormonal
control of homeostasis.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
26
Unit 17 Disorders of Glucose Metabolism
References
Auer, R.N., Olsson Y. & Siesjo, B.K. (1984). Hypoglycemic brain injury
in the rat. Correlation of density of brain damage with the EEG isoelectric
time: A quantitative study. Diabetes, 33, 1090-1098.
Baker, A.B. (1938). Cerebral lesions in hypoglycemia. II. Some
possibilities of irrevocable damage from insulin shock. Arch. Pathol, 26, 765776.
Canadian Diabetes Association, CDA Position Statement Regarding the
UKPDS and Revision of Diabetes Clinical Practice Guidelines Accounting for the
UKPDS Results, Retrieved October 26, 2000 from the World Wide Web
http://www.diabetes.ca/prof/cpg_ukpdsposition.html
Canadian Diabetes Association, Clinical practice guidelines for the
management of diabetes in Canada. 1998. Retrieved October 26, 2000 from the
World Wide Web http://www.diabetes.ca/prof/publications/cpg98eng.pdf
Diabetes Control and Complications Trial Research Group. (1993):
The effect of intensive treatment of diabetes on the development and
progression of long-term complications in insulin-dependent diabetes
mellitus. New England Journal of Medicine, 329, 977.
Gerstein, H.C., Hanna, A., Rowe, R., Leiter, L., & MacGregor, A.
MDCDA position statement regarding the UKPDS and revision of diabetes
clinical practice guidelines accounting for the UKPDS results. Retreived
Actober 26, 2000 from the World Wide Web
http://www.diabetes.ca/prof/cpg_ukpdsposition.html
Harris, S.B., & Lank, C.N. (1998). 1998 Clinical practice guidelines for
the management of diabetes in Canada. Canadian Diabetes, 12(1), 3-10.
Meltzer, S. et.al. (1998). 1998 Clinical practice guidelines for the
management of diabetes in Canada. Retrieved October 26, 2000 form the
World Wide Web http://www.diabetes.ca/prof/publications/cpg98eng.pdf
Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health
Staes (7th ed.). Philadelphia: Lippincott.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
27
Glossary
Note: A glossary of diabetes related terms can be accessed at
Diabetes Institute of the University of Minnesota
http://www.diabetesinstitute.org/glo.htm - B
diabetes mellitus: Is a metabolic disease characterized by the presence of
hyperglycemia due to defective insulin secretion, insulin action or both.
gestational diabetes mellitus: Is diabetes that is diagnosed during
pregnancy.
type 1 diabetes: Is diabetes that is primarily a result of pancreatic beta-cell
destruction and thus these patients are prone to ketoacidosis.
type 2 diabetes: Is a form of diabetes mellitus that may range from insulin
resistance with relative insulin deficiency to a predominant secretory defect
with insulin resistance.
Acronym List
ACE
Angiotensin converting enzyme
CAPD
Continuous ambulatory peritoneal dialysis
DCCT
Diabetes Control and Complications Trial
DKA
Diabetic ketoacidosis
FPG
Fasting plasma glucose
GDM
Gestational diabetes mellitus
GI
Gastrointestinal
HHNKS
Hyperosmolar HyperglycemicNonKetotic Syndrome
HLA
Human leukocyte antigens
IDDM
Insulin dependent diabetes mellitus
NIDDM
Noninsulin dependent diabetes mellitus
OGTT
Oral glucose tolerance test
PG
Plasma glucose
UKPDS
United Kingdom Prospective Diabetes Study
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
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Unit 17 Disorders of Glucose Metabolism
Checklist of Requirements
 Pre-test
Required Readings

Harris, S.B., & Lank C.N., (1998). 1998 Clinical Practice Guidelines for
the Management of Diabetes in Canada. Canadian Diabetes, 12(1), 3-10.

Canadian Diabetes Association, Guidelines for the Nutritional
Management of Diabetes Mellitus in the Millennium. Retrieved October 26, 2000
from the World Wide Web http://www.diabetes.ca/prof/index.html, pages
3-6.

Porth, C. M. (2005). Pathophysiology – Concepts of Altered Health
States (7th ed.). Philadelphia: Lippincott.
 Print Companion: Disorders of Glucose Metabolism
Learning Activities
 Learning Activity #1
 Learning Activity #2
 Learning Activity #3
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
Answers to Learning Activities
Answers to the Pretest
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
c
a
c
b
d
b
c
c
a
a
c
d
a
c
c
b
a
a
a
b
a
Answers to Learning Activity #1
1. a, b.
2. b, c.
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
29
30
Unit 17 Disorders of Glucose Metabolism
Answers to Learning Activity #2
1. a. 1, b. 2, c. 2, d. 1, e. 1, f. 2
2. a. Familial inheritance is a bigger risk factor in Type 2 than in Type 1
diabetes.
b. Obesity of the trunk is closely associated with Type 2 diabetes.
c. True
d. Autoimmune destruction of beta cells is the primary cause of
Type 1 diabetes.
3. a. True
b. The symptoms of hyperglycemia are the same in Type 1 and
Type 2 diabetes
c. Weight loss is the usual treatment of choice in Type 2 diabetes.
d. Exercise is important in blood glucose control for Type 2
diabetes.
e. True
4. a, b, f
5. 1. dietary intervention
2. exercise
3. oral hypoglycemic agents
4. human recombinant insulin
6. Consider the major pathophysiologic factor in Type 2 diabetes.
7. patient education
exogenous insulin injections
dietary carbohydrate consistency
monitoring of condition
blood glucose testing
urine ketone testing prn
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary
Unit 17 Disorders of Glucose Metabolism
31
Answers to Learning Activity #3
1. regular ophthalmologic examination
adequate blood glucose control
adequate control of any hypertension
2. hyperglycemia causing inadequate chemotaxis
vascular insufficiency
neuropathic insensitivity
3. parasympathetic damage (autonomic neuropathy) caused by diabetes
results in lack of pain during coronary insufficiency as from a
myocardial infarction.
4. a. F, b. T, c. T
Rankin, Reimer & Then. © 2000 revised edition. NURS 461 Pathophysiology, University of Calgary