BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease PaperDiabetes in America
Western Michigan University
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
1.0 Abstract
This paper explores the clinical variations of diabetes–diabetes mellitus and diabetes insipidus–
emphasizing both the diseases significance to human health as well as its prevalence among
American society. For the sake of brevity this work will focus mostly on diabetes mellitus. All
bases will be covered including but not limited to the following: epidemiology, pathology,
cellular and molecular basis for the problem, and etiology. Given that both variations of diabetes
cover the renal and endocrine system, biochemical basis for each condition will be explained in
detail. Epidemiology pertaining to the United States will be given by (Greenspan & Forsham,
1983) to explain both demographics and patterns associated with those effected. Pathology will
delve into how these diseases are diagnosed using supporting information from various sources.
Cellular and molecular basis for the problem will articulate how diabetes mellitus is a form of
“sugar diabetes” with its combined effect on insulin with respect to glucose regulation within
cells. Diabetes insipidus will be further explicated using (Zingg, Bourque, & Bichet, 1998) to
breakdown insensitivity induced by antidiuretic hormone. The forms of treatment and monitoring
will be covered with various sources and a conclusion will be made tying up outlook for
diabetes.
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
1.1 Introduction to Diabetes
Diabetes is a disease concerning both the renal and endocrine system in the human body. Two
primary types of diabetes are what most individuals have, and they are as follows: diabetes
mellitus and insipidus. Diabetes mellitus is what is commonly referred to as “sugar diabetes” and
has two subtypes: type 1 and 2. Type 1 diabetes according to (Widmaier, Raff, Strang, &
Shoepe, 2019, p. 599) is commonly referred to as insulin-dependent diabetes mellitus or juvenile
diabetes. In type 1(T1DM) the patient is completely dependent on insulin, needing regular
injections to maintain regular glucose absorption. Type 2 diabetes mellitus (T2DM) according to
(Widmaier, Raff, Strang, & Shoepe, 2019, p. 599) is commonly referred to as non-insulin
dependent diabetes. This is where not as much (if any) insulin is needed but cells throughout the
body begin to resist the absorption of insulin.
Diabetes insipidus is much more uncommon and for it is characterized as a form of diabetes
where your body has an inappropriate response to antidiuretic hormone known as vasopressin.
Two forms of diabetes insipidus exist and they are as follows: central and nephrogenic. Central
diabetes insipidus (CDI) according to (Widmaier, Raff, Strang, & Shoepe, 2019, p. 506) is
caused by the failure of axons with cell bodies of the hypothalamus and synapses on blood
vessels in the posterior pituitary to synthesize or release vasopressin. Now Widmaier (2019)
states that nephrogenic diabetes insipidus (NDI) is cause by “the inability of kidneys to respond
to vasopressin” (p.506).
1.2 Epidemiology
While looking into diabetes with patterns associated demographically with the condition one will
find that even though some are more vulnerable to the condition because of genetically inherited
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
traits, most develop the condition because of dietary choices. The scope of this work
epidemiologically will be focusing on T1DM and T2DM, or variants of sugar diabetes due to
being much more prevalent throughout society. CDI and NDI are just not common and in fact
very rare. Hadden (1983) states that “the hallmark of diabetes and the basis for its diagnosis is
the body’s inability to adequately metabolize glucose circulation” (p.1). To characterize who is
most vulnerable among the American population, empirical testing was done by (Hadden &
Harris, 1987) with a sample size of 27,801 Americans from 6-74 years of age. All were
administered “oral glucose tolerance tests” (OGTT). According to Hadden (1983) these are the
merits of conducting proper OGTT and blood glucose analysis by the National Diabetes Data
Group (NDDG) recommendation: Subjects fast overnight for 10-16 hours; OGTT’s are
performed in the morning; a fasting blood sample is taken; subjects drink flavored water
containing 75 grams of glucose or carbohydrate equivalent; and additional blood samples are
taken. (p.5) The blood samples were obtained, and plasma was separated from the blood via
centrifugation. Once blood was frozen it was shipped to the Center for Disease Control (CDC)
for analysis.
Out of the 27,081 Americans taken in the sample, 8,686 represented those that followed NDDG
recommendations. For the sake of brevity, we will be following highlights by Hidden (1983):
The prevalence of both diagnosed and undiagnosed diabetes increased with age and were
higher for black persons than for white persons. Sex differences were smaller, but ages
20-44 years women were more likely than men to have diabetes. The prevalence of
diabetes increased with level of obesity. Persons who were 50 percent above ideal body
weight had diabetes at five times the rate of persons of ideal weight or lighter. . . Using
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
NDDG criteria, it appears that 11.2 percent of the U.S population aged 20-74 years
exhibit abnormal glucose tolerance, either diabetes or IGT. Using WHO criteria, 18.0
percent were glucose intolerant. (p.3)
With OGTT blood concentrations of glucose in the range of 70-100 mg/dL or considered normal
range,101-125 are pre-diabetes range and anything 125 or greater is diabetes. There is no doubt
that disadvantaged racial and ethnic groups are among those that are at increased risk. Such
living conditions typically lead to an increase in sedentary lifestyle, less adequate nutrition, and a
reduced amount of aerobic activity which are all helpful in reducing individuals’ chances of
developing Impaired Glucose Tolerance (IGT). It is made clear by (Morewitz, 2006) that “more
than 90% of cases of type 2 diabetes could be prevented by following a healthy lifestyle that
included moderate to vigorous physical activity for at least a half hour per day, good nutrition,
wight control, and smoking cessation” (p.31-32). More of this will be covered later in forms of
treatment. It just must be
made clear the things that
cause disadvantaged society
to become susceptible to
such diseases. Table 1 above
shows the prevalence of
diabetes by demographic.
One major trend should be
noticed, the prevalence of
diabetes increases with age.
As people get older,
Table 1 Prevalence of diabetes in adults aged 20-74 years, by
race, sex, and age: United States, 1976-1980 (Hadden & Harris,
1987, p. 12)
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
statistically their chances for being diagnosed with IGT or diabetes is higher. Take for example
both sexes in all races from table 1 above, only 2% of individuals between the ages of 20-44
years have IGT compared to 17.7%. The other demographic which must be noticed is that
women are more likely than men to develop IGT across every demographic as seen in the table
above. Now this data from (Hadden & Harris, 1987) is in fact over 30 years old but similar paints
remain and to this day have only been exacerbated with increasing prevalence of processed foods
and sugar throughout the American diet.
1.3 Pathology
Diabetes insipidus is “characterized by the passage of copious amounts of very dilute urine”
(Greenspan & Forsham, 1983, p. 124).
This would be the primary presenting
symptom of DI if a patient had
concerns for such a scenario involving
their renal system. However, it is
confirmed by (Tamparo & Lewis,
2000) that “most cases of diabetes
insipidus are idiopathic, especially
those cases arising during childhood”
(p.249). This is achieved by several
different avenues depending on
whether it is vasopressin sensitive
diabetes insipidus (CDI) or
Table 2 Differential diagnosis of diabetes insipidus
(Greenspan & Forsham, 1983, p. 126)
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
nephrogenic diabetes insipidus (NDI) and this topic will be covered in more detail later in
sections 1.4 and 1.5. How DI is diagnosed requires what is known as a differential diagnosis as
seen in table 2 above. As it can be seen, subjects will have their osmolality of plasma and urine
measured. This osmolality test will be followed by a dehydration test, serum vasopressin test at
dehydration test conclusion and vasopressin injection. The bodies response following these
different tests will be noted and an endocrinologist and/or urologist will have the ability to
narrow down which form of disease the patient has. By taking plasma and urine osmolarity it can
be concluded as to the concentration of the patient’s urine. According to Greenspan (1983) the
urine will be less concentrated than the plasma, whereas the plasma osmolality will be higher
than normal (p.126). Following the first procedure the next step is water deprivation. A urine
sample will be taken systematically throughout the test (which usually last up to 18 hours) and
checked for density and osmolality. These first steps that can be followed in table 1 are to
distinguish DI from polydipsia. The final step after the water deprivation according to Greenspan
(1983) is to give 5 units subcutaneously and measure urine osmolality after 1 hour; patients with
vasopressin-sensitive diabetes insipidus will show an increase in urine osmolality to value above
that of the plasma. Other forms of diagnoses include vasopressin radioimmunoassay following
the water deprivation test. It just must be noted that this form of testing takes longer and if a
patient is experiencing extreme symptoms and a dire need, they may not be best.
Diabetes mellitus is confirmed with a definite prognosis according to Greenspan (1983) with “a
fasting plasma glucose above 140 mg/dL on more than one occasion establishes the diagnosis of
diabetes mellitus” (p.520). Signs and symptoms again include polyuria (large amounts of dilute
urine) and other irregularities associated with incorrect glucose levels. A perfect example can be
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
seen from the effects of insulin and glucose on level of activity and alertness from laboratory
seen in table 3 below. Normoglycemia shows individuals exhibiting regular smooth behavior.
Hyperglycemia fish exhibit
Table 3 Endocrine system: effects of blood glucose levels on
fish laboratory simulation
fast and darting movements.
Fish experiencing
hypoglycemia have slower
and more lethargic
movements. Even though this
experiment dealt with fish,
the same concept can be
taken with people for signs
and symptoms. It must be noted that type II diabetes mellitus (formerly known as non-insulin
dependent diabetes mellitus “NIDDM”) has a much more gradual symptoms that are difficult to
detect. Typically, NIDDM is not identified until testing due to other underlying conditions. Once
symptoms are detected tests can be performed to identify whether a patient has type I or type II
diabetes mellitus.
The first type of test to confirm blood glucose concentrations is an oral glucose tolerance test
(OGTT) as stated previously. Patients in preparation for the test should have a low carbohydrate
diet in the days leading up to the test. The testing procedure goes as follows: “Adults are given
75 g of glucose in 300 mL of water; children are given 1.75 g of glucose per kilogram of ideal
body weight. The glucose load is consumed within 5 minutes. Blood samples for plasma glucose
are obtained at 0, 30, 60, 90, and 120 minutes after ingestion of glucose” (Greenspan & Forsham,
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
1983, p. 520). OGTT tests are considered normal if after 2 hours the value falls below 140
mg/dL. It must be made clear though that none of the values at any point can exceed 200 mg/dL
for this is a sure sign of diabetes mellitus.
1.4 Cellular and Molecular Basis of the Problem
The human body makes constant adjustments to maintain blood glucose level between 70-100
mg/mL. These adjustments involve constant additions or reductions in insulin, catecholamines
and steroids. According to (Nelson & Cox, 2017) diabetes mellitus is a “derangement in the
signaling pathway that control glucose metabolism” (p.930). The figure 1 shows the path that
glucose takes throughout the body and how the enzyme insulin effects its metabolic pathway.
Immediately following gustation, the resulting glucose, fat, and protein enter the liver having
come from the small intestine. These nutrients are carried to the liver via blood in blood vessels.
When the term ‘blood’ is
used it is important to note
why the substance has
carrying capacity and
where it lies. Blood
according to (Widmaier,
Raff, Strang, & Shoepe,
2019, p. 363) is “composed
of formed elements (cells
and cell fragments) suspended
in a liquid called plasma”.
Figure 1 Well fed state: lipogenic liver (Nelson & Cox, 2017, p.
931)
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
The blood plasma is responsible for carrying organic metabolites, wastes and proteins. This
means that it carries glucose, amino acids, ketone bodies and very low-density lipoproteins that
are all directly involved in the metabolic
pathway seen above. Once the metabolites
reach the liver, glucose in turned to glycogen
for storage in the liver itself. Glucose also is
sent to the brain and follows all the way to
become very low-density lipoprotein for fat
storage via adipose tissue throughout the
body. When glucose is ‘sensed’ in the blood
stream the pancreas secretes insulin. This can
Figure 2 The endocrine system of the pancreas
(Nelson & Cox, 2017, p. 932)
be seen in Figure 2 to the right, where the βcell is shown. Β-cells secret insulin from the pancreas in response to changes in blood glucose.
Glucose functions as a signaling molecule to glucose transporter (GLUT2) channel proteins in
extracellular space. Glucose is changed from a standard D-aldose sugar to Glucose 6-phosphate
Figure 3 Glucose regulation of insulin secretion by
pancreatic β cells. (Nelson & Cox, 2017, p. 932)
once phosphorylated with ATP.
Figure 3 to the left shows the next
step with the change to Glucose 6phosphate. Next comes glycolysis,
the citric acid cycle and oxidative
phosphorylation to leading to a
surplus of ATP. These closes ATPgated K+ channels in the plasma
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
membrane. With reduced flux of potassium, the membrane becomes depolarized leading to the
uptake of calcium by voltage gated calcium channel. Once the surplus of calcium anions enters
the cell, they lead to insulin secretion by granules via exocytosis. Type I diabetes mellitus is
caused from the “autoimmune destruction of pancreatic β cells and a consequent inability to
produce sufficient insulin” (Nelson & Cox, 2017, p. 938). When it comes to type II diabetes
mellitus a resistance to insulin results in buildup of adipose connective tissue.
Diabetes insipidus is caused by “inadequate secretion of the antidiuretic hormone from the
pituitary gland” (Falvo, 1999, p. 208). In figure 4 below the role in which vasopressin plays with
AQP2 aquaporin duct can be seen. Vasopressin functions as a ligand, binding to the vasopressin
receptor. This then allow for secondary messengers to participate in the Biosignaling cascade
which leads to ‘uniport’ of water through the cell membrane. According to Zingg (1998) “In the
large majority of cases, NDI is an X-linked recessive disorder caused by mutations in the AVP
V2 receptor gene. In
the remaining cases,
the disease is
autosomal recessive
or dominate and for
these patients,
mutations in the
aquaporin 2 gene
(AQP2) have been
reported” (p.387).
Figure 4 Regulation and function of aquaporins (AQPs) in the collectingduct cells to increase water reabsorption. (Widmaier, Raff, Strang, &
Shoepe, 2019, p. 505)
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
1.5 Expected Life
Once either of these forms of diabetes are identified in a patient and treatment is received
individuals can expect a normal life if following proper treatment programs. The issue with
diabetes is typically patients that have IGT or diabetes insipidus is that they do not identify the
illness in its early stages and continue to live with the disease and its complications throughout
life. This leads to the formation of many other underlying conditions and/or illnesses as a result
of diabetes going untreated. For diabetes mellitus in particular, the chances of acquiring other
major illness dealing with cardiovascular, respiratory, and neurological systems increases
significantly. For example, in neuroscience, it has become common language to refer to glucose
intolerance in the brain as “type III” diabetes. Once someone has any form of diabetes mellitus,
their chances of contracting many forms of degenerative neurological disease increases
dramatically. In conclusion, early detections and diagnoses with diabetes is critical. This will
avoid many of the disease that result from symptoms and bodily conditions that are created as a
result of inadequate treatment.
Individuals with T1DM or T2DM can expect to be constantly monitoring the glycated
hemoglobin levels in their blood. This is commonly referred to as “a1c” testing. According to
Greenspan (1983):
Glycohemoglobin is produced by a reaction between glucose and the N-terminal amino
acid of both beta chains of the hemoglobin molecule. The major form og
glycohemoglobin is hemoglobin A1c which normally comprises only 4-6% of total
hemoglobin. The remaining glycohemoglobins (2-4% of total hemoglobin) contain
phosphorylated glucose or fructose and are termed hemoglobin A1a and A1b, respectively.
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
The hemoglobin A1c fraction is abnormally elevated in diabetics with chronic
hyperglycemia and appears to correlate positively with metabolic control. (p.519)
This is why A1c is the common term that is thrown around when diabetics talk about monitoring
their blood sugar. Oral glucose tolerance tests are harder to perform accurately without
centrifugation. The ability to detect levels of glycated hemoglobin can be performed with
unseparated blood using some form of photometry measuring absorption at a given wavelength.
1.6 Treatments
Diabetes mellitus in particular can be effectively managed with several forms of treatment. For
example, insulin dependent diabetes mellites (IDDM) or type 1 diabetes can be effectively
treated with blood glucose monitors and insulin injections through multiple means. If proper diet
and exercise are utilized by the patient and normal life can ensue. Diabetes mellitus in the form
of type 2 also known as non-insulin dependent diabetes mellitus (NIDDM) can be controlled
with proper diet and exercise (generally speaking). In many cases patients may only have to
subject themselves to insulin treatments once they get farther along in life.
Diabetes insipidus is much rarer and has to be treated in very particular ways. Given that many
forms of this disease are caused by secretory issues with the pituitary gland forms of injection
with vasopressin are the common denominator. According to Greenspan (1983):
The treatment of choice at present is with desmopressin acetate (DDAVP), a synthetic
analog of vasopressin prepared in aqueous solution containing 0.10 mg/mL. It is
administered intranasally via a calibrated plastic catheter in doses of 5-20 µg (0.05-0.20
mL) every 12 hours. This agent provides excellent control of polyuria and polydipsia in
patients with pituitary diabetes insipidus. It is essential to monitor serum osmolality at
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
regular intervals (initially every 1-2 weeks, later every 3 months) to be certain the doses
are appropriate. (p.127)
This is a common form is treatment for those that have this type of diabetes. Water is used as a
solvent for the delivery of the polar drug product. Other forms of treatment exist and are
administered via intramuscular injection but have all been phased out. The primary reason for
this is most solutions in which drug product are suspended for intramuscular injections must be
lipid based. Given that vasopressin and its synthetic analogs are primarily polar they do not mix
well. This is why it is known to be “difficult to suspend, irregularly absorbed, and produced
‘peaks’ and ‘valleys’ in its effect” (Greenspan & Forsham, 1983, p. 127).
What happens if the disease is not treated? This is a common issue that must be expressed that
makes diabetes mellitus particularly deadly. According to Nelson (2017):
If diabetes is untreated, blood glucose levels may rise to severalfold higher than normal.
These high glucose levels are believed to be at least one cause of the serious long-term
consequences of untreated diabetes–kidney failure, cardiovascular disease, blindness and
impaired would healing. (p.248)
As explained in section 1.5 Expected life, if diabetes goes untreated the expected complications
can become quite severe. This means a significantly increased risk for many common health
problems dealing with major organ systems. This can occur just as a result of too much glucose
in the blood. Another common issue when diabetes goes untreated is the buildup of ketone
bodies when a diabetic is in a fasted state. The human body commonly produces three primary
ketone bodies: acetone, acetoacetate and D-β-hydroxybutyrate. These are formed in the liver and
exported to other organs as fuel. “Increased blood levels of acetoacetate and D-βhydroxybutyrate lower the blood pH, causing condition known as acidosis. Extreme acidosis can
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
lead to coma and in some cases death” (Nelson & Cox, 2017, p. 670). A general increase in all
ketone bodies can lead to ketosis. When these two conditions occur together, they become
known as ketoacidosis.
1.7 Conclusion
In conclusion diabetes is a relatively common disease, according to Nelson (2017) “about 9% of
the U.S. population, and nearly 25% of the U.S. population over the age of 65, show some
degree of abnormality in glucose metabolism. . . ” (p.938). This is a more up to data statistic
compared to some of the sources used early in the work, and as one may note the numbers have
increased slightly. A general rule of thumb with loved ones; poor diet coupled with high simple
sugar intake and a skinny figure are common orientation of undiagnosed T1DM. Typical
physiology of one with undiagnosed T2DM would be overweight–visceral fat buildup– or
adipose tissue is a clear result if insulin resistance. If one is having issues with water and urine
retention and has dilute urine–polyuria–this can be early signs of DI. The best avoidance of this
disease is to eat a healthy well-balanced diet and include exercise. One thing is certain, avoid
simple sugars.
BIOS 2400 – Human Physiology – Western Michigan University – Student Example of Disease Paper
References
Falvo, D. R. (1999). Medical and Psychosocial Aspects of Chronic Illness and Disability (2nd
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Greenspan, F. S., & Forsham, P. H. (Eds.). (1983). Basic and Clinical Endocrinology. Lange
Medical Publications, 124-128, 513-544.
Hadden, W. C., & Harris, M. I. (1987). Prevalence of Diagnosed Diabetes, Undiagnosed
Diabetes, and Impaired Glucose Tolerance in Adults 20-74 Years of Age United States,
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Health and Human Services, Hyattsville,1,5,12.
Morewitz, S. J. (2006). Chronic Diseases and Health Care. New York, United States of America:
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Nelson, D. L., & Cox, M. M. (2017). Principles of Biochemistry (Vol. 7th). New York, New
York, United States of America: W.H. Freeman and Company, 248,423,620,670,938.
Tamparo, C. D., & Lewis, M. A. (2000). Diseases of the Human Body. Philadelphia,
Pennsylvania, United States of America: F.A. Davis Company, 249-258.
Widmaier, E. P., Raff, H., Strang, K. T., & Shoepe, T. C. (2019). Human Physiology. New York,
New York, United States of America: McGraw-Hill, 505-506,599-601.
Zingg, H. H., Bourque, C. W., & Bichet, D. G. (Eds.). (1998). Vasopressin and Oxytocin
Molecular, Cellular, and Clinical Advances (Vol. 449). New York, New York, United
States of America: Plenum Press, 387.
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