Minjung Kim

BIOEN 315 HW 1

Short and Sweet Review of Diabetes Mellitus

Introduction to Diabetes Pathology
Diabetes stems from the Greek word for siphon, and mellitus is Latin for honey. Therefore
diabetes mellitus translates into the flow of honey. As the name hints, diabetes mellitus is a disease
characterized by the uncontrolled glucose level in the blood. In healthy bodies, homeostasis is achieved
by negative feedback of insulin and glucagon (Figure 1). After a meal, the pancreas secretes a hormone
called insulin. Selective cells throughout the body have insulin receptors embedded in their plasma
membranes. The insulin binds to the insulin receptor substrate (IRS) protein, and a cascade of reactions
happen within the cell that allows the cell to take up the glucose in the blood. As a result, the glucose
levels eventually drop to normal in the blood. In type 1 diabetes, the body destroys its own insulin
secreting cells in the pancreas and therefore the cells do not receive the signals to take up glucose. In
patients with type 2 diabetes, there are many pathways to prevent the glucose uptake. The IRS proteins in
the cell membranes can become less sensitive to insulin or be degraded altogether via phosphorylation
and dephosphorylation.1 Inflammatory cytokines can interrupt the signaling cascade inside the cell.1
There are also Nuclear factor kB and IkB that work together in the nucleus to control gene regulation of
inflammatory responses that that is also linked to insulin resistance.1 The possibilities are endless for type
2 diabetes: defect in mitochondrial metabolism with lipid oxidation, beta cell dysfunction, glucose
toxicity, lipotoxicity, and the list goes on.1
Bittersweet Trends in Populations and Social Implications
Although 90 to 95% of all diagnosed diabetes is categorized as type 2 diabetes2, this might be an
underestimation because some predict that there are 7 million undiagnosed cases of type 2 diabetes in the
U.S. This suggests that more than 95% of diabetics, diagnosed and undiagnosed, in the population are
type 2. Without sugar coating the current population trends, the statistics reveal that diabetes will become
more prevalent worldwide.
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BIOEN 315 HW 1

U.S.: The number of diabetes cases doubled from 10 million to 20 million in a decade in the United States
from mid 90s to mid 00s (Figure 3). Although the increase in cases may not be exponential yet, it is
clear that the rate of increase is increasing. The trend in the U.S. can be broken down by race and
ethnicities and by income levels. There are racial disparities in rates of diabetes. According to the CDC,
Asian Americans, Hispanics, non-Hispanic blacks, are respectively 18, 66, and 77% more likely to get
diagnosed with diabetes compared to non Hispanic white adults.2 Even within these ethnicities, there are
greater disparities. Mexicans and Puerto Ricans are 87% and 94% more likely to get diabetes,
respectively, compared to non Hispanic white adults.2 Economically, there has been a moderately strong
correlation between income levels and diabetes rates (Figure 4) in a study of over 3,000 counties, where
poorer counties had significantly higher rates of diabetes.
World: The world population of diabetics is estimated to go up by 40% in the next twenty years (340
million to 470 million).3 Interestingly, the rate of diabetes follows increasing GDP and Dr. Hu of Harvard
notes that these epicenters of diabetes are also epicenters of globalization. In the last thirty years, China
went from having less than 1% to almost 10% of its population with diagnosed diabetes. It is also noted
that before China became the global leader in diabetes, India was in the lead (and it must be noted that
India still has pockets of areas where the 20% of its population has diabetes).
When looking at these general trends, the data seems very counter intuitive and hypocritical.
Countries of higher GDP have higher rates of diabetes, and in the case of India and China, cases of
diabetes increase with increasing GDP. Therefore just looking at this data, we could postulate that
diabetes follow wealth. But if we look at the data within the U.S., it is clear that the lower income
populations have higher rates of diabetes (Figure 4). These puzzling, contradictory data make more sense
when comparing Pima populations living in Mexico and the U.S. The Pima population in the U.S. is eight
times more likely to develop diabetes than its counterpart in Mexico (Figure 5). From this, we can see a
correlation of Western diet and the drastic difference in the rates of diabetes between the populations
across the border. Connecting this with the earlier data presented, the increasing GDP follows
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BIOEN 315 HW 1

Westernization (Western diet and Western sedentary lifestyle) more so than obesity since the Asian
countries with booming diabetic populations have very low rates of obesity.3 And within Western societal
structures, the poorer populations have less access to fresh food and are more prone to be trapped in
pockets of food scarcity. Therefore the increasing rates of diabetes could be another manifestation of the
economic disparity that comes with Westernization within populations.
Market for Diagnostics and Treatment
Traditionally, Hippocrates used to taste patients urine for glucose to diagnose diabetes mellitus
because the kidneys could not filter out all of the glucose in the blood, and his diagnostic method was
used for thousands of years.4 Fortunately, there are other three blood tests available for diagnosis of
diabetes today. One of the most common diagnostic tests for type 2 diabetes is A1C (also called
hemoglobin A1C, HbA1c, and glycated hemoglobin). The test determines what percentage of the
hemoglobin cells are sugar coated.5 The results reflect glucose level of the patient in the past two to three
months prior to the test. 6.5% or above is an indication of diabetes (Figure 2). Fasting plasma glucose is
another diagnostics test that is taken after a patient has fasted for 8 hours. The patient is considered
diabetic if the results are 126 mg/dL or above. There is also an oral glucose tolerance test. Glucose is
given to a patient and the test reflects how quickly it is taken up by the cells in the body. The patient is
diagnosed with diabetes if the results come back 200 mg/dL or above.
For treatments, both type 1 and type 2 diabetics need lancets (finger pricking device), test strips,
and a glucose monitor. Type 1 diabetics also need insulin, needles, insulin pump reservoir, insulin pump
infusion set, and insulin pump. MedTronic is the only company that has a continuous glucose meter that
fuses both the glucose monitor and the insulin pump so that both devices can communicate with each
other. Although this is a step forward in medical technology, this meter does not automatically regulate
the insulin levels but rather the insulin pump shuts off when the glucose levels are too low. There are two
companies Novo Nordisk and Oramed that are currently developing oral insulin pills to eliminate the need

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BIOEN 315 HW 1

for needles, and Novo Nordisk is already one of the giants in injectable insulin. Type 2 patients
treatments are usually tailored to meet their specific needs. In some cases, obesity is viewed as the cause
of type 2 diabetes and patients can get gastric bypass to treat obesity and indirectly treat diabetes.
The pump is usually the most expensive biomedical instrument that diabetics use on a day to day
basis, but since these patients use other products such as the insulin or the test strips on a day to day basis,
the costs can add up to thousands of dollars per year for the patient. On top of this, both types of diabetes
indirectly cause many other forms of serious medical conditions. Both types of diabetes have been linked
to micro and macrovascular medical complications that lead to a wide array of diseases such as diseases
of the artery, cardiovascular diseases, nephrophathy, and retinopathy.6,7,8 It has also been linked with
depression.9 Because diabetes is a prime burgeoning point for many other costly diseases, it is hard to
account for the true economic expenditure on the disease, but it has been estimated that compared to the
non-diabetic individuals, the diabetics need two to three times more health care resources over their
lifetime. Also, it is estimated that 15% of the health care budget goes into diabetes.10 On a global scale,
the U.S. uses about half the worlds diabetes expenditure health care costs and less than 10% of the world
diabetes expenditure goes into treating 70% of the world diabetes population.11
Possible Biomedical Solutions
For type 1 diabetes, there is a need for a device that integrates both glucose meters and insulin
pumps that acts as an artificial pancreas. Currently, patients have to manually calculate and control the
insulin pump after determining their blood glucose level, but a device that reads the glucose level and
appropriately calculates and signals the pump to release a certain dosage of insulin. This instrument will
be easier to use for children, youth, and adults alike.
Another need is more portable and affordable diagnostic systems since there are pre-diabetics that
are close to being diabetic and there are millions of undiscovered diabetic cases. Early detection of
diabetes will allow doctors to treat hypo and hyperglycemia earlier, and earlier control of diabetes will
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BIOEN 315 HW 1

prevent other medical complications, which will be more cost efficient. There is a possibility for paper
diagnostic tool for diabetes where we can create wells lined with chemicals that react with sugar and a
patient can drop their blood or urine onto the paper. A specific color would indicate the presence or
absence of sugar molecules. This would be a more portable and accessible test for people in the U.S. and
in developing countries.

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BIOEN 315 HW 1

References
1. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and
therapy. Lancet. 2005 Apr 9-15;365(9467):1333-46.
2. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates
and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA:
U.S. Department of Health and Human Services, Centers for Disease Control and Prevention,
2011. <http://www.cdc.gov//diabetes/pubs/pdf/ndfs_2011.pdf>
3. Hu FB. Globalization of Diabetes. Diabetes Care. 2011 Jun; 34(6):1249-57.
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114340/>
4. Fournier A. Diagnosing Diabetes. Journal of General Internal Medicine. Aug
2000;15(8):603-604. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495577/#__ffn_sectitle
5. Tests and Procedures: A1C Test. Published online Jan 30, 2013.
<http://www.mayoclinic.org/tests-procedures/a1c-test/basics/definition/prc-20012585>
6. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology,
pathophysiology, and management. The Journal of the American Medical Association. 2002
May 15; 287(19):2570-81.
<http://jama.jamanetwork.com/article.aspx?articleid=194930>
7. Haffner SM, Lehto S, et al. Mortality from coronary heart disease in subjects with type 2
diabetes and in nondiabetic subjects with and without prior myocardial infarction. New
England Journal of Medicine. 1998 Jul 23;339(4):229-34.
<http://www.nejm.org/doi/full/10.1056/nejm199807233390404>
8. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: The
Framingham Study. American Journal of Cardiology. 1974 Jul;34(1):29-34.
<http://www.sciencedirect.com/science/article/pii/0002914974900897>
9. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression
in adults with diabetes: a meta-nalysis. Diabetes Care. 2001 Jun;24(6):1069-78.
10. Chapter 1: Burden: mortality, morbidity and risk factors. Global Status report on
noncommunicable diseases 2010. <
<http://www.who.int/nmh/publications/ncd_report_full_en.pdf>
11. Zhang P, Zhang X, Brown J, et al. Global healthcare expenditure on diabetes for 2010 and
2013. Diabetes Research and Clinical Practice. 2010 Mar;87(3):293-301. <
http://www.sciencedirect.com/science/article/pii/S0168822710000495>

Minjung Kim
BIOEN 315 HW 1

Figure 1 Insulin and Glucagon provide negative feedback for a homeostatic system. Source:
Freeman, Scott. Biological Science Pearson Education. 5th Edition. San Francisco: Benjamin
Cummings; 2013.

Minjung Kim
BIOEN 315 HW 1

Figure 2: Diagnostic thresholds for diabetes. Source: Adapted from American Diabetes Association.
Standards of medical care in diabetes2012. Diabetes Care. 2012;35(Supp 1):S12, table 2.

Figure 3: Percentage of population and number of people with diabetes over time. Source: CDC Division
of Diabetes Translation. Long-Term Trends in Diagnosed Diabetes 1958-2010. Oct 2011.

Figure 4: Data from 3139 counties in the U.S.. The wealthiest population includes 630 counties with
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BIOEN 315 HW 1

mean poverty rate 8.2% while the poorest population has poverty rate of 25%. Source: Levine, James A.
Poverty and Obesity in the U.S. Diabetes. Nov 2011; 60(11):2667-2668.

Figure 5: Age adjusted prevalence of diabetes in non Pima Mexicans, Mexican Pima Indians, and US
Pima Indians. Source: Schultz, L. O., P. H. Bennett, E. Ravussin, et al. Effects of traditional and western
environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the U.S. Diabetes Care
2006 Aug; 29(8): 18661871.