Mackenzie Andrews

BIOEN 315
April 4, 2016

Diabetes mellitis: The global Epidemic

Overview

Diabetes mellitis is a group of diseases characterized by prolonged periods of

high blood pressure. Diabetes is broken down into three main groups; type 1 (childhood
onset), type 2 (adult onset), and gestational diabetes. Over 99% of the diabetic
population has either type 1 or type 2 diabetes. Diabetes affects an estimated 415
million people globally with staggering increases over recent years.​1​ Due to the high and
growing number of affected individuals, national and global expenditures on the disease
have been increasing at a near exponential rate.
There is currently no cure for diabetes and current treatments can be costly,
painful, and inconvenient. Efforts to find a cure for diabetes have been gaining
momentum over recent years and research in the field of regenerative medicine has
been showing promise for a long term treatment and cure for the disease.

Cause and Pathology

Type 1

Type 1 diabetes (T1D) is an autoimmune disease resulting in the destruction of

the beta cells in the pancreas. Beta cells produce insulin, the hormone responsible for
the absorption of glucose from the bloodstream into skeletal muscle and fat cells. The
destruction of those beta cells results in high blood sugar which can lead to symptoms
such as frequent urination, increased thirst, hunger, and weight loss.​2
T1D is usually diagnosed in childhood or early adulthood and makes up about
10% of the diabetic population.​3​ Individuals with T1D must carefully monitor their blood
sugar and self administer insulin to maintain a healthy blood glucose level. Failure to
administer insulin can cause severe complications such as diabetic ketoacidosis, heart
disease, kidney failure, stroke, and eye damage leading to blindness.
The inherent cause of T1D is currently unknown, but factors such as genetics,
environment, and viruses or drugs that target the pancreas have been linked to the
development of T1D.​4
Type 2

Type 2 diabetes makes up 90% of the diabetic population and is defined as a

metabolic disorder resulting in chronic high blood sugar caused by insulin resistance.​5
Like type 1, common symptoms are frequent urination, increased thirst, and weight loss,
also general fatigue and sores that won’t heal. The cause of type 2 diabetes is usually
linked to an unhealthy lifestyle including poor eating habits, obesity, and lack of
exercise. Genetic predisposition also plays a role in a person’s chances of developing
type 2 diabetes.
Overconsumption of sugary or fat heavy foods and lack of exercise can lead to
insulin resistance coupled with decreased beta cell activity. In non-affected individuals,
insulin suppresses glucose release from muscle, fat, and liver cells. In diabetic, insulin
resistant individuals, the body is unable to respond to normal insulin levels and will
release excess amounts of glucose into the bloodstream resulting in high blood sugar.
Type 2 diabetics must closely monitor their blood sugar levels. Anti-diabetic
medications such as Metformin are often prescribed to help aid the body in managing
blood glucose levels.​6 ​Insulin injections are also sometimes necessary. Without proper
treatment, type 2 diabetes can also lead to diabetic ketoacidosis, heart disease, kidney
failure, stroke, and eye damage, among other correlated complications.

Impact

Individual Outlook

Individuals with diabetes have a decreased life expectancy of approximately 11

years in men and 14 years in women.​7​ The shorter life expectancy is due to the number
of complications associated with the disease. In addition, non-fatal complications of the
disease include diabetic nerve pain, blindness, decreased cognitive function, and
general fatigue among others.​8​ Individuals with diabetes also often have dietary
restrictions and type 2 diabetics often suffer from complications of obesity all resulting in
a general decrease in quality of life. If managed properly however, diabetics can live an
otherwise healthy and normal life. However, the cost of treatment for an individual is
estimated at $7,900/yr for diabetes related medical expenditures alone.​9

National and Global Trends

The national and global impact of diabetes has become a growing concern in
recent years. From 1980 through 2014, the number of diagnosed cases in the US alone
has almost quadrupled from 5.5 to 22.0 million, with an additional estimation of 8.1
million undiagnosed cases.​10​ Globally, 415 million people have diabetes with the
majority of cases occurring in developed countries.​11​ Deaths due to diabetes have been
increasing rapidly as well. In the US, diabetes contributed to at least 75,000 deaths in
2013 making it the 7th leading cause of death.​12​ Globally, there is a diabetes related
death happening every 6 seconds (5 million per year).​11
The increasing incidence of diabetes has been strongly correlated to the
increasing population of obese persons. Since 1980, obesity rates have more than
tripled, aligning with the quadrupling of diabetes incidents since that same year.​13​ The
obesity trend also follows an ethnicity correlation. Both obesity rates and diabetes rates
are highest among non-hispanic blacks.​14

Market Analysis

These staggering trends carry over into the market and economy as well. In the
US alone, the total costs of diagnosed diabetes rose 41% over a 5 year period from
$174 billion in 2007 to $245 billion in 2012.​15 ​ Approximately 12% of the global health
expenditure is spent on diabetes or diabetes related conditions.​16​ Direct health
expenditures include cost of hospital inpatient care, medications, antidiabetic agents,
and physician fees. Indirect costs due to diabetes also have an impact on the US
economy. An accrued $68 billion are lost in the US alone due to factors such as
increased absenteeism, reduced productivity, inability to work, and early mortality.​16
These indirect costs definitely cause a hit to the US economy, however much of
the financial burden is on the individuals suffering from the disease. Most of the money
spent on diabetes in the US comes from the consumer and goes to the pharmaceutical
companies. Globally, insulin sales alone are at an annual $15.4 billion (a 400% increase
since 2000).​17
Efforts to research diabetes also accrue a large expenditure. The NIH alone
spends over $1 billion dollars on diabetes research annually.​18​ With diabetes becoming
a growing concern, the push to find effective treatments and an ultimate cure has been
gaining weight in recent years.

Bioengineering Solution

In designing a cure for diabetes, two major problems exist. The first being
decreased function or destruction of the insulin producing beta cells. The second being
the insulin resistance of glucose releasing cells in the liver and fat tissues. The beta cell
decrease affects both type 1 and type 2 diabetics and is a major target of research. The
root cause of the beta cell destruction is unknown, but methods for reversing the loss of
beta cells once diabetes has been diagnosed are underway.
Previous methods of replacing beta cells involved pancreas or islet-cell
transplants. However, both methods require an organ donor and with almost a third of
the population either diagnosed or at risk for diabetes, there are not nearly enough
organs to go around. The shortage of donors has spurred research in other areas such
as islet expansion, islet xenografts, human islet cell-lines, and stem cells.​19

Stem Cell Therapy

Stem-cell therapy lies under the umbrella of regenerative medicine. In the case of
diabetes, stem cell therapy is aimed at replacing the diseased or lost bet cells using
pluripotent or multipotent stem cells. Stem cells can be derived either from an embryo,
called embryonic stem cells (ESC) or from an adult, called induced pluripotent stem
cells (iPSCs). The stem cells can then be differentiated using synthetic techniques to
generate surrogate beta cells that can be implanted in the patient to restore the
beta-cell function.
Current research into stem cell therapy has been focused on type 1 diabetes.
Mouse models have shown hyperglycemia reversal after the implantation of
ESC-derived pancreatic progenitor cells.​20​ The challenge with extending the same
research to type 2 was the development of an effective mouse model of type 2 diabetes.
Recently, a team at UBC was able to develop such a model and tested ESC cells for
treatment with the same results as seen in the type 1 model.​21
The next step in the research is the translation to clinical trials. Currently,
ESC-derived pancreatic progenitor cells are being tested for 3 major criteria during the
first phase of clinical trials. Once the safety, tolerability, and efficacy of the ESCs has
been assured, human trials will go under way.​22

Conclusion

Diabetes is one of the fastest growing diseases worldwide, affecting or

threatening nearly one-third of the population including all ages and racial subsets. The
number of deaths and life altering complications resulting from diabetes has been
increasing with no projection of slowing down. Billions of dollars are spent every year by
the health care system and consumers on managing the disease while the national
GDP takes annual hits due to decreased productivity caused by the disease.
Research into treatments and cures for diabetes has been gaining momentum
with solutions all over the board from artificial organs to stem cells to gut biome
replacement. Current research into stem cell therapy has been showing promise and
beginning to make its way to clinical trials.
As research progresses, the best mode of action for all is to maintain a healthy
lifestyle. The major risk factors for developing diabetes are poor diet, lack of exercise,
and genetic predisposition leading to obesity. So limiting the amount of sugary and fatty
foods one eats while staying active are good preventative measures for reducing the
risk of developing diabetes.

References
1. "Update 2015"​. ​IDF​. International Diabetes Federation. p. 13. Retrieved 21 Mar
2016.
2. Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics".
Pediatr Rev​ 29 (11): 374–84; quiz 385.
3. "Type 1 Diabetes"​. ​American Diabetes Association​. American Diabetes
Association. Retrieved 26 October 2014.
4. Knip M, Veijola R, Virtanen SM, Hyöty H, Vaarala O, Akerblom HK (2005).
"Environmental Triggers and Determinants of Type 1 Diabetes". ​Diabetes​ 54:
S125–S136. ​doi​:​10.2337/diabetes.
5. Shi, Yuankai; Hu, Frank B (7 June 2014). ​"The global implications of diabetes
and cancer"​. ​The Lancet
6. Ripsin CM, Kang H, Urban RJ (January 2009). "Management of blood glucose in
type 2 diabetes mellitus". ​Am Fam Physician
7. Livingstone, SJ; Levin, D; Looker, HC; Lindsay, RS; Wild, SH; Joss, N; Leese, G;
Leslie, P; McCrimmon, RJ; Metcalfe, W; McKnight, JA; Morris, AD; Pearson, DW;
Petrie, JR; Philip, S; Sattar, NA; Traynor, JP; Colhoun, HM; Scottish Diabetes
Research Network epidemiology, group; Scottish Renal, Registry (6 January
2015). "Estimated life expectancy in a Scottish cohort with type 1 diabetes,
2008-2010.".
8. Cukierman, T (8 Nov 2005). ​"Cognitive decline and dementia in
diabetes—systematic overview of prospective observational studies"​.
Springer-Verlag. Retrieved 28 Apr 2013.
9. American Diabetes, Association (Apr 2013).​"Economic costs of diabetes in the
U.S. in 2012."​.​Diabetes Care
10. "Number (in Millions) of Civilian, Non-Institutionalized Persons with Diagnosed
Diabetes, United States, 1980-2014." ​Centers for Disease Control and
Prevention​. Centers for Disease Control and Prevention, 01 Dec. 2015. Web.
11. "Diabetes Globally." ​Diabetes Globally​. Diabetes Australia, 2015. Web.
12. "Diabetes." ​Centers for Disease Control and Prevention​. Centers for Disease
Control and Prevention, 22 Feb. 2016. Web.
13. Fryar CD, Carroll MD and Ogden, CL. ​Prevalence of Overweight, Obesity, and
Extreme Obesity Among Adults: United States, Trends 1960-1962 Through
2009-2010​. National Center for Health Statistics E-Stat, 2012.
14. "Age-Adjusted Rates of Diagnosed Diabetes per 100 Civilian,
Non-institutionalized Population, by Race and Sex, United States, 1980–2014."
Centers for Disease Control and Prevention​. Centers for Disease Control and
Prevention, 01 Dec. 2015. Web.
15. "The Cost of Diabetes." ​American Diabetes Association​. N.p., 22 June 2015.
Web.
16. Zhang, P., and G. Nichols. "Result Filters." ​National Center for Biotechnology
Information​. U.S. National Library of Medicine, 19 Feb. 2010. Web.
17. Farhe, Sean. "Trying to Cure Diabetes." ​Seeking Alpha​. N.p., 27 June 2011.
Web.
18. "Estimates of Funding for Various Research, Condition, and Disease Categories
(RCDC)." ​NIH Categorical Spending -NIH Research Portfolio Online Reporting
Tools (RePORT)​. US Department of Health and Human Services, 10 Feb. 2016.
Web.
19. Hussain, Mehboob A. "Stem-cell Therapy for Diabetes Mellitus." ​The
Lancet​364.9429 (2004): 203-05. ​Science Direct​. Rapid Review, July 2004. Web.
20. Rezania et al., 2013​ A. Rezania, J.E. Bruin, J. Xu, K. Narayan, J.K. Fox, J.J.
O’Neil, T.J. Kieffer Enrichment of human embryonic stem cell-derived
NKX6.1-expressing pancreatic progenitor cells accelerates the maturation of
insulin-secreting cells in vivo Stem Cells, 31 (2013), pp. 2432–2442
21. Bruin, Jennifer E., and Timothy J. Keiffer. "Treating Diet-Induced Diabetes and
Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells
and Antidiabetic Drugs." ​Stem Cell Reports​ 4.4 (2015): 605-20. ​Science Direct​.
14 Apr. 2015. Web.
22. "A Safety, Tolerability, and Efficacy Study of VC-01™ Combination Product in
Subjects With Type I Diabetes Mellitus." ​ClinicalTrials.gov​. U.S. National
Institutes of Health, Dec. 2015. Web.