Effects of Gluten Consumption and Medical Treatment on Type 1 Diabetes

Jennifer Hartsock

ANTH 330 Professor Eichelberger Winter 2014

Hartsock 2 I. INTRODUCTION Type 1 diabetes is a polygenetic autoimmune disease that attacks pancreatic beta cells and their production of insulin. During the Younger Dyras, Northern Europeans reacted to plummeting environmental temperatures by migrating south or rapidly adapting by elevating blood glucose levels and depressing the freezing point of bodily tissues. Those who survived the Younger Dryas migrated to other parts of the continent and passed their mutated gene to the next generation. As medical technology increased, diabetics gained longer life expectancy and therefore more offspring inherited genetic susceptibility. However, genetic vulnerability is dependent on environmental factors. About 8,000 years of consuming gluten aids to leaky gut syndrome and the seepage of toxin and antigen molecules from the small intestine into the bloodstream and into the pancreas. In addition, life-saving technology in the 20th century increased life expectancy from 1 month post diagnosis to nearly 60 years. The susceptibility gene for diabetes, gluten consumption, and life-saving technology are prevalent in Europe and the USA, moderate in Asia, and gradually rising in Africa. This suggests gluten consumption plays a heavy role in triggering the disease, and while the prevalence of diabetes and the consumption of wheat in developed nations keeps rising, life-saving technology as an environmental pressure favors diabetes as a trait. However, while the incidence of diabetes and the consumption of wheat in under-developed nations keeps rising, the lack of life-saving technology disfavors diabetes as a trait. Consequently, high levels of glucose in the blood stream began as an isolated environmental adaption in Northern Europe, but its favorability is now heavily dependent on lifesaving technology in developed nations.

Hartsock 3 II. OVERVIEW OF DIABETES For individuals not genetically predisposed to type 1 diabetes, pancreatic beta cells (bcells) produce a hormone called insulin. When someone consumes glucose, these b-cells release insulin that circulates throughout the bloodstream until binding to insulin receptors and absorbing into various bodily tissues. Insulin basically eliminates glucose from the bloodstream, regulating blood glucose levels (Todd 1995). The hereditary HLA-DQ8 gene is the primary risk locus for type 1 diabetes. In people not predisposed to diabetes, the residue on this gene is negatively charged; however, current experimentation on non-obese diabetic mice demonstrate how a mutation changes this residue from a negative to a neutral charge, thus shifting the surrounding region to a positive charge and unfortunately attracting auto-aggressive t-cells that damage pancreatic b-cells. Prolonged high blood glucose levels cause apoptosis, the main form of b-cell death. It takes, on average, about five years before b-cell death causes insulin deficiency and full-blown diabetes. This process is trigged by an environmental pressure (Todd 1995).

III. ORIGINS OF TYPE 1 DIABETES Since type 1 diabetes is most prevalent in Northern European populations, it is hypothesized that when Northern Europe experienced glacial-like conditions in the Younger Dryas about 14,000-11,000 years ago, high blood glucose levels became an evolutionary adaptation for surviving in extremely cold climates. During this brief period, people only lived to about twenty-five years old and, as we now know, it takes about five years before b-cell death causes full-blown diabetes and, at this time, imminent death.

Hartsock 4 Temperatures during the Younger Dryas dropped 10 degrees Fahrenheit in Northern Europe in only a couple decades. Inhabitants either found warmth from fashioning furs and hides, migrating south to parts of southern Europe (where diabetes rates are currently high), or developing genetic mutations that aided in adapting to their environment. Normally, adaptation to a new environment is a prolonged process, but epigenetic factors may account for the sudden adaptation of diabetes. Certain heritable, chemical reactions change the function of genes without altering basic DNA structures, producing adaptations in just a few generations. Northern Europeans who survived these colder temperatures and migrated to other parts of the continent lived to pass on their heritable extreme-cold adapted HLA-DQ8 gene (Ling 2009). Likewise, the HLA-DQ8 gene is similar to several gene mutations in modern wild animals that have an evolutionary advantage to extremely cold temperatures. For example, the wood frogs kidney reacts to a cold environment by pouring glucose into its bloodstream. High levels of blood glucose actually depress the freezing point of bodily fluids in several ways: high blood glucose levels promote the release of glycerol and lipid storage for winter body heat. It also increases urination so that the organism is in a semi-dehydration state that lower[s] the freezing point of tissues and blood, providing increased protection against the cold. Brown adipose tissue is incredibly important for surviving cold temperatures; unlike other body tissues, brown tissue doesnt require insulin to absorb glucose in fact, when the body is cold, the pancreas lowers insulin levels in order to increase glucose levels in the bloodstream so as to become absorbed by brown tissue and create body heat. Wood frogs and diabetes share the same level of high blood glucose, and brown adipose tissue accounts for 1% of fat in human adults (Moalem 2005: 8-16).

Hartsock 5 Today, most people who are diagnosed with diabetes live near the poles. After diagnosis, they experience higher blood glucose levels in the winter months via an increase in lipolysis, the foundation for creating body heat (Ling 2009).

Hartsock 6 IV. ENVIORNMENTAL PRESSURES

Wheat Consumption Although the HLA-DQ8 gene codes for susceptibility to diabetes, several environmental factors such as acquiring a virus, moving from one extreme climate to another, or consuming gluten actually trigger the disease. Zonulin is a natural molecule that allows water to leak into our bowel to create diarrhea and flush out antigens and toxins in food. However, when we digest gliadin (a protein found in gluten that mimics foreign bacteria), there is an increase in zonulin secretion that causes small intestinal permeability (leaky gut), allowing these antigens and toxins to enter the bloodstream (Watts 2005:2916-2921). It is hypothesized that these antigens and toxins migrate from the bloodstream to the pancreatic lymph nodes, sparking an autoimmune response that attacks pancreatic b-cells. However, it is still unclear why the autoimmune response attacks b-cells (Cartailler 2013). About 8,000 years of wheat production sprouted in Asia and the Middle East, then in Europe in the Bronze Age, and is now also prevalent in the USA and Canada. Major strains of wheat (einkorn, emmer, and spelt) originated from one common ancestor 10,000 years ago. Einkorn used to have high levels of protein, fat, and vitamins and minerals. It then pollinated with an indigenous species and produced emmer between 4,000 and 1,000 BCE. Emmer and goatgrass cross-fertilized to become T. aestrivum, a common modern bread wheat high in gluten. In 1927, the USA welcomed wonder bread, making T. aestrivum easily accessible. India and Africa experienced an increase in gluten consumption between 2000 and 2009 due to wheat importation (Morris 1993).

Hartsock 7 There is now a correlation between gluten consumption, celiac disease, and type 1 diabetes. About 3.9-12.3% of diabetics have celiac disease due to sharing the HLA-DQ2 gene (highly linked to celiac) and the HLA-DQ8 gene (highly linked to diabetes). These genes cause a 40% susceptibility for developing either disease environmental factors such as gluten consumption (beginning with breakfast cereals for children) actually trigger the diseases (Achenbach 2005). Both diabetes and gluten consumption are most prevalent in Northern Europe and the USA. People from Finland are forty times more likely than Japanese to develop diabetes, who are then one hundred times more likely to develop diabetes than Chinese (Norelle 2012). Diabetes is steadily rising in Asia, and rapidly rising in under-developed countries such as Africa and the Mediterranean (Gale 2014). Celiac disease is less common in Asia, and is rare but increasing in Africa. The HLA-DQ2 gene has a 5-10% prevalence in Southeast Asia and subSaharan Africa (Norelle 2012).

Table 1. Rate of people with type 1 diabetes and celiac disease N. Europe/USA Type 1 Diabetes Celiac Disease Prevalent, rising Prevalent, rising Asia Africa

Low, steadily rising Low, rapidly rising Average, rising Low, rising

Since it is unclear if genetic susceptibility has recently risen worldwide, it is hypothesized that the escalating incidents (probability of diagnosis) for type 1 diabetes is due to environmental pressures like increased gluten consumption. The rate of prevalence (total number diagnosed and alive) depends on another environmental factor: life-saving medical technology.

Hartsock 8 Modern Technology During the Younger Dryas, when life expectancy was only a short twenty-five years, humans didnt live long enough to acquire long-term complications from high blood glucose levels (Ling 2009). As life expectancy increased, humans began experiencing serious health repercussions. Prior to insulin technology and strict blood glucose control in developed nations during the early 20th century, most type 1 diabetics died within a month of diagnosis. Egyptians in 1,500 BC used spices, herbs, and indigenes plants to treat people with honey urine. India during the fifth and sixth centuries, and Arabia during the ninth and 11th centuries, avoided alcohol, sexual activity, salty cereals, and prescribed spices and herbs with hypoglycemic indexes to lower blood glucose levels. Needless to say, without the secretion of insulin, these natural remedies werent enough to prevent ketoacidosis and death (Lasker 2010). In the 19th century, scientists removed the pancreas from deceased diabetic dogs to better understand its functions. They provided evidence of ketoacidosis, the pancreas effect on metabolism, and its production of glycogen and insulin (Lasker 2010). From the first synthesized pancreatic extract in the early 1900s to recombinant DNA human insulin in 1980, the 20th century in developed nations provided intensive blood glucose control and, consequently, the reduction of long-term complications. In the beginning, relatively impure insulin from beef and pork animals was injected twice daily. Monitoring of glucose and ketone levels was done by urinating on tablets; specific colors represented different ranges. The first recombinant DNA human insulin, Regular, was released in 1922 and provided better blood glucose control. The introduction of NPH in 1950 delivered semi-accommodating basal insulin, however the absorption rate was inconsistent from one daily injection to the next, causing a fluctuation of hypo- and hyperglycemia. The first diabetic detection drive, as well as a study on

Hartsock 9 coronary artery disease, took place in 1950 and aided in developing better dietary and exercise regimens. A 10-year-old child diagnosed with diabetes during this year was expected to live 45 more years. It wasnt until 1980 that diabetics began testing their A1C (the average blood glucose level over 6 weeks), and it wasnt until 1993 that diabetics could purchase at-home glucose meters for multiple daily testing. In 2000, diabetics welcomed a basal insulin called Lantus that produced a consistent absorption rate that helped prevent glucose levels from dropping or spiking out of range. The first commercial insulin pump (a somewhat computerized pancreas) was released in 2003, allowing the user to account for fluctuating digestion rates by scheduling specific insulin ratios (carbohydrates/unit of insulin) for different times of the day. Diagnosed children born in or after the 20th century now have a life expectancy of 69 years (Lasker 2010). Life-saving technology in under-developed nations is outdated and inaccessible in comparison. People in Africa diagnose diabetes when urine attracts ants, similar to methods used in ancient Egypt. Although adequate data is difficult to achieve, high mortality rates due to diabetes are estimated for India, Asia, and sub-Saharan Africa. Access to modern life-saving technology and treatment is often infrequent and in short supply (Ogle 2013).

Table 2. Prevalence of modern, life-saving diabetic technology N. Europe/USA Asia Africa

Modern Technology Prevalent, low mortality Average, high mortality Low, high mortality

While incidence for diabetes continues to rise worldwide, newly diagnosed diabetics are favored by developed nations with life-saving technology. Newly diagnosed diabetics who

Hartsock 10 inhabit under-developed nations are therefore disfavored due to the lack of life-saving technology.

V. CONCLUSION The environment determines the fitness of a population. When modern humans were confronted with rapid drops in temperature in Northern Europe during the Younger Dryas, a portion of the population adapted to their environment via a gene mutation that caused glucose to pour into the bloodstream. Survivors eventually migrated south and passed their heritable mutated gene to future generations. During the 14,000 years of changing environmental factors that increased life-expectancy from 25 years to 69 years, the gene increased the incidence of diabetes-prone offspring in worldwide populations. Although gluten consumption is increasing worldwide, the high prevalence of wheat products in developed nations leads to an increase in the prevalence of diabetes, as opposed to an average to low prevalence in under-developed nations. As well, diabetics who live in developed nations successfully gain access to life-saving recourses, while those diagnosed in underdeveloped countries have limited to no access. Uneven distribution of and access to life-saving technology create competition between populations. Type 1 diabetics living in developed nations have greater reproductive success. This suggests diabetes may saturate developed populations over time, creating natural variation between developed and under-developed nations. As the incidence rate continues to rise in under-developed nations, so will their mortality rates unless greater life-saving technology is introduced into their environment.

Hartsock 11 References Achenbach, Peter, and Ezio Bonifacio, Kerstin Koczwara and Anette-G. Ziegler 2005 Gale, E.A.M. 2014 Geography of type 1 diabetes. Diapedia 34. Natural History of Type 1 Diabetes. Diabetes 54(suppl 2 S25-S31).

Jean-Philippe Cartailler, Ph.D 2013 Insulin - from secretion to action. Beta Cell Biology Consortium.

Ling, Charlotte, and Leif Groop 2009 Epigenetics: A Molecular Link Between Environmental Factors and Type 2 Diabetes. American Diabetes Association 58(12). Moalem, Sharon, and K.B. Storeyb, M.E. Percyc, M.C. Perose, and D.P. Perl 2005 The sweet thing about Type 1 diabetes: A cryoprotective evolutionary adaptation. ELSEVIER 65(1):8-16. Morris, Michael L., and Derek Byerlee 1993 Narrowing the Wheat Gap in Sub-Saharan Africa: A Review of Consumption and Production Issues. Economic Development and Cultural Change 41(4). Norelle, Reilly, and Green, Peter 2012 Epidemiology and clinical presentations of celiac disease. Seminars in Immunopathology 34(4). Ogle, Graham, and Angie Middlehurst and Robyn Short-Hobbs 2013 Children and Diabetes: Success and Challenge in the Developing Word. International Diabetes Federation. http://www.idf.org/children-and-diabetessuccess-and-challenge-developing-world

Hartsock 12 Todd, John A 1995 Genetic Analysis of Type 1 Diabetes Using Whole Genome Approaches. Proceedings of the National Academy of Sciences of the United States of America 92(19). Watts, Tammara, and Irene Berti, Anna Sapone, Tania Gerarduzzi, Tarcisio Not, Ronald Zielke, Alessio Fasano and Maria Iandolo. 2005 Role of the Intestinal Tight Junction Modulator Zonulin in the Pathogenesis of Type I Diabetes in BB Diabetic-Prone Rats. Proceedings of the National Academy of Sciences of the United States of America 102(8):2916-2921.