Mona Morstein, ND

Tolle Totum

Etiological Factors

The worldwide statistics regarding diabetes are frightening. In 2011, 366 million people around the world were diagnosed with diabetes, and it is projected that, by 2030, up to 552 million people will have it—nearly 10% of the world’s adult population. In the US, there are 29 million people with diabetes, and approximately 1.25 million have type 1 diabetes mellitus (T1DM), including 1 out of every 300 children. In fact, the most recent US data indicates the occurrence of T1DM increased by 21% between 2001 and 2009.

Worldwide, there are 70,000 new cases annually, and T1DM occurrence is rising by an estimated 3% each year. Around 24% of T1DM pediatric patients live in European countries; 23% are in Southeast Asia, and 19% are in North America and the Caribbean. Unfortunately, in Sub-Saharan countries where insulin may be difficult to get and use, there is a high mortality rate of 42.6 deaths per 100,000, while in the US, there are only 0.63 deaths per 100,000.¹

Aside from pediatric-onset T1DM, adult-onset T1DM is also growing. Known as latent autoimmune diabetes of the adult, or LADA, this type of T1DM is still commonly mistaken for type 2 diabetes. Occurring in patients generally over 35 years old, around 4-14% of patients diagnosed with T2DM have diabetes-associated antibodies or LADA.²

What is driving the increasing incidence of T1DM? There are many factors that are being studied.

The Role of Genetics

There are multiple HLA genes associated with turning on the auto-immune activity directed against the pancreatic beta cells, leading to the lack of insulin secretion that is the keynote characteristic of T1DM. Nonetheless, T1DM is not considered to be hereditary: 80% of children with a parent who has T1DM will not develop T1DM.

When T1DM seems to transcend multiple family generations, investigating for mature onset diabetes of the adult (MODY) through Athena Labs is pertinent. MODY consists of several genetic defects that do not produce T1DM, and do not elevate the auto-antibodies usually discernible in a T1DM patient, but can produce inter-generational presentations of a mild T1DM problem.

The Environmental Determinants of Diabetes in the Young (TEDDY) study is being undertaken by six consortiums of physicians around the world. They are following children with positive T1DM genes to see if they do develop T1DM and, if so, what are the associated factors. The TEDDY study is analyzing many factors, including gestational health of the mother, early infections of the child, differences in food introduction timing, vitamin deficiencies (vitamin D3, vitamin E, antioxidants), immunization and timing, lack of early infections, drinking water purity (especially nitrates from fertilizers), exposure to pets and other allergens, excessive weight gain, and emotional stress. Children will be followed from birth to age 15 years old. It will be fascinating to see the conclusions, but there are still years to go before the study ends.

Exploring Other Risk Factors

Some studies have already identified etiological risk factors. Finland has the highest per capita occurrence of T1DM in the world: 57.2 per 100,000 people. That is, 1 of every 200 children under the age of 15 years old in Finland has T1DM. In population studies performed by Finnish researchers, infant intakes of vitamin D3 and omega-3 oils were inversely correlated with the onset of T1DM occurrence.^3,4 In addition, in preliminary observational research, supplementing infants’ diets with cod liver oil was associated risk reduction. ⁵

Avoidance of cow’s milk and gluten may be helpful for prevention. In particular, milk is high in the A1 variant of beta-casein, rather than the A2 variant, seems to be more closely linked to T1DM. The A1 casein variant has histidine in the amino acid 67 position, while proline is found in this position in the A2 peptide.⁶ Although infant milk consumption in Scandinavia, where the A1 casein peptide is highly present, has been correlated with higher risk of T1DM, in one study, milk from Iceland, which has lower quantities of A1 milk peptide, was not associated with T1DM onset.⁷ Higher consumption of meat and dairy protein also seems to be a risk for development of T1DM, while cereal grains, fats, vegetables, and fruits are may be protective.⁸

Celiac disease is associated with T1DM; approximately 8–15% of T1DM patients have celiac disease.⁹ What is fascinating to note is that if a child is found to have celiac disease and gluten is fully removed, their risk of subsequently developing T1DM drops to zero.¹⁰ I believe this is such a powerful tool for prevention that performing a celiac screening by the time a child is 1–2 years old should be part of every pediatrician’s protocol. One wonders why it is not.

Environmental toxicity has been shown to be another risk factor for increasing both type 1 and type 2 diabetes. There are more associations with type 2 than type 1; however, more researchers are wondering about the connection between higher environmental toxins and higher onset of T1DM. Toxins such as n-nitroso compounds, air pollutants, and persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) are associated specifically with T1DM.¹¹

In a South Korean study, children with higher levels of POPs had lower beta cell function and reduced insulin secretion from ages 7-9 years old.¹² A good website for studies and research about environmental toxins and diabetes is www.diabetesandenviroement.org.

Gut Health and Type 1 Diabetes Risk

The gut microbiome is also highly suspected to be a risk factor for T1DM. The human gut microbiome can be negatively affected by many factors: Cesarean-section birth, bottle-feeding, antibiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs, food poisoning, alcohol, coffee, genetically modified organisms, obesity, and a poor diet (low in fiber and clean, whole foods, and lacking dietary diversity). Disturbances in the microbiome are associated with nutrient deficiencies, intestinal permeability, gut inflammation, loss of immune regulation, and systemic conditions such as allergic disorders, asthma, and auto-immunity.¹³

In children with beta-cell auto-immunity, analyzing their microbiome showed that they had decreased colonization with butyrate-producing bacteria, which provide and important energy source for colonocytes, and an increase in bacteroidetes, which are thought to be harmful when present at high levels.¹⁴

The term pre-type 1 diabetes is used to denote the presence of an HLA gene pattern and the appearance of multiple auto-antibodies associated with pancreatic beta cell dysfunction, but no clinical presentation of the condition. It can sometimes take 9–12 years before there is the actual onset of clinical diabetes. For example, in pre-T1DM patients, zonulin was detected in 70% of patients, and preceded the clinical onset of T1DM by approximately 3.5 years. Increased zonulin is also associated both with leaky gut and auto-immunity.¹⁵ Children with T1DM have been shown to have increased small intestinal permeability.¹⁶ Increased tight junction permeability precedes T1DM onset and seems to initiate auto-immunity.¹⁷

The Question Naturally Arises: Can healing the gut prevent T1DM?

In a rat model, when the leaky gut was healed, fewer rats developed T1DM. Associated with leaky gut, a significant number of viruses have been considered possible T1DM etiological factors. Implicated viruses include rotavirus, mumps virus, and cytomegalovirus. The prime candidates, however, are the enteroviruses. Patients with T1DM are more likely to have evidence of infection with enteroviruses, especially coxsackie B viruses. Enterovirus infection is more common in siblings who develop T1DM compared with siblings who do not, and has been found in mothers whose children later develop T1DM.¹⁸ It has been proposed that exposure to enteroviruses in genetically predisposed people can increase inflammation and up-regulate the immune system and its auto-antibody production.¹⁸ In one study, enteroviruses were identified in the pancreatic beta cells of newly diagnosed T1DM patients.¹⁹

Looking at the Whole Picture

In summary, these are key areas to analyze in patients with Pre-T1DM or actual T1DM:

1. Type 1 diabetes mellitus-associated gene patterns
2. Vitamin D3 and omega-3 status
3. Ruling out Celiac disease (before removing gluten!)
4. Factors that increase exposure to environmental chemicals, such as home use of exterminators, home refurbishing that is not “green,” workplace exposure, etc.
5. Were they breast fed, and for how long? If not, what type of formula was used? (Interestingly, elemental formulas with hydrolyzed casein do not seem to increase risk of T1DM.)
6. Dairy and gluten intake
7. Gut influences: Antibiotic and other medication history, food poisoning history, alcohol and coffee intake, and diet diary analysis.
8. Intestinal permeability analysis such as a IgG food sensitivity test, leaky gut analysis with lactulose and maltose, and/or measuring zonulin levels.
9. Family history of auto-immune diseases
10. Immunization schedule (timing before onset of T1DM)
11. Viral exposure
12. Supplements
13. Psychological stress

Why bother focusing on the above when curing T1DM is going to occur?

First and foremost, all T1DM patients (as well as type 2 diabetes patients) must be helped to attain excellent control of their diabetes, allowing them long healthy lives and preventing the onset of potentially catastrophic complications. The Low Carb Diabetes Association, of which I am Executive Director, directs medical practitioners to focus on a low carbohydrate, whole foods diet, optimal exercise, sleep, stress management, healing the gut and its microbiome, environmental detoxification, supplementation, and medication use to bring much better control into the lives of all diabetes patients.

In addition, for patients who present with T1DM, analyzing and balancing the above may have a strong capacity to prevent the patient from developing other T1DM associated auto-immune diseases, including celiac disease, Hashimoto’s and Graves diseases, Addison’s disease, and inflammatory bowel disease. In my experience, it is not uncommon for a T1DM patient to already have another auto-immune condition; in fact, up to 33% of T1DM children already have another auto-immune disease at the time of diagnosis.²⁰ Working to prevent additional auto-immunity can have a huge benefit to T1DM patients.

Delving into the Complex Etiological Nature of T1DM

Understanding the complex etiological nature of T1DM can help identify people at risk, and help strengthen them to avoid clinical onset. If a T1DM patient shows up for medical care, doing a deeper analysis can indeed help in maximizing their glucose levels and overall health, and guide efforts to prevent other auto-immune conditions from developing later down the line.

[References]

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2. Laugesan E, Ostegaard J, Leslie R, et al. Latent autoimmune diabetes of the adult: current knowledge and uncertainty. Diabet Med. 2015;32(7):843–853.
3. Hypponen E, Laara E, Reunanen A, et al. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358(9292):1500–1503.
4. Norris JM, Yin X, Lamb MM, et al. Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes. JAMA. 2007;298(12):1420–1428.
5. Stene LC, Joner G; The Norwegian Childhood Diabetes Study Group. Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study. Am J Clin Nutr. 2003;78(6):1128–1134.
6. Sodhi M, Mukesh M, Kataria RS, et al. Milk proteins and human health: A1/A2 milk hypothesis. Indian J Endocrinol Metab. 2012;16(5):856.
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10. Schmid S, Buuck D, Knopff A, et al. BABYDIET, a feasibility study to prevent the appearance of islet autoantibodies in relatives of patients with type 1 diabetes by delaying exposure to gluten. Diabetologia 2004;47:1130–1131.
11. Howard SG, Lee DH. What is the role of human contamination by environmental chemicals in the development of type 1 diabetes? J Epidemiol Community Health. 2012; 66(6):479–481.
12. Park SH, Ha E, Hong YS, Park H. Serum levels of persistent organic pollutants and insulin secretion among children age 7-9 years: A prospective cohort study. Environ Health Perspect. 2016;124(12):1924–1930.
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16. Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55(5);1443–1449.
17. Bosi E, Molteni L, Radaelli MG, et al. Increased intestinal permeability precedes clinical onset of type 1 diabetes. Diabelogia. 2006;49(12):2824–2827.
18. Filippi CM, von Herrath MG, Viral trigger for type 1 diabetes: pros and cons. Diabetes. 2008;57(11):2863-2871.
19. Krogvold L, Edwin B, Buanes T, et al. Detection of low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes. 2015;64(5):1682–1687.
20. Triolo TM, Armstrong TK, McFann K, et al. Additional autoimmune disease found in 33% of patients at type 1 diabetes onset. Diabetes Care. 2011;34(5):1211–1213.
    

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    Mona Morstein, ND, is a naturopathic physician at Arizona Integrative Medical Solutions in Tempe, AZ and an expert on pre-diabetes and diabetes. Dr Morstein is a frequent lecturer at medical conferences, and produced an 11-week diabetes webinar through MedicalTalkPro.com. She is the Founder and Executive Director of the Low Carb Diabetes Association, www.lowcarbdiabetes.org, a non-profit designed to educate patients, care-givers, medical practitioners, businesses, and the worldwide community about using integrative care to prevent and treat diabetes. Her book, Mastering Diabetes: The Comprehensive Approach to Successfully Treating Type 1 and Type 2 Diabetes, will be published in the spring of 2017.