Elsevier

Medical Hypotheses

Volume 84, Issue 4, April 2015, Pages 336-340
Medical Hypotheses

Type 1 diabetes epidemic in Finland is triggered by zinc-containing amorphous silica nanoparticles

https://doi.org/10.1016/j.mehy.2015.01.021Get rights and content

Abstract

Type 1 diabetes (T1D), an autoimmune disease, breaks out in some of the children who has genetic susceptibility to T1D. Besides genetic susceptibility some environmental factor(s) are required to trigger the disease. The incidence of T1D in Finland is highest in the world, so we must seek an environmental factor, that is typical for Finland and can declare many aspects of T1D epidemiology and biology. In the literature most popular trigger has been enterovirus infections. It is difficult however to find why enteroviruses would be in this role in Finland in contrary to neighbouring countries e.g. Sweden.

Colloidal amorphous silica (ASi) is typical for Finnish environment in consequency of the geohistory of Finland, great part of Finland is an ancient lake and sea bottom. ASi concentrations in natural waters are high in April–June and in November, only traces can be found in the rest of months. Pure colloidal ASi is not a strong trigger for T1D, but ASi particle which has surface adsorbed tetrahedrally coordinated zinc (ASiZn) is probably the trigger which has kept it’s secret up to date. Zn functions as address label which conducts the ASiZn particle to the beta cell, whose content of zinc is highest in the body. ASi particle adheres to membrane proteins distorting their tertiary structure revealing new epitopes. If the fetus has not met these epitopes at proper time during intrauterine development, the consequence is that the negative selection of lymphocytes in the thymus and bone marrow and fetal liver is not perfect. When a child later in postnatal life becomes predisposed to ASiZn particles the immune system reacts to these as to nonself proteins. As a consequence the insulin producing beta cells are destroyed.

Many observations from diabetes research support the hypothesis, some to mentioned. 1. Three common autoantigens (ZnT8, ICA512/IA-2, GAD65) are membrane proteins whose function zinc regulates. 2. Geographical variation in Finland is convergent with surface water manganese concentrations. Manganese is the principal Zn scavenger and high manganese in water reduces ASiZn particle formation and the incidence of T1D. 3. The incidence of T1D depends of drinking water pH. The highest incidence can be found within water pH 6.2–6.9. Zn coordination changes from octahedral (unphysiologic) to tetrahedral (physiologic) at pH 6.56. In the text are presented five more supporting observations e.g. the similarity between the soils in Sardinia and Finland in respect to ASi.

Introduction

Type 1 diabetes (T1D) is a disease in which the beta cells in the islets of pancreas are destroyed and there is total lack of insulin in the patients system. T1D is an autoimmune disease. Patients own immunologic system destroys the beta cells. As a rule the disease is diagnosed before the age of 15 years. Large epidemiological data concerning T1D has been collected in Europe longer time than in USA. At global level the incidence and prevalence of T1D varies greatly. It can be found about 350-fold variation in T1D incidence among different countries [1].

The incidence of T1D has been increasing throughout the world for decades. In Finland the incidence of T1D is highest in the world and it has increased 4.5-fold from the early 1950s [2]. In Sardinia the incidence of T1D is almost as high as in Finland (in Finland about 60 cases per 100,000 per year, in Sardinia about 40 cases per 100,000 per year). In the neighboring countries of Finland the incidence is about one-third that of Finland [1].

T1D breaks out in some of the children who has a genetic susceptibility to T1D [3]. However only 1 of 15–20 with HLA conferred susceptibility progresses to the clinical disease [2]. It is obvious that besides the genetic susceptibility some environmental factor(s) are needed for disease to develop. In spite of tremendous research, the progress in the field of environmental factor(s) or trigger(s) has been limited. More success has been achieved in the field of genetics and in the knowledge of the function of immune system [1].

I think that we have enough knowledge to resolve the T1D enigma in Finland. A good guideline in resolving the enigma is what Milton Terris wrote: “Epidemiology must draw upon and synthesize knowledge from the biological sciences of man and of his parasites, from the numerous sciences of the physical environment and from the sciences concerned with human society”.

Section snippets

Characteristic features of Finnish environment (soil and water environment)

Up to now T1D research has not analyzed the special features of Finnish environment. The last glaciation came to an end in Finland about 10,000 years ago. Earth’s crust had been sank under the ice sheet especially around the Gulf of Bothnia (the northern long gulf of the Baltic Sea). When ice smelted the land began to uplift and the uplift continues still. Most of Finland is therefore the ancient sea and lake bottom (there is also in the post-glacial development of the Baltic Sea the 1800 year

Changes in the social environment after World War II in Finland

Significant changes in the water distribution has been taken place after the 1940’s. Before that time in the countryside the drinking water was taken from the own wells. The wells had been dug as a rule into moraine or clayed ground. After the 1940’s the municipal water distribution has become prevalent. Raw water is taken from the sandy aquifers which however often get water from near located lake or pond (synclinal aquifers). These sandy aquifers are often so called concealed eskers, sandy

Unique zinc

Zinc (Zn) participates in many biological reactions. Zinc has many unique properties that make it suitable for many functions that are essential part of the life [10]. Because Zn is spectroscopically silent the significance of Zn in metabolic processes was understood much later than e.g. iron. Zn does not undergo easily oxidation or reduction reactions. The most significant feature of Zn is it’s flexible coordination geometry. Zn coordinates both tetrahedrally (coordination number 4) and

Hypothesis

T1D is an autoimmune disease that precipitates in genetically susceptible individuals by environmental trigger(s). In Finland the environmental trigger is colloidal ASi into whom Zn is adsorbed as tetrahedral coordination complex (ASiZn). Zn functions as an address label for ASiZn to gain access into the beta cell. It is known that the functions of transporter proteins, receptor proteins and various channels is based more on the coordination state of the transported material than the size of

Observations that support the hypothesis

  • 1.

    Autoantibodies. Almost all T1D patients have autoantibodies against zinc transporter ZnT8 [1]. ZnT8 is zinc transporter specific to beta cells [15]. Another common autoantibody in T1D, ICA512/IA-2 is directed towards tyrosine phosphatase like intrinsic membrane protein of secretory granules in the beta cells [16]. This protein is homologous to the receptor type protein tyrosine phosphatase. Zinc regulates the function of this protein in picomolar concentrations [17]. This protein participates

Discussion

Nanotechnology has developed rapidly in recent years. Titanium dioxide and silica dioxide nanoparticles (Si in the form of either crystalline or amorphous one) are used as food additives and in cosmetics. Asi nanoparticles are also used in drug delivery devices and in gene therapy. Therefore it is surprising how little attention naturally occurring nanoparticles in the surrounding has received. ASi is typical for many soils and waters in the northern hemisphere. Many autoimmune diseases are

Funding

No grants.

Conflict of interest

None declared.

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