The Canary Islands have the highest incidence of type 1 diabetes mellitus in children in Spain and one of the highest in Europe. The studies carried out to date place the range between 30 and 35 cases per 100,000 boys and girls per year, a figure that practically doubles the average for the entire national territory (17/100,000). The reasons for this marked difference are not entirely clear. According to experts, the development of this autoimmune disease is influenced by environmental factors, such as exposure to certain foods from an early age, vitamin D levels or suffering from viral infections, but also a genetic predisposition.
An article recently published in BMC Pediatrics, an open access journal that publishes peer-reviewed research studies and is part of the Springer Nature publishing house, offers a “plausible hypothesis, based on evidence and with enough weight” to explain, at less in part, that island peculiarity: the North African genetic load.
Pediatric endocrinologist Yeray Nóvoa, member of the Canarian Association for Pediatric Research, is the main author of an article signed by thirteen other specialists from different health branches. The study hypothesis is that “a common genetic background,” resulting from the migration of Arab and North African populations and the resulting genetic mixing, “may help explain” the higher incidence of type 1 childhood diabetes (boys and girls up to 14 years) in “Arab, North African, Sardinian and Canarian” populations.
The starting point is the studies led by Carlos Flores, a doctor from the University of La Laguna, on the genetic composition of the population of the Canary Islands, unique in Europe. The current inhabitants of the Islands are “a historical mix of Western Europeans, North Africans and sub-Saharan Africans.” An article published at the end of 2022 in the journal Scientific Reports, from the Nature group, estimated between 17 and 23% the imprint of North Africa in the DNA of contemporary canaries. It is the distinctive feature of the Archipelago. No other European region has such a high proportion of that ancestry. The influence of the Iberian Peninsula (mainly Galicia and Portugal) exceeds 70% and the sub-Saharan Peninsula is around 3%. Those studies also confirmed that the last admixture event occurred approximately fourteen generations ago.
The study published in September analyzes the DNA of 309 children diagnosed with type 1 diabetes in Gran Canaria and 222 without this disease. The main author of the article explains that most of the genes linked to this pathology are associated with the immune system. The research focuses on a genomic region, called HLA, that represents “up to 50% of the genetic risk” of type 1 diabetes mellitus.
Nóvoa points out that, within that region there are genes that predispose to the disease and others that protect against it. The main finding of the study is the low prevalence in the entire child population of Gran Canaria (not only in those with type 1 diabetes) of protective molecules called HLA-DQB1 with aspartic acid in position 57. In the population of control (minors without diabetes), 58% of the genes analyzed lacked this amino acid with a protective effect against the disease. This data is similar to that of other populations that also have high rates of diabetes.
“Type 1 diabetes has a genetic basis that does not follow the classical Mendelian laws, that is, it does not follow the direct inheritance pattern in which, if you have one or two certain genes, you have the disease. In diabetes there is a genetic predisposition. This means that there are people who have that genetic load and develop diabetes and there are people who have that genetic load and do not develop it. That is, genetics does not predict with 100% certainty that you will develop the disease, but it makes it more likely,” Nóvoa explains.
The study establishes several correlations. Firstly, the higher incidence of the disease in the Canary Islands and the low prevalence of this protective gene. On the other hand, there are regions of the genome of the island population in which North African ancestry has “a lot of weight.” And among them, with a burden that is around 50%, is HLA. Another piece of information reinforces the hypothesis. The map of countries with the highest incidence of type 1 diabetes in the world includes, for example, Algeria or Tunisia, as well as other regions of the Arabian Peninsula or Sardinia. In this “migratory extension”, in that corridor from the Arabian Peninsula to North Africa, Sardinia and the Canary Islands, a higher incidence of the disease is seen.
The pediatrician points out that there are no studies on the incidence of the disease in Morocco, but there is indirect data. For example, of people originating from this country who reside in Spain or Italy. And a high incidence has also been detected. Nóvoa insists. With current knowledge and evidence, we cannot yet speak of a causal relationship, but we can speak of a correlation. The results of the study open a way to continue exploring, with larger-scale research, the role of these genes in the origin of type 1 diabetes. “This article does not explain everything, which is why we must continue to delve deeper into the genetic study to understand the differences better,” he says. Other research on the genetics of type 1 diabetes in the Canary Islands is currently being carried out through collaborative studies in which hospitals from most of the Islands participate.
“The paradigm is changing”
Nóvoa explains that the paradigm in the treatment of the disease is changing. “We are not curing type 1 diabetes, what we are doing is ensuring that people with diabetes can survive, yes, with an increasingly higher quality of life. When we are able to detect it in the early stages, at the moment when autoimmune activity begins to appear, without producing an increase in blood glucose levels, we already begin to have treatments that can delay its appearance by two or three years.” For this reason, pediatric endocrinology continues, population screening strategies are beginning to be considered to detect those people who may develop it in the future.
Type 1 diabetes is an autoimmune disease. It occurs because the body’s defensive cells “destroy” those that produce insulin. This hormone is what allows sugar to pass from the blood into the cells for use as a source of energy. It is the most common type of diabetes in pediatric age and its mechanisms are different from type 2. The difference is that in the latter “there is no autoimmune destruction, but rather a resistance to the action of insulin, especially related to obesity, with excess fatty tissue, which makes it more difficult for insulin to act to lower sugar levels, overloading the pancreas so much that it can no longer respond.”
The mechanisms are different and so are the causes. In type 2 diabetes there is a clear association between the onset of the disease and obesity, related to lower socioeconomic levels. In studies on type 1 diabetes mellitus, environmental and genetic conditions are often talked about, but at the moment there is not “100% certainty about the factors that really predispose” to suffering from it.
“In autoimmune diseases we talk about the hygiene theory. It has been observed that people from developing countries, where there is normally a low incidence of autoimmune diseases, who emigrate to more developed countries, begin to present autoimmune diseases with rates similar to those in the countries of adoption. It is thought that the low exposure to infectious diseases in childhood in developed countries makes the development of the immune system different and predisposes to more autoimmune diseases,” explains the pediatrician.
“We are trying to deepen our knowledge of the mechanisms of diabetes in the Canary Islands. This may make it easier for us, in the not too distant future, to develop screening strategies aimed at our population, thus achieving greater effectiveness,” Nóvoa concludes.
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