Smoking and using smokeless tobacco increase the risk of two types of diabetes

Diet and lifestyle 15. sep 2022 3 min PhD student Jessica Edstorp Written by Kristian Sjøgren

A new study shows that both smoking and using smokeless tobacco increase the risk of developing latent autoimmune diabetes among adults (LADA). The study also indicates that the increased risk is proportional to the quantity of smoking or smokeless tobacco used. A researcher says that high-risk genotypes also strengthen the association between smoking, using smokeless tobacco and the development of LADA.

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Previous research has established that smoking increases the risk of developing type 2 diabetes. Now a new study shows that this also applies to the risk of developing LADA.

The results show that the more people smoke or use smokeless tobacco, the greater the risk.

According to a researcher, the study is the largest of its kind to find this association.

“Previous studies have had varying results, with some finding that smoking increases the risk of developing LADA and some that it decreases the risk. However, our results are unequivocal: using tobacco products was associated with an increased risk of developing LADA. Further, we found that certain high-risk genotypes strengthen the association, and we identified a potential mechanism that links the consumption of tobacco to the development of LADA,” explains a researcher behind the study, Jessica Edstorp, a PhD student at Karolinska Institutet, Stockholm, Sweden.

The research has been published in Diabetologia.

Little-known type of diabetes is more common than people think

Most people have heard of type 1 and type 2 diabetes, but few know about LADA. Nevertheless, LADA is more common than you might think and is often confused with type 2 diabetes.

LADA is a hybrid between type 1 and type 2 diabetes. It is genetically associated with type 1 diabetes, in which the immune system attacks the pancreas, but is clearly linked to lifestyle, just like type 2 diabetes, in which an unhealthy lifestyle can cause the disease to develop.

The researchers wanted to determine how tobacco consumption affects the risk of developing LADA. Previous studies have shown that smoking is associated with an increased risk of developing type 2 diabetes, but other studies found that smoking during pregnancy is associated with a reduced risk of the child developing type 1 diabetes.

“Since LADA is similar to both type 1 and type 2 diabetes, we envision that smoking and using smokeless tobacco could either increase or reduce the risk. We therefore wanted to create clarity around this,” says Jessica Edstorp.

Data from Sweden and Norway

The researchers used databases in Sweden and Norway to identify data on people with LADA and type 2 diabetes and controls.

From a database covering Scania, Sweden, the researchers found 593 people with LADA, 2,038 people with type 2 diabetes and 3,036 controls.

From a database covering Trøndelag County, Norway, the researchers found data on 245 people with LADA, 3,726 people with type 2 diabetes and 74,326 controls.

Then the researchers investigated how smoking, using smokeless tobacco, being a heavy smoker, being a heavy consumer of smokeless tobacco or being a heavy consumer of both cigarettes and smokeless tobacco are associated with the risk of developing LADA. They also examined how genetics might influence any associations.

Using smokeless tobacco and smoking increase the risk of developing LADA

The results were clear.

  • Smoking increased the risk of developing LADA by 30%.
  • Currently using smokeless tobacco increased the risk of developing LADA by 29%.
  • Heavy smoking increased the risk of developing LADA by 54%.
  • Heavy use of smokeless tobacco increased the risk of developing LADA by 97%.
  • Being both a current smoker and using smokeless tobacco increased the risk of developing LADA almost 2.5-fold.
  • The researchers also confirmed previous findings of smoking being associated with an increased risk of developing type 2 diabetes.

“The results contribute to understanding the factors that can influence the risk of developing LADA. There is genetic predisposition to developing LADA, but lifestyle plays an important role, similar to type 2 diabetes, and smoking and using smokeless tobacco also clearly increase the risk of developing LADA. Tobacco use appears to be especially harmful to those with a genetic predisposition to developing LADA,” explains Jessica Edstorp.

Genetics influences the association between tobacco and LADA

The researchers also investigated whether high-risk genotypes for LADA are associated with the increased risk of developing LADA by using tobacco.

The HLA gene complex plays an important role in developing LADA. HLA has different genotypes, with some being associated with greater increased risk of developing LADA than others.

The researchers investigated whether HLA genotypes interact with smoking or using smokeless tobacco in the risk of developing LADA. They found that if people had high-risk HLA genotypes and smoked or used smokeless tobacco, this increased their risk of developing LADA even more.

The researchers also found that 27% of the LADA cases exposed to both current smoking and a high genetic predisposition could be attributed to this joint exposure.

Finally, the researchers investigated potential underlying mechanisms for the link between tobacco use and developing LADA. This suggests that smoking increases insulin resistance (cells becoming less able to absorb glucose) also in LADA rather than strengthening autoimmunity.

“We might envision that smoking would affect the development of LADA by making the immune system increase its attack on the pancreas. However, the mechanism instead seems to be increased insulin resistance. The research results are pieces of a large puzzle of incomplete understanding of the factors that promote or trigger LADA. Our study also shows that stopping smoking can play a role in preventing LADA,” concludes Jessica Edstorp.

Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults” has been published in Diabetologia. The Novo Nordisk Foundation co-funded the study, including a postdoctoral fellowship to co-author Bahareh Rasouli.

Jessica Edstorp is a PhD candidate in diabetes epidemiology at Karolinska Institutet, Sweden. Her main research interest is risk factors for adult-ons...

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