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Diet and lifestyle

The link between sweetened beverages and the risk of diabetes: a possible explanation

New research shows that sweetened beverages do not solely increase the risk of various types of diabetes by making people gain weight. Differences in genetic variants appear to determine how people react to drinking sweetened beverages and how this affects their insulin sensitivity.

For the past decade, researchers have shown in numerous studies that sweetened beverages can increase the risk of developing type 2 diabetes. A few studies have also shown that children who drink lots of sweetened beverages have an increased risk of developing type 1 diabetes. However, one study has shown that sweetened beverages increase the risk of developing latent autoimmune diabetes in adults (LADA), a lesser-known form of diabetes.

A question common to all three types of diabetes has been whether the increased risk solely results from the obesity caused by drinking sweetened beverages or whether some genetic or other environmental factors contribute.

A new case–control study including people with LADA and people with type 2 diabetes now shows that genetics contributes to the risk of developing these types of diabetes. However, the most surprising finding was that people without known genetic susceptibility had the highest risk of developing these types of diabetes from drinking sweetened beverages.

“Sweetened beverages are not healthy and reducing how much people drink is therefore vital, especially for children. In this study, we found a possible mechanism that links the role of sweetened beverages with the risk of developing different types of diabetes,” explains a main researcher behind the study, Josefin Löfvenborg, Karolinska Institutet, Stockholm, Sweden.

Josefin Löfvenborg has published her research results in the European Journal of Nutrition.

Examined association between genetic variants and the risk of diabetes from drinking sweetened beverages

The researchers wanted to clarify whether any other factor than body mass index (BMI) contributed to how drinking sweetened beverages influences the risk of developing type 2 diabetes and LADA.

Obesity is the most important risk factor associated with developing type 2 diabetes, whereas genes more strongly influence the development of LADA. Obesity also affects the risk of developing LADA, although to a lesser extent than genes, and the same applies to genes in the risk of developing type 2 diabetes. The genes linked to human leucocyte antigen (HLA), the transcription factor 7-like 2 (TCF7L2) gene and the fat mass and obesity-associated (FTO) gene are known to be involved.

Previous research has shown the following.

• Variants in HLA genes are linked with the autoimmune aspect of type 1 diabetes and LADA, meaning that the risk of disease increases significantly if a person is carrying a pathogenic variant of the HLA gene. These variants explain half the genetic risk of developing type 1 diabetes.

• TCF7L2 is one of the genes with the highest risk associated with developing type 2 diabetes. TCF7L2 is involved in various signalling processes in the body, and variants of TCF7L2 can result in the signal pathways not functioning optimally, which can lead to type 2 diabetes.

• Variants of FTO are associated with an increased risk of obesity, which is then associated with developing type 2 diabetes.

BMI can only explain some of the risk of developing diabetes

The researchers examined 386 people with LADA, 1253 individuals with type 2 diabetes and 1545 controls. The researchers examined the genetic susceptibility of the trial participants to develop diabetes, asked them how many sweetened beverages they drink and measured their BMI.

The researchers used an advanced statistical model to analyse the data and determined how much each risk factor contributed to the overall risk of developing the various types of diabetes.

Not surprisingly, the results showed that drinking sweetened beverages is associated with an increased risk of developing both type 2 diabetes and LADA. However, BMI could not explain all the increased risk, only accounting for 17% of the risk of developing LADA and 56% of the risk of developing type 2 diabetes.

“Obesity is not as strong a risk factor for developing LADA as it is for type 2 diabetes but is still important for the risk of developing this type of diabetes. This is in accordance with expectations, since LADA is largely an autoimmune form of diabetes,” explains Josefin Löfvenborg.

Genetic susceptibility does not increase the overall risk of diabetes caused by drinking sweetened beverages

However, the researchers discovered that a high intake of sweetened beverages did not significantly increase the risk of developing LADA among people who had the high-risk variants of HLA genes.

In contrast, people with a high intake of sweetened beverages and low-risk HLA genes had an increased risk of developing LADA.

“This suggests that people with the high-risk variants of HLA genes do not increase their risk of developing LADA by drinking many sweetened beverages. This is only a risk factor for developing LADA among people who do not have the high-risk variants of HLA genes,” says Josefin Löfvenborg.

Probably influences insulin sensitivity in cells

Josefin Löfvenborg speculates that the explanation for this surprising phenomenon may be that environmental factors, such as drinking sweetened beverages, may have more influence among people not genetically predisposed to developing LADA or type 2 diabetes. This is what the researchers found.

The researchers cannot yet explain how the sugar in sweetened beverages influences the risk of developing diabetes, but perhaps it affects the insulin sensitivity of the cells.

“We might have expected that the sugar affects the production of insulin by the beta cells, but instead the sugar appears to affect the insulin sensitivity of the cells. However, we need to examine this topic more closely before making any conclusions,” says Josefin Löfvenborg.

A surprising discovery

The researchers were surprised that the TCF7L2 or FTO genes did not modify the risk associated with drinking sweetened beverages.

According to Josefin Löfvenborg, the study suggests overall that people should not think that genetic susceptibility of developing diabetes is a pre-condition for sweetened beverages to increase the risk of developing the various types of diabetes.

Instead, the study suggests that anyone risks developing these two types of diabetes when they put a sweetened beverage to their lips. Their genetics makes no difference. For LADA, it almost does not even matter whether drinking sweetened beverages makes you gain weight. The risk is present anyway.

“Don’t drink them,” concludes Josefin Löfvenborg.

Josefin Löfvenborg hopes that future research will address how artificial sweeteners contribute to the risk of developing diabetes. Several studies have implied that drinking artificially sweetened low- and zero-calorie beverages can be associated with just as much risk of developing diabetes as drinking beverages sweetened with sugar.

Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes” has been published in the European Journal of Nutrition. In 2017, the Novo Nordisk Foundation awarded a grant to Sofia Carlsson, a main author, for the project LADA – Latent Autoimmune Diabetes in Adults: Risk Factors and Prognosis.

Sofia Carlsson
Senior lecturer
My work aims to expand knowledge of incidence, risk factors and complications related to autoimmune diabetes. An important cornerstone of this work is the ESTRID study (epidemiological study of risk factors for LADA-latent autoimmune diabetes in adults and type 2 diabetes), an ongoing multicenter study conducted at IMM. ESTRID is the largest and most detailed study of LADA to date and will provide unique opportunities to study the influence of both environmental and genetic factors on the disease onset and prognosis. The overall aim of my research is to identify environmental factors that can be used to prevent autoimmune diabetes, to identify factors contributing to poor prognosis and to spread awareness about diabetes.