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New way of measuring BMI can predict the risk of type 2 diabetes in individuals of normal weight

Photo of researcher in a lab.
Filip Ottosson extracts metabolites from samples of blood plasma. The researchers have identified metabolic alterations associated with obesity that can increase the risk of developing type 2 diabetes. Photo: Petra Olsson

Obesity and excess weight increase the risk of developing type 2 diabetes, but individuals of normal weight can also develop the disease. Researchers at Lund University have discovered that it is possible to identify at-risk individuals by measuring BMI in a new way. The authors of the study have identified metabolic alterations associated with obesity that can increase the risk of developing type 2 diabetes.

Type 2 diabetes can be linked to a sedentary lifestyle which in turn can lead to excess weight and obesity. Up to 20 percent of type 2 diabetes patients are of normal weight, and it is important to identify individuals with a normal BMI who are at risk. An early detection of the disease can reduce the risk of developing common complications of diabetes, such as cardiovascular diseases and kidney disease. An international team of researchers has investigated whether it is possible to identify at-risk individuals of normal weight by measuring the levels of some of the metabolites that are relevant for metabolism.

“In our study, we identified a group of individuals with normal BMI who nonetheless had metabolic alterations associated with obesity in their metabolism,” says Filip Ottosson*, corresponding author for the study published in Diabetes Care.

Measured metabolites

The researchers measured the levels of 108 metabolites associated with diabetes in blood samples of 7663 participants in three different population-based cohorts in Sweden and Italy. The participants were divided into five different groups based on their metabolic BMI. Individuals with a metabolic BMI five BMI units higher than their BMI based on height and weight were investigated further. This group had a twofold risk of developing type 2 diabetes compared to individuals with a normal BMI based on their weight, height, and metabolism.

Olle Melander, professor of internal medicine and research group leader at Lund University Diabetes Centre (LUDC), is one of the authors of the study:

“We hope that our research will be used to identify individuals with a hidden risk of developing the disease. If we can find these individuals before the disease debuts, we would be able to initiate preventive actions. This could potentially save society a lot of money as type 2 diabetes often leads to a variety of different complications,” he says.

Preventive actions

The research team used machine learning methods to classify participants with different metabolic profiles to calculate the risk for type 2 diabetes. The team then followed up participants who developed type 2 diabetes in the population-based Malmö Diet Cancer (MDC) cohort in Sweden, which has a follow-up time of 20 years. The results will need to be verified in other cohorts and further studies are also needed to investigate a larger number of metabolites. 

“This could become a new method for screening for type 2 diabetes and for initiating preventive measures for people of normal weight who are at high risk of developing the disease. Weight loss strategies will not benefit this group, which seemingly requires alternative interventions. In the long-term perspective, we may develop drugs that would lower the levels of some of the metabolites,” says Filip Ottosson.

* Filip Ottosson carried out the research project while employed at Lund University and Statens Serum Institut (SSI) in Denmark. He is currently employed at Statens Serum Institut and affiliated with Lund University, where he is carrying out a research project in collaboration with Olle Melander and is supervising a PhD student. 

Body shapes from underweight to obese.
Illustration: Alexander Ryabintsev/iStock

Two ways of measuring BMI

BMI (body mass index) is a measure of body fat based on height and weight, which is used to evaluate if a person is underweight, of normal weight, or obese. The researchers behind the study in Diabetes Care have developed a BMI based on metabolism. They selected 108 metabolites associated with type 2 diabetes and measured the levels in participants from three population-based cohorts. The participants were divided into five groups based on the relationship between the BMI linked to weight and height and their metabolic BMI.

The five groups

  • Individuals with a normal BMI based on weight, height, and metabolism.
  • Overweight individuals based on weight, height, and metabolism.
  • Obese individuals based on weight, height, and metabolism.
  • Individuals in this group had a normal BMI based on height and weight. Their metabolic BMI had metabolic alterations associated with obesity.
  • Individuals in this group had a metabolic BMI which was lower than their BMI based on weight and height.

Facts about the study

Subject: Type 2 diabetes, metabolism
Research area: Epidemiological research
Publication: Peer-reviewed publication
Study design: Quantitative study, researcher-initiated study, register-based study
Observational study: Prospective, cohort study
Number of groups in the study: 5
Number of patients in the study: 7663
Patient groups: Healthy volunteers

Link to the study in Diabetes Care

 

Photo of Filip Ottosson.

Contact

Filip Ottosson, researcher in metabolomics at Statens Serum Institut (SSI) and affiliated with Lund University
+46 73 959 90 00
filip [dot] ottosson [at] med [dot] lu [dot] se

Link to Filip Ottosson’s profile in Lund University’s research portal 
 

Photo of Olle Melander.

Contact

Olle Melander, professor of internal medicine at Lund University
+46 40 39 12 21
+46 40 39 12 09
olle [dot] melander [at] med [dot] lu [dot] se

Link to Olle Melander’s profile in Lund University’s research portal

 

Type 2 diabetes

It is estimated that around 537 million people in the world are living with diabetes (20-79 years, 2021). The number is expected to increase to 783 million in 2045. Type 2 diabetes is the most common type of diabetes, accounting for around 90 percent of all diabetes cases. 

The disease is generally characterised by insulin resistance, where the body does not fully respond to insulin. Because insulin cannot work properly, blood glucose levels keep rising, releasing more insulin. For some people with type 2 diabetes this can eventually exhaust the pancreas, resulting in the body producing less and less insulin, causing even higher blood sugar levels.

Source: Diabetesatlas
 

Funding

Swedish Research Council (EXODIAB: Excellence of diabetes research in Sweden), Swedish Foundation for Strategic Research (LUDC-IRC), AIR Lund (Artificially Intelligent Use of Registers at Lund University), Lund University infrastructure grants for population-based cohorts and metabolomics platforms, European Research Council, Novo Nordisk Foundation, Swedish Heart-Lung Foundation, Ernhold Lundstrom Research Foundation, Hulda and E Conrad Mossfelts Foundation, and the Albert Pahlsson Foundation.