Two new studies reveal that low birthweight is associated with an increased risk of developing type 2 diabetes. Low birthweight is also associated with a more severe trajectory of type 2 diabetes, including earlier onset and general worse health at the time of diagnosis. A researcher says that birthweight should be included in assessing the risk of developing type 2 diabetes.
Two new studies reveal that low birthweight is associated with an increased risk of developing type 2 diabetes. Low birthweight is also associated with a more severe trajectory of type 2 diabetes, including earlier onset and general worse health at the time of diagnosis. A researcher says that birthweight should be included in assessing the risk of developing type 2 diabetes.
At birth, a healthcare professional registers a few numbers, including the child’s height and weight. These figures can be valuable to know later in life because birthweight is one factor that may determine whether a person develops type 2 diabetes or not.
This is the conclusion of two new studies showing that low birthweight is associated with an increased risk of developing a more severe type of type 2 diabetes with earlier onset and with more illness in general.
According to a researcher behind the studies, the results are groundbreaking and clearly indicate that the fetal environment determines part of the risk of developing type 2 diabetes. The results may also have potential for clinical application.
“For people with low birthweight and overweight, we should consider giving higher priority to lifestyle changes and perhaps even drug-induced weight loss because these people have an increased risk of developing type 2 diabetes for a lower degree of overweight and furthermore are at risk of having a more severe disease trajectory. This will benefit both individuals and society, since type 2 diabetes is a lifelong, serious as well as expensive disease,” explains Allan Vaag, Consultant and Professor, Steno Diabetes Center Copenhagen and Lund University, Sweden.
The two studies have been published in Diabetologia. Rasmus Wibæk is the first author of one study, and Alexander Lühr Hansen is the first author of the other study.
Low birthweight associated with increased risk of developing type 2 diabetes
In the first study, the researchers examined data from the Inter99 cohort.
The study cohort included 4,590 people born between 1939 and 1971 and was created in a collaboration between the Center for Clinical Research and Prevention at Bispebjerg and Frederiksberg Hospital, the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and Steno Diabetes Center Copenhagen.
The researchers previously obtained information on the participants’ birthweight from midwifery records in the Danish National Archives when they investigated the association between low birthweight and the risk of developing type 2 diabetes when the cohort participants were first studied in 1999. However, in 1999 the participants averaged only 46 years old, which means that very few had developed type 2 diabetes.
In the new study, the researchers excluded the people who had already been diagnosed with type 2 diabetes in 1999, and then investigated whether people with low birthweight differed from people with normal or high birthweight in the risk of developing type 2 diabetes in 1999–2020.
Closely associated with the degree of overweight
In addition, the researchers adjusted for the known genetic risk of developing type 2 diabetes and for the currently known genes influencing birthweight. Researchers are currently aware of 568 genetic variants that predispose to developing type 2 diabetes.
From 1999 to 2020, 492 people developed type 2 diabetes, and the researchers found that the risk was clearly greater among people with low birthweight versus higher birth weight.
“We also found that as the people with low birthweight grew older, their risk of developing type 2 diabetes continued to increase relatively faster than people with normal or high birthweight. In addition, the risk was closely associated with the degree of overweight. Thus, the excess risk of type 2 diabetes almost was not visible in the individuals with low birthweight who avoided having obesity during the 20-year follow-up,” says Allan Vaag.
Developed type 2 diabetes 7 years earlier
In the second study, the researchers used the DD2 cohort and retrieved information on 6,866 people with newly diagnosed type 2 diabetes from all of Denmark.
Again, the researchers had access to these people’s birthweight through the Danish National Archives. The participants averaged 62 years old and weighed 1–6 kilograms at birth.
The researchers investigated whether the severity of type 2 diabetes differed between people born with low, normal and/or high birthweight.
The results showed that low birthweight is not only associated with the risk of developing type 2 diabetes but also with the timing of disease onset. Thus, the people who weighed 2.5 kilograms at birth developed type 2 diabetes 7 years earlier on average than people who weighed 4.5 kilograms at birth.
“This is a very important result, because 2.5 kilograms is not completely uncommon,” explains Allan Vaag.
This is not just about genetics and lifestyle
In addition to earlier onset of type 2 diabetes, low birthweight was associated with a more severe disease trajectory.
People with low birthweight needed more blood pressure–lowering medication and more diabetes medication and had lung disease more often. People with low birthweight were also slimmer when they developed type 2 diabetes.
“We now have important new knowledge we can use to develop algorithms that can more precisely determine an individual’s risk of developing type 2 diabetes. This is not just about genetics and lifestyle, but also about the fetal environment and birthweight. Such an algorithm may help to identify who, because of low birthweight, should be extra careful not to become overweight, since they have a greater risk of developing early and more severe type 2 diabetes,” says Allan Vaag.
Organs’ energy metabolism is dysregulated for life
According to Allan Vaag, the fetal environment is key to the association between low birthweight and the risk of developing type 2 diabetes.
Factors such as smoking, poor diet, stress and infections can affect the fetal environment and cause low birthweight. These same factors can affect the development of various organs, including the pancreas, adipose tissue, muscles, intestines, liver, heart and brain, all of which influence the development of type 2 diabetes.
Allan Vaag says that the organs learn to manage energy intake appropriately during fetal development, and the organs not learning this can cause major problems later in life and thus develop type 2 diabetes 60 years after birth.
According to Allan Vaag, this new knowledge may also be considered in the debate on whom to give priority in the treatment of overweight.
“Now we know that some people are more vulnerable to being overweight, and that they have a greater risk of developing type 2 diabetes with early onset as well as a more severe type of diabetes. We may therefore need to consider whether people with low birthweight and overweight later in life should be offered more targeted intervention against overweight to reduce their risk of a relatively more severe type 2 diabetes subtype,” concludes Allan Vaag.
