Rates of diabetes are on the rise globally, so there’s an urgent need to identify risk factors and prevention strategies. One recent study published in the journal Nature Medicine may have uncovered another piece worth adding to the toolbox of diabetes prevention: the presence of certain metabolites, or molecules in the blood, that may be associated with risk of developing Type 2 diabetes.
The study, which was conducted by researchers at Mass General Brigham and the Albert Einstein College of Medicine, also revealed that lifestyle and genetic factors could play a role in formation of these metabolites. Crucially, the scientists also identified metabolic signatures that can be used to predict future risk of diabetes and better pinpoint prevention strategies.
“We found over 200 of those small molecules are associated with future risk and a lot of those molecules represent specific biological pathways that may play a role in the development of diabetes,” Dr. Jun Li, an epidemiologist and assistant professor of medicine at Harvard Medicine School who is the co-corresponding author of the study, told Flow Space. “We also found that different lifestyle factors, like physical activity, adiposity and intake of food and beverages, can potentially change those disease-related metabolites.”
Researchers looked at data from 26,634 people from diverse ethnic backgrounds across 10 cohorts (including several that included midlife women) who didn’t initially have Type 2 diabetes and followed up with them for up to 26 years; everyone examined didn’t initially have Type 2 diabetes.
Then, they analyzed data related to lifestyle habits like exercise and diet, plus genetics, and looked at 469 metabolites in blood samples. They identified 235 metabolites that either decreased or increased the risk of later developing diabetes, including 67 new ones.
Certain lifestyle factors influenced metabolite levels, too: for example, those who had higher physical activity levels had more metabolites associated with lower diabetes risk. Li said that this suggests that lifestyle interventions that are known to decrease the risk of diabetes may work on some people more than others. The results were consistent across both men and women of different age ranges.
“It’s essentially that if a person has certain metabolites and diet or lifestyle factors can modify that metabolite to a normal level, that suggests that, for those people, those dietary and lifestyle factors are more likely to work on them to prevent disease,” she explained.
She also further emphasized the importance of practicing key habits linked to lower risk of diabetes, like eating a nutritious diet and getting enough consistent exercise.
However, this doesn’t mean that only some people should incorporate these habits. “Regardless of whether you are at risk, those lifestyle factors will play a beneficial role,” she said.
Of course, it’s important to remember that this is an observational study, so it can’t confirm causality. Li said that experimental studies and clinical trials are needed to validate the findings but that the results are a starting point.
“We’ve already seen that not everyone responds to similar diet, lifestyle or medical therapies the same way, and those metabolites can help us understand why people respond differently,” she explained. “By understanding that more, we can potentially identify subtypes of diabetes that can help us better refine prevention for people who are at risk due to different reasons… that’s one thing we’re working towards.”
Midlife Women and Diabetes
The study’s findings reinforce the idea that diabetes is multifactorial and that prevention strategies need to take this into account. For example, midlife is emerging as a key prevention window for diabetes, which makes sense considering several of the 34 symptoms of menopause include metabolic changes, like increased insulin resistance and weight gain that are caused by hormonal shifts.
Further understanding as to why specific populations are at increased risk of diabetes is necessary for prevention. “Women need to understand that these are changes that are part of normal physiology, and as you start to see them happening, you really want to be aware that you’re not just being lazy… your body is really starting to shift,” Dr. Ava Port, a board-certified endocrinologist at MedStar Georgetown University Hospital, previously told Flow Space.
For her part, Li said she’d like to see more studies focusing on diabetes prevention specifically in post-menopausal women and that she’s interested to see how the menopausal transition could impact metabolite levels.
“A good thing about metabolites is that those small molecules can give you information on a lot of different pathways,” she said before noting that hormones play a major role in regulating different biological pathways as well. “One thing I think that’s definitely worth studying is to see whether this menopause transition can affect different metabolic pathways, especially the pathways that are contributing to future disease risk.”