Effect of Diabetes Medicines on MS Risk Varies by Age, Sex in US Study

Among people with type 2 diabetes, the use of anti-hyperglycemic medications is associated with a reduced risk of multiple sclerosis (MS) for younger individuals, but an increased risk for older patients, particularly women.

That’s according to the study “Age and sex differences on anti-hyperglycemic medication exposure and risk of newly diagnosed multiple sclerosis in propensity score matched type 2 diabetics,” published in Heliyon.

“These findings represent an important call to action for better understanding the interplay between the endocrine [hormonal], immune, and nervous systems and the need for a precision medicine approach for prevention of multiple sclerosis in vulnerable populations,” the researchers wrote.

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Diabetes occurs when the body is unable to properly regulate blood sugar levels

Diabetes is a condition in which the body cannot properly regulate blood sugar levels. Anti-hyperglycemic medications, or A-HgM, include insulin and other medicines that are used to control blood sugar levels in people with type 2 diabetes.

A few studies have suggested that people with type 2 diabetes might be more likely to develop MS, but any connection between the two diseases remains unclear. Here, a team led by scientists at the University of Arizona conducted an analysis to find out whether the use of A-HgM affects MS risk.

“To our knowledge, this is the largest and most comprehensive study to-date to examine the impact of individual anti-hyperglycemic therapies on MS risk,” the team wrote.

For the analysis, the researchers retrospectively analyzed data from a U.S. insurance claims database called Mariner, which contains health records of 122 million people collected from 2010 to 2018.

While the use of insurance data allowed them to analyze a large number of patients, the team noted that this type of data does not provide a comprehensive clinical picture, which is a limitation of this study.

These findings represent an important call to action for better understanding the interplay between the endocrine [hormonal], immune, and nervous systems and the need for a precision medicine approach for prevention of multiple sclerosis in vulnerable populations

The team identified more than 5 million people diagnosed with type 2 diabetes, who were divided into two groups based on their age at diagnosis: before or after 45 years of age.

A propensity score matching analysis was conducted. Basically, the team identified diabetes patients with records of receiving anti-hyperglycemic medications and those who did not, but were otherwise very similar in terms of demographics and clinical parameters.

The analysis ultimately included 143,613 younger diabetes patients and 638,625 older patients who were treated with A-HgM, plus matched patients who were not taking the treatments but likely controlling their diabetes with diet/exercise. All had Mariner records for six months prior and at least three years after diagnosis, and no prior history of neurodegenerative disease.

Then, the researchers evaluated whether the risk of MS differed between the A-HgM and non-A-HgM groups. MS development was assessed one year after the diabetes diagnosis either by an MS diagnosis or use of MS treatments recorded in the database.

Results showed that among patients diagnosed with diabetes before age 45, those taking A-HgM were significantly less likely to develop MS in the subsequent year, by about 78%, compared with those not on the medications. Similar results were obtained across sexes.

“However, the incidence of MS is still greater in the younger [group] when accounting for total population, which is consistent with national trends and data for MS prevalence,” the team wrote.

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Older patients on diabetes medications had 36% higher MS risk

By contrast, in patients diagnosed after age 45, those on A-HgM had a 36% higher risk of developing MS relative to those not taking A-HgM. This increase in risk was more pronounced among women than in men (53% vs. 17% higher risk).

This sex-related difference may be due to changes in the immune system during the transition to menopause, in addition to the fact that “diabetes, similar to MS, is linked to a proinflammatory state,” the team wrote.

Comparisons of different types of A-HgM therapies generally yielded similar results, though in the older group, insulin was associated with a significantly higher MS risk (84% increased risk) compared with other therapies (24%–38% increased risk).

“This can be explained, in part, by severity of the disease, [blood sugar] control or socioeconomic status of patients receiving insulin,” the researchers wrote.

These findings highlight that “both age and sex regulate response to A-HgM exposure to impact MS risk profiles,” the team wrote.

“It will become increasingly important to understand the neuro-immunological changes that occur during the [near-to-menopause] transition and how these changes may affect brain health and disease risk in aging populations,” they concluded.