Blood marker for insulin resistance tied to higher risk of severe MG

An elevated triglyceride-glucose (TyG) index, a blood marker of insulin resistance, may be a useful biomarker to identify people at risk of developing myasthenia gravis (MG) associated with a thymoma, or thymus tumor, a study suggested.

Insulin resistance refers to the body’s impaired response to insulin, a hormone that regulates levels of blood sugar (glucose). This can lead to high glucose levels diabetes.

“These findings provide novel … evidence linking metabolic markers of insulin resistance with thymoma-associated MG, but clinical translation requires further validation,” the researchers wrote.

The study, “Elevated triglyceride-glucose index and risk of thymoma-associated myasthenia gravis: a prospective analysis from the UK Biobank,” was published in Cardiovascular Diabetology.

MG is an autoimmune disease caused by self-reactive antibodies that mistakenly target healthy proteins at the site of communication between nerve and muscle cells, leading to muscle weakness and fatigue.

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Thymoma and MG

Thymoma is a rare tumor that forms in the thymus, a gland involved in immune system function. Some 30% to 50% of people with thymoma develop MG, while up to 15% of MG patients have a thymoma.

When the two conditions occur together, symptoms are often more severe, with higher risks of disease flare-ups, recurrence, and death than when either condition occurs alone. Because thymoma-associated MG can be particularly serious, there is a need for better ways to identify people at higher risk so treatment can begin earlier.

Growing evidence suggests that metabolic problems such as insulin resistance, abnormal levels of fatty molecules, and obesity may influence how the immune system behaves. These metabolic changes can promote inflammation and alter immune cell activity, potentially contributing to autoimmune diseases such as MG.

Two established metabolic markers, the TyG index and the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio, have been shown to be markers of insulin resistance and “prognostic indicators in metabolic and cardiovascular disorders,” the researchers wrote. Triglycerides and HDL cholesterol are two distinct types of fatty molecules.

However, their role in autoimmune conditions, including thymoma-associated MG, remains unclear.

To assess whether these routine blood measures could help identify people at higher risk for thymoma-associated MG, a team of scientists in China analyzed data from the UK Biobank, a large follow-up study involving more than 500,000 people.

Data from about 422,000 people, including 265 new cases of thymoma-associated MG, were used in the analyses for each metabolic marker. Participants were grouped by TyG index and TG/HDL-C ratio, from lowest to highest.

People with the highest TyG index values were less likely to be women, and were significantly older and significantly more likely to be obese than those with the lowest TyG index values.

Thymoma-associated MG was more common among people with the highest TyG index levels than among those with the lowest. A similar association was observed for the TG/HDL-C ratio.

Statistical models showed that people in the highest TyG index group had a 66% higher risk of developing thymoma-associated MG than those in the lowest group. This increased risk remained even after adjusting for factors such as age, sex, smoking, alcohol use, socioeconomic status, and education level.

When the TyG index was analyzed as a continuous measure, each unit increase in the index was associated with a 42% higher risk of thymoma-associated MG.

A similar pattern was seen for the TG/HDL-C ratio, although the association was weaker. The group with the highest TG/HDL-C ratio had a 54% higher risk of developing thymoma-associated MG than those in the lowest ratio group. When modeled continuously, a unit increase in the TG/HDL-C ratio was linked to a 6% increase in the risk of thymoma-associated MG.

Further analyses showed that the relationship between TyG index levels and disease risk was not linear. Instead of risk rising evenly as TyG increased, the chance of developing thymoma-associated MG stayed relatively low at lower TyG levels, then increased much more sharply once the TyG index passed about 8.7.

For the TG/HDL-C ratio, “risk remained relatively flat at lower ratios but rose progressively at higher levels, with an inflection around 2.8,” the researchers wrote. These findings “support the interpretation that higher levels of both indices are associated with increased risk, with the TyG index demonstrating a clearer and more robust gradient of risk.”

The association between a higher TyG index and thymoma-associated MG was most evident in people of normal weight and those with obesity. However, because the number of MG cases was small, these subgroup findings should be interpreted cautiously, the team noted.

Additional analyses showed similar associations between the two markers and the risk of MG alone, although these were stronger for the TyG index. The results “raise the possibility that insulin resistance may also contribute to the [development] of MG more broadly, beyond thymoma-associated forms, although further mechanistic and clinical studies are needed,” the team wrote.

“These findings indicate the TyG index is effective for identifying high-risk individuals for thymoma-associated MG and highlight its clinical relevance,” the researchers concluded.