A large new study has found that older adults with high triglyceride-glucose levels—a marker tied to insulin resistance and metabolic health—do not appear to be at increased risk for developing depression. While previous research has suggested that metabolic dysfunction may play a role in mental health problems, the new findings suggest that the triglyceride-glucose index is not a reliable predictor of future depression in people in their 70s and 80s. The findings were published in the Journal of Affective Disorders.
Triglycerides are a type of fat found in the blood, while glucose is a form of sugar that serves as the body’s main source of energy. Both are routinely measured in blood tests and are important indicators of metabolic health. When levels of both are high—especially after fasting—it can signal insulin resistance, which has been linked to conditions like type 2 diabetes and heart disease.
The triglyceride-glucose index, or TyG, combines these two values using a mathematical formula. Because insulin resistance and depression sometimes occur together, researchers have been exploring whether TyG might also help identify people at risk for mood disorders.
Several earlier studies, mostly based on data collected at a single point in time, found that higher TyG levels were associated with more depressive symptoms. These results led to speculation that TyG might be a useful early marker of depression risk. However, cross-sectional studies cannot show whether high TyG comes before depression or is a consequence of it. To better understand the direction of this relationship, researchers from Australia and the United States conducted a large, long-term study tracking changes in metabolic and mental health over time.
“I’m fascinated by what makes older adults vulnerable to developing depression,” said study author Malcolm Forbes, a research fellow at the Institute for Mental & Physical Health and Clinical Translation at Deakin University. “Metabolic dysfunction and depression often go hand-in-hand, yet most evidence is cross-sectional. The triglyceride–glucose (TyG) index is a simple, inexpensive surrogate for insulin resistance. We wanted to see whether TyG could prospectively flag people at higher risk of developing depressive symptoms.”
The study included more than 19,000 adults from the ASPREE and ASPREE-XT studies. All participants were aged 70 or older (or 65 and older for some racial and ethnic minorities in the U.S.) and living independently when they enrolled. They were relatively healthy at the outset, with no history of dementia, cardiovascular disease, or serious physical disability. Participants were followed for up to 11 years, with annual check-ins that included fasting blood tests and mental health assessments.
To calculate the TyG index, the researchers used fasting blood samples to measure triglyceride and glucose levels. They then followed participants for at least one year to see whether those with higher TyG values were more likely to score above a threshold for depression on a widely used 10-item screening questionnaire. A score of 8 or more was used to indicate the presence of depressive symptoms.
The researchers used statistical models that accounted for a wide range of factors that could influence both metabolic health and depression, including age, sex, education, smoking, alcohol use, body mass index, chronic diseases, and use of medications such as antidepressants and statins.
In the unadjusted model, participants in the highest TyG quartile were about 23% more likely to show signs of depression one year later than those in the lowest quartile. But this link weakened once the researchers adjusted for other health and lifestyle variables. In the fully adjusted model, the difference was no longer statistically significant. Additional analyses using different cutoffs for depression, or excluding people with conditions like diabetes or metabolic syndrome, yielded similar results.
“Given prior cross-sectional links between insulin resistance and depression, we expected at least a modest longitudinal signal,” Forbes told PsyPost. “The complete loss of association after full adjustment suggests confounding factors (e.g., obesity, chronic illness) are doing the heavy lifting.”
The researchers also looked at long-term outcomes using a different model that followed participants over an average of nearly seven years. Again, they found no meaningful difference in the likelihood of developing depression between those with high versus low TyG levels after accounting for other variables. These findings held up even when the researchers examined subgroups based on sex or age. For example, people in their mid-60s to early 70s showed a small increase in depression risk with higher TyG, but this trend did not appear in older age groups and did not reach statistical significance when considering all participants together.
The study’s authors note that TyG may still be relevant in other ways. For example, higher TyG has been associated with cognitive problems in other research, which could eventually contribute to depression. But that was not the case here. It is also possible that metabolic problems in midlife—not old age—are more predictive of later depression, and this study focused on people who were already in their 70s or 80s.
“For people in their 70s and 80s, having a high TyG index didn’t translate into a greater likelihood of future depression after we accounted for other health and lifestyle factors,” Forbes said. “In other words, keeping your blood sugars and lipids in check remains vital for heart and metabolic health, but it doesn’t appear to be a stand-alone predictor of mood problems.”
One important consideration is the way depression was measured. The study relied on a self-report questionnaire rather than clinical diagnoses. While the tool used is validated and widely accepted, it may miss some cases or overestimate symptoms that are mild or temporary.
The researchers also acknowledge that their participants were relatively healthy and may not reflect the broader population of older adults, especially those with more serious medical or psychiatric conditions. Most participants were white, and those who joined the follow-up study tended to be in better health than those who did not.
Even with these limitations, the study offers a valuable contribution to the conversation about metabolic health and mental well-being in older age. It suggests that while managing blood sugar and lipid levels is important for physical health, these measures do not appear to offer additional insight into a person’s future risk of depression.
The authors are now planning further research to explore whether other biological markers are more closely tied to depression risk in older adults. By investigating a wider range of biological and environmental factors, the researchers hope to better understand the complex pathways that influence emotional health in late life. We’re examining links between inflammation (C-reactive protein, tumour necrosis factor alpha levels) and depression rates,” Forbes said.
The study, “Triglyceride-glucose index and its association with depressive symptoms in older adults: a longitudinal analysis,” was authored by Malcolm Forbes, Mohammadreza Mohebbi, Robyn L. Woods, Mojtaba Lotfaliany, Charles F. Reynolds III, Adrienne O’Neil,John J. McNeil, and Michael Berk.