Low Soluble Neuropilin-1 Levels Linked to Depression in Newly Diagnosed Type 2 Diabetes Patients: Study

The study revealed that individuals with newly diagnosed type 2 diabetes and low levels of soluble neuropilin-1 (sNRP-1) were more likely to experience depression. Notably, 45% of patients with depression had reduced sNRP-1 levels compared to just 22% among those without depressive symptoms, underscoring a strong link between low sNRP-1 and the presence of depression.

The neuropilin-1 (NRP-1) receptor is a crucial transmembrane glycoprotein that plays a significant role in the development of the nervous and cardiovascular systems, immune modulation, and potentially in diabetes-related complications. Its widespread presence in tissues such as the brain, heart, kidneys, retina, pancreatic beta cells, and adipose tissue macrophages suggests its broad physiological impact. Given its biological relevance, E. O. Melin PhD, Diabetes Research Laboratory, Biomedical Center, Lund University, Lund, Sweden, and colleagues aimed to investigate the relationship between sNRP-1 levels and depression in individuals with newly diagnosed type 2 diabetes, highlighting a potential biomarker for early mental health assessment in this population.

For this purpose, the researchers conducted a multicentre, cross-sectional study involving adults with newly diagnosed type 2 diabetes confirmed through blood tests. They collected data on several factors, including sex, levels of soluble neuropilin-1 (with low sNRP-1 defined as less than 226 ng/mL), depression and anxiety assessed using psychological tests, use of antidepressants, body mass index (BMI), haemoglobin A1c, C-peptide levels, and history of cardiovascular disease. To better understand the associations, they performed multiple regression analyses, using depression and low sNRP-1 levels as the main outcomes.

The key findings of the study were as follows:

• The study included 837 adults aged 18–94 years, with 38% under 60.
• Depressed patients (n=119) showed higher rates of anxiety (64% vs. 14%), antidepressant use (36% vs. 14%), low sNRP-1 levels (45% vs. 22%), physical inactivity (42% vs. 29%), smoking (20% vs. 12%), and higher BMI compared to non-depressed individuals (n=718).
• Depression was independently associated with anxiety (adjusted odds ratio [AOR] 11.7), low sNRP-1 (AOR 3.3), higher BMI (AOR 1.1 per kg/m²), and physical inactivity (AOR 1.8).
• In younger patients (<60 years), low sNRP-1 was independently linked to depression (AOR 3.3), a history of myocardial infarction (AOR 3.8), and younger age (AOR 0.97 per year).
• In older patients (≥60 years), low sNRP-1 was associated with depression (AOR 3.1) and younger age within the group (AOR 0.97 per year).

The findings showed that low levels of soluble neuropilin-1 were strongly linked to depression in adults with newly diagnosed type 2 diabetes. This association was evident across all age groups. Among younger patients (under 60 years), low sNRP-1 levels were also independently associated with pre-existing myocardial infarction and younger age, highlighting a more complex relationship in this subgroup. In older patients, depression and younger age within the group remained significantly linked to reduced sNRP-1 levels.

"These findings suggest that sNRP-1 may serve as a potential biomarker for identifying individuals at higher risk of depression in early-stage T2D," the authors concluded.

Reference:

Melin EO, Thunander M, Wanby P, et al. Low levels of soluble neuropilin-1 were associated with depression in adults with newly diagnosed type 2 diabetes. Diabetes Obes Metab. 2025;1‐10. doi:10.1111/dom.16347