We found that, no matter under the definition of UPF1 or UPF2, a significant positive association between diabetes and depression was present only in the non-old adult population with high consumption of UPF (OR: 1.596, 95% CI: 1.127 to 2.260 for UPF1 and OR: 6.726, 95% CI: 2.625 to 17.233 for UPF2). The gene discussed is UPF1; the disease is major depressive disorder.