Abstract:AIM: To investigate the levels of the triglyceride-glucose (TyG) index and sex hormone-binding globulin (SHBG) in patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy (DR), and to explore their correlations with biochemical parameters and the homeostasis model assessment of insulin resistance (HOMA-IR) in DR patients. METHODS: Patients with T2DM and healthy individuals were enrolled. Age and body mass index (BMI) of the participants were collected, TyG of the subjects was calculated using the formula, SHBG level of the subjects was detected, and blood biochemical indexes were measured at the same time. The changes of each index among the groups were statistically analyzed, and the relationship between TyG, SHBG, DR and each index was analyzed. RESULTS: A total of 150 patients with T2DM and 64 healthy individuals as normal controls (NC, 28 males and 36 females, mean age 54.49±10.10y) were enrolled following ophthalmic evaluation. Patients were categorized into non-DR group (42 males and 36 females, mean age 56.68±8.02y) and DR group (35 males and 37 females, mean age, 53.83±11.10y). TyG levels were significantly elevated in both non-DR (7.25±0.62) and DR groups (8.02±0.82) compared to controls (6.85±0.48), with the DR group demonstrating higher TyG values than the non-DR group (P<0.05). The level of SHBG (nmol/L) in DR group (25.05±14.06) was lower than that in control group (41.90±22.6) and non-DR group (36.27±20.00; P<0.05). TyG exhibited significant inverse correlations with SHBG (r=-0.455) and high density lipoprotein (HDL; r=-0.430) levels (P<0.05). It was positively correlated with BMI, fasting blood glucose (FBG), 2h postprandial blood glucose (PBG), fasting C-peptide (FCP), glycated hemoglobin A1c (HbA1c), HOMA-IR, total cholesterol (TC) and triglycerides (TG) (r=0.406, 0.768, 0.386, 0.393, 0.475, 0.250, 0.242, 0.888, respectively, P<0.05). SHBG was negatively correlated with BMI, FBG, FCP, HbA1c and TyG (r=-0.440, -0.304, -0.407, -0.209, -0.455, respectively, P<0.05), and positively correlated with age, TG and HDL (r=0.238, 0.034, 0.227, respectively, P<0.05). Further multiple regression analysis showed that SHBG was negatively correlated with TyG (P=0.006). CONCLUSION: Elevated TyG index, reduces SHBG levels, and their negative correlation in the DR group suggest potential roles of TyG and SHBG in the pathogenesis and progression of DR. Combined assessment of SHBG and TyG may provide valuable insights for DR prediction and diagnosis.