Association between systemic immune-inflammation index and symptoms of depression and anxiety in patients with type 2 diabetes mellitus

Table 1 Participant demographics and baseline characteristics according to systemic immune-inflammation index tertiles

Variables	Total (n = 402)	Q1 (n = 134)	Q2 (n = 134)	Q3 (n = 134)	P value
Age (years)	55.15 ± 13.09	54.87 ± 12.20	53.75 ± 13.55	56.84 ± 13.39	0.146
Diabetes duration (years)	6.48 ± 6.92	6.01 ± 6.97	5.75 ± 6.04	7.66 ± 7.55	0.049
Sex (male)	249 (61.94)	81 (60.45)	89 (66.42)	79 (58.96)	0.412
Smoking	97 (24.13)	39 (29.10)	35 (26.12)	23 (17.16)	0.059
Drinking	119 (29.60)	49 (36.57)	43 (32.09)	27 (20.15)	0.010
SBP (mmHg)	133.02 ± 17.61	130.58 ± 18.48	132.20 ± 16.83	136.28 ± 17.10	0.024
DBP (mmHg)	80.77 ± 12.26	79.37 ± 11.88	81.51 ± 12.47	81.43 ± 12.39	0.267
BMI (kg/m2)	25.61 ± 4.08	25.98 ± 3.90	25.43 ± 4.27	25.43 ± 4.08	0.448
HbA1c (%)	8.72 ± 2.17	8.71 ± 1.98	8.89 ± 2.29	8.56 ± 2.22	0.467
FBG (mmol/L)	8.32 ± 2.91	8.39 ± 2.79	8.64 ± 3.19	7.95 ± 2.70	0.145
ALT (U/L)	27.46 ± 22.05	26.72 ± 20.42	27.29 ± 19.09	28.37 ± 26.16	0.826
AST (U/L)	23.77 ± 15.09	23.37 ± 16.11	23.56 ± 13.64	24.39 ± 15.51	0.841
TC (mmol/L)	4.66 ± 1.35	4.59 ± 1.33	4.74 ± 1.54	4.64 ± 1.17	0.647
TG (mmol/L)	1.97 ± 1.89	2.04 ± 1.82	1.91 ± 1.51	1.96 ± 2.27	0.848
LDL-C (mmol/L)	2.91 ± 1.01	2.90 ± 0.91	3.02 ± 1.08	2.80 ± 1.04	0.215
HDL-C (mmol/L)	1.13 ± 0.31	1.14 ± 0.34	1.14 ± 0.29	1.10 ± 0.30	0.392
Scr (µmol/L)	65.94 ± 29.54	61.95 ± 25.21	66.10 ± 24.92	69.78 ± 36.64	0.096
UA (µmol/L)	321.45 ± 89.29	310.59 ± 83.26	325.99 ± 90.18	327.74 ± 93.78	0.229
BUN (mmol/L)	6.50 ± 2.21	6.14 ± 1.83	6.48 ± 1.82	6.88 ± 2.78	0.024
WBC (× 109/L)	6.36 ± 1.58	5.86 ± 1.55	6.35 ± 1.59	6.88 ± 1.46	< 0.001
Neutrophil (× 109/L)	3.58 ± 1.12	2.86 ± 0.84	3.48 ± 0.91	4.39 ± 1.02	< 0.001
Lymphocyte (× 109/L)	2.14 ± 0.85	2.47 ± 0.96	2.16 ± 0.75	1.78 ± 0.67	< 0.001
PLT (× 109/L)	199.94 ± 60.02	165.83 ± 45.11	203.15 ± 48.61	230.85 ± 65.72	< 0.001
CKD	77 (19.15)	17 (12.69)	26 (19.40)	34 (25.37)	0.031
Hypertension	187 (46.52)	58 (43.28)	61 (45.52)	68 (50.75)	0.454
MASLD	191 (47.51)	67 (50.00)	67 (50.00)	57 (42.54)	0.369
CAD	37 (9.20)	13 (9.70)	14 (10.45)	10 (7.46)	0.679
Stroke	46 (11.44)	15 (11.19)	15 (11.19)	16 (11.94)	0.976
PHQ-9	4.31 ± 2.80	3.28 ± 2.34	4.39 ± 2.79	5.27 ± 2.89	< 0.001
GAD-7	3.19 ± 2.59	1.99 ± 1.59	3.57 ± 2.75	4.01 ± 2.80	< 0.001
Depression	197 (49.00)	42 (31.34)	66 (49.25)	89 (66.42)	< 0.001
Anxiety	106 (26.37)	9 (6.72)	41 (30.60)	56 (41.79)	< 0.001

Data are presented as n (%) or mean ± SD. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; BUN: Blood urea nitrogen; CAD: Coronary artery disease; CKD: Chronic kidney disease; DBP: Diastolic blood pressure; FBG: Fasting blood glucose; GAD-7: 7-item Generalized Anxiety Disorder scale; HbA1c: Glycated hemoglobin; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; MASLD: Metabolic dysfunction-associated steatotic liver disease; PHQ-9: 9-item Patient Health Questionnaire; PLT: Platelet count; SBP: Systolic blood pressure; Scr: Serum creatinine; SII: Systemic immune-inflammation index; TC: Total cholesterol; TG: Triglycerides; UA: Uric acid; WBC: White blood cell count.

Table 2 Demographic and baseline characteristics of participants grouped according to depressive and anxiety symptoms

Variables	Depression			Anxiety
	No (n = 205)	Yes (n = 197)	P value	No (n = 296)	Yes (n = 106)	P value
Age (years)	53.65 ± 13.04	56.72 ± 12.99	0.019	55.01 ± 12.96	55.56 ± 13.52	0.711
Diabetes duration (years)	6.10 ± 6.42	6.87 ± 7.39	0.268	6.29 ± 6.73	7.00 ± 7.41	0.362
Sex (male)	133 (64.88)	116 (58.88)	0.216	192 (64.86)	57 (53.77)	0.044
Smoking	55 (26.83)	42 (21.32)	0.197	83 (28.04)	14 (13.21)	0.002
Drinking	67 (32.68)	52 (26.40)	0.167	102 (34.46)	17 (16.04)	< 0.001
SBP (mmHg)	130.75 ± 18.16	135.38 ± 16.73	0.008	131.48 ± 17.92	137.32 ± 16.01	0.003
DBP (mmHg)	80.15 ± 12.95	81.42 ± 11.49	0.298	80.16 ± 11.82	82.47 ± 13.33	0.096
BMI (kg/m2)	25.81 ± 3.99	25.41 ± 4.18	0.329	25.91 ± 3.84	24.77 ± 4.63	0.024
HbA1c (%)	8.44 ± 1.98	9.01 ± 2.32	0.009	8.78 ± 2.07	8.55 ± 2.41	0.386
FBG (mmol/L)	8.64 ± 2.89	8.00 ± 2.90	0.027	8.48 ± 2.86	7.90 ± 3.00	0.078
ALT (U/L)	26.20 ± 19.75	28.78 ± 24.20	0.242	26.76 ± 20.04	29.41 ± 26.93	0.292
AST (U/L)	23.10 ± 15.03	24.47 ± 15.16	0.365	23.42 ± 15.46	24.76 ± 14.02	0.434
TC (mmol/L)	4.66 ± 1.33	4.65 ± 1.38	0.942	4.68 ± 1.42	4.59 ± 1.15	0.556
TG (mmol/L)	1.98 ± 1.97	1.97 ± 1.80	0.965	1.99 ± 1.96	1.92 ± 1.66	0.748
LDL-C (mmol/L)	2.96 ± 1.03	2.86 ± 0.99	0.316	2.91 ± 1.01	2.91 ± 1.03	0.994
HDL-C (mmol/L)	1.14 ± 0.31	1.12 ± 0.31	0.517	1.12 ± 0.31	1.14 ± 0.30	0.613
Scr (µmol/L)	62.30 ± 25.97	69.71 ± 32.46	0.012	65.23 ± 29.37	67.92 ± 30.03	0.423
UA (µmol/L)	315.90 ± 92.93	327.15 ± 85.27	0.210	320.81 ± 89.01	323.22 ± 90.45	0.812
BUN (mmol/L)	6.08 ± 1.62	6.94 ± 2.62	< 0.001	6.43 ± 2.10	6.70 ± 2.48	0.280
WBC (× 109/L)	6.35 ± 1.67	6.38 ± 1.50	0.876	6.25 ± 1.53	6.69 ± 1.69	0.015
Neutrophil (× 109/L)	3.43 ± 1.07	3.73 ± 1.15	0.008	3.46 ± 1.08	3.90 ± 1.15	< 0.001
Lymphocyte (× 109/L)	2.29 ± 0.93	1.97 ± 0.72	< 0.001	2.19 ± 0.86	1.99 ± 0.82	0.034
PLT (× 109/L)	196.31 ± 60.41	203.72 ± 59.53	0.216	196.98 ± 60.87	208.23 ± 57.05	0.098
CKD	28 (13.66)	49 (24.87)	0.004	51 (17.23)	26 (24.53)	0.101
Hypertension	84 (40.98)	103 (52.28)	0.023	135 (45.61)	52 (49.06)	0.541
MASLD	105 (51.22)	86 (43.65)	0.129	148 (50.00)	43 (40.57)	0.095
CAD	19 (9.27)	18 (9.14)	0.964	26 (8.78)	11 (10.38)	0.626
Stroke	16 (7.80)	30 (15.23)	0.019	29 (9.80)	17 (16.04)	0.083
SII			< 0.001			< 0.001
Q1	92 (44.88)	42 (21.32)		125 (42.23)	9 (8.49)
Q2	68 (33.17)	66 (33.50)		93 (31.42)	41 (38.68)
Q3	45 (21.95)	89 (45.18)		78 (26.35)	56 (52.83)

Data are presented as n (%) or mean ± SD. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; BUN: Blood urea nitrogen; CAD: Coronary artery disease; CKD: Chronic kidney disease; DBP: Diastolic blood pressure; FBG: Fasting blood glucose; HbA1c: Glycated hemoglobin; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; MASLD: Metabolic dysfunction-associated steatotic liver disease; PLT: Platelet count; SBP: Systolic blood pressure; Scr: Serum creatinine; SII: Systemic immune-inflammation index; TC: Total cholesterol; TG: Triglycerides; UA: Uric acid; WBC: White blood cell count.

Table 3 Multivariable logistic regression analysis of the systemic immune-inflammation index and depressive and anxiety symptoms

Variables		Model 1		Model 2		Model 3		Model 4
		OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Depression	Q1	1.00 (reference)		1.00 (reference)		1.00 (reference)		1.00 (reference)
	Q2	2.13 (1.29–3.50)	0.003	2.19 (1.32–3.62)	0.002	2.13 (1.27–3.55)	0.004	2.02 (1.16–3.54)	0.014
	Q3	4.33 (2.60–7.23)	< 0.001	4.25 (2.52–7.17)	< 0.001	4.09 (2.39–6.97)	< 0.001	3.93 (2.18–7.08)	< 0.001
Anxiety	Q1	1.00 (reference)		1.00 (reference)		1.00 (reference)		1.00 (reference)
	Q2	6.12 (2.84–13.22)	< 0.001	6.22 (2.84–13.61)	< 0.001	6.16 (2.80–13.55)	< 0.001	6.30 (2.83–14.04)	< 0.001
	Q3	9.97 (4.67–21.29)	< 0.001	9.20 (4.24–19.93)	< 0.001	9.15 (4.19–19.98)	< 0.001	9.21 (4.16–20.39)	< 0.001

Model 1: Crude model; Model 2: Adjusted for sex, smoking, drinking, age, diabetes duration, and body mass index; Model 3: Adjusted for sex, smoking, drinking, age, diabetes duration, body mass index, hypertension, coronary artery disease, stroke, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease; Model 4: Adjusted for sex, smoking, drinking, age, diabetes duration, body mass index, hypertension, coronary artery disease, stroke, chronic kidney disease, metabolic dysfunction-associated steatotic liver disease, glycated hemoglobin, fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, serum creatinine, uric acid, and blood urea nitrogen. CI: Confidence interval; OR: Odds ratio.

Table 4 Baseline characteristics according to comorbid depressive and anxiety symptoms

Variables	No anxiety or depression (n = 180)	Anxiety or depression (n = 141)	Anxiety and depression (n = 81)	P value
Age (years)	53.86 ± 12.81	55.96 ± 13.42	56.62 ± 13.02	0.192
Diabetes duration (years)	6.01 ± 6.52	6.73 ± 6.83	7.08 ± 7.88	0.445
Sex (male)	121 (67.22)	83 (58.87)	45 (55.56)	0.129
Smoking	54 (30.00)	30 (21.28)	13 (16.05)	0.032
Drinking	65 (36.11)	39 (27.66)	15 (18.52)	0.013
SBP (mmHg)	129.91 ± 18.22	134.43 ± 17.15	137.48 ± 15.84	0.003
DBP (mmHg)	80.30 ± 12.68	79.79 ± 11.29	83.53 ± 12.68	0.071
BMI (kg/m2)	25.89 ± 3.81	25.82 ± 4.14	24.64 ± 4.47	0.054
HbA1c (%)	8.37 ± 1.95	9.31 ± 2.13	8.44 ± 2.48	< 0.001
FBG (mmol/L)	8.48 ± 2.78	8.69 ± 3.10	7.33 ± 2.62	0.002
ALT (U/L)	26.85 ± 20.85	25.72 ± 17.40	31.89 ± 30.23	0.120
AST (U/L)	23.34 ± 15.87	23.15 ± 13.74	25.82 ± 15.58	0.394
TC (mmol/L)	4.65 ± 1.35	4.73 ± 1.47	4.55 ± 1.14	0.626
TG (mmol/L)	2.04 ± 2.08	1.85 ± 1.65	2.04 ± 1.84	0.642
LDL-C (mmol/L)	2.91 ± 1.00	2.98 ± 1.06	2.79 ± 0.95	0.407
HDL-C (mmol/L)	1.12 ± 0.30	1.15 ± 0.34	1.10 ± 0.27	0.462
Scr (µmol/L)	62.56 ± 26.93	67.76 ± 30.55	70.22 ± 32.62	0.102
UA (µmol/L)	317.95 ± 94.89	320.93 ± 79.36	329.95 ± 93.42	0.605
BUN (mmol/L)	6.00 ± 1.57	7.01 ± 2.49	6.72 ± 2.65	< 0.001
WBC (× 109/L)	6.30 ± 1.64	6.27 ± 1.47	6.67 ± 1.65	0.150
Neutrophil (× 109/L)	3.38 ± 1.06	3.62 ± 1.12	3.93 ± 1.16	< 0.001
Lymphocyte (× 109/L)	2.31 ± 0.93	2.05 ± 0.75	1.91 ± 0.76	< 0.001
PLT (× 109/L)	194.69 ± 60.34	201.84 ± 61.46	208.31 ± 56.23	0.214
CKD	23 (12.78)	33 (23.40)	21 (25.93)	0.012
Hypertension	76 (42.22)	67 (47.52)	44 (54.32)	0.185
MASLD	97 (53.89)	59 (41.84)	35 (43.21)	0.069
CAD	15 (8.33)	15 (10.64)	7 (8.64)	0.763
Stroke	13 (7.22)	19 (13.48)	14 (17.28)	0.039
SII				< 0.001
Q1	89 (49.44)	39 (27.66)	6 (7.41)
Q2	57 (31.67)	47 (33.33)	30 (37.04)
Q3	34 (18.89)	55 (39.01)	45 (55.56)

Data are presented as n (%) or mean ± SD. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BMI: Body mass index; BUN: Blood urea nitrogen; CAD: Coronary artery disease; CKD: Chronic kidney disease; DBP: Diastolic blood pressure; FBG: Fasting blood glucose; HbA1c: Glycated hemoglobin; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; MASLD: Metabolic dysfunction-associated steatotic liver disease; PLT: Platelet count; SBP: Systolic blood pressure; Scr: Serum creatinine; SII: Systemic immune-inflammation index; TC: Total cholesterol; TG: Triglycerides; UA: Uric acid; WBC: White blood cell count.

Table 5 Multivariable logistic regression analysis of the systemic immune-inflammation index and comorbid depressive and anxiety symptoms

Variables		Model 1		Model 2		Model 3		Model 4
		OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
SII	Q1	1.00 (reference)		1.00 (reference)		1.00 (reference)		1.00 (reference)
	Q2	3.03 (1.88–4.89)	< 0.001	3.04 (1.87–4.94)	< 0.001	3.02 (1.85–4.93)	< 0.001	3.03 (1.82–5.05)	< 0.001
	Q3	6.15 (3.78–10.01)	< 0.001	5.86 (3.57–9.61)	< 0.001	5.67 (3.43–9.36)	< 0.001	5.41 (3.21–9.11)	< 0.001

Model 1: Crude model; Model 2: Adjusted for sex, smoking, drinking, age, diabetes duration, and body mass index; Model 3: Adjusted for sex, smoking, drinking, age, diabetes duration, body mass index, hypertension, coronary artery disease, stroke, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease; Model 4: Adjusted for sex, smoking, drinking, age, diabetes duration, body mass index, hypertension, coronary artery disease, stroke, chronic kidney disease, metabolic dysfunction-associated steatotic liver disease, glycated hemoglobin, fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, serum creatinine, uric acid, and blood urea nitrogen. CI: Confidence interval; OR: Odds ratio; SII: Systemic immune-inflammation index.