L-shaped association between fasting blood glucose and comorbid anxiety in Chinese patients with first-episode untreated major depressive disorder

Table 1 Baseline characteristics between major depressive disorder comorbid anxiety and non-comorbid anxiety, n (%)

Variables	FBG tertile (mmol/L)			P value
	T1 (3.7-5.0)	T2 (5.1-5.5)	T3 (5.6-8.2)
n	571	572	575
Age (years)	34.0 ± 12.2	34.9 ± 12.4	35.7 ± 12.7	0.077
Duration of illness (months)	4.0 (3.0-7.0)	5.5 (3.0-8.0)	6.0 (3.0-9.0)	< 0.001
Age at onset (years)	33.9 ± 12.1	34.7 ± 12.2	35.5 ± 12.5	0.09
HAMD	29.5 ± 2.9	30.2 ± 2.9	31.2 ± 2.8	< 0.001
HAMA	20.4 ± 3.2	20.5 ± 3.4	21.4 ± 3.7	< 0.001
TSH (uIU/mL)	3.8 ± 2.4	5.0 ± 2.0	6.4 ± 2.6	< 0.001
TPOAb (IU/L)	16.7 (12.2-28.9)	16.6 (12.2-33.3)	19.5 (12.7-49.0)	< 0.001
TGAb (IU/L)	20.4 (14.3-30.1)	21.6 (13.9-37.0)	22.4 (15.4-89.8)	< 0.001
FT3 (pmol/L)	4.9 ± 0.7	4.9 ± 0.7	4.9 ± 0.7	0.862
FT4 (pmol/L)	16.7 ± 3.2	16.6 ± 3.0	16.7 ± 3.1	0.85
TC (mmol/L)	4.9 ± 1.0	5.3 ± 1.0	5.6 ± 1.1	< 0.001
TG (mmol/L)	2.1 ± 1.0	2.1 ± 0.9	2.3 ± 1.0	< 0.001
HDL-C (mmol/L)	1.3 ± 0.3	1.2 ± 0.3	1.1 ± 0.3	< 0.001
LDL-C (mmol/L)	2.7 ± 0.8	3.0 ± 0.8	3.2 ± 0.9	< 0.001
BMI (kg/m2)	24.1 ± 1.9	24.5 ± 1.9	24.5 ± 2.0	< 0.001
Systolic pressure (mmHg)	116.1 ± 11.0	119.6 ± 10.5	122.7 ± 10.2	< 0.001
Diastolic pressure (mmHg)	74.8 ± 6.7	75.6 ± 6.4	77.4 ± 6.8	< 0.001
Gender				0.332
Male	209 (36.6)	187 (32.7)	192 (33.4)
Female	362 (63.4)	385 (67.3)	383 (66.6)
Education				0.84
Junior high school	127 (22.2)	138 (24.1)	148 (25.7)
Senior high school	260 (45.5)	247 (43.2)	253 (44.0)
College	153 (26.8)	155 (27.1)	141 (24.5)
Postgraduate	31 (5.4)	32 (5.6)	33 (5.7)
Marital status				0.457
Single	177 (31.0)	166 (29.0)	159 (27.7)
Marriage	394 (69.0)	406 (71.0)	416 (72.3)
Psychotic symptoms				< 0.001
No	532 (93.2)	524 (91.6)	491 (85.4)
Yes	39 (6.8)	48 (8.4)	84 (14.6)
Suicide attempt				< 0.001
No	477 (83.5)	484 (84.6)	411 (71.5)
Yes	94 (16.5)	88 (15.4)	164 (28.5)
Comorbid anxiety				< 0.001
No	131 (22.9)	125 (21.9)	82 (14.3)
Yes	440 (77.1)	447 (78.1)	493 (85.7)

Variables are indicated by n (%) or mean ± SD or median (quartiles 1-3). FBG: Fasting blood glucose; HAMD: 17-item Hamilton Rating Scale for Depression; HAMA: 14-item Hamilton Anxiety Rating Scale; TSH: Thyroid-stimulating hormone; TGAb: Thyroglobulin antibody; TPOAb: Thyroid peroxidase antibody; FT3 and FT4: Free triiodothyronine and thyroxine, respectively; TC: Total cholesterol; HDL-C: High density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; TG: Triglyceride; BMI: Body mass index.

Table 2 Baseline characteristics between major depressive disorder comorbid anxiety and non-comorbid anxiety, n (%)

Variables	Comorbid anxiety (n =1380)	Non-comorbid anxiety (n = 338)	F/χ2/z	P value
Age (years)	34.96 ± 12.48	34.51 ± 12.25	0.346	0.556
Age at onset (years)	34.75 ± 12.35	34.29 ± 12.15	0.378	0.539
Duration of illness (months)	6.32 ± 4.68	6.26 ± 4.94	0.462	0.829
HAMD	30.84 ± 2.81	28.08 ± 2.35	278.199	< 0.001
HAMA	21.89 ± 2.95	16.31 ± 0.81	1190.192	< 0.001
FBG (mmol/L)	5.43 ± 0.66	5.28 ± 0.56	13.112	< 0.001
TSH (uIU/mL)	5.29 ± 2.69	4.19 ± 1.70	51.26	< 0.001
TPOAb (IU/L)	18.90 (12.62-38.12)	18.83 (13.03-26.96)	-7.097	< 0.001
TGAb (IU/L)	22.16 (15.10-54.45)	18.33 (13.03-26.96)	-5.051	< 0.001
FT3 (pmol/L)	4.91 ± 0.71	4.87 ± 0.77	1.198	0.274
FT4 (pmol/L)	16.72 ± 3.10	16.65 ± 3.07	0.135	0.713
TC (mmol/L)	5.35 ± 1.10	4.78 ± 0.99	78.589	< 0.001
TG (mmol/L)	2.20 ± 0.98	2.05 ± 0.99	5.539	0.019
HDL-C (mmol/L)	1.21 ± 0.29	1.24 ± 0.26	2.578	0.109
LDL-C (mmol/L)	3.06 ± 0.86	2.68 ± 0.78	55.443	< 0.001
BMI (kg/m2)	24.37 ± 1.93	24.37 ± 1.89	0.0001	0.991
Systolic pressure (mmHg)	120.1 ± 11.03	116.96 ± 10.05	22.692	< 0.001
Diastolic pressure (mmHg)	76.37 ± 6.81	74.23 ± 6.16	27.771	< 0.001
Gender			0.118	0.731
Male	475 (34.42)	113 (33.43)
Female	905 (65.58)	225 (66.57)
Education			2.399	0.494
Junior high school	332 (24.06)	81 (23.96)
Senior high school	602 (43.62)	158 (46.75)
College	371 (26.88)	78 (23.08)
Postgraduate	75 (5.44)	21 (6.21)
Marital status			0.320	0.572
Single	399 (28.91)	103 (30.47)
Marriage	981 (71.09)	235 (69.53)
Psychotic symptoms			43.788	< 0.001
No	1210 (87.68)	337 (99.70)
Yes	170 (12.32)	1 (0.30)
Suicide attempt			74.592	< 0.001
No	1045 (75.72)	327 (96.75)
Yes	335 (24.28)	11 (3.25)

HAMD: 17-item Hamilton Rating Scale for Depression; HAMA: 14-item Hamilton Anxiety Rating Scale; FBG: Fasting blood glucose; TSH: Thyroid-stimulating hormone; TGAb: Thyroglobulin antibody; TPOAb: Thyroid peroxidase antibody; FT3 and FT4: Free triiodothyronine and thyroxine, respectively; TC: Total cholesterol; HDL-C: High density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; TG: Triglyceride; BMI: Body mass index.

Table 3 Relationship of fasting blood glucose with comorbid anxiety in different models

Variable	Crude Model		Model I		Model II		Model III		Model IV
	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
FBG	1.43 (1.18, 1.73)	< 0.001	1.43 (1.18, 1.73)	< 0.001	1.25 (1.01, 1.53)	0.038	0.93 (0.74, 1.16)	0.497	0.98 (0.77, 1.24)	0.853
FBG (tertile)
T1	0.94 (0.71, 1.24)	0.659	0.94 (0.71, 1.24)	0.670	0.95 (0.71, 1.26)	0.699	1.23 (0.91, 1.69)	0.187	1.16 (0.84, 1.60)	0.361
T2	Reference		Reference		Reference		Reference		Reference
T3	1.68 (1.24, 2.28)	< 0.001	1.69 (1.24, 2.29)	< 0.001	1.41 (1.03, 1.94)	0.034	1.16 (0.83, 1.64)	0.381	1.19 (0.84, 1.68)	0.338
P for trend	< 0.001		< 0.001		0.045		0.327		0.987

The Crude Model: Unadjusted; Model I adjusted for demographic variables (gender, age and education); Model II additionally adjusted for disease-related variables (suicide attempts, psychotic symptoms, 17-item Hamilton Rating Scale for Depression); Model III further adjusted for metabolic indicators (total cholesterol, triglyceride, low-density lipoprotein cholesterol, diastolic and systolic blood pressures); Model IV further adjusted for thyroid function indicators (thyroid-stimulating hormone, Thyroglobulin antibody, Thyroid peroxidase antibody). FBG: Fasting blood glucose.

Table 4 Two-piecewise logistic regression model results

Inflection point of FBG	Effect size (OR)	95%CI	P value
< 4.8 (mmol/L)	0.20	0.06-0.67	0.009
≥ 4.8 (mmol/L)	1.22	0.91-1.63	0.188
Log likelihood ratio test			0.005

Effect: Comorbid anxiety; Cause: Fasting blood glucose (mmol/L); Adjusted for gender, age, education, Hamilton Rating Scale for Depression, total cholesterol, triglyceride, thyroid-stimulating hormone, thyroglobulin antibody, thyroid peroxidase antibody, low-density lipoprotein cholesterol, diastolic and systolic blood pressures, suicide attempts and psychotic symptoms. FBG: Fasting blood glucose.