Role of CCM3 in lead-induced neurological damage in diabetes

Table 1 Multivariate analysis of variance results of blood glucose in mice at week 8

Factors	F value	P value
Genotype	0.157	0.694
Diabetes	7.591	0.009
Pb exposure	268.756	< 0.001
Genotype × diabetes	5.131	0.030
Genotype × Pb	0.001	0.974
Diabetes × Pb	7.726	0.009
Genotype × diabetes × Pb	5.619	0.024

Pb: Lead.

Table 2 Multivariate analysis of variance results of blood lead levels in each group of mice

Factors	F value	P value
Genotype	0.002	0.964
Diabetes	23.619	< 0.001
Pb exposure	198.072	< 0.001
Genotype × diabetes	0.499	0.486
Genotype × Pb	0.006	0.937
Diabetes × Pb	20.556	< 0.001
Genotype × diabetes × Pb	0.415	0.525

Pb: Lead.

Table 3 Multivariate analysis of variance results on the escape latency of mice on day 5

Factors	F value	P value
Genotype	0.056	0.814
Diabetes	9.999	0.002
Pb exposure	6.091	0.016
Genotype × diabetes	0.033	0.856
Genotype × Pb	0.009	0.923
Diabetes × Pb	0.729	0.397
Genotype × diabetes × Pb	0.001	0.998

Pb: Lead.

Table 4 Multivariate analysis of variance for glutathione levels in the hippocampus of mice

Factors	F value	P value
Genotype	80.520	< 0.001
Diabetes	21.955	< 0.001
Pb	228.467	< 0.001
Genotype × diabetes	8.943	0.009
Genotype × Pb	18.901	< 0.001
Diabetes × Pb	6.684	0.020
Genotype × diabetes × Pb	1.760	0.203

Pb: Lead.

Table 5 General characteristics of different lead groups in urine

Characteristic	Group		P value
	Low urinary lead group (n = 341)	High urinary lead group (n = 113)
Age (year, mean ± SD)	56.20 ± 12.80	60.91 ± 12.04	0.007
Sex, n (%)			0.202
Male	174 (71.31)	70 (28.69)
Female	121 (77.07)	36 (22.93)
Urinary lead levels (μg/L, mean ± SD)	1.02, 0.86	3.19, 1.81	< 0.001
Fasting blood glucose (mmol/L, M, IQR)	5.99, 3.05	6.41, 3.99	0.837
BMI (kg/m2, M, IQR)	24.10, 4.31	23.67, 4.22	0.059
VMA (μg/mL, M, IQR)	1.17, 1.91	3.17, 4.53	< 0.001
5-HIAA (μg/mL, M, IQR)	1.90, 4.10	1.75, 2.16	0.808
DOPAC (μg/mL, M, IQR)	6.76, 9.43	7.63, 9.43	0.034
HVA (μg/mL, M, IQR)	1.36, 1.89	3.68, 5.00	< 0.001

BMI: Body mass index; VMA: Vanillylmandelic acid; HVA: Homovanillic acid; DOPAC: 3,4-dihydroxyphenylacetic acid; 5-HIAA: 5-hydroxyindole acetic acid; IQR: Interquartile range.

Table 6 Interaction of urinary lead levels, blood glucose levels and rs6784267 locus with four neurotransmitter metabolites

Interactive factors	Target	F value	P value
Urinary lead × blood sugar	VMA	14.298	< 0.001
	5-HIAA	0.911	0.404
	DOPAC	2.693	0.070
	HVA	7.856	< 0.001
Urinary lead × rs6784267 locus	VMA	14.939	< 0.001
	5-HIAA	0.116	0.891
	DOPAC	2.274	0.105
	HVA	7.031	< 0.001
Blood sugar × rs6784267 locus	VMA	5.038	0.007
	5-HIAA	2.282	0.104
	DOPAC	0.792	0.454
	HVA	1.955	0.144
Urinary lead × blood sugar × rs6784267 locus	VMA	9.838	< 0.001
	5-HIAA	0.856	0.465
	DOPAC	1.984	0.118
	HVA	4.788	0.003

VMA: Vanillylmandelic acid; HVA: Homovanillic acid; DOPAC: 3,4-dihydroxyphenylacetic acid; 5-HIAA: 5-hydroxyindole acetic acid.