Increased blood urea nitrogen levels and compromised peripheral nerve function in patients with type 2 diabetes

doi:10.4239/wjd.v16.i4.101966

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Apr 15, 2025 (publication date) through Feb 28, 2025

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World Journal of Diabetes

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1948-9358

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Diabetes. Apr 15, 2025; 16(4): 101966
Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.101966

Table 1 Clinical features of the recruited patients with type 2 diabetes, n (%)

Variables	Total	Quartiles of BUN levels				Test statistic	P for trend
Variables	Total	Q1	Q2	Q3	Q4	Test statistic	P for trend
BUN (mmol/L) (range)	5.79 ± 1.64 (2.03-16.28)	3.94 ± 0.49 (2.03-4.56)	5.08 ± 0.31 (4.57-5.65)	6.16 ± 0.36 (5.66-6.86)	8.00 ± 1.17 (6.87-16.28)	-	-
n	585	147	147	146	145	-	-
Age (year)	54.7 ± 12.9	51.5 ± 13.6	51.6 ± 13.6	56.5 ± 11.3	59.0 ± 11.6	34.779¹	< 0.001
Female	210 (35.9)	69 (46.9)	56 (38.1)	47 (32.2)	38 (26.2)	14.701²	< 0.001
BMI (kg/m²)	25.3 ± 3.9	25.8 ± 4.1	25.3 ± 3.8	25.1 ± 3.7	24.8 ± 3.8	5.232¹	0.023
SBP (mmHg)	135 ± 19	137 ± 19	135 ± 20	135 ± 19	133 ± 17	4.081¹	0.044
DBP (mmHg)	83 ± 12	85 ± 10	84 ± 14	83 ± 13	81 ± 10	10.324¹	0.001
Diabetes duration (year)	5.0 (1.0-10.0)	3.0 (0.2-10.0)	4.0 (0.9-10.0)	6.0 (2.0-10.0)	8.0 (3.0-15.0)	5.638³	< 0.001
Hypoglycemic drugs
Insulin	265 (45.3)	55 (37.4)	64 (43.5)	58 (39.7)	88 (60.7)	12.757²	< 0.001
Secretagogues	55 (9.4)	13 (8.8)	17 (11.6)	9 (6.2)	16 (11.0)	0.011²	0.916
Metformin	302 (51.6)	88 (59.9)	77 (52.4)	80 (54.8)	57 (39.3)	10.213²	0.001
TZDs	94 (16.1)	22 (15.0)	21 (14.3)	24 (16.4)	27 (18.6)	0.927²	0.336
AGIs	21 (3.6)	5 (3.4)	6 (4.1)	4 (2.7)	6 (4.1)	0.015²	0.901
DPP-4Is	82 (14.0)	19 (12.9)	21 (14.3)	23 (15.8)	19 (13.1)	0.025²	0.874
SGLT-2Is	265 (45.3)	63 (42.9)	61 (41.5)	81 (55.5)	60 (41.4)	0.277²	0.599
GLP-1RAs	156 (26.7)	41 (27.9)	41 (27.9)	44 (30.1)	30 (20.7)	1.383²	0.240
Hypertension	235 (40.2)	54 (36.7)	63 (42.9)	62 (42.5)	56 (38.6)	0.087²	0.768
Statins uses	141 (24.1)	27 (18.4)	32 (21.8)	46 (31.5)	36 (24.8)	3.404²	0.065
ALT (U/L)	20 (14-31)	25 (14-41)	20 (14-31)	19 (15-28)	20 (13-28)	-2.395³	0.017
ALB (g/L)	39.2 ± 4.0	39.0 ± 3.6	39.7 ± 4.1	39.3 ± 4.1	38.7 ± 4.3	0.738¹	0.391
TG (mmol/L)	1.65 (1.16-2.71)	1.95 (1.29-3.17)	1.60 (1.14-2.98)	1.65 (1.11-3.00)	1.48 (1.07-2.22)	-3.019³	0.003
TC (mmol/L)	4.59 ± 1.27	4.70 ± 1.01	4.67 ± 1.44	4.46 ± 1.25	4.52 ± 1.32	2.500¹	0.114
UA (μmol/L)	323 ± 155	311 ± 100	337 ± 261	309 ± 89	333 ± 100	0.422¹	0.516
CysC (mg/L)	0.73 (0.57-0.92)	0.66 (0.52-0.83)	0.71 (0.54-0.90)	0.76 (0.63-0.94)	0.85 (0.66-1.03)	5.043³	< 0.001
eGFR (mL/minute/1.73 m²)	113.23 ± 29.74	122.46 ± 33.15	116.43 ± 31.23	109.98 ± 24.00	103.68 ± 26.48	33.962¹	< 0.001
ACR (mg/g/cr)	15.3 (8.5-42.5)	13.4 (8.0-33.9)	21.8 (9.8-50.7)	15.6 (7.8-45.4)	13.5 (7.3-39.2)	0.012 ³	0.990
Fasting C-peptide (ng/mL)	1.67 ± 1.15	1.75 ± 1.21	1.56 ± 0.96	1.70 ± 1.12	1.69 ± 1.30	0.007¹	0.934
Hemoglobin (g/L)	140 ± 18	138 ± 18	140 ± 19	142 ± 16	141 ± 17	2.633¹	0.105
HbA1c (%)	8.35 ± 1.56	8.03 ± 1.47	8.19 ± 1.66	8.38 ± 1.49	8.41 ± 1.60	5.197¹	0.023
Overall composite Z-score for latency	0.04 ± 0.66	-0.18 ± 0.56	0.01 ± 0.64	-0.01 ± 0.57	0.32 ± 0.77	38.996¹	< 0.001
Overall composite Z-score for amplitude	-0.03 ± 0.58	0.18 ± 0.49	0.06 ± 0.59	-0.09 ± 0.55	-0.27 ± 0.61	50.972¹	< 0.001
Overall composite Z-score for NCV	-0.03 ± 0.75	0.20 ± 0.64	-0.01 ± 0.77	0.01 ± 0.73	-0.31 ± 0.79	30.636¹	< 0.001

¹Linear polynomial contrasts of analysis of variance (F value).

²Linear-by-linear association of χ² test (χ² value).

³Jonckheere-Terpstra test (Z value).

BUN: Blood urea nitrogen; BMI: Body mass index; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; TZDs: Thiazolidinediones; AGIs: Α-glucosidase inhibitors; DPP-4Is: Dipeptidyl peptidase-4 inhibitors; SGLT-2Is: Sodium-glucose cotransporter 2 inhibitors; GLP-1RAs: Glucagon-like peptide 1 receptor agonists; ALT: Alanine aminotransferase; ALB: Albumin; TG: Triglyceride; TC: Total cholesterol; UA: Uric acid; CysC: Cystatin C; eGFR: Estimated glomerular filtration rate; ACR: Urinary albumin /creatinine ratio; HbA1c: Glycosylated hemoglobin A1c; NCV: Nerve conduction velocity.

Table 2 Pearson’s correlation analysis for associations between blood urea nitrogen levels and peripheral nerve functional indices

Item	BUN levels
Item	r	P value
Motor nerves
MN motor latency	0.163	< 0.001
MN motor amplitude	-0.191	< 0.001
MN motor NCV	-0.135	0.001
UN motor latency	0.222	< 0.001
UN motor amplitude	-0.196	< 0.001
UN motor NCV	-0.123	0.003
CPN motor latency	0.202	< 0.001
CPN motor amplitude	-0.187	< 0.001
CPN motor NCV	-0.194	< 0.001
PTN motor latency	0.213	< 0.001
PTN motor amplitude	-0.201	< 0.001
PTN motor NCV	-0.190	< 0.001
Composite Z-score for motor latency	0.266	< 0.001
Composite Z-score for motor amplitude	-0.287	< 0.001
Composite Z-score for motor NCV	-0.202	< 0.001
Sensory nerves
MN sensory latency	0.139	< 0.001
MN sensory amplitude	-0.226	< 0.001
MN sensory NCV	-0.125	0.003
UN sensory latency	0.240	< 0.001
UN sensory amplitude	-0.271	< 0.001
UN sensory NCV	-0.228	< 0.001
SPN sensory latency	0.200	< 0.001
SPN sensory amplitude	-0.206	< 0.001
SPN sensory NCV	-0.190	< 0.001
SN sensory latency	0.215	< 0.001
SN sensory amplitude	-0.195	< 0.001
SN sensory NCV	-0.216	< 0.001
Composite Z-score for sensory latency	0.242	< 0.001
Composite Z-score for sensory amplitude	-0.268	< 0.001
Composite Z-score for sensory NCV	-0.229	< 0.001
Overall
Overall composite Z-score for latency	0.288	< 0.001
Overall composite Z-score for amplitude	-0.325	< 0.001
Overall composite Z-score for NCV	-0.243	< 0.001

BUN: Blood urea nitrogen; NCV: Nerve conduction velocity; MN: Median nerve; UN: Ulnar nerve; CPN: Common peroneal nerve; PTN: Posterior tibial nerve; SPN: Superficial peroneal nerve; SN: Sural nerve.

Table 3 Effects of blood urea nitrogen levels on overall peripheral nerve function according to multivariable linear regression analysis

Models	B (95%CI)	β	t	P value	R²
Overall composite Z-score for latency
Model 0	0.117 (0.085, 0.148)	0.288	7.263	< 0.001	0.081
Model 1	0.056 (0.024, 0.088)	0.137	3.433	< 0.001	0.196
Model 2	0.071 (0.036, 0.106)	0.172	4.032	< 0.001	0.257
Model 3	0.069 (0.034, 0.104)	0.166	3.864	< 0.001	0.256
Overall composite Z-score for amplitude
Model 0	-0.115 (-0.142, -0.088)	-0.325	-8.289	< 0.001	0.104
Model 1	-0.052 (-0.078, -0.025)	-0.142	-3.785	< 0.001	0.287
Model 2	-0.070 (-0.098, -0.041)	-0.193	-4.777	< 0.001	0.336
Model 3	-0.067 (-0.095, -0.038)	-0.184	-4.577	< 0.001	0.353
Overall composite Z-score for NCV
Model 0	-0.112 (-0.148, -0.076)	-0.243	-6.055	< 0.001	0.058
Model 1	-0.041 (-0.078, -0.004)	-0.087	-2.170	0.030	0.188
Model 2	-0.060 (-0.098, -0.021)	-0.126	-3.023	0.003	0.285
Model 3	-0.055 (-0.094, -0.016)	-0.117	-2.787	0.006	0.289

Model 0: Unadjusted; Model 1: Adjusted for age, sex, diabetes duration, body mass index, systolic/diastolic blood pressure, hypertension and statin treatment; Model 2: Additionally adjusted for alanine aminotransferase, albumin, triglyceride, total cholesterol, uric acid, cystatin C, estimated glomerular filtration rate, albumin/creatinine ratio, C-peptide, hemoglobin and glycosylated hemoglobin A1c; Model 3: Additionally adjusted for hypoglycemic drugs. CI: Confidence interval; NCV: Nerve conduction velocity.

Table 4 Effects of blood urea nitrogen levels on motor nerve function according to multivariable linear regression analysis

Models	B (95%CI)	β	t	P value	R²
Composite Z score of motor latency
Model 0	0.117 (0.082, 0.152)	0.266	6.651	< 0.001	0.069
Model 1	0.054 (0.019, 0.089)	0.122	3.056	0.002	0.197
Model 2	0.072 (0.034, 0.109)	0.160	3.772	< 0.001	0.266
Model 3	0.070 (0.032, 0.108)	0.155	3.623	< 0.001	0.262
Composite Z score of motor amplitude
Model 0	-0.112 (-0.142, -0.081)	-0.287	-7.224	< 0.001	0.081
Model 1	-0.054 (-0.084, -0.023)	-0.135	-3.393	< 0.001	0.209
Model 2	-0.078 (-0.112, -0.044)	-0.193	-4.491	< 0.001	0.243
Model 3	-0.076 (-0.110, -0.042)	-0.188	-4.395	< 0.001	0.263
Composite Z score of motor NCV
Model 0	-0.100 (-0.139, -0.060)	-0.202	-4.990	< 0.001	0.039
Model 1	-0.041 (-0.071, -0.011)	-0.060	-1.447	0.148	0.147
Model 2	-0.056 (-0.097, -0.014)	-0.110	-2.598	0.010	0.263
Model 3	-0.049 (-0.091, -0.007)	-0.098	-2.299	0.022	0.271

Table 5 Effects of blood urea nitrogen levels on sensory nerve function according to multivariable linear regression analysis

Models	B (95%CI)	β	t	P value	R²
Composite Z score of sensory latency
Model 0	0.123 (0.083, 0.163)	0.242	6.023	< 0.001	0.057
Model 1	0.052 (0.012, 0.091)	0.102	2.586	0.010	0.216
Model 2	0.065 (0.022, 0.108)	0.127	2.972	0.003	0.252
Model 3	0.063 (0.019, 0.106)	0.123	2.845	0.005	0.252
Composite Z score of sensory amplitude
Model 0	-0.141 (-0.182, -0.099)	-0.268	-6.698	< 0.001	0.070
Model 1	-0.056 (-0.095, -0.016)	-0.105	-2.763	0.006	0.269
Model 2	-0.080 (-0.122, -0.037)	-0.150	-3.668	< 0.001	0.319
Model 3	-0.076 (-0.118, -0.033)	-0.143	-3.495	< 0.001	0.331
Composite Z score of sensory NCV
Model 0	-0.116 (-0.156, -0.076)	-0.229	-5.670	< 0.001	0.051
Model 1	-0.050 (-0.090, -0.010)	-0.099	-2.449	0.015	0.188
Model 2	-0.061 (-0.104, -0.018)	-0.120	-2.786	0.006	0.242
Model 3	-0.059 (-0.102, -0.015)	-0.116	-2.660	0.008	0.241

Citation: Wang R, Xu YX, Xu F, Wang CH, Zhao LH, Wang LH, Chen WG, Wang XQ, Duan CW, Su JB. Increased blood urea nitrogen levels and compromised peripheral nerve function in patients with type 2 diabetes. World J Diabetes 2025; 16(4): 101966
URL: https://www.wjgnet.com/1948-9358/full/v16/i4/101966.htm
DOI: https://dx.doi.org/10.4239/wjd.v16.i4.101966