Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus

Cao, Yurou; Wang, Xueqin

doi:10.1016/j.clinsp.2024.100392

Acessibilidade / Reportar erro

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original articles • Clinics 79 • 2024 • https://doi.org/10.1016/j.clinsp.2024.100392 copy

Correlation between islet α cell function and peripheral neuropathy in patients with type 2 diabetes mellitus

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Background:

This study explored the correlation between pancreatic islet α cell function, as reflected by the plasma glucagon levels, and Diabetic Peripheral Neuropathy (DPN) in patients with Type 2 Diabetes Mellitus (T2DM).

Methods:

A total of 358 patients with T2DM were retrospectively enrolled in this study and divided into the Non-DPN (NDPN) group (n = 220) and the DPN group (n = 138). All patients underwent an oral glucose tolerance test to detect levels of blood glucose, insulin and glucagon, and the Area Under the Curve (AUC) for Glucagon (AUCglu) was used to estimate the overall glucagon level. The Peripheral Nerve Conduction Velocity (PNCV), Amplitude (PNCA) and Latency (PNCL) were obtained with electromyography, and their Z scores were calculated.

Results:

There were significant differences regarding the age, disease duration, serum levels of alanine aminotransferase, aspartate aminotransferase, urea nitrogen, high-density lipoprotein, and 2h-C peptide between these two groups (p < 0.05). The NDPN group had higher glucagon levels at 30, 60 and 120 min and AUCglu (p < 0.05). The Z-scores of PNCV and PNCA showed an increasing trend (p < 0.05), while the Z-score of PNCL showed a decreasing trend (p < 0.05). The glucagon levels were positively correlated with PNCV and PNCA, but negatively correlated with PNCL, with Gluca30min having the strongest correlation (p < 0.05). Gluca30min was independently related to PNCV, PNCL, PNCA and DPN, respectively (p < 0.05). The function of pancreatic α islet cells, as reflected by the plasma glucagon level, is closely related to the occurrence of DPN in T2DM patients.

Conclusion:

Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN.

Keywords:
Islet α-cell function; Glucagon; Type 2 diabetes; Peripheral neuropathy; Peripheral nerve conduction velocity; Peripheral nerve conduction latency; Peripheral nerve conduction amplitude

HIGHLIGHTS

The correlation between pancreatic islet α cell function and diabetic peripheral neuropathy

Gluca30min may be a potentially valuable independent predictor for the occurrence of DPN

Clinical features	NDPN (n = 220)	DPN (n = 138)	T/Z/X²	p
Age (years)	54 (45‒60)	57 (49.75‒64)	–2.527	0.012
Gender (Female)	91 (41.4)	44 (31.9)	3.244	0.072
Disease duration (years)	3 (0.5–8)	7 (2–14)	–4.710	<0.001
BMI (kg/m²)	25.39 (23.10‒27.67)	24.91 (22.50‒27.78)	–1.407	0.159
SBP (mmHg)	135.00 (124.00‒147.00)	132.00 (117.00‒143.00)	–1.540	0.124
DBP (mmHg)	83.00 (76.00‒90.75)	80.00 (72.50‒90.00)	–1.674	0.094
Alanine aminotransferase (U/L)	23.00 (17.00‒37.00)	18.00 (13.00‒28.00)	–4.047	0.001
Aspartate aminotransferase (U/L)	18.00 (15.00‒25.75)	17.00 (13.00‒21.05)	–2.506	0.012
Urea nitrogen(mmoL/L)	5.34 (4.32‒6.39)	5.79 (4.72‒7.19)	–2.899	0.004
Creatinine (μmoL/L)	59.50 (50.03‒69.58)	61.40 (51.65‒75.45)	–1.692	0.091
Uric acid (μmoL/L)	312.70 (266.30‒383.30)	313.90 (236.75‒409.45)	–0.077	0.939
Triglycerides (mmoL/L)	1.95 (1.33‒3.23)	1.75 (1.09‒2.97)	–1.914	0.056
Total cholesterol (mmoL/L)	4.49 (3.80‒5.21)	4.48 (3.99‒5.16)	–0.384	0.701
Low density lipoprotein (mmoL/L)	2.68±0.84	2.67±0.75	0.140	0.889
High-density lipoprotein (mmoL/L)	1.04 (0.88‒1.19)	1.09 (0.96‒1.24)	–2.802	0.005
Fasting blood glucose (mmoL/L)	6.26 (4.89‒7.63)	6.34 (5.08‒8.48)	–1.769	0.077
Glycated hemoglobin A1c (%)	9.75 (8.14‒11.20)	9.76 (8.33‒11.73)	–0.422	0.673
0h-C peptide (ng/mL)	1.65 (1.09‒2.54)	1.48 (0.86‒2.33)	–1.962	0.050
2h-C peptide (ng/mL)	6.25 (4.58‒8.01)	4.09 (3.05‒5.17)	–6.923	<0.001
Gluca0min (pmoL/L)	12.36 (8.27‒18.24)	11.37 (7.45‒15.93)	–1.347	0.178
Gluca30min (pmoL/L)	18.30 (12.77‒14.36)	12.26 (9.10‒18.26)	–6.309	<0.001
Gluca60min (pmoL/L)	12.37(8.76–17.33)	10.31 (6.83‒13.92)	–3.50	0.002
Gluca120min (pmoL/L)	9.48 (6.62‒13.29)	7.61 (5.38‒11.09)	–3.009	0.003
Gluca180min (pmoL/L)	8.57 (5.44‒12.13)	8.29 (5.14‒11.71)	–1.048	0.295
AUCgla	2138.48 (1484.06‒2883.15)	1196.32 (966.99‒2348.62)	–3.741	0.001

	Gluca0min		Gluca30min		Gluca60min		Gluca120min		Gluca180min		AUCgla
	r	p	r	p	r	p	r	p	r	p	r	p
Left median nerve MCV	0.057	0.279	0.202	0.001	0.108	0.041	0.127	0.016	0.068	0.197	0.139	0.009
Right median nerve MCV	0.094	0.075	0.218	0.002	0.122	0.021	0.135	0.011	0.05	0.348	0.143	0.007
Left ulnar nerve MCV	0.069	0.191	0.179	0.003	0.081	0.125	0.09	0.09	0.021	0.687	0.105	0.047
Right ulnar nerve MCV	0.062	0.241	0.214	0.002	0.113	0.033	0.111	0.035	0.033	0.535	0.128	0.016
Left tibial nerve MCV	0.142	0.007	0.264	<0.001	0.182	0.001	0.152	0.004	0.096	0.07	0.196	0.002
Right tibial nerve MCV	0.103	0.052	0.24	<0.001	0.17	0.001	0.157	0.003	0.07	0.185	0.179	0.001
Left common peroneal nerve MCV	0.126	0.017	0.26	<0.001	0.179	0.001	0.155	0.003	0.058	0.276	0.186	<0.001
Right common peroneal nerve MCV	0.151	0.004	0.277	<0.001	0.203	<0.001	0.157	0.003	0.094	0.076	0.206	<0.001
Left median nerve SCV	0.114	0.032	0.209	0.002	0.177	0.001	0.157	0.003	0.102	0.055	0.176	0.001
Right median nerve SCV	0.088	0.098	0.186	0.001	0.157	0.003	0.139	0.009	0.08	0.131	0.155	0.003
Left ulnar nerve SCV	0.106	0.046	0.232	0.002	0.186	<0.001	0.178	0.001	0.083	0.119	0.191	0.002
Right ulnar nerve SCV	0.108	0.043	0.243	0.002	0.19	<0.001	0.161	0.002	0.054	0.311	0.19	0.003
Left superficial peroneal nerve SCV	0.116	0.034	0.24	0.001	0.159	0.004	0.157	0.004	0.088	0.108	0.185	0.001
Right superficial peroneal nerve SCV	0.093	0.092	0.204	<0.001	0.182	0.001	0.175	0.001	0.091	0.099	0.186	0.001
Left sural nerve SCV	0.114	0.036	0.28	<0.001	0.227	<0.001	0.204	<0.001	0.135	0.013	0.231	<0.001
Right sural nerve SCV	0.090	0.094	0.204	<0.001	0.201	<0.001	0.177	0.001	0.118	0.028	0.195	<0.001

		Gluca0min		Gluca30min		Gluca60min		Gluca120min		Gluca180min		AUGgla
		r	p	r	p	r	p	r	p	r	p	r	p
Sports	Left median nerve latency
	Wrist-APB	0.005	0.924	0.079	0.136	0.017	0.745	–0.006	0.914	–0.053	0.322	0.018	0.728
	Elbow-wrist	–0.015	0.771	0.062	0.239	–0.006	0.907	–0.022	0.675	–0.059	0.269	0	0.999
	Right median nerve latency
	Wrist-APB	0.0202	0.705	0.097	0.069	0.071	0.182	–0.003	0.962	–0.022	0.683	0.042	0.426
	Elbow-wrist	0.0120	0.824	0.070	0.187	0.033	0.533	–0.027	0.617	–0.038	0.476	0.015	0.782
	Left ulnar nerve latency
	Wrist-ADM	0.058	0.271	0.100	0.059	0.051	0.331	–0.003	0.962	0.022	0.678	0.049	0.360
	Below elbow - wrist	0.043	0.415	0.089	0.094	0.041	0.444	–0.006	0.908	–0.002	0.962	0.034	0.524
	Right ulnar nerve latency
	Wrist-ADM	0.007	0.893	0.102	0.055	0.032	0.550	–0.038	0.472	0.024	0.644	0.027	0.615
	Below elbow - wrist	–0.014	0.787	0.086	0.103	0.022	0.675	–0.035	0.509	0.018	0.735	0.018	0.732
	Left tibial nerve latency
	Ankle-AH	–0.050	0.343	0.048	0.368	0.018	0.730	0.066	0.210	–0.041	0.435	0.032	0.540
	Popliteal fossa-ankle	–0.062	0.242	0.041	0.441	0.016	0.757	0.034	0.518	–0.057	0.278	0.016	0.769
	Right tibial nerve latency
	Ankle-AH	0.013	0.799	0.101	0.057	0.070	0.188	0.088	0.095	–0.024	0.651	0.071	0.183
	Popliteal fossa-ankle	0.021	0.698	0.126	0.017	0.091	0.086	0.089	0.094	–0.02	0.710	0.085	0.107
	Left common peroneal nerve latency
	Ankle-EDB	0.152	0.004	0.173	0.001	0.144	0.007	0.130	0.014	0.057	0.283	0.145	0.006
	below knee-ankle	0.116	0.028	0.176	0.001	0.152	0.004	0.121	0.023	0.042	0.425	0.141	0.008
	Right common peroneal nerve latency
	Ankle-EDB	0.077	0.148	0.127	0.017	0.097	0.068	0.113	0.032	0.061	0.249	0.11	0.038
	below knee-ankle	0.090	0.090	0.169	0.001	0.129	0.015	0.141	0.008	0.073	0.171	0.141	0.008
Sensation	Left median nerve latency	–0.009	0.870	0.115	0.030	0.017	0.750	0.007	0.888	–0.060	0.256	0.031	0.565
	Right median nerve latency	0.032	0.550	0.167	0.002	0.080	0.132	0.063	0.237	–0.015	0.777	0.091	0.087
	Left ulnar nerve latency	–0.077	0.147	0.095	0.074	–0.006	0.907	0.007	0.888	–0.116	0.029	0.005	0.920
	Right ulnar nerve latency	0.026	0.630	0.142	0.008	0.056	0.290	0.025	0.640	–0.089	0.093	0.055	0.301
	Left superficial peroneal nerve latency	0.081	0.142	0.179	0.001	0.090	0.102	0.085	0.120	0.013	0.811	0.115	0.036
	Right superficial peroneal nerve latency	0.069	0.209	0.155	0.005	0.063	0.255	0.052	0.347	–0.024	0.666	0.079	0.153
	Left sural nerve latency	0.014	0.797	0.153	0.005	0.054	0.324	0.038	0.481	–0.043	0.433	0.061	0.260
	Right sural nerve latency	0.026	0.626	0.173	0.001	0.090	0.094	0.093	0.086	0.006	0.916	0.103	0.055

		Gluca0min		Gluca30min		Gluca60min		Gluca120min		Gluca180min		AUGgla
		r	p	r	p	r	p	r	p	r	p	r	p
Sports	Left median nerve latency
	Wrist-APB	–0.094	0.074	–0.179	0.001	–0.136	0.010	–0.150	0.004	–0.066	0.210	–0.145	0.006
	Elbow-wrist	–0.073	0.166	–0.193	<0.001	–0.132	0.012	–0.176	0.001	–0.068	0.198	–0.155	0.003
	Right median nerve latency
	Wrist-APB	–0.044	0.406	–0.164	0.009	–0.137	0.010	–0.136	0.010	–0.045	0.395	–0.131	0.014
	Elbow-wrist	–0.061	0.250	–0.195	<0.001	–0.149	0.005	–0.179	0.001	–0.069	0.191	–0.16	0.002
	Left ulnar nerve latency
	Wrist-ADM	–0.141	0.008	–0.245	<0.001	–0.189	<0.001	–0.184	<0.001	–0.091	0.086	–0.2	<0.001
	Below elbow - wrist	–0.054	0.305	–0.168	0.001	–0.081	0.124	–0.108	0.040	–0.005	0.931	–0.104	0.049
	Right ulnar nerve latency
	Wrist-ADM	–0.112	0.034	–0.211	<0.001	–0.127	0.016	–0.123	0.020	–0.072	0.176	–0.148	0.005
	Below elbow - wrist	–0.065	0.223	–0.178	0.001	–0.087	0.102	–0.113	0.033	–0.014	0.797	–0.111	0.035
	Left tibial nerve latency
	Ankle-AH	–0.097	0.066	–0.151	0.004	–0.093	0.080	–0.102	0.053	–0.043	0.420	–0.111	0.037
	Popliteal fossa-ankle	–0.083	0.115	–0.176	0.001	–0.104	0.049	–0.116	0.028	–0.020	0.700	–0.122	0.020
	Right tibial nerve latency
	Ankle-AH	–0.096	0.070	–0.14	0.008	–0.075	0.155	–0.109	0.039	–0.049	0.356	–0.107	0.043
	Popliteal fossa-ankle	–0.068	0.199	–0.159	0.003	–0.085	0.108	–0.114	0.031	–0.006	0.904	–0.109	0.040
	Left common peroneal nerve latency
	Ankle-EDB	–0.089	0.095	–0.145	0.006	–0.106	0.045	–0.122	0.021	–0.025	0.634	–0.114	0.031
	below knee-ankle	–0.083	0.117	–0.111	0.036	–0.109	0.040	–0.112	0.034	–0.058	0.273	–0.103	0.052
	Right common peroneal nerve latency
	Ankle-EDB	–0.079	0.137	–0.122	0.021	–0.088	0.096	–0.121	0.022	–0.062	0.246	–0.104	0.051
	Below knee-ankle	–0.079	0.136	–0.159	0.003	–0.093	0.080	–0.118	0.026	–0.035	0.511	–0.112	0.034
Sensation	Left median nerve latency	–0.06	0.258	–0.189	0.001	–0.143	0.007	–0.152	0.004	–0.051	0.334	–0.15	0.004
	Right median nerve latency	–0.032	0.554	–0.153	0.004	–0.103	0.052	–0.108	0.042	–0.015	0.779	–0.105	0.047
	Left ulnar nerve latency	–0.046	0.390	–0.164	0.002	–0.087	0.101	–0.113	0.033	0.018	0.732	–0.107	0.045
	Right ulnar nerve latency	–0.048	0.373	–0.197	<0.001	–0.108	0.042	–0.095	0.075	0.027	0.610	–0.114	0.032
	Left superficial peroneal nerve latency	–0.089	0.103	–0.183	0.001	–0.110	0.044	–0.143	0.009	–0.016	0.770	–0.142	0.009
	Right superficial peroneal nerve latency	–0.104	0.057	–0.219	0.001	–0.150	0.006	–0.158	0.004	–0.037	0.505	–0.168	0.002
	Left sural nerve latency	–0.084	0.122	–0.211	<0.001	–0.127	0.020	–0.139	0.011	–0.060	0.271	–0.152	0.005
	Right sural nerve latency	–0.078	0.149	–0.175	0.002	–0.096	0.074	–0.107	0.048	–0.003	0.960	–0.114	0.035

Variables	Total number	Q1	Q2	Q3	Q4	X²/F	p
Gluca30min	15.80 (11.01‒22.35)	8.59 (6.78‒10.03)	13.16 (12.23‒13.16)	18.59 (17.31‒20.37)	26.28 (24.15‒32.20)	–	–
n	358	89	90	90	89	–	–
Age (years)	55 (47‒62.0)	58.5 (51.25‒65.0)	56 (47‒61)	54 (44‒60)	55 (43‒60)	11.374	0.010
Gender (Female)	135 (37.7)	36 (40.4)	36 (40.4)	30 (33.3)	33 (37.1)	1.234	0.745
DPN	138 (38.5)	57 (64.0)	35 (38.9)	34 (37.8)	12 (13.5)	48.056	0.001
Duration of disease (years)	5 (0.65‒10)	6.50 (1.00‒12.75)	6.00 (2.00‒10.00)	4.00 (0.88‒10.00)	2.00 (0.5‒8)	10.986	0.012
Body mass index (kg/m²)	25.2 (22.86‒27.69)	24.15 (21.91‒27.24)	24.94 (22.98‒26.81)	25.35 (23.11‒28.03	26.80 (23.46‒28.69)	14.041	0.003
Systolic blood pressure (mmHg)	133 (121‒145)	130 (117.25‒141)	134.5 (120‒145.50)	132 (120.75‒143.25)	140 (127.50‒152.00)	11.793	0.008
Diastolic blood pressure (mmHg)	82(75–90)	80.00 (73.0‒87.75)	82.50 (72.75‒90.25)	82.00 (76.0‒91.00)	85.00 (77.50‒92.5)	6.895	0.075
Alanine aminotransferase (U/L)	21.00 (15.00‒32.00)	18.00 (12.00‒29.00)	21.50 (16.25‒36.50)	20.00 (15.00‒29.50)	25.00 (17.00‒37.00)	12.855	0.005
Aspartate aminotransferase (U/L)	18.00(14.00–24.00)	18.00 (13.00‒23.00)	18.00 (15.00‒25.75)	16.00 (13.00‒21.00)	18.00 (15.00‒25.25)	7.699	0.053
Urea nitrogen (mmoL/L)	5.44 (4.45‒6.76)	5.60(4.47–7.60)	5.71 (4.55‒6.80)	4.97 (4.22‒5.89)	5.60 (4.70‒6.52)	9.827	0.020
Creatinine (μmoL/L)	60.10 (50.58‒71.50)	60.95 (50.28‒74.28)	57.85 (49.10‒69.88)	59.40 (52.4‒69.15)	62.55 (53.7‒73.93)	2.457	0.483
Uric acid (μmoL/L)	313.35 (255.08‒390.03)	306.55 (229.58‒390.45)	297.45 (241.65‒392.53)	319.90 (274.15‒385.7)	319.1 (268.95‒398.38)	2.556	0.465
Triglycerides (mmoL/L)	1.88 (1.25‒3.15)	1.54 (0.98‒2.32)	1.68 (1.15‒3.19)	2.27 (1.40‒3.70)	2.12 (1.40‒3.87)	–1.914	0.056
Total cholesterol (mmoL/L)	4.49 (3.87‒5.21)	4.51 (3.96‒5.09)	4.33 (3.76‒5.20)	4.62 (3.94‒5.55)	4.53 (3.76‒5.17)	–0.384	0.701
Low density lipoprotein (mmoL/L)	2.68±0.81	2.66±0.65	2.63±0.77	2.77±0.94	2.64±0.84	0.61	0.609
High-density lipoprotein (mmoL/L)	1.06 (0.91‒1.22)	1.11 (0.94‒1.27)	1.04 (0.92‒1.21)	1.04 (0.89‒1.20)	1.05 (0.90‒1.21)	–2.802	0.005
Diabetes treatment plan Simple lifestyle (%)	13 (3.6)	2 (2.2)	5 (5.6)	2 (2.2)	4 (4.5)	2.14	0.544
Insulin therapy (%)	155 (43.3)	55 (61.8)	35 (38.9)	34 (37.8)	31 (34.8)	16.835	0.001
Insulin secretagogue (%)	36 (10.1)	11 (12.4)	7 (7.8)	11 (12.2)	7 (7.9)	1.978	0.577
Biguanide drugs (%)	186 (52.0)	40 (44.9)	44 (48.9)	54 (60.0)	48 (53.9)	4.565	0.207
Insulin sensitizer (%)	54 (15.1)	12 (13.5)	17 (18.9)	12 (13.3)	13 (14.6)	1.426	0.699
Fasting blood glucose (mmoL/L)	6.27 (5.00‒7.80)	5.75 (4.53‒7.43)	6.09 (4.87‒7.93)	7.04 (5.53‒8.16)	6.27 (5.21‒7.22)	–1.769	0.077
Glycated hemoglobin A1c (%)	9.76 (8.19‒11.33)	9.96 (8.53‒11.90)	9.70 (7.85‒11.5)	9.86 (8.28‒11.53)	9.46 (7.99‒10.73)	–0.422	0.673
CP2h (ng/mL)	5.26 (3.59‒7.44)	4.36 (3.07‒6.72)	5.25 (3.39‒7.63)	5.08 (3.58‒6.86)	6.36 (4.87‒8.91)	28.431	<0.001
AUCgla	1972.2 (1359.64‒2688.22)	1195.45 (908.4‒1343.55)	1669.42 (1420.46‒1906.95)	2250.22 (2022.94‒2639.7)	3171.75 (2720.92‒3972.82)	–3.741	0.002
Composite Z-score for nerve conduction velocity	–	–0.46±1.12	0.03±0.99	0.02±0.97	0.41±0.69	12.269	<0.001
Composite Z-score for nerve conduction latency	–	0.49±1.17	-0.15±0.96	–0.07±0.90	–0.27±0.76	11.113	<0.001
Composite Z-score for nerve conduction amplitude	–	–0.39±1.05	0.13±0.97	–0.06±0.96	0.32±0.88	8.551	<0.001

Models	β	t	p	R² after correction
Comprehensive Z-score for PNCV
Model 0	0.270	5.299	<0.001	0.071
Model 1	0.194	3.391	0.001	0.134
Comprehensive Z-score for PNCL
Model 0	–0.218	–4.21	<0.001	0.045
Model 1	–0.166	–2.901	0.004	0.126
Comprehensive Z-score for PNCA
Model 0	0.178	3.409	0.001	0.029
Model 1	0.103	1.715	0.048	0.112

Model	Regression coefficient	Standard error	Wald	p-value	Odds ratio (OR)	95% CI
Model 0	–0.091	0.017	30.401	<0.001	0.913	0.884–0.943
Model 1	–0.089	0.017	27.275	<0.001	0.915	0.884–0.946
Model 2	–0.086	0.018	23.663	0.002	0.917	0.886–0.950
Model 3	–0.101	0.022	21.653	0.008	0.904	0.867–0.943

Indicator	Threshold	Sensitivity (%)	Specificity (%)	AUC (95% CI)	p
2h-CP (ng/mL)	5.05	74.64	68.18	0.717 (0.668‒0.763)	<0.001
Disease duration	6	55.07	69.09	0.646 (0.594‒0.696)	<0.001
Gluca30min	18.68	82.61	48.18	0.698 (0.648‒0.745)	<0.001

Faculdade de Medicina / USP Rua Dr Ovídio Pires de Campos, 225 - 6 and., 05403-010 São Paulo SP - Brazil, Tel.: (55 11) 2661-6235 - São Paulo - SP - Brazil
E-mail: clinics@hc.fm.usp.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] *Corresponding author. E-mail address:m13585229212@163.com (X. Wang).