High TNF-alpha plasma levels and macrophages iNOS and TNF-alpha expression as risk factors for painful diabetic neuropathy

Figures & data

Table 1 Characteristics of diabetic neuropathy patients

Variable	N	Range	Mean ± SD
Age (years)	110	37–65	54.11 ± 7.64
Gender
Women	61
Men	49
Duration of DM (years)	110	2–10	5.30 ± 3.05
PDN
Yes	59
No	51
Fasting blood sugar (mg %)	110	65–363	167 ± 70
Blood sugar 2 hours pp (mg %)	110	102–588	255 ± 105
HbA1C (%)	110	3.30–18.60	9.69 ± 3.49
Plasma TNF-α (pg/mL)	110	5.40–56.64	15.06 ± 7.01
TNF-α expression (%)	110	0–40	12.43 ± 10.36
iNOS expression (%)	110	0–38	9.22 ± 9.33

Abbreviations: DM, type 2 diabetes; HbA_1c, glycosylated hemoglobin; iNOS, inducible nitric oxide synthase; pp, post prandial; SD, standard deviation; TNF-α, tumor necrosis factor alpha.

Table 2 Comparison of clinical data of painful DN (cases) and painless DN (controls)

Characteristics	Case mean ± SD	Control mean ± SD	P
Age (years)	53.97 ± 8.26	54.27 ± 6.94	0.834
Duration of diabetes (years)	5.31 ± 3.13	5.29 ± 2.99	0.985
Fasting blood sugar (mg %)	168.96 ± 73.02	165.31 ± 69.14	0.789
Blood sugar 2 hours pp (mg %)	259.37 ± 109.51	251.96 ± 100.77	0.714
HbA1C (%)	10.40 ± 3.61	8.88 ± 3.18	0.023a
Plasma TNF-α (pg/mL)	17.44 ± 8.23	12.30 ± 3.76	<0.001a
iNOS expression (%)	12.18 ± 10.27	5.80 ± 6.41	<0.001a
TNF-α expression (%)	16.15 ± 11.05	8.13 ± 7.56	<0.001a

a Note: Statistically significant.

Abbreviations: DN, diabetic neuropathy; HbA_1C, glycosylated hemoglobin; iNOS, inducible nitric oxide synthase; pp, post prandial; SD, standard deviation; TNF-α, tumor necrosis factor alpha.

Figure 1 Scatter plots illustrating plasma TNF-α levels, iNOS and TNF-α expression in patients with Painless DN (n = 51), mild PDN (n = 34) and severe PDN (n = 25). The short horizontal line marks median values. (A) Patients with severe PDN had higher plasma TNF-α levels than patients with mild PDN (P < 0.001) and Painless DN (P < 0.001) (B) Patients with severe PDN had higher iNOS expression than patients with mild PDN (P < 0.001) and Painless DN (P < 0.001). (C) Patients with severe PDN had higher plasma TNF-α levels than patients with mild PDN (P < 0.001) and Painless DN (P < 0.001). In patients with PDN plasma TNF-α levels were 1.4 (P < 0.05), iNOS expression was 2.1 (P < 0.05), and TNF-α expression were 1.98 (P < 0.05) fold higher than in Painless DN.

Abbreviations: PDN, painful diabetic neuropathy; TNF-α, tumor necrosis factor alpha; HbA_1C, glycosylated hemoglobin; iNOS, inducible nitric oxide synthase; pp, post prandial.

Table 3 Correlation between pain intensity and some risk factors of painful diabetic neuropathy

Variable	Pain intensity
	R	P
Age	−0.144	0.275
Duration of diabetes	−0.101	0.448
Fasting blood sugar	0.196	0.136
Blood sugar 2 hours post prandial	0.177	0.180
HbA1C	0.138	0.298
Plasma TNF-α	0.330	0.011a
iNOS expression	0.284	0.029a
TNF-α expression	0.275	0.035a

a Note: Statistically significant.

Abbreviations: TNF-α, tumor necrosis factor alpha; HbA_1C, glycosylated hemoglobin; iNOS, inducible nitric oxide synthase.

Figure 2 Pathophysiological relationship between TNF-α, iNOS, and painful diabetic neuropathy.

Abbreviations: eNOS, endothelial nitric oxide synthase; NFκB, nuclear factor kappa beta; iNOS, inducible nitric oxide synthase; NO, nitric oxide; PG, prostaglandins; TNF-α, tumor necrosis factor alpha.