Diabetic cardiac autonomic neuropathy: Do we have any treatment perspectives?

Table 1 N-terminal fragment of the prohormone brain natriuretic peptide level and lipid metabolism parameters after 3-mo of omega-3 polyunsaturated fatty acid therapy

Parameter	Patients with T2DM and CAN (n = 36)
	Control (n = 15)	ω-3 PUFA (n = 21)
	Group 1	Group 2
NT-proBNP	-3.0 ± 1.1	-6.8 ± 1.1a
LDL cholesterol	-8.3 ± 1.4	-12.8 ± 1.9
HDL cholesterol	4.1 ± 1.0	7.1 ± 0.5a
ТG	-8.3 ± 1.2	-35.4 ± 2.6c
TC	-6.7 ± 1.0	-8.2 ± 1.1

The results are presented as % change from baseline, (Δ%, Mean ± SEM);

^aP < 0.05,

^cP < 0.001. T2DM: Type 2 diabetes mellitus; CAN: Cardiac autonomic neuropathy; ω-3 PUFA: Omega-3 polyunsaturated fatty acid; NT-proBNP: N-terminal fragment of the prohormone brain natriuretic peptide; LDL cholesterol: Low density lipoprotein cholesterol; HDL cholesterol: High density lipoprotein cholesterol; ТG: Triglycerides; TC: Total cholesterol.

Table 2 Changes of the immunoreactive insulin, leptin, high reactive C-reactive protein and tumor necrosis factol alpha levels after 3-mo of treatment

Parameter	Patients with T2DM and CAN (n = 81)
	1st group	2nd group	3rd group	4th group	5th group
	(n = 15)	(n = 21)	(n = 12)	(n = 18)	(n = 15)
IRI	-6.8 ± 2.0	-10.3 ± 1.1	-12.7 ± 1.4a	-15.9 ± 1.6be	-20.9 ± 0.9cfij
Leptin	-7.1 ± 1.8	-15.8 ± 1.7b	-6.4 ± 1.4f	-16.3 ± 1.2ci	-18.4 ± 1.4ci
hsCRP	-7.2 ± 1.6	-14.8 ± 2.4a	-13.3 ± 2.1a	-15.2 ± 1.9b	-22.6 ± 1.6cehk
TNF-α	-6.1 ± 1.0	-14.1 ± 2.1b	-10.2 ± 1.6a	-14.7 ± 1.8c	-19.8 ± 1.6cdil

The results are presented as % change from baseline, (Δ%, Mean ± SEM);

^aP < 0.05,

^bP < 0.01,

^cP < 0.001 - compared to 1^st group;

^dP < 0.05,

^eP < 0.01,

^fP < 0.001 - compared to 2^nd group;

^hP < 0.01,

ⁱP < 0.001 - compared to 3^rd group;

^jP < 0.05,

^kP < 0.01,

^lP < 0.001 - compared to 4^th group. T2DM: Type 2 diabetes mellitus; CAN: Cardiac autonomic neuropathy; IRI: Immunoreactive insulin; hsCRP: High reactive C-reactive protein; TNF-α: Tumor necrosis factol alpha.

Table 3 Changes of the lipid metabolism parameters after 3-mo of treatment

Parameter	Patients with T2DM and CAN (n = 81)
	1st group	2nd group	3rd group	4th group	5th group
	(n = 15)	(n = 21)	(n = 12)	(n = 18)	(n = 15)
LDL cholesterol	-8.3 ± 1.4	-12.8 ± 1.9	-7.6 ± 1.0d	-14.2 ± 1.8ah	-33.1 ± 2.4cfil
HDL cholesterol	4.1 ± 1.0	7.1 ± 0.5a	5.7 ± 0.6	7.8 ± 0.7bg	13.9 ± 1.3cfil
ТG	-8.3 ± 1.2	-35.4 ± 2.6c	-13.3 ± 3.4f	-9.3 ± 1.1f	-27.9 ± 3.9chl
TC	-6.7 ± 1.0	-8.2 ± 1.1	-7.1 ± 1.2	-10.7 ± 1.3ag	-27.2 ± 1.9cfil

The results are presented as % change from baseline, (Δ%, Mean ± SEM);

^aP < 0.05,

^bP < 0.01,

^cP < 0.001 - compared to 1^st group;

^dP < 0.05,

^fP < 0.001 - compared to 2^nd group;

^gP < 0.05,

^hP < 0.01,

ⁱP < 0.001 - compared to 3^rd group;

^lP < 0.001 - compared to 4^th group. T2DM: Type 2 diabetes mellitus; CAN: Cardiac autonomic neuropathy; LDL cholesterol: Low density lipoprotein cholesterol; HDL cholesterol: High density lipoprotein cholesterol; ТG: Triglycerides; TC: Total cholesterol.

Table 4 Arterial stiffness parameters in patients with type 2 diabetes mellitus and cardiac autonomic neuropathy

Parameter	Control (n = 12)	Patients with T2DM without CVD and CAN (n = 12)	Patients with T2DM and CAN (n = 21)
	1st group	2nd group	3rd group
AIxao (%)	20.6 ± 1.71	26.7 ± 1.84a	33.7 ± 1.24ce
AIxbr (%)	-33.7 ± 2.86	-23.4 ± 1.91b	-7.9 ± 2.67cf
PWV (m/s)	7.2 ± 0.31	8.9 ± 0.25c	11.1 ± 0.39cf
AASI	0.3 ± 0.02	0.36 ± 0.02a	0.47 ± 0.03ce

Δ%, Mean ± SEM;

^aP < 0.05,

^bP < 0.01,

^cP < 0.001 - compared to 1^st group;

^eP < 0.01,

^fP < 0.001 - compared to 2^nd group. T2DM: Type 2 diabetes mellitus; CAN: Cardiac autonomic neuropathy; CVD: Cardiovascular diseases; AIxao: Aortha augmentation index; AIxbr: Brachial augmentation index; PWV: Pulse wave velocity; AASI: Ambulatory arterial stiffness index.

Table 5 Changes of day arterial stiffness parameters after 3 mo omega-3 polyunsaturated fatty acid therapy

	Patients with T2DM and CAN (n = 39)
	Groups	Baseline	After treatment	% change from baseline
AIxao (%)	Control group	30.4 ± 1.97	28.4 ± 1.68	-4.3% ± 4.76%
	Treatment group	32.0 ± 1.32	26. 4 ± 1.12b	-16.2% ± 3.12%
AIxbr (%)	Control group	-10.6 ± 3.37	-12.0 ± 3.11	-19.3% ± 12.14%
	Treatment group	-9.8 ± 2.76	-14.3 ± 2.84	-42.8% ± 9.0%
PWV (m/s)	Control group	10.2 ± 0.4	9.6 ± 0.4	-6.0% ± 2.21%
	Treatment group	11.0 ± 0.35	9.7 ± 0.39a	-11.6% ± 2.09%

The results are given as absolute values and as % change from baseline, (Δ%, Mean ± SEM);

^aP < 0.05,

^bP < 0.01, - compared to baseline. T2DM: Type 2 diabetes mellitus; CAN: Cardiac autonomic neuropathy; AIxao: Aortha augmentation index; AIxbr: Brachial augmentation index; PWV: Pulse wave velocity.

Table 6 Changes of night arterial stiffness parameters after 3 mo omega-3 polyunsaturated fatty acid therapy

	Patients with T2DM and CAN (n = 39)
	Groups	Baseline	After treatment	% change from baseline
AIxao (%)	Control group	33.2 ± 1.98	30.1 ± 1.27	-6.6% ± 4.15%
	Treatment group	36.6 ± 1.65	31.7 ± 1.23a	-11.2% ± 4.2%
AIxbr (%)	Control group	-4.2 ± 2.8	-5.9 ± 2.48	-10.0% ± 17.23%
	Treatment group	-1.6 ± 2.79	-10.4 ± 3.23a	-98.0% ± 18.1%
PWV (m/s)	Control group	10.9 ± 0.4	10.3 ± 0.36	-4.93% ± 1.41%
	Treatment group	11.3 ± 0.48	9.0 ± 0.44b	-18.9% ± 3.9%

The results are given as absolute values and as % change from baseline, (Δ%, Mean ± SEM);

^aP < 0.05,

^bP < 0.01, - compared to baseline. T2DM: Type 2 diabetes mellitus; CAN: Cardiac autonomic neuropathy; AIxao: Aortha augmentation index; AIxbr: Brachial augmentation index; PWV: Pulse wave velocity.