Effects of sarpogrelate, eicosapentaenoic acid and pitavastatin on arterioslcerosis obliterans-related biomarkers in patients with type 2 diabetes (SAREPITASO study)

Figures & data

Figure 1 Schema of study protocol.

Abbreviations: ABI, ankle branchial pressure index; BT, blood test; EPA, eicosapentaenoic acid; IC, informed consent; M, months; ST, special test.

Table 1 Demographic and clinical characteristics of the T2DM patients and nondiabetic controls

	Controls (n=50)	T2DM (n=84)	P-value
Men/women (no.)	29/21	48/36	NS
Age (years)	62±13	74±10	<0.05
ABI (ratio)	1.13±0.25	0.93±0.23	<0.05
BMI (kg/m^2)	22.1±4.1	24.5±3.9	<0.05
FBG (mg/dL)	108±37	129±42	<0.01
HbA1c (%)	5.3±1.9	7.2±1.2	<0.001
TC (mg/dL)	221±47	212±41	NS
HDL-C (mg/dL)	53±16	52±14	NS
LDL-C (mg/dL)	129±39	126±37	NS
Risk factor, n (%)
Current smoking complication, n (%)	5 (10.0)	11 (13.1)	NS
Angina pectoris	7 (14.0)	15 (17.9)	NS
Heart failure	2 (4.0)	8 (9.5)	NS
Cerebral infarction	4 (8.0)	9 (10.7)	NS
Hypertension medication, n (%)	11 (22.0)	24 (28.6)	NS
ARBs	10 (20.0)	19 (22.6)	NS
Ca antagonists	5 (10.0)	14 (16.7)	NS
Aspirin	7 (14.0)	13 (15.5)	NS
Sulfonylureas	0 (0.0)	52 (61.9)	<0.01
α-GI	0 (0.0)	56 (66.7)	<0.001
DPP4-I	0 (0.0)	47 (55.9)	<0.01
Insulin therapy	0 (0.0)	41 (48.8)	<0.01

Notes: Data are shown as mean±SD. P-value, T2DM patients vs nondiabetic controls.

Abbreviations: α-GI, α-glucosidase inhibitor; ABI, ankle brachial pressure index; ARB, angiotensin II receptor blocker; BMI, body mass index; DPP4-I, DPP4 inhibitor; FBG, fasting blood glucose; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NS, not significant; T2DM, type 2 diabetes mellitus; TC, total cholesterol.

Table 2 Multiple regression analysis of ABI in T2DM patients

Analysis	Univariate		Multivariate
	β	P-value	β	P-value
Age (years)	0.2247	0.08956
Sex (men)	−0.1128	0.31257
BMI (kg/m^2)	−0.3395	0.00343*	−0.2139	0.07914
HbA1c (%)	−0.4216	0.00287*	−0.2969	0.04972*
UA (mg/dL)	0.0219	0.56475
TC (mg/dL)	−0.1869	0.11239
HDL (mg/dL)	0.2418	0.09774
LDL (mg/dL)	−0.3125	0.00963*	−0.2537	0.05649
CRP (mg/dL)	−0.4129	0.00166*	−0.3218	0.01024*
IL-6 (pg/mL)	0.1433	0.13207
MCP-1 (pg/mL)	−0.3127	0.01236	−0.2027	0.08961
sE-selectin (ng/mL)	−0.2686	0.04423*	−0.1366	0.09897
sVCAM-1 (ng/mL)	−0.2762	0.04124*	−0.1966	0.09567
PDMP (U/mL)	−0.5029	0.00012*	−0.3984	0.01356*
PAI-1 (ng/mL)	−0.5244	0.01029*	−0.4313	0.01129*
Adiponectin (μg/mL)	0.3235	0.02867*	0.2047	0.09833

Note:

* P<0.05.

Abbreviations: ABI, ankle brachial pressure index; BMI, body mass index; CRP, C-reactive protein; HbA1c, hemoglobin A1c; HDL, high-density lipoprotein; IL-6, interleukin-6; LDL, low-density lipoprotein; MCP-1, monocyte chemoattractant protein-1; PAI-1, plasminogen activator inhibitor-1; PDMP, platelet-derived microparticle; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule 1; T2DM, type 2 diabetes mellitus; TC, total cholesterol; UA, uric acid.

Figure 2 Changes in ABI, BMI, HbA1c, IL-6 and MCP-1 in response to treatment with PS or PE in T2DM patients.

Notes: Bars show the mean±SD. 0: before; M: months (after). P-values are for comparison with each baseline parameter (0 vs 6 and 12 months). ANOVA (PS vs PE).
Abbreviations: ABI, ankle brachial pressure index; ANOVA, analysis of variance; BMI, body mass index; HbA1c, hemoglobin A1c; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; NS, nonsignificant; PE, pitavastatin with eicosapentaenoic acid; PS, pitavastatin with sarpogrelate; T2DM, type 2 diabetes mellitus.

Figure 3 Changes in sE-selectin, sVCAM-1, PAI-1, PDMP and adiponectin in response to treatment with PS or PE of T2DM patients.

Notes: Bars show the mean±SD. 0: before M: months (after). P-values are for comparison with each baseline parameter (0 vs 6 and 12 months). ANOVA (PS vs PE).
Abbreviations: ANOVA, analysis of variance; NS, nonsignificant; PAI-1, plasminogen activator inhibitor-1; PDMP, platelet-derived microparticle; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule 1; PE, pitavastatin with eicosapentaenoic acid; PS, pitavastatin with sarpogrelate; T2DM, type 2 diabetes mellitus.

Table 3 Demographic and clinical characteristics of the PS and PE groups

	PS (n=38)	PE (n=38)	P-value
Men/women (no.)	23/15	24/14	NS
Age (years)	72±10	76±9	NS
ABI (ratio)	0.94±0.19	0.93±0.21	NS
BMI (kg/m^2)	24.8±5.5	24.3±3.1	NS
FBG (mg/dL)	123±39	127±44	NS
HbA1c (%)	7.3±1.3	7.1±0.9	NS
TC (mg/dL)	203±36	216±45	NS
HDL-C (mg/dL)	54±12	50±16	NS
LDL-C (mg/dL)	124±34	127±39	NS
Risk factor, n (%)
Current smoking complication, n (%)	4(10.5)	6 (15.8)	NS
Angina pectoris	8 (21.1)	7 (18.4)	NS
Heart failure	4 (10.5)	3 (7.9)	NS
Cerebral infarction	4 (10.5)	4 (10.5)	NS
Hypertension medication, n (%)	10 (26.3)	13 (34.2)	NS
ARBs	8 (21.1)	8 (21.1)	NS
Ca antagonists	6(15.8)	5 (13.2)	NS
Aspirin	6 (15.8)	5 (13.2)	NS
Sulfonylureas	25 (65.8)	26 (68.4)	NS
α-GI	24 (63.2)	23 (60.5)	NS
DPP4-I	28 (73.7)	27 (71.1)	NS
Insulin therapy	19 (50.0)	22 (57.9)	NS

Notes: Data are shown as mean±SD. P-value, PE vs PS.

Abbreviations: α-GI, α-glucosidase inhibitor; ABI, ankle brachial pressure index; ARB, angiotensin II receptor blocker; BMI, body mass index; DPP4-I, DPP4 inhibitor; FBG, fasting blood glucose; HbA1c, hemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; NS, not significant; PE, pitavastatin with eicosapentaenoic acid; PS, pitavastatin with sarpogrelate; TC, total cholesterol.