Anti-atherosclerotic effects of sitagliptin in patients with type 2 diabetes mellitus

Figures & data

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

	Nondiabetes	Diabetes	P-value
n	72	113
Men/women (n)	39/33	60/53
Age (years)	62±6	63±8	NS
BMI (kg/m^2)	26.1±3.9	27.9±4.6	NS
FBG (mg/dL)	102±21	239±57	<0.001
HbA1c(%)	5.1±0.9	7.6±1.5	<0.01
TC (mg/dL)	220±28	236±37	NS
HDL-C (mg/dL)	47±12	44±13	NS
LDL-C (mg/dL)	133±32	141±42	NS
Complications, n (%)
Angina pectoris	9 (12.5)	16 (14.2)	NS
Heart failure	5 (6.9)	7 (6.2)	NS
Cerebral infarction	4 (5.6)	10 (8.8)	NS
Medication, n (%)
Statins	21 (29.2)	27 (23.9)	NS
ARBs	30 (41.7)	39 (34.5)	NS
Ca antagonists	21 (29.2)	26 (23.0)	NS
Aspirin	7 (9.7)	13 (11.5)	NS

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

Abbreviations: BMI, body mass index; FBG, fasting blood glucose; HbA_1c, hemoglobin A_1c; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ARBs, angiotensin II receptor blockers; NS, not significant; SD, standard deviation.

Table 2 Plasma levels of soluble factors, chemokines, and adiponectin in the nondiabetic controls and diabetic patients

	Nondiabetes	Diabetes	P-value
n	72	113
BUN (mg/dL)	18.9±8.8	26.6±14.9	<0.05
S-CRTN (mg/dL)	0.62±0.19	1.95±1.07	<0.05
AST (mg/dL)	30±12	34±15	NS
ALT (mg/dL)	28±14	32±19	NS
T-BIL (mg/dL)	0.71±0.34	0.87±0.51	NS
LD (U/L)	218±66	232±82	NS
CRP (mg/dL)	0.82±0.79	1.24±0.85	<0.05
MCP-1 (pg/mL)	344±82	566±129	<0.01
sP-selectin (ng/mL)	232±73	278±104	<0.05
sE-selectin (ng/mL)	72±39	95±48	<0.05
sVCAM-1 (ng/mL)	632±139	924±148	<0.01
sRAGE (pg/mL)	1,030±478	1,220±670	NS
Adiponectin (μg/mL)	4.54±1.01	2.52±1.43	<0.01

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

Abbreviations: BUN, blood urea nitrogen; S-CRTN, serum creatinine; AST, aspartate aminotransferase; ALT, alanine transaminase; T-BIL, total bilirubin; LD, lactate dehydrogenase; CRP, C-reactive protein; MCP-1, monocyte chemoattractant protein-1; sP-selectin, soluble P-selectin; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule-1; sRAGE, soluble receptor for advanced glycation end product; NS, not significant; SD, standard deviation.

Table 3 Multiregression analysis on HbA_1c in diabetic patients

Analysis	Univariate		Multivariate
	β	P-value	β	P-value
Age (years)	0.2155	0.08793
Sex (men)	−0.0775	0.36417
BMI (kg/m^2)	0.3847	0.00917*	0.2755	0.73116
Angina pectoris (%)	0.3277	0.04726*	0.2311	0.10339
Heart failure (%)	0.1753	0.26354
Cerebral infarction (%)	0.2346	0.06617
TC (mg/dL)	−0.0896	0.25331
HDL-C (mg/dL)	−0.1279	0.36972
LDL-C (mg/dL)	0.4533	0.00172*	0.3159	0.05379
CRP (mg/dL)	0.2374	0.07223
sP-selectin (ng/mL)	0.4377	0.00188*	0.3284	0.04549*
sE-selectin (ng/mL)	0.3982	0.00774*	0.2863	0.06127
sVCAM-1 (ng/mL)	0.4328	0.00196*	0.3218	0.04673*
MCP-1 (pg/mL)	0.5985	0.00017*	0.4233	0.01163*
sRAGE (pg/mL)	−0.3699	0.01029*	−0.2611	0.07356
Adiponectin (μg/mL)	−0.6172	<0.00001*	−0.5672	0.00234*

Note:β indicates standardized regression coefficients.

* indicates statical significance (P<0.05)

Abbreviations: HbA_1c, hemoglobin A_1c; BMI, body mass index; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CRP, C-reactive protein; sP-selectin, soluble P-selectin; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1; sRAGE, soluble receptor for advanced glycation end product.

Figure 1 Plasma concentrations of sP-selectin (A), sE-selectin (B), sVCAM-1 (C), MCP-1 (D), sRAGE (E), and adiponectin (F) before and after sitagliptin treatment in diabetic patients.

Notes: Data are shown as mean ± SD. P-value, 0 versus 3 or 6 months (M).
Abbreviations: sP-selectin, soluble P-selectin; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1; sRAGE, soluble receptor for advanced glycation end product; NS, not significant; SD, standard deviation.

Figure 2 Changes in sP-selectin (A), sE-selectin (B), sVCAM-1 (C), MCP-1 (D), sRAGE (E), and adiponectin (F) in response to treatment with sitagliptin of patients with type 2 diabetes with and without significant improvements in adiponectin.

Notes: Responder: with a significant improvement of adiponectin. Nonresponder: without a significant improvement of adiponectin. Bars show the mean ± SD. 0, before 3 and 6 months (M) after. P-values are for comparison with each baseline parameter (0 vs 3 and 6 M). ANOVA: nonresponder versus responder.
Abbreviations: sP-selectin, soluble P-selectin; ANOVA, analysis of variance; NS, not significant; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule-1; MCP-1, monocyte chemoattractant protein-1; sRAGE, soluble receptor for advanced glycation end product; SD, standard deviation.