Product of C-reactive protein and fasting C-peptide indicates cardiovascular risk in type 2 diabetes: A real-world study

Table 1 Characteristics of patients with type 2 diabetes mellitus according to the C-reactive protein-fasting C-peptide product quartiles

Variables	Q1 (n = 1937)	Q2 (n = 2429)	Q3 (n = 2403)	Q4 (n = 1717)	P value1	P value2
CRP-FCP product	< 0.73	0.73-2.30	2.31-6.86	> 6.86	-	-
Male	1141 (58.9)	1389 (57.2)	1274 (53.0)	857 (49.9)	< 0.001	< 0.001
Age (years)	58 ± 12	59 ± 12	59 ± 13	60 ± 13	< 0.001	< 0.001
DD (months)	108 (45-168)	96 (36-156)	84 (24-132)	72 (24-132)	< 0.001	< 0.001
Hypertension	821 (42.4)	1231 (50.7)	1385 (57.6)	1098 (63.9)	< 0.001	< 0.001
Obesity	455 (23.5)	1027 (42.3)	1327 (55.2)	1101 (64.1)	< 0.001	< 0.001
Alcohol	330 (17.0)	404 (16.6)	401 (16.7)	250 (14.7)	0.169	0.652
Smoking	575 (29.7)	757 (31.2)	733 (30.5)	474 (27.6)	0.085	0.019
APAs	956 (49.4)	1227 (50.5)	1191 (49.6)	860 (50.1)	0.866	0.756
AHAs	739 (38.2)	1114 (45.9)	1298 (54.0)	1018 (59.3)	< 0.001	< 0.001
LLD	587 (30.3)	966 (39.8)	1078 (44.9)	722 (42.1)	< 0.001	< 0.001
SBP (mmHg)	130 ± 18	131 ± 17	134 ± 17	135 ± 17	< 0.001	< 0.001
DBP (mmHg)	79 ± 9	80 ± 9	81 ± 9	81 ± 9	< 0.001	< 0.001
WC (cm)	84.1 ± 9.6	88.7 ± 9.4	91.8 ± 9.7	94.2 ± 10.1	< 0.001	< 0.001
BMI (kg/m2)	22.94 ± 2.97	24.55 ± 3.07	25.62 ± 3.26	26.52 ± 3.58	< 0.001	< 0.001
WBC (× 109/L)	5.7 (4.8-6.6)	6.0 (5.1-7.1)	6.3 (5.4-7.4)	6.7 (5.6-8.0)	< 0.001	0.001
FPG (mmol/L)	7.2 (5.8-9.3)	7.5 (6.2-9.6)	7.9 (6.5-9.9)	8.4 (6.8-10.3)	< 0.001	0.008
2h PPG (mmol/L)	12.6 (9.4-16.0)	13.3 (10.1-16.6)	13.6 (10.7-16.9)	14.2 (11.0-17.4)	< 0.001	< 0.001
HbA1C (%)	9.21 ± 2.54	8.84 ± 2.24	8.87 ± 2.17	8.86 ± 2.01	< 0.001	< 0.001
HbA1C (mmol/mol)	77 ± 28	73 ± 25	73 ± 24	73 ± 22	< 0.001	< 0.001
2h C-P (ng/mL)	2.68 (1.37-4.87)	4.46 (2.68-7.17)	5.77 (3.60-8.75)	7.32 (4.89-9.91)	< 0.001	< 0.001
TG (mmol/L)	1.01 (0.74-1.40)	1.42 (1.01-2.09)	1.69 (1.17-2.46)	1.75 (1.26-2.58)	< 0.001	< 0.001
TC (mmol/L)	4.70 ± 1.06	4.78 ± 1.18	4.9 ± 1.23	4.84 ± 1.16	< 0.001	< 0.001
HDL-C (mmol/L)	1.29 ± 0.37	1.13 ± 0.29	1.08 ± 0.28	1.03 ± 0.25	< 0.001	< 0.001
LDL-C (mmol/L)	2.96 ± 0.92	3.04 ± 0.92	3.075 ± 0.94	3.08 ± 0.95	< 0.001	0.320
ALT (U/L)	17 (13-24)	19 (14-27)	22 (15-33)	24 (15-37)	< 0.001	< 0.001
SUA (μmol/L)	282 (237-335)	308 (257-368)	325 (271-382)	339 (282-401)	< 0.001	< 0.001
UAE (mg/24 hours)	9.4 (6.1-20.2)	10.5 (6.6-24.4)	12.0 (7.2-33.3)	16.4 (8.2-52.5)	< 0.001	0.007
eGFR (mL/minute/1.73 m2)	115 (96-138)	111 (94-133)	109 (90-132)	105 (82-129)	< 0.001	< 0.001

¹P values for trend from unadjusted models.

²P values for trend from models adjusted for age and sex.

Values are expressed as the mean ± SD, or median with interquartile range, or percentages. P values indicate P values for trend across quartiles of the C-reactive protein-fasting C-peptide product. CRP: C-reactive protein; FCP: Fasting C-peptide; DD: Duration of diabetes; APAs: Antiplatelet agents; AHAs: Antihypertensive agents; LLDs: Lipid-lowering drugs; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; WC: Waist circumference; BMI: Body mass index; WBC: White blood cell count; FPG: Fasting plasma glucose; 2h PPG: 2-hour postprandial plasma glucose; HbA1c: Glycosylated hemoglobin; 2h C-P: 2-hour postprandial C-peptide; TG: Total triglycerides; TC: Total cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; ALT: Alanine aminotransferase; SUA: Serum uric acid; UAE: Urinary albumin excretion; eGFR: Estimated glomerular filtration rate.

Table 2 Associations of C-reactive protein, fasting C-peptide, and C-reactive protein-fasting C-peptide product with cardiovascular, cerebrovascular, and cardio-cerebrovascular events, OR (95%CI)

	CVEs	P value	CBVEs	P value	CCBVEs	P value
CRP
Model 1	1.130 (0.997-1.281)	0.056	1.351 (1.241-1.470)	< 0.001	1.286 (1.194-1.384)	< 0.001
Model 2	1.113 (0.979-1.265)	0.102	1.246 (1.141-1.360)	< 0.001	1.213 (1.121-1.311)	< 0.001
Model 3	1.049 (0.920-1.196)	0.475	1.182 (1.081-1.293)	< 0.001	1.155 (1.066-1.251)	< 0.001
Model 4	1.055 (0.919-1.212)	0.445	1.180 (1.079-1.291)	< 0.001	1.152 (1.061-1.250)	0.001
Model 5	1.042 (0.896-1.212)	0.594	1.176 (1.062-1.302)	0.002	1.146 (1.047-1.254)	0.003
Model 6	1.176 (0.987-1.402)	0.070	1.149 (1.026-1.287)	0.016	1.155 (1.045-1.277)	0.005
FCP
Model 1	1.187 (1.058-1.332)	0.003	0.998 (0.925-1.077)	0.960	1.071 (1.002-1.146)	0.045
Model 2	1.339 (1.193-1.503)	< 0.001	1.026 (0.948-1.111)	0.526	1.141 (1.063-1.226)	< 0.001
Model 3	1.248 (1.106-1.408)	< 0.001	0.977 (0.898-1.063)	0.589	1.094 (1.016-1.178)	0.017
Model 4	1.233 (1.088-1.398)	0.001	0.972 (0.893-1.058)	0.514	1.071 (0.993-1.155)	0.076
Model 5	1.291 (1.127-1.480)	< 0.001	1.022 (0.929-1.124)	0.658	1.145 (1.053-1.244)	0.001
Model 6	1.190 (1.009-1.403)	0.039	1.100 (0.922-1.311)	0.290	1.212 (1.054-1.394)	0.007
CRP-FCP product
Model 1	1.017 (1.007-1.028)	0.001	1.021 (1.014-1.028)	< 0.001	1.023 (1.016-1.029)	< 0.001
Model 2	1.018 (1.008-1.029)	< 0.001	1.015 (1.008-1.023)	< 0.001	1.020 (1.013-1.028)	< 0.001
Model 3	1.013 (1.002-1.024)	0.019	1.011 (1.003-1.019)	0.005	1.014 (1.007-1.022)	< 0.001
Model 4	1.016 (1.005-1.027)	0.005	1.011 (1.003-1.019)	0.006	1.016 (1.008-1.023)	< 0.001
Model 5	1.018 (1.006-1.030)	0.003	1.012 (1.004-1.021)	0.004	1.018 (1.010-1.026)	< 0.001
Model 6	1.014 (1.001-1.027)	0.041	1.014 (1.004-1.024)	0.006	1.017 (1.009-1.026)	< 0.001

Model 1: Unadjusted; Model 2: Adjusted for age, sex, duration of diabetes; Model 3: Further adjusted for smoking, alcohol drinking, obesity, hypertension; Model 4: Further adjusted for lipid-lowering drugs, antihypertensive agents, antiplatelet agents; Model 5: Further adjusted for systolic blood pressure, diastolic blood pressure, waist circumference, body mass index; Model 6: Further adjusted for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total triglycerides, estimated glomerular filtration rate, serum uric acid, urinary albumin excretion, fasting plasma glucose, postprandial plasma glucose, glycosylated hemoglobin A1c, white blood cell, 2h postprandial C-peptide. CRP: C-reactive protein; FCP: Fasting C-peptide; CVEs: Cardiovascular events; CBVEs: Cerebrovascular events; CCBVEs: Cardio-cerebrovascular events.