Predictors of High Cardiovascular Risk Among Nonobese Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease in a Chinese Population

Figures & data

Figure 1 Flow chart of study design and patient enrollment.

Table 1 Demographic and Clinical Characteristics of Non-Obese T2DM Patients by the Presence of NAFLD

Characteristic	Non-NAFLD (n=103)	NAFLD (n=142)	P-value
Age (year)	52(46,58)	54(47,58)	0.393
Male, n (%)	65(63.1)	75(52.8)	0.108
BMI (kg/m^2)	21.98±1.57	22.85±1.36	<0.001
WC (cm)	80.45±5.36	83.83±5.12	<0.001
HC (cm)	91.00(87.50,93.00)	91.80(89.00,94.00)	0.005
WHR	0.89±0.05	0.91±0.05	0.003
Men	0.90±0.05	0.92±0.04	0.015
Women	0.88±0.05	0.90±0.05	0.023
VFA (cm^2)	64.47±23.75	77.37±20.12	<0.001
SFA (cm^2)	131.91±27.34	153.58±32.04	<0.001
SBP (mmHg)	119±16	122±17	0.224
DBP (mmHg)	73±10	73±11	0.938
History of HT, n (%)	30(29.1)	61(43.0)	0.027
Smoke, n (%)	30(29.1)	29(20.4)	0.116
Course of T2DM (month)	88(28,126)	62(8,126)	0.098
FBG (mmol/L)	6.84(5.40,8.73)	6.99(5.83,9.17)	0.409
PBG (mmol/L)	15.26±4.81	15.00±4.33	0.713
FINS (pmol/L)	23.210(8.970,33.380)	33.825(23.203,47.415)	<0.001
PINS (pmol/L)	94.770(46.405,199.775)	140.400(78.310,274.200)	0.047
HOMA-IR	1.07(0.43,1.82)	1.66(1.10,2.87)	<0.001
TyG index	8.76±0.66	9.09±0.70	0.001
FC (pmol/L)	352.000(194.900,536.000)	500.450(321.800,714.725)	<0.001
PC (pmol/L)	918.050(503.800,1794.250)	1081.500(639.625,1702.750)	0.375
HbA1c (%)	9.7(7.4,11.5)	8.7(7.1,10.5)	0.023
ALT (U/L)	12.3(9.0,19.0)	17.0(12.5,25.7)	<0.001
AST (U/L)	14.0(12.2,17.3)	16.5(14.0,20.9)	<0.001
ALP (U/L)	67.0(57.0,81.0)	73.0(58.5,88.5)	0.063
γ-GT (U/L)	16.0(11.0,21.0)	19.0(14.0,28.0)	<0.001
BUN (mmol/L)	5.5(4.4,6.7)	5.2(4.4,6.5)	0.360
Cr (umol/L)	63.0(55.0,74.5)	61.0(51.0,73.8)	0.337
UA (umol/L)	270.3±72.7	292.8±91.4	0.045
TG (mmol/L)	1.17(0.82,1.53)	1.46(1.13,2.17)	<0.001
TC (mmol/L)	4.07±0.77	4.32±0.99	0.035
HDL-C (mmol/L)	1.07(0.88,1.23)	1.03(0.89,1.24)	0.715
LDL-C (mmol/L)	2.58(2.20,3.10)	2.48(1.99,2.96)	0.157
UA/Cr	10.75(6.85,28.52)	9.85(6.13,18.95)	0.295
UAP (dB/m)	221.097(214.246,230.140)	263.948(254.184,278.264)	<0.001
LSM (kPa)	5.484±1.289	5.490±1.035	0.970
FIB-4	0.968(0.754,1.286)	0.931(0.746,1.364)	0.930
APRI	0.18(0.13,0.22)	0.19(0.15,0.27)	0.010
CIMT > 1.0 mm, n (%)	28(34.1)	40(34.8)	0.926
Carotid plaque, n (%)	49(57.6)	54(46.6)	0.120
AIP	0.029±0.251	0.141±0.224	0.001
AI	2.760±0.787	3.044±0.989	0.021

Notes: Continuous values consistent with normal distribution are shown as mean ± SD, while non-normally distributed values are presented as median with IQR. Categorical values are shown as frequency and percentage (%).

Abbreviations: BMI, body mass index; WC, waist circumference; HC, hip circumference; WHR, waist-to-hip ratio; VFA, visceral fat area; SFA, subcutaneous fat area; SBP, systolic blood pressure; DBP, diastolic blood pressure; HT, hypertension; T2DM, type 2 diabetes; FBG, fasting blood glucose; PBG, postprandial blood glucose; FINS, Fasting insulin; PINS, postprandial insulin; HOMA-IR, homeostasis model assessment of insulin resistance; TyG index, triglyceride-glucose index; FC, fasting C-peptide; PC, postprandial C-peptide; HbA1c, glycosylated hemoglobin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; γ-GT, γ-glutamyl transpeptidase; BUN, blood urea nitrogen; Cr, creatinine; UA, uric acid; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; UACr, urinary microalbumin creatinine ratio; UAP, ultrasound attenuation parameter; LSM, liver stiffness measurement; APRI, AST to platelet ratio index; CIMT, carotid intima-media thickness; AIP, atherogenic index of plasma; AI, atherosclerosis index.

Table 2 Demographic and Clinical Characteristics of Non-Obese T2DM Patients with NAFLD by UAP

Characteristic	T1(n=47) UAP<256.97	T2(n=48) 256.97≤UAP<272.44	T3(n=47) UAP>272.44	P-value
Age (year)	55(46,61)	52(47,58)	53(47,58)	0.708
Male, n(%)	27(57.4)	27(56.3)	21(44.7)	0.391
BMI (kg/m^2)	22.90(21.70,23.60)	22.80(21.70,23.82)	23.30(22.70,23.90)^ab	0.015
WC (cm)	82.07±6.35	84.44±4.20^a	85.17±3.82^a	0.01
HC (cm)	91.00(87.70,94.00)	91.50(89.00,94.00)	92.00(90.00,94.00)	0.802
WHR	0.89±0.05	0.92±0.03^a	0.91±0.04^a	<0.001
VF (cm^2)	67.84±21.74	82.51±19.92^a	81.77±15.02^a	0.001
SF (cm^2)	143.18±35.88	155.50±30.88	161.61±26.94^a	0.030
SBP (mmHg)	121±17	121±18	123±14	0.730
DBP (mmHg)	72±11	73±12	74±9	0.548
History of HT, n(%)	20(42.6)	18(37.5)	23(48.9)	0.302
Smoke, n(%)	9(19.1)	12(25)	8(17)	0.606
Course of T2DM (month)	79(13,154)	50(4,126)	62(13,122)	0.732
FBG (mmol/L)	6.94(5.76,9.38)	6.97(5.84,9.75)	7.15(5.91,8.78)	0.976
PBG (mmol/L)	13.22±4.41	15.40±4.70^a	16.10±3.46^a	0.020
FINS (pmol/L)	26.590(11.970,41.585)	32.990(20.570,46.283)	42.660(29.905,68.515)^a	0.020
PINS (pmol/L)	99.660(49.765,177.350)	132.100(60.795,266.750)	170.000(133.000,402.000)^a	0.007
HOMA-IR	1.40(0.73,2.23)	1.62(0.99,3.00)	1.99(1.33,3.97)^a	0.048
TyG index	8.83±0.62	9.17±0.73^a	9.22±0.70^a	0.022
FC (pmol/L)	379.902±234.386	553.111±286.514^a	654.956±282.991^a	<0.001
PC (pmol/L)	854.391±612.068	1342.126±830.481^a	1532.263±730.221^a	<0.001
HbAlc (%)	8.9(7.5,10.4)	8.7(7.0,10.6)	8.1(7.0,10.6)	0.829
ALT (U/L)	16.0(11.0,22.0)	17.0(11.2,22.4)	19.0(13.7,28.3)	0.154
AST (U/L)	16.1(12.2,20.0)	16.0(13.4,19.1)	17.1(14.2,21.4)	0.392
ALP (U/L)	77.0(64.0,100.0)	75.0(55.0,87.0)	70.0(58.0,83.0)	0.452
γ-GT (U/L)	16.0(12.0,24.0)	21.5(14.0,28.8)	22.0(17.0,31.0)^a	0.012
BUN (mmol/L)	5.7(4.8,6.8)	5.1(4.3,6.3)	5.0(4.3,6.1)	0.138
Cr (umol/L)	65.0(56.0,75.0)	59.0(51.0,73.6)	60.0(49.0,75.0)	0.430
UA (umol/L)	292.9±73.4	280.1±94.7	305.3±103.5	0.419
TG (mmol/L)	1.37(0.93,1.89)	1.40(1.16,2.41)	1.63(1.21,2.33)^a	0.031
TC (mmol/L)	4.35±1.06	4.40±0.99	4.21±0.94	0.648
HDL-C (mmol/L)	1.05(0.93,1.19)	1.14(0.91,1.26)	0.97(0.87,1.20)	0.272
LDL-C (mmol/L)	2.64±0.93	2.59±0.88	2.50±0.68	0.650
UA/Cr	8.90(5.80,22.55)	10.55(6.30,18.95)	9.85(6.55,17.65)	0.893
Proteinuria, n(%)	5(10.6)	3(6.3)	4(8.5)	0.744
UAP (dB/m)	250.801(242.931,254.195)	263.947(261.882,267.097)^a	282.375(278.230,290.388)^ab	<0.001
LSM (kPa)	5.272±0.921	5.322±0.930	5.915±1.159^ab	0.012
FIB-4	0.937(0.755,1.419)	0.967(0.807,1.397)	0.885(0.646,1.216)	0.224
APRI	0.18(0.15,0.28)	0.20(0.15,0.25)	0.19(0.15,0.27)	0.990
CIMT > 1.0 mm, n (%)	10(27.8)	17(39.5)	13(36.1)	0.308
Carotid plaque, n (%)	20(55.6)	22(50.0)	12(33.3)	0.092
AIP	0.084±0.216	0.123±0.245	0.225±0.190^a	0.019
AI	2.879±1.039	2.869±0.944	3.379±0.912^ab	0.027

Notes: ^aP<0. 05 compared with Tertile 1, ^bP<0. 05 compared with Tertile 2.

Table 3 Univariate and Multivariate Logistic Regression Analyses of Risk Factors of Cardiovascular Disease in Non-Obese T2DM Patients with NAFLD

Exposure	Univariate			Multivariate
	OR	(95% CI)	P-value	OR	(95% CI)	P-value
Age (year)	1.114	(1.051–1.180)	<0.001	1.153	(1.016–1.308)	0.027
BMI (kg/m^2)	0.996	(0.735–1.349)	0.978
WC (cm)	0.993	(0.923–1.068)	0.855
HC (cm)	0.934	(0.851–1.024)	0.147
WHR	43.269	(0.058–32,211.878)	0.264
VF (cm^2)	1.006	(0.989–1.023)	0.493
SF (cm^2)	1.001	(0.989–1.013)	0.913
SBP (mmHg)	1.033	(1.008–1.058)	0.009	1.068	(1.017–1.121)	0.008
DBP (mmHg)	1.007	(0.972–1.043)	0.713
Course of T2DM (month)	1.007	(1.002–1.012)	0.011	1.002	(0.993–1.011)	0.625
FBG (mmol/L)	0.892	(0.779–1.021)	0.098
PBG (mmol/L)	1.002	(0.913–1.101)	0.958
FINS (pmol/L)	0.998	(0.985–1.012)	0.789
PINS (pmol/L)	0.999	(0.996–1.003)	0.669
HOMA-IR	0.952	(0.778–1.166)	0.637
TyG index	0.775	(0.431–1.392)	0.393
FC (pmol/L)	1.001	(0.999–1.002)	0.442
PC (pmol/L)	1.000	(1.000–1.000)	0.952
HbAlc (%)	0.918	(0.768–1.097)	0.345
Hb (g/L)	0.983	(0.957–1.009)	0.197
Platelet count (10^9/L)	1.000	(0.994–1.007)	0.884
ALT (U/L)	1.004	(0.991–1.017)	0.568
AST (U/L)	1.013	(0.989–1.037)	0.303
ALP (U/L)	1.003	(0.996–1.010)	0.355
γ-GT (U/L)	1.005	(0.997–1.013)	0.234
BUN (mmol/L)	1.080	(0.851–1.371)	0.527
Cr (umol/L)	1.019	(0.997–1.041)	0.091
UA (umol/L)	1.003	(0.999–1.007)	0.196
TG (mmol/L)	0.780	(0.550–1.106)	0.164
TC (mmol/L)	1.149	(0.778–1.696)	0.484
HDL-C (mmol/L)	2.107	(0.481–9.238)	0.323
LDL-C (mmol/L)	4.761	(2.109–10.746)	<0.001	10.191	(2.539–40.916)	0.001
UAP (dB/m)	0.989	(0.965–1.014)	0.376
LSM (kPa)	0.786	(0.613–1.007)	0.057
FIB-4	2.922	(1.149–7.434)	0.024	1.603	(0.187–13.705)	0.667
APRI	2.768	(0.380–20.152)	0.315
AIP	20.094	(2.129–189.619)	0.009	46.211	(1.148–1860.121)	0.042
AI	0.972	(0.637–1.484)	0.896
Male	0.746	(0.347–1.603)	0.453
History of HT	3.312	(1.492–7.350)	0.003	2.937	(0.723–11.930)	0.132
Smoke	0.747	(0.291–1.920)	0.545

Figure 2 Risk scores of cardiovascular disease in non-obese T2DM patients with NAFLD.

Figure 3 Receiver operator characteristic (ROC) curve that predicts cardiovascular disease for non-obese T2DM patients with NAFLD.