Associations of Metabolic/Obesity Phenotypes with Insulin Resistance and C-Reactive Protein: Results from the CNTR Study

Figures & data

Table 1 Baseline Characteristics of the Study Participants (N = 1113)

Characteristics	All (n = 1113)	Obesity(n=463)		p	Non-Obesity(n=650)		p
		MHO (n = 94)	MUO (n = 369)		MHNO (n = 233)	MUNO (n = 417)
Age,mean(SD;years)	46.55(12.89)	40.85(12.03)	47.07(11.60)	<0.001	40.20(12.80)	50.92(12.31)	<0.001
Sex, n (%)
Male	728(65.4%)	45(47.9%)	277(75.1%)		119(51.1%)	287(68.8%)
Female	385(34.6%)	49(52.1%)	92(24.9%)	<0.001	114(48.9%)	130(31.2%)	<0.001
zygosity, n (%)
MZ	688(61.8%)	49(52.1%)	228(61.8%)		134(57.5%)	277(66.4%)
DZ	425(38.2%)	45(47.9%)	186(38.2%)	0.113	99(42.5%)	140(33.6%)	0.030
Place,n (%)
Qingdao	218(19.6%)	16(17.0%)	96(26.0%)		29(12.5%)	77(18.5%)
Jiangsu	437(39.2%)	37(39.4%)	133(36.0%)	0.203	94(40.3%)	173(41.5%)	0.211
Sichuan	122(11.0%)	12(12.8%)	94(40.3%)	0.145	36(15.5%)	37(8.9%)	0.009
Zhejiang	336(30.2%)	29(30.9%)	173(41.5%)	0.196	74(31.8%)	130(31.2%)	0.147
Smoking, n (%)
Never smoker	621(56.2%)	71(75.5%)	170(46.6%)		160(69.3%)	220(53.1%)
Current smoker	362(32.8%)	17(18.1%)	146(40.0%)	<0.001	56(24.2%)	143(34.5%)	0.016
Former smoker	121(11.0%)	6(6.4%)	49(13.4%)	0.005	15(6.5%)	51(12.3%)	0.003
Drinking, n (%)
Never drinker	715(64.8%)	77(81.9%)	222(61.2%)		177(76.6%)	239(57.5%)
Current drinker	365(33.1%)	15(16.0%)	132(36.4%)	0.002	50(21.7%)	168(40.4%)	<0.001
Former drinker	24(2.2%)	2(2.1%)	9(2.5%)	0.443	4(1.7%)	9(2.2%)	0.932
Physical activities, mean (SD;MET/week)	5986.2(6797.2)	6634.7(6961.8)	5649.8(6565.7)	0.564	6335.5(6605.9)	5928.3(7063.8)	0.526
BMI,mean(SD;kg/m^2)	24.48(3.62)	27.10(2.81)	27.44(2.83)	0.071	21.58(2.52)	22.92(2.47)	<0.001
WC,mean(SD;cm)	86.11(10.45)	93.00(5.94)	96.02(6.91)	0.001	76.82(6.86)	80.95(6.53)	<0.001
WHR,mean(SD)	0.90(0.09)	0.92(0.05)	0.95(0.13)	<0.001	0.84(0.05)	0.87(0.05)	<0.001
PBF,mean(SD)	27.45(11.34)	33.33(9.88)	31.50(11.75)	0.161	23.64(8.76)	24.69(10.90)	0.149
SBP,median (IQR; mmHg)	131.50(25.50)	121.50(14.00)	139.00(22.00)	<0.001	115.50(15.08)	136.50(23.83)	<0.001
DBP,median (IQR; mmHg)	79.33(15.00)	75.50(11.00)	85.00(13.67)	<0.001	70.50(9.33)	81.00(13.50)	<0.001
TG,median (IQR; mmol/L)	1.32(1.12)	1.23(0.52)	1.84(1.53)	<0.001	0.94(0.52)	1.32(1.17)	<0.001
TC,median (IQR; mmol/L)	4.77(1.35)	4.31(1.04)	5.13(1.17)	<0.001	4.20(1.06)	4.87(1.31)	<0.001
HDL-C,median (IQR; mmol/L)	1.38(0.43)	1.26(0.45)	1.35(0.40)	0.004	1.35(0.45)	1.46(0.45)	0.001
LDL-C,median (IQR; mmol/L)	2.15(0.77)	2.01(0.64)	2.37(0.73)	<0.001	1.85(0.66)	2.19(0.78)	<0.001
Fasting glucose,median (IQR; mmol/L)	5.30(1.12)	4.97(0.78)	5.67(1.24)	<0.001	4.91(0.63)	5.58(1.30)	<0.001
HOMA-IR,median (IQR)	2.03(1.98)	2.26(1.67)	2.94(2.62)	0.022	1.34(1.30)	1.74(1.78)	<0.001
Uric_acid,median (IQR; μmol/L)	327.25(124.95)	321.30(107.10)	368.90(124.95)	<0.001	285.60(101.15)	327.25(119.00)	<0.001
hsCRP,median (IQR; mg/L)	0.81(1.20)	0.99(1.47)	1.20(1.45)	0.774	0.45(0.70)	0.74(0.98)	0.164

Note: Data are presented as means (SD)/median (IQR) for continuous variables and numbers (percentage) for categorical variables.

Abbreviations: MZ, monozygotic; DZ, dizygotic; MET, metabolic equivalent of task; BMI, body mass index; WC, waist circumstance; WHR, waist hip ratio; PBF, percent body fat; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity CRP; IQR, interquartile range; SD, standard deviation; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; MHNO, metabolically healthy non-obesity; MUNO, metabolically unhealthy non-obesity.

Table 2 Results of Mixed Linear Regression Models on the Association of Serum HOMA-IR and hsCRP Levels with Metabolic Status in All Twins

Exposure	Model 1		Model 2		Model 3
	β (95% CI)	p	β (95% CI)	p	β (95% CI)	p
HOMA-IR
Metabolic status
MH(ref)
MU	0.52(0.43,0.62)	<0.001	0.53(0.43,0.62)	<0.001	0.32(0.22,0.41)	<0.001
Metabolic status in obesity
MHO(ref)
MUO	0.38(0.23,0.53)	<0.001	0.40(0.24,0.56)	<0.001	0.32(0.17,0.47)	<0.001
CRP
Metabolic status
MH(ref)
MU	0.34(0.20,0.47)	<0.001	0.34(0.20,0.48)	<0.001	0.17(0.03,0.30)	0.018
Metabolic status in obesity
MHO(ref)
MUO	0.20(−0.01,0.41)	0.057	0.18(−0.03,0.40)	0.09	0.11(−0.09,0.32)	0.277

Notes: Model 1 was adjusted for sex, zygosity, place and age; model 2 was adjusted for model 1 plus lifestyle factors (smoking status, drinking status, and MET values); model 3 was adjusted for model 2 plus BMI, PBF and WHR.

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity CRP; MH, metabolically healthy; MU, metabolically unhealthy; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; BMI, body mass index; PBF, percent body fat; WHR, waist hip ratio.

Table 3 Results of Mixed Linear Regression Models on the Association of Serum HOMA-IR and CRP Levels with Metabolic/Obesity Phenotypes in All Twins

Exposure	Model 1		Model 2		Model 3
	β (95% CI)	p	β (95% CI)	p	β (95% CI)	p
HOMA-IR
Metabolic/obesity phenotype
MHNO (ref)
MUNO	0.46(0.35,0.57)	<0.001	0.48(0.37,0.59)	<0.001	0.39(0.28,0.51)	<0.001
MHO	0.54(0.39,0.69)	<0.001	0.53(0.37,0.68)	<0.001	0.51(0.36,0.67)	<0.001
MUO	0.90(0.79,1.01)	<0.001	0.90(0.78,1.01)	<0.001	0.79(0.67,0.91)	<0.001
hsCRP
Metabolic/obesity phenotype
MHNO (ref)
MUNO	0.30(0.14,0.46)	<0.001	0.33(0.17,0.50)	<0.001	0.27(0.10,0.44)	0.002
MHO	0.57(0.35,0.80)	<0.001	0.60(0.37,0.82)	<0.001	0.59(0.36,0.81)	<0.001
MUO	0.72(0.55,0.88)	<0.001	0.71(0.55,0.88)	<0.001	0.63(0.46,0.80)	<0.001

Notes: Model 1 was adjusted for sex, zygosity, place and age; model 2 was adjusted for model 1 plus lifestyle factors (smoking status, drinking status, and MET values); model 3 was adjusted for model 2 plus TC and HA1bc.

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity CRP; MetS, metabolic syndrome; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; MHNO, metabolically healthy non-obesity; MUNO, metabolically unhealthy non-obesity; TC, total cholesterol.

Figure 1 (A) Association between obesity status, number of MetS components and level of HOMA-IR.  (B) Association between obesity status, number of MetS components and level of hsCRP. The bolded number means the correlation was significant at p<0.05. The adjusted covariates included sex, zygosity, place, age, lifestyle factors (smoking, drinking, and physical activity), TC and HA1bC. 

Abbreviations: MetS, metabolic syndrome; HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity CRP.

Table 4 Results of Fixed Linear Regression Models on the Association of Serum HOMA-IR and hsCRP Levels with Metabolic Status in Twin Pairs

Exposure	MZ		DZ
	β (95% CI)	p	β (95% CI)	p
HOMA-IR
Metabolic status
MH(reference group)
MU	0.18(0.01,0.35)	0.037	0.28(0.08,0.48)	0.006
Metabolic status in obesity
MHO(ref)
MUO	−0.06(−0.46,0.34)	0.751	0.72(0.24,1.20)	0.005
CRP
Metabolic status
MH(reference group)
MU	0.00(−0.31,0.32)	0.985	0.14(−0.17,0.44)	0.372
Metabolic status in obesity
MHO(ref)
MUO	−0.03(−0.57,0.50)	0.904	−0.19(−0.97,0.60)	0.627

Note: Models were adjusted for lifestyle factors (smoking status, drinking status, and MET values), BMI, PBF and WHR.

Abbreviations: HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity CRP; MH, metabolically healthy; MU, metabolically unhealthy; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; BMI, body mass index; PBF, percent body fat; WHR, waist hip ratio.

Table 5 Results of Fixed Linear Regression Models on the Association of Serum HOMA-IR and hsCRP Levels with Metabolic/Obesity Phenotypes in Twin Pairs

Exposure	MZ		DZ
	β (95% CI)	p	β (95% CI)	p
HOMA-IR
Metabolic/obesity phenotype
MHNO (ref)
MUNO	0.42(0.21,0.64)	<0.001	0.56(0.30,0.82)	<0.001
MHO	0.68(0.36,1.00)	<0.001	0.51(0.17,0.85)	0.003
MUO	0.69(0.46,0.91)	<0.001	1.05(0.79,1.32)	<0.001
HsCRP
Metabolic/obesity phenotype
MHNO (ref)
MUNO	0.21(−0.15,0.58)	0.249	0.33(−0.01,0.67)	0.061
MHO	0.74(0.21,1.27)	0.007	0.51(0.06,0.95)	0.025
MUO	0.54(0.16,0.93)	0.006	0.66(0.32,1.01)	<0.001

Note: Models were adjusted for lifestyle factors (smoking status, drinking status, and MET values).

Abbreviations: MZ, monozygotic; DZ, dizygotic; HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity CRP; MetS, metabolic syndrome; MHO, metabolically healthy obesity; MUO, metabolically unhealthy obesity; MHNO, metabolically healthy non-obesity; MUNO, metabolically unhealthy non-obesity.