Metabolic score for insulin resistance is associated with adverse cardiovascular events in patients with type 2 diabetes

Table 2 Risk of primary and secondary outcomes based on metabolic score for insulin resistance in type 2 diabetes patient

Outcome	Events/n	Non-adjusted		Model 1		Model 2		Model 3
		HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
MACEs
METS-IR	-	1.01 (1.01-1.01)	< 0.00001	1.01 (1.01-1.02)	< 0.00001	1.01 (1.01-1.01)	< 0.00001	1.01 (1.00-1.01)	0.0004
Q1	402/2548	Reference	-	Reference	-	Reference	-	Reference	-
Q2	418/2547	1.05 (0.92-1.20)	0.4837	1.07 (0.94-1.23)	0.3044	1.02 (0.89-1.17)	0.7661	1.00 (0.87-1.15)	0.9647
Q3	482/2548	1.22 (1.07-1.39)	0.0036	1.31 (1.14-1.49)	< 0.0001	1.23 (1.07-1.41)	0.0035	1.20 (1.05-1.38)	0.0090
Q4	510/2548	1.32 (1.15-1.50)	< 0.0001	1.50 (1.31-1.71)	< 0.00001	1.31 (1.14-1.52)	0.0002	1.25 (1.08-1.45)	0.0024
Per 1 SD	-	1.12 (1.07-1.17)	< 0.00001	1.18 (1.12-1.23)	< 0.00001	1.12 (1.06-1.18)	< 0.00001	1.10 (1.04-1.16)	0.0004
P for trend	-	-	< 0.00001	-	< 0.00001	-	< 0.00001	-	0.0003
CVD mortality
METS-IR	-	1.02 (1.01-1.02)	< 0.0001	1.02 (1.02-1.03)	< 0.00001	1.02 (1.01-1.03)	< 0.0001	1.02 (1.01-1.03)	< 0.0001
Q1	147/2548	Reference	-	Reference	-	Reference	-	Reference
Q2	124/2547	0.85 (0.67-1.08)	0.1790	0.88 (0.70-1.12)	0.3102	0.83 (0.65-1.06)	0.1382	0.80 (0.63-1.02)	0.0778
Q3	176/2548	1.22 (0.98-1.52)	0.0764	1.38 (1.10-1.72)	0.0045	1.28 (1.02-1.60)	0.0361	1.23 (0.98-1.54)	0.0808
Q4	216/2548	1.54 (1.25-1.90)	< 0.0001	1.92 (1.55-2.38)	< 0.0001	1.66 (1.32-2.09)	< 0.0001	1.55 (1.23-1.96)	0.0003
Per 1 SD	-	1.20 (1.12-1.29)	< 0.0001	1.32 (1.22-1.42)	< 0.00001	1.25 (1.15-1.36)	< 0.0001	1.22 (1.12-1.32)	< 0.0001
P for trend	-	-	< 0.0001	-	< 0.0001	-	< 0.0001	-	< 0.0001
Non-fatal MI
METS-IR	-	1.01 (1.00-1.01)	0.0020	1.01 (1.01-1.02)	< 0.00001	1.01 (1.00-1.01)	0.0466	1.00 (1.00-1.01)	0.1933
Q1	203/2548	Reference	-	Reference	-	Reference	-	Reference	-
Q2	228/2547	1.13 (0.94-1.37)	0.1978	1.14 (0.95-1.38)	0.1633	1.09 (0.90-1.32)	0.3753	1.07 (0.88-1.30)	0.4836
Q3	241/2548	1.20 (0.99-1.44)	0.0597	1.25 (1.04-1.51)	0.0178	1.17 (0.96-1.42)	0.1152	1.13 (0.93-1.38)	0.2198
Q4	258/2548	1.31 (1.09-1.57)	0.0043	1.43 (1.18-1.72)	0.0002	1.24 (1.01-1.51)	0.0385	1.16 (0.94-1.42)	0.1588
Per 1 SD	-	1.10 (1.04-1.18)	0.0020	1.14 (1.07-1.22)	< 0.00001	1.08 (1.00-1.15)	0.0466	1.05 (0.98-1.13)	0.1933
P for trend	-	-	0.0037	-	0.0001	-	0.0307	-	0.1388
Non-fatal stroke
METS-IR	-	1.01 (1.00-1.01)	0.1472	1.01 (1.00-1.02)	0.0119	1.01 (1.00-1.02)	0.1492	1.01 (1.00-1.02)	0.1576
Q1	103/2548	Reference	-	Reference	-	Reference	-	Reference	-
Q2	125/2547	1.23 (0.94-1.59)	0.1255	1.26 (0.97-1.64)	0.0836	1.20 (0.92-1.56)	0.1818	1.19 (0.91-1.56)	0.1980
Q3	139/2548	1.28 (0.99-1.66)	0.0618	1.37 (1.06-1.78)	0.0169	1.31 (1.00-1.71)	0.0489	1.32 (1.01-1.73)	0.0443
Q4	126/2548	1.27 (0.98-1.65)	0.0703	1.45 (1.11-1.88)	0.0064	1.29 (0.97-1.72)	0.0751	1.29 (0.97-1.72)	0.0835
Per 1 SD	-	1.07 (0.98-1.17)	0.1472	1.12 (1.03-1.23)	0.0119	1.08 (0.97-1.19)	0.1492	1.07 (0.97-1.19)	0.1576
P for trend	-	-	0.0720	-	0.0052	-	0.0620	-	0.0645
Total mortality
METS-IR	-	1.01 (1.00-1.01)	< 0.0001	1.02 (1.01-1.02)	< 0.0001	1.01 (1.01-1.02)	< 0.0001	1.01 (1.01-1.02)	< 0.0001
Q1	448/2548	Reference	-	Reference	-	Reference	-	Reference
Q2	448/2547	1.01 (0.88-1.15)	0.9213	1.07 (0.93-1.22)	0.3417	1.01 (0.88-1.15)	0.909	0.99 (0.87-1.13)	0.8556
Q3	491/2548	1.12 (0.98-1.27)	0.0891	1.30 (1.14-1.47)	< 0.0001	1.20 (1.05-1.37)	0.0082	1.17 (1.02-1.34)	0.0233
Q4	556/2548	1.31 (1.15-1.48)	< 0.0001	1.70 (1.50-1.93)	< 0.0001	1.47 (1.28-1.68)	< 0.0001	1.39 (1.21-1.59)	< 0.0001
Per 1 SD	-	1.10 (1.05-1.15)	< 0.0001	1.22 (1.17-1.28)	< 0.0001	1.15 (1.10-1.21)	< 0.0001	1.13 (1.08-1.19)	< 0.0001
P for trend	-	-	< 0.0001	-	< 0.0001	-	< 0.0001	-	< 0.0001
CHF
METS-IR	-	1.03 (1.02-1.03)	< 0.0001	1.04 (1.03-1.04)	< 0.0001	1.03 (1.02-1.04)	< 0.0001	1.03 (1.02-1.04)	< 0.0001
Q1	124/2548	Reference	-	Reference	-	Reference	-	Reference	-
Q2	132/2547	1.07 (0.84-1.37)	0.5656	1.13 (0.89-1.45)	0.3203	1.06 (0.83-1.36)	0.6457	1.04 (0.80-1.34)	0.7809
Q3	196/2548	1.62 (1.30-2.03)	< 0.0001	1.86 (1.48-2.33)	< 0.0001	1.82 (1.44-2.30)	< 0.0001	1.76 (1.39-2.23)	< 0.0001
Q4	239/2548	2.09 (1.69-2.60)	< 0.0001	2.65 (2.13-3.31)	< 0.0001	2.31 (1.82-2.92)	< 0.0001	2.22 (1.74-2.82)	< 0.0001
Per 1 SD	-	1.35 (1.26-1.44)	< 0.0001	1.48 (1.38-1.59)	< 0.0001	1.42 (1.31-1.53)	< 0.0001	1.40 (1.29-1.52)	< 0.0001
P for trend	-	-	< 0.0001	-	< 0.0001	-	< 0.0001	-	< 0.0001
Major CHD
METS-IR	-	1.01 (1.01-1.02)	< 0.0001	1.02 (1.01-1.02)	< 0.0001	1.01 (1.01-1.02)	< 0.0001	1.01 (1.01-1.02)	< 0.0001
Q1	379/2548	Reference	-	Reference	-	Reference	-	Reference	-
Q2	426/2547	1.14 (0.99-1.31)	0.0596	1.16 (1.01-1.33)	0.0410	1.10 (0.95-1.27)	0.1887	1.07 (0.93-1.24)	0.3298
Q3	495/2548	1.34 (1.17-1.53)	< 0.0001	1.41 (1.23-1.61)	< 0.0001	1.31 (1.14-1.51)	0.0001	1.26 (1.10-1.45)	0.0012
Q4	544/2548	1.50 (1.32-1.72)	< 0.0001	1.65 (1.44-1.89)	< 0.0001	1.43 (1.24-1.66)	< 0.0001	1.35 (1.17-1.56)	< 0.0001
Per 1 SD	-	1.17 (1.12-1.23)	< 0.0001	1.22 (1.17-1.28)	< 0.0001	1.16 (1.10-1.22)	< 0.0001	1.13 (1.08-1.19)	< 0.0001
P for trend	-	-	< 0.0001	-	< 0.0001	-	< 0.0001	-	< 0.0001

Data are expressed as hazard ratio and 95% confidence intervals (reported in parentheses) as assessed by multivariable Cox regression analysis. Model 1 adjusted for age, sex. Model 2 adjusted for model 1 covariables plus race, cardiovascular disease history, previous hypertension, duration of diabetes, proteinuria, heart failure, depression, education, smoke, systolic blood pressure, diastolic blood pressure, glycated hemoglobin, total cholesterol, low-density lipoprotein, estimated glomerular filtration rate, alanine aminotransferase. Model 3 Adjusted for model 2 covariables plus the medications use, calcium channel blockers, beta-blockers, biguanides, thiazolidinediones, insulins, aspirin, statins, cholesterol absorption inhibitors. MACEs: Major adverse cardiovascular events; CVD: Cardiovascular disease; MI: Myocardial infarction; CHF: Congestive heart failure; CHD: Coronary heart disease; METS-IR: Metabolic score for insulin resistance; CI: Confidence interval; HR: Hazard ratio; SD: Standard deviation.