TABLE 1

Clinical and biochemical characteristics of the study patients in cohort design and new-user cohort design

Variables at enrollmentCohort designNew-user cohort design*
Insulin nonusersInsulin usersPInsulin nonusersInsulin usersP
n3,6509731,935971
Age (years)56 (20)58 (20)0.002258 (21)58 (20)
Smoking status0.0005
    Former482 (13.2%)176 (18.1%)348 (18.0%)175 (18.0%)
    Current567 (15.5%)150 (15.4%)297 (15.4%)149 (15.4%)
Male sex1,678 (46.0%)453 (46.6%)0.7452964 (49.8%)451 (46.5%)0.0863
Alcohol use0.00210.1164
    Former385 (10.6%)140 (14.4%)257 (13.3%)139 (14.3%)
    Current304 (8.3%)68 (7.0%)178 (9.2%)68 (7.0%)
BMI (kg/m2)24.8 (4.8)24.5 (5.1)0.007024.9 (4.9)24.5 (5.1)0.0014
Duration of diabetes (years)4 (8)8 (8)<0.00014 (9)8 (8)<0.0001
Systolic blood pressure (mmHg)133 (25)136 (29)0.0004135 (26)136 (29)0.1787
Diastolic blood pressure (mmHg)75 (13)76 (15)0.102575 (14)76 (15)0.0413
A1C (%)6.9 (1.7)8.1 (2.5)<0.00017.1 (2.0)8.1 (2.5)<0.0001
LDL cholesterol (mmol/l)3.10 (1.21)3.20 (1.2)0.00043.00 (1.26)3.20 (1.2)<0.0001
HDL cholesterol (mmol/l)1.27 (0.43)1.21 (0.46)<0.00011.26 (0.43)1.21 (0.46)0.0002
Triglyceride (mmol/l)1.32 (0.96)1.45 (1.14)0.00041.40 (0.99)1.45 (1.14)0.3057
Total cholesterol (mmol/l)5.10 (1.30)5.20 (1.30)0.00115.05 (1.40)5.20 (1.30)<0.0001
ACR (mg/mmol)1.39 (4.44)5.00 (26.27)<0.00011.93 (8.76)4.96 (26.79)<0.0001
    Microalbuminuria23.6% (863)32.2% (313)<0.000126.5% (513)32.0% (311)<0.0001
    Macroalbuminuria9.8% (356)26.3% (256)15.3% (296)26.4% (256)
eGFR (ml/min−1 per 1.73 m2)106.2 (36.6)100.9 (50.3)<0.0001101.2 (38.1)100.9 (50.3)0.1342
    <604.7% (173)14.9% (145)<0.00017.3% (142)14.9% (145)<0.0001
Retinopathy612 (16.8%)355 (36.5%)<0.0001454 (23.5%)354 (36.5%)<0.0001
Prior myocardial infarction55 (1.5%)13 (1.3%)0.694242 (2.2%)13 (1.3%)0.1207
Prior stroke144 (4.0%)43 (4.4%)0.504896 (5.0%)43 (4.4%)0.5255
Medications at enrollment
    Antihypertensive drugs other than ACEIs/ARBs1,351 (37.0%)377 (38.8%)0.3210828 (42.8%)375 (38.6%)0.0313
Events and medications after enrollment§
    Cancer during follow-up169 (4.6%)32 (3.3%)0.0683120 (6.3%)32 (3.3%)0.0009
    Follow-up time to cancer, years4.78 (4.43)6.04 (3.55)<0.00010.70 (1.23)3.01 (3.51)<0.0001
    Incidence of cancer, per 1,000 person-years9.7 (8.3–11.1)§5.8 (3.8–7.8)§0.008249.2 (40.6–57.8)§10.2 (6.7–13.7)§<0.0001
    Death during follow-up169 (4.6%)133 (13.7%)<0.0001125 (6.5%)132 (13.6%)<0.0001
    Follow-up time to death, years4.78 (4.43)6.04 (3.55)<0.00010.77 (1.57)3.09 (3.45)<0.0001
    Incidence of death, per 1,000 person-years9.6 (8.1–11.0)§24.0 (19.9–28.0)§<0.000146.5 (38.5–54.4)§41.2 (34.3–48.1)§0.8307
    ACEIs or ARBs1,750 (48.0%)705 (72.5%)<0.00011,009 (52.1%)703 (72.4%)<0.0001
    Statins1,088 (29.8%)506 (52.1%)<0.0001605 (31.2%)506 (52.1%)<0.0001
    Fibrates327 (9.0%)121 (12.4%)0.0011163 (8.4%)120 (12.4%)0.0007
    Acarbose287 (7.9%)269 (27.7%)<0.0001177 (9.2%)269 (27.7%)<0.0001
    Glibenclimide1,046 (28.7%)396 (40.7%)<0.0001482 (24.9%)395 (40.7%)<0.0001
    Gliclazide1,692 (46.4%)603 (62.0%)<0.0001956 (50.1%)602 (62.0%)<0.0001
    Glimepiride38 (1.0%)33 (3.4%)<0.000124 (1.2%)33 (3.4%)0.0001
    Glipizide399 (10.4%)197 (20.3%)<0.0001221 (11.4%)197 (20.3%)<0.0001
    Metformin2,680 (73.4%)837 (86.0%)<0.00011,442 (74.5%)835 (86.0%)<0.0001
    Pioglitazone25 (0.7%)17 (1.8%)0.001918 (0.9%)17 (1.8%)0.0558
    Rosiglitazone106 (2.9%)110 (11.3%)<0.000164 (3.3%)110 (11.3%)<0.0001
    Tolbutamide10 (0.3%)22 (2.3%)<0.00018 (0.4%)21 (2.2%)<0.0001
  • Data are median (interquartile range; from 25th-75th percentiles), % (n), and n (%).

  • *Matched on age, smoking status, likelihood of using insulin, and time before insulin use.

  • †Derived from Wilcoxon two-sample test.

  • ‡Derived from χ2 test.

  • §From enrollment to the earliest date of cancer, death, or censoring (95% CIs).

  • ‖Derived from univariate Cox model analysis. ACEIs, angiotensin-converting enzyme inhibitors; ARBs, angiotensin II receptor blockers.