Table 1.

Hazard Ratios for Glycemic Exposure Variables Estimated by Cox Proportional Hazards Model in ACCORD and VADT

	Model-1		Model-2		Model-3
	Age adjustment		Multivariate adjustment		Model 2 + cumulative HbA1c
	HR (95% CI)	P value	HR (95% CI)	P value	HR (95% CI)	P value
ACCORD
Primary Composite (n = 1106) a
Log(CV)-glucose	1.35 (1.25-1.44)	<0.001	1.19 (1.10-1.29)	<0.001	1.18 (1.09-1.28)	<0.001
ARV-glucose	1.27 (1.20-1.35)	<0.001	1.15 (1.07-1.23)	<0.001	1.14 (1.06-1.22)	<0.001
Nephropathy (n = 269) b
Log(CV)-glucose	1.34 (1.18-1.53)	<0.001	1.29 (1.12-1.47)	<0.001	1.28 (1.12-1.47)	<0.001
ARV-glucose	1.30 (1.17-1.45)	<0.001	1.25 (1.11-1.40)	<0.001	1.24 (1.10-1.39)	<0.001
Retinopathy (n = 880) C
Log(CV)-glucose	1.35 (1.25-1.46)	<0.001	1.13 (1.03-1.23)	0.005	1.12 (1.03-1.22)	0.010
ARV-glucose	1.26 (1.18-1.35)	<0.001	1.08 (1.00-1.18)	0.052	1.07 (0.99-1.17)	0.091
VADT
Primary Composite (n = 186) d
Log(CV)-glucose	1.58(1.32-1.89)	<0.001	1.43(1.18-1.73)	<0.001	1.39(1.14-1.69)	<0.001
ARV-glucose	1.31(1.16-1.48)	<0.001	1.20(1.04-1.38)	<0.001	1.17(1.01-1.35)	<0.001
Nephropathy (n = 42) e
Log(CV)-glucose	2.31(1.59-3.35)	<0.001	1.92(1.30-2.83)	0.001	1.91(1.27-2.86)	0.002
ARV-glucose	1.53(1.22-1.91)	<0.001	1.36(1.06-1.75)	0.016	1.34(1.03-1.75)	0.027
Retinopathy (n = 154) f
Log(CV)-glucose	1.43 (1.18-1.73)	<0.001	1.29(1.05-1.59)	0.004	1.31(1.06-1.63)	0.005
ARV-glucose	1.26 (1.10-1.45)	<0.001	1.18(1.01-1.38)	0.031	1.19(1.01-1.40)	0.043

In Model 2, glycemic control variables that were significant in age-adjusted models (Model-1) were further adjusted for significantly different baseline factors (see Supplementary Tables 2 and 3 (13)). For the primary outcome, in Model 2, we additionally adjusted race, diabetes duration, CVD history, history of heart failure, history of eye disease, smoker status, baseline DBP, baseline SBP, baseline HDL, baseline triglycerides, baseline HbA1c, baseline albumin to creatinine ratio (ACR), and baseline eGFR for ACCORD and duration of diabetes, pack-years of cigarette smoked, baseline SBP, and baseline ACR. In Model-3, models were additionally adjusted for cumulative mean of HbA1c as a reflection of average glycemic control.

P values < 0.05 (bold font) are considered significant.

n = event number.

Abbreviations: ACCORD, Action to Control Cardiovascular Risk in Diabetes; ARV, average real variability; CV, coefficient of variation; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin A1c; HR, hazard ratio; VADT, Veteran Affairs Diabetes Trial.

^a Primary composite: development of end-stage renal disease (ESRD, ie, initiation of dialysis or a rise of serum creatinine to 3.3 mg/dL [291.72 μmol/L]) or photocoagulation or vitrectomy.

^b Nephropathy: renal failure or ESRD or serum creatine >3.3 mg/dL (291.72 μmol/L).

^c Retinopathy: photocoagulation or vitrectomy.

^d Primary composite: Nephropathy or Retinopathy;

^e Nephropathy: 2 consecutive values of serum creatinine ≥3.3mg per deciliter (291.72 μmol/L or eGFR < 30 mL/min/1.73 m²).

^f Retinopathy: Photocoagulation or Vitrectomy.