Background
Methods
Patients and baseline procedures
Long-term glycemic variability measurements
Follow-up and outcomes assessment
Statistical analyses
Results
Baseline characteristics
Characteristics | All patients (n = 654) | 1st-tertile HbA1c-SD ≤ 0.45% (n = 218) | 2nd-tertile HbA1c-SD 0.46–0.85% (n = 218) | 3rd-tertile HbA1c-SD ≥ 0.86% (n = 218) | p value |
---|---|---|---|---|---|
Age (years) | 60.1 (9.6) | 61.2 (9.4) | 59.9 (9.9) | 58.7 (9.4) | 0.007 |
Male sex (%) | 38.1 | 42.2 | 37.6 | 34.4 | 0.26 |
BMI (kg/m2) | 29.7 (4.8) | 29.9 (4.6) | 29.7 (5.0) | 29.6 (5.0) | 0.84 |
Smoking, current/past (%) | 45.1 | 48.2 | 40.8 | 46.3 | 0.29 |
Physical activity (%) | 22.4 | 23.4 | 23.5 | 20.2 | 0.64 |
Diabetes duration (years) | 8.0 (3.0–15.0) | 5.0 (1.4–12.3) | 10.0 (4.0–17.5) | 9.0 (5.0–15.0) | < 0.001 |
Chronic diabetic complications (%) | |||||
Cerebrovascular disease | 9.0 | 11.5 | 5.5 | 10.1 | 0.075 |
Coronary artery disease | 15.6 | 14.7 | 15.1 | 17.0 | 0.83 |
Peripheral artery disease | 17.0 | 15.7 | 17.1 | 18.3 | 0.76 |
Retinopathy | 32.7 | 27.1 | 34.1 | 36.7 | 0.087 |
Nephropathy | 31.0 | 22.0 | 27.3 | 43.6 | < 0.001 |
Peripheral neuropathy | 29.0 | 26.5 | 31.2 | 29.2 | 0.56 |
Cardiovascular autonomic neuropathy | 18.1 | 14.9 | 17.4 | 21.8 | 0.24 |
Diabetes treatment (%) | |||||
Metformin | 87.9 | 89.4 | 86.2 | 88.1 | 0.61 |
Sulfonylureas | 43.3 | 44.5 | 43.6 | 41.7 | 0.86 |
Insulin | 48.9 | 29.8 | 51.8 | 65.1 | < 0.001 |
Aspirin | 90.9 | 91.2 | 87.6 | 94.0 | 0.068 |
Dyslipidemia (%) | 87.3 | 87.2 | 86.7 | 88.1 | 0.93 |
Statins use (%) | 77.5 | 79.7 | 75.6 | 77.1 | 0.57 |
Arterial hypertension (%) | 86.5 | 84.4 | 88.1 | 87.2 | 0.51 |
Number of anti-hypertensive drugs | 3 (1–4) | 3 (1–4) | 3 (1–4) | 3 (1–4) | 0.97 |
ACE inhibitors/AR blockers (%) | 83.0 | 82.0 | 82.0 | 85.0 | 0.65 |
Diuretics (%) | 67.7 | 68.4 | 66.5 | 68.1 | 0.92 |
Calcium channel blockers (%) | 31.7 | 35.4 | 33.0 | 26.6 | 0.14 |
Beta-blockers (%) | 50.1 | 47.6 | 51.0 | 51.7 | 0.68 |
Blood pressures (mmHg) | |||||
Clinic SBP | 147 (25) | 147 (25) | 145 (25) | 149 (24) | 0.12 |
Clinic DBP | 84 (13) | 83 (13) | 84 (13) | 86 (14) | 0.072 |
Ambulatory 24 h SBP | 128 (15) | 126 (15) | 128 (15) | 131 (16) | 0.002 |
Ambulatory 24 h DBP | 74 (10) | 72 (9) | 74 (10) | 75 (11) | 0.009 |
Laboratory variables | |||||
Baseline FG (mmol/l) | 8.97 (3.86) | 7.53 (2.54) | 8.83 (3.40) | 10.54 (4.71) | < 0.001 |
Mean 12-month FG | 8.10 (2.42) | 6.90 (1.46) | 7.98 (2.04) | 9.35 (2.78) | < 0.001 |
Mean 24-month FG | 8.09 (2.39) | 6.93 (1.47) | 7.97 (2.07) | 9.35 (2.78) | < 0.001 |
Baseline HbA1c (%) | 8.1 (1.9) | 7.0 (1.3) | 8.0 (1.6) | 9.1 (2.1) | < 0.001 |
(mmol/mol) | 65 (20.8) | 53 (14.2) | 64 (17.5) | 76 (23.0) | |
Mean 12-month HbA1c (%) | 7.8 (1.5) | 6.8 (0.7) | 7.7 (1.2) | 9.0 (1.4) | < 0.001 |
(mmol/mol) | 62 (16.4) | 51 (7.7) | 61 (13.1) | 75 (15.3) | |
Mean 24-month HbA1c (%) | 7.8 (1.4) | 6.8 (0.8) | 7.7 (1.2) | 9.0 (1.4) | < 0.001 |
(mmol/mol) | 62 (15.3) | 51 (8.7) | 61 (13.1) | 75 (15.3) | |
Triacylglycerol (mmol/l) | 2.0 (1.5) | 1.8 (1.2) | 2.0 (1.6) | 2.2 (1.6) | 0.064 |
HDL-cholesterol (mmol/l) | 1.11 (0.30) | 1.10 (0.27) | 1.12 (0.33) | 1.11 (0.32) | 0.79 |
LDL-cholesterol (mmol/l) | 3.03 (1.00) | 2.96 (0.91) | 3.00 (1.08) | 3.13 (0.99) | 0.20 |
Glomerular filtration rate (ml/min/1.73 m2) | 81 (20) | 80 (19) | 82 (20) | 80 (22) | 0.53 |
Albuminuria (mg/24 h) | 13 (7–42) | 10 (6–22) | 13 (7–41) | 19 (8–90) | < 0.001 |
Macrovascular outcomesa | |||||
Total CVEs | 128 (2.56) | 36 (2.20) | 34 (1.99) | 58 (3.67) | 0.005 |
Major CVEs | 96 (1.86) | 24 (1.42) | 24 (1.38) | 48 (2.93) | 0.001 |
Cardiovascular mortality | 67 (1.26) | 16 (0.92) | 15 (0.85) | 36 (2.07) | 0.002 |
All-cause mortality | 158 (2.97) | 44 (2.52) | 49 (2.77) | 65 (3.74) | 0.10 |
Microvascular outcomesb | |||||
Retinopathy (incident/worsening) (n = 533) | 152 (4.88) | 30 (2.63) | 50 (4.89) | 72 (7.96) | < 0.001 |
Renal composite (n = 615) | 183 (4.71) | 54 (4.11) | 47 (3.63) | 82 (6.58) | < 0.001 |
Microalbuminuria (incident) (n = 436) | 89 (3.23) | 31 (2.88) | 25 (2.80) | 33 (4.26) | 0.21 |
Renal failure (n = 615) | 91 (2.15) | 19 (1.35) | 24 (1.72) | 48 (3.42) | < 0.001 |
Peripheral neuropathy (incident/worsening) (n = 471) | 96 (20.4%) | 21 (13.5%) | 35 (22.0%) | 40 (25.5%) | 0.011 |
Peripheral neuropathy (incident) (n = 338) | 42 (12.4%) | 11 (9.4%) | 9 (8.2%) | 22 (19.8%) | 0.005 |
Characteristics | All patients (n = 654) | 1st-tertile FG-SD ≤ 1.40 mmol/l (n = 218) | 2nd-tertile FG-SD 1.41–2.60 mmol/l (n = 218) | 3rd-tertile FG-SD ≥ 2.61 mmol/l (n = 218) | p value |
---|---|---|---|---|---|
Age (years) | 60.1 (9.6) | 60.6 (9.8) | 60.5 (9.2) | 59.1 (9.5) | 0.16 |
Male sex (%) | 38.1 | 38.7 | 36.2 | 39.9 | 0.45 |
BMI (kg/m2) | 29.8 (4.6) | 29.9 (4.6) | 29.9 (5.0) | 29.5 (5.0) | 0.63 |
Smoking, current/past (%) | 45.1 | 46.5 | 38.5 | 50.9 | 0.031 |
Physical activity (%) | 22.4 | 27.6 | 20.2 | 18.9 | 0.017 |
Diabetes duration (years) | 8 (3–15) | 4 (1–10) | 10 (5–15) | 10 (5–17) | < 0.001 |
Chronic diabetic complications (%) | |||||
Cerebrovascular disease | 9.0 | 6.9 | 6.4 | 13.3 | 0.019 |
Coronary artery disease | 15.6 | 11.1 | 15.1 | 21.1 | 0.015 |
Peripheral artery disease | 17.0 | 10.6 | 19.9 | 20.6 | 0.008 |
Retinopathy | 32.7 | 19.2 | 36.4 | 41.4 | < 0.001 |
Nephropathy | 31.0 | 22.4 | 26.0 | 45.8 | < 0.001 |
Peripheral neuropathy | 29.0 | 20.4 | 30.4 | 37.3 | 0.001 |
Cardiovascular autonomic neuropathy | 18.1 | 12.4 | 21.2 | 21.4 | 0.042 |
Diabetes treatment (%) | |||||
Metformin | 87.9 | 90.8 | 91.3 | 80.7 | 0.001 |
Sulfonylureas | 43.3 | 40.6 | 50.9 | 39.4 | 0.029 |
Insulin | 48.9 | 24.9 | 52.3 | 68.8 | < 0.001 |
Aspirin | 90.9 | 87.5 | 90.2 | 94.5 | 0.040 |
Dyslipidemia (%) | 87.3 | 88.0 | 87.2 | 86.7 | 0.92 |
Statins use (%) | 77.5 | 78.2 | 77.9 | 76.0 | 0.84 |
Arterial hypertension (%) | 86.5 | 83.9 | 89.0 | 86.6 | 0.29 |
Number of anti-hypertensive drugs | 3 (1–4) | 2 (1–3) | 3 (2–4) | 3 (1–4) | 0.001 |
ACE inhibitors/AR blockers (%) | 83.0 | 80.6 | 84.2 | 84.8 | 0.47 |
Diuretics (%) | 67.7 | 59.7 | 75.7 | 68.6 | 0.002 |
Calcium channel blockers (%) | 31.7 | 26.7 | 35.6 | 34.3 | 0.11 |
Beta-blockers (%) | 50.1 | 43.2 | 54.0 | 53.9 | 0.043 |
Blood pressures (mmHg) | |||||
Clinic SBP | 147 (25) | 143 (22) | 149 (26) | 149 (25) | 0.012 |
Clinic DBP | 84 (13) | 83 (12) | 85 (14) | 85 (14) | 0.11 |
Ambulatory 24 h SBP | 128 (15) | 125 (13) | 129 (15) | 131 (17) | 0.001 |
Ambulatory 24 h DBP | 74 (10) | 73 (9) | 74 (9) | 75 (11) | 0.078 |
Laboratory variables | |||||
Baseline FG (mmol/l) | 8.99 (3.89) | 7.55 (2.83) | 9.27 (3.72) | 10.16 (4.44) | < 0.001 |
Mean 12-month FG | 8.10 (2.42) | 6.77 (1.67) | 7.94 (2.11) | 9.55 (2.45) | < 0.001 |
Mean 24-month FG | 8.09 (2.39) | 6.83 (1.67) | 7.88 (2.11) | 9.55 (2.44) | < 0.001 |
Baseline HbA1c (%) | 8.1 (1.9) | 7.1 (1.5) | 8.1 (1.7) | 9.0 (2.1) | < 0.001 |
(mmol/mol) | 65 (20.8) | 54 (16.4) | 65 (18.6) | 75 (23.0) | |
Mean 12-month HbA1c (%) | 7.8 (1.5) | 6.9 (1.0) | 7.7 (1.1) | 8.9 (1.5) | < 0.001 |
(mmol/mol) | 62 (16.4) | 52 (10.9) | 61 (12.0) | 74 (16.4) | |
Mean 24-month HbA1c (%) | 7.8 (1.4) | 6.9 (0.9) | 7.7 (1.1) | 8.9 (1.4) | < 0.001 |
(mmol/mol) | 62 (15.3) | 52 (9.8) | 61 (12.0) | 74 (15.3) | |
Triacylglycerol (mmol/l) | 2.0 (1.5) | 1.9 (1.4) | 1.9 (1.2) | 2.3 (1.8) | 0.081 |
HDL-cholesterol (mmol/l) | 1.11 (0.30) | 1.11 (0.28) | 1.11 (0.28) | 1.09 (0.34) | 0.47 |
LDL-cholesterol (mmol/l) | 3.03 (1.00) | 3.10 (1.01) | 2.97 (0.93) | 3.05 (1.09) | 0.48 |
Glomerular filtration rate (ml/min/1.73 m2) | 81 (20) | 82 (18) | 81 (20) | 79 (23) | 0.22 |
Albuminuria (mg/24 h) | 13 (7–42) | 10 (6–23) | 13 (7–28) | 20 (9–98) | < 0.001 |
Macrovascular outcomesa | |||||
Total CVEs | 128 (2.56) | 29 (1.69) | 39 (2.38) | 60 (3.89) | < 0.001 |
Major CVEs | 96 (1.86) | 21 (1.20) | 28 (1.67) | 47 (2.92) | < 0.001 |
Cardiovascular mortality | 67 (1.26) | 14 (0.77) | 20 (1.17) | 33 (1.94) | 0.007 |
All-cause mortality | 158 (2.97) | 36 (1.99) | 46 (2.69) | 76 (4.47) | < 0.001 |
Microvascular outcomesb | |||||
Retinopathy (incident/worsening) (n = 533) | 152 (4.88) | 32 (2.73) | 42 (4.15) | 78 (8.84) | < 0.001 |
Renal composite (n = 615) | 183 (4.71) | 43 (3.16) | 57 (4.64) | 83 (6.71) | < 0.001 |
Microalbuminuria (incident) (n = 436) | 89 (3.23) | 25 (2.30) | 33 (3.61) | 31 (4.30) | 0.048 |
Renal failure (n = 615) | 91 (2.15) | 16 (1.10) | 25 (1.85) | 50 (3.63) | < 0.001 |
Peripheral neuropathy (incident/worsening) (n = 471) | 96 (20.4%) | 20 (12.1%) | 34 (22.1%) | 42 (28.4%) | < 0.001 |
Peripheral neuropathy (incident) (n = 338) | 42 (12.4%) | 13 (9.7%) | 13 (12.4%) | 16 (16.8%) | 0.11 |
Endpoints occurrence during follow-up
Risks associated with increased long-term glycemic variability
Outcome | Glycemic parameter | 12-month glycemic variability | 24-month glycemic variability | ||||
---|---|---|---|---|---|---|---|
Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | ||
Total CV events n = 128 | FG-SD | 1.48 (1.28–1.70)* | 1.30 (1.10–1.54)† | 1.23 (1.00–1.51) | 1.54 (1.34–1.78)* | 1.41 (1.18–1.67)* | 1.36 (1.09–1.69)† |
FG-VC | 1.48 (1.25–1.74)* | 1.33 (1.10–1.61)† | 1.26 (1.04–1.54)‡ | 1.58 (1.33–1.88)* | 1.44 (1.18–1.75)* | 1.37 (1.12–1.69)† | |
HbA1c-SD | 1.33 (1.15–1.53)* | 1.22 (1.05–1.42)† | 1.11 (0.91–1.34) | 1.39 (1.21–1.60)* | 1.29 (1.11–1.49)† | 1.20 (1.00–1.44) | |
HbA1c-VC | 1.26 (1.09–1.46)† | 1.19 (1.03–1.38)‡ | 1.10 (0.93–1.30) | 1.32 (1.14–1.52)* | 1.25 (1.08–1.44)† | 1.17 (0.99–1.38) | |
HbA1c-MEANa | – | – | 1.24 (0.96–1.60) | – | – | 1.18 (0.93–1.49) | |
Major CV events n = 96 | FG-SD | 1.51 (1.28–1.77)* | 1.33 (1.09–1.61)† | 1.19 (0.94–1.51) | 1.54 (1.30–1.82)* | 1.35 (1.10–1.65)† | 1.23 (0.96–1.59) |
FG-VC | 1.46 (1.20–1.77)* | 1.31 (1.05–1.63)‡ | 1.24 (0.99–1.57) | 1.53 (1.25–1.87)* | 1.34 (1.06–1.69)‡ | 1.29 (1.01–1.64)‡ | |
HbA1c-SD | 1.40 (1.19–1.63)* | 1.28 (1.08–1.51)† | 1.19 (0.97–1.46) | 1.44 (1.23–1.68)* | 1.31 (1.11–1.55)† | 1.23 (1.00–1.51)‡ | |
HbA1c-VC | 1.34 (1.14–1.57)* | 1.25 (1.06–1.47)† | 1.17 (0.98–1.41) | 1.37 (1.17–1.61)* | 1.28 (1.08–1.50)† | 1.21 (1.01–1.44)‡ | |
HbA1c-MEANa | – | – | 1.14 (0.85–1.53) | – | – | 1.16 (0.88–1.52) | |
CV mortality n = 67 | FG-SD | 1.51 (1.26–1.82)* | 1.47 (1.17–1.86)* | 1.29 (0.97–1.73) | 1.65 (1.36–2.00)* | 1.64 (1.29–2.09)* | 1.50 (1.10–2.03)† |
FG-VC | 1.51 (1.21–1.89)* | 1.48 (1.14–1.92)† | 1.37 (1.04–1.81)‡ | 1.70 (1.34–2.16)* | 1.64 (1.25–2.15)* | 1.56 (1.17–2.06)† | |
HbA1c-SD | 1.51 (1.27–1.80)* | 1.38 (1.14–1.67)* | 1.24 (0.97–1.58) | 1.54 (1.29–1.85)* | 1.42 (1.17–1.72)* | 1.26 (0.99–1.61) | |
HbA1c-VC | 1.43 (1.20–1.71)* | 1.35 (1.12–1.62)† | 1.23 (1.00–1.52)‡ | 1.44 (1.21–1.73)* | 1.37 (1.13–1.65)* | 1.24 (1.01–1.54)‡ | |
HbA1c-MEANa | – | – | 1.28 (0.88–1.84) | – | – | 1.27 (0.91–1.79) | |
All-cause mortality n = 158 | FG-SD | 1.51 (1.34–1.71)* | 1.42 (1.23–1.65)* | 1.44 (1.20–1.73)* | 1.60 (1.41–1.81)* | 1.54 (1.32–1.79)* | 1.59 (1.32–1.93)* |
FG-VC | 1.53 (1.33–1.77)* | 1.45 (1.24–1.71)* | 1.43 (1.20–1.69)* | 1.66 (1.42–1.93)* | 1.55 (1.31–1.85)* | 1.53 (1.28–1.82)* | |
HbA1c-SD | 1.41 (1.25–1.60)* | 1.29 (1.13–1.48)* | 1.25 (1.06–1.47)† | 1.42 (1.25–1.61)* | 1.30 (1.14–1.49)* | 1.23 (1.04–1.46)‡ | |
HbA1c-VC | 1.35 (1.19–1.52)* | 1.26 (1.11–1.44)* | 1.21 (1.04–1.40)‡ | 1.34 (1.18–1.52)* | 1.25 (1.10–1.43)* | 1.19 (1.02–1.38)‡ | |
HbA1c-MEANa | – | – | 1.07 (0.84–1.35) | – | – | 1.08 (0.87–1.34) |
Outcome | Glycemic parameter | 12-month glycemic variability | 24-month glycemic variability | ||||
---|---|---|---|---|---|---|---|
Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | ||
Retinopathy (incident or worsening) n = 152 | FG-SD | 1.54 (1.35–1.76)* | 1.27 (1.08–1.49)† | 1.12 (0.93–1.35) | 1.49 (1.31–1.69)* | 1.28 (1.09–1.51)† | 1.11 (0.91–1.35) |
FG-VC | 1.48 (1.27–1.71)* | 1.18 (1.00–1.39)‡ | 1.12 (0.94–1.34) | 1.48 (1.27–1.72)* | 1.20 (1.01–1.43)‡ | 1.13 (0.93–1.36) | |
HbA1c-SD | 1.27 (1.12–1.43)* | 1.16 (1.00–1.33)‡ | 0.99 (0.83–1.18) | 1.31 (1.16–1.47)* | 1.21 (1.05–1.39)† | 1.05 (0.89–1.25) | |
HbA1c-VC | 1.21 (1.06–1.38)† | 1.12 (0.97–1.30) | 1.00 (0.85–1.18) | 1.27 (1.11–1.44)* | 1.17 (1.02–1.34)‡ | 1.06 (0.91–1.24) | |
HbA1c-MEANa | – | – | 1.27 (1.00–1.60)‡ | – | – | 1.27 (1.03–1.58)‡ | |
Composite renal outcome n = 183 | FG-SD | 1.29 (1.14–1.47)* | 1.19 (1.03–1.39)‡ | 1.15 (0.97–1.36) | 1.37 (1.20–1.55)* | 1.30 (1.12–1.51)† | 1.25 (1.05–1.48)‡ |
FG-VC | 1.24 (1.08–1.42)† | 1.14 (0.98–1.33) | 1.11 (0.94–1.30) | 1.30 (1.13–1.49)* | 1.21 (1.04–1.41)‡ | 1.19 (1.01–1.40)‡ | |
HbA1c-SD | 1.24 (1.09–1.40)† | 1.14 (0.99–1.30) | 1.06 (0.90–1.26) | 1.29 (1.14–1.46)* | 1.19 (1.04–1.37)‡ | 1.12 (0.95–1.32) | |
HbA1c-VC | 1.19 (1.05–1.36)† | 1.11 (0.97–1.27) | 1.05 (0.90–1.22) | 1.23 (1.09–1.40)† | 1.15 (1.01–1.31)‡ | 1.09 (0.94–1.26) | |
HbA1c-MEANa | – | – | 1.15 (0.91–1.46) | – | – | 1.12 (0.91–1.39) | |
Microalbuminuria (incident) n = 89 | FG-SD | 1.21 (0.98–1.48) | 1.24 (0.98–1.56) | 1.21 (0.91–1.62) | 1.27 (1.04–1.56)‡ | 1.34 (1.06–1.69)‡ | 1.34 (1.00–1.79)‡ |
FG-VC | 1.14 (0.93–1.41) | 1.17 (0.93–1.48) | 1.15 (0.90–1.48) | 1.21 (0.98–1.48) | 1.26 (1.00–1.58)‡ | 1.25 (0.98–1.60) | |
HbA1c-SD | 1.13 (0.92–1.40) | 1.11 (0.89–1.39) | 1.02 (0.76–1.37) | 1.20 (0.98–1.47) | 1.19 (0.96–1.47) | 1.12 (0.84–1.49) | |
HbA1c-VC | 1.11 (0.89–1.37) | 1.08 (0.87–1.35) | 1.01 (0.78–1.31) | 1.17 (0.95–1.43) | 1.15 (0.93–1.42) | 1.08 (0.85–1.38) | |
HbA1c-MEANa | – | – | 1.03 (0.74–1.45) | – | – | 1.00 (0.73–1.37) | |
Renal failure n = 91 | FG-SD | 1.54 (1.31–1.83)* | 1.27 (1.05–1.55)‡ | 1.22 (0.98–1.53) | 1.70 (1.44–2.01)* | 1.43 (1.16–1.77)† | 1.37 (1.08–1.74)† |
FG-VC | 1.50 (1.24–1.82)* | 1.25 (1.01–1.53)‡ | 1.18 (0.95–1.46) | 1.64 (1.34–2.00)* | 1.32 (1.06–1.64)‡ | 1.29 (1.02–1.61)‡ | |
HbA1c-SD | 1.51 (1.29–1.76)* | 1.34 (1.12–1.60)† | 1.27 (1.02–1.58)‡ | 1.53 (1.30–1.79)* | 1.35 (1.12–1.63)† | 1.25 (1.00–1.60)‡ | |
HbA1c-VC | 1.43 (1.22–1.68)* | 1.33 (1.11–1.59)† | 1.26 (1.03–1.53)‡ | 1.43 (1.22–1.68)* | 1.31 (1.09–1.57)† | 1.23 (1.01–1.50)‡ | |
HbA1c-MEANa | – | – | 1.20 (0.85–1.70) | – | – | 1.28 (0.96–1.70) | |
Peripheral neuropathy (incident or worsening) n = 96 | FG-SD | 1.37 (1.10–1.71)† | 1.09 (0.82–1.44) | 0.96 (0.69–1.34) | 1.58 (1.25–2.00)* | 1.31 (0.98–1.76) | 1.21 (0.86–1.70) |
FG-VC | 1.38 (1.10–1.73)† | 1.16 (0.87–1.54) | 1.04 (0.77–1.40) | 1.56 (1.24–1.96)* | 1.38 (1.04–1.83)‡ | 1.25 (0.93–1.68) | |
HbA1c-SD | 1.42 (1.15–1.76)† | 1.30 (1.01–1.66)‡ | 1.11 (0.82–1.50) | 1.51 (1.21–1.87)* | 1.37 (1.07–1.75)‡ | 1.17 (0.86–1.60) | |
HbA1c-VC | 1.33 (1.07–1.65)‡ | 1.22 (0.95–1.55) | 1.08 (0.83–1.42) | 1.41 (1.14–1.74)† | 1.26 (0.99–1.61) | 1.12 (0.86–1.47) | |
HbA1c-MEANa | – | – | 1.55 (1.03–2.32)‡ | – | – | 1.53 (1.09–2.15)‡ | |
Peripheral neuropathy (incident) n = 42 | FG-SD | 1.33 (0.96–1.84) | 1.10 (0.75–1.63) | 0.95 (0.60–1.50) | 1.44 (1.03–2.01)‡ | 1.23 (0.83–1.84) | 1.09 (0.68–1.74) |
FG-VC | 1.26 (0.91–1.75) | 1.12 (0.76–1.65) | 1.03 (0.68–1.55) | 1.31 (0.95–1.82) | 1.20 (0.81–1.77) | 1.12 (0.74–1.69) | |
HbA1c-SD | 1.66 (1.27–2.17)* | 1.63 (1.19–2.22)† | 1.73 (1.15–2.60)† | 1.76 (1.33–2.32)* | 1.67 (1.22–2.27)* | 1.82 (1.20–2.75)† | |
HbA1c-VC | 1.63 (1.25–2.14)* | 1.58 (1.16–2.16)† | 1.55 (1.09–2.20)‡ | 1.72 (1.30–2.26)* | 1.62 (1.18–2.21)† | 1.60 (1.12–2.28)† | |
HbA1c-MEANa | – | – | 0.91 (0.47–1.74) | – | – | 0.85 (0.47–1.57) |
Outcome | Glycemic parameter | 12-month glycemic variability | 24-month glycemic variability | ||||
---|---|---|---|---|---|---|---|
Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | ||
Total CV events n = 128 | FG-SD | 2.85 (1.79–4.54)* | 2.08 (1.22–3.54)† | 1.71 (0.94–3.10) | 2.39 (1.52–3.77)* | 1.60 (0.95–2.72) | 1.22 (0.68–2.21) |
FG-VC | 2.35 (1.49–3.68)* | 1.82 (1.10–3.01)‡ | 1.62 (0.97–2.71) | 2.54 (1.62–3.99)* | 1.97 (1.18–3.31)‡ | 1.76 (1.04–3.00)‡ | |
HbA1c-SD | 1.93 (1.26–2.95)† | 1.44 (0.91–2.28) | 1.04 (0.59–1.82) | 1.87 (1.22–2.87)† | 1.43 (0.90–2.25) | 1.03 (0.59–1.79) | |
HbA1c-VC | 1.76 (1.15–2.71)‡ | 1.47 (0.94–2.29) | 1.18 (0.72–1.92) | 2.01 (1.31–3.11)† | 1.69 (1.07–2.66)‡ | 1.38 (0.84–2.26) | |
Major CV events n = 96 | FG-SD | 2.74 (1.63–4.61)* | 1.83 (1.01–3.32)‡ | 1.37 (0.70–2.68) | 2.64 (1.56–4.48)* | 1.64 (0.89–3.03) | 1.24 (0.63–2.44) |
FG-VC | 1.92 (1.16–3.19)‡ | 1.42 (0.81–2.49) | 1.31 (0.73–2.33) | 2.37 (1.42–3.97)† | 1.69 (0.94–3.05) | 1.54 (0.85–2.80) | |
HbA1c-SD | 2.47 (1.51–4.05)* | 1.73 (1.03–2.93)‡ | 1.39 (0.75–2.57) | 2.42 (1.47–3.99)† | 1.67 (0.98–2.86) | 1.30 (0.70–2.43) | |
HbA1c-VC | 2.17 (1.34–3.51)† | 1.71 (1.04–2.82)‡ | 1.43 (0.83–2.44) | 2.33 (1.43–3.79)† | 1.78 (1.07–2.97)‡ | 1.49 (0.86–2.57) | |
CV mortality n = 67 | FG-SD | 3.26 (1.73–6.13)* | 2.67 (1.28–5.59)† | 1.85 (0.81–4.24) | 3.27 (1.72–6.22)* | 2.50 (1.17–5.33)‡ | 1.72 (0.75–3.96) |
FG-VC | 2.26 (1.20–4.24)‡ | 1.92 (0.94–3.94) | 1.60 (0.76–3.37) | 3.23 (1.68–6.21)* | 2.82 (1.34–5.95)† | 2.41 (1.13–5.17)‡ | |
HbA1c-SD | 3.18 (1.77–5.71)* | 2.60 (1.38–4.91)† | 2.07 (0.97–4.40) | 3.02 (1.65–5.51)* | 2.40 (1.25–4.62)† | 1.72 (0.80–3.71) | |
HbA1c-VC | 2.74 (1.53–4.89)† | 2.22 (1.22–4.06)† | 1.78 (0.92–3.44) | 2.81 (1.57–5.02)* | 2.33 (1.26–4.32)† | 1.81 (0.93–3.54) | |
All-cause mortality n = 158 | FG-SD | 3.20 (2.14–4.79)* | 2.62 (1.64–4.17)* | 2.60 (1.55–4.37)* | 2.80 (1.86–4.21)* | 2.05 (1.28–3.27)† | 1.82 (1.09–3.06)‡ |
FG-VC | 2.45 (1.63–3.69)* | 2.07 (1.31–3.28)† | 1.96 (1.22–3.14)† | 2.71 (1.79–4.08)* | 2.21 (1.39–3.51)* | 2.06 (1.28–3.31)† | |
HbA1c-SD | 2.15 (1.45–3.20)* | 1.64 (1.07–2.51)‡ | 1.35 (0.80–2.25) | 1.95 (1.31–2.91)* | 1.48 (0.96–2.28) | 1.10 (0.66–1.83) | |
HbA1c-VC | 2.12 (1.43–3.15)* | 1.72 (1.15–2.59)† | 1.51 (0.97–2.35) | 2.19 (1.46–3.27)* | 1.76 (1.16–2.69)† | 1.49 (0.95–2.34) |
Outcome | Glycemic parameter | 12-month glycemic variability | 24-month glycemic variability | ||||
---|---|---|---|---|---|---|---|
Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | Model 1 HR (95% CI) | Model 2 HR (95% CI) | Model 3 HR (95% CI) | ||
Retinopathy (incident or worsening) n = 152 | FG-SD | 2.78 (1.84–4.21)* | 1.66 (1.04–2.65)‡ | 1.17 (0.69–1.98) | 3.24 (2.14–4.92)* | 1.89 (1.18–3.02)† | 1.36 (0.79–2.33) |
FG-VC | 2.47 (1.64–3.71)* | 1.50 (0.96–2.33) | 1.31 (0.82–2.09) | 2.47 (1.64–3.70)* | 1.45 (0.93–2.25) | 1.23 (0.77–1.96) | |
HbA1c-SD | 2.59 (1.70–3.94)* | 1.68 (1.07–2.64)‡ | 1.13 (0.66–1.95) | 3.02 (1.96–4.65)* | 2.01 (1.26–3.19)† | 1.44 (0.84–2.46) | |
HbA1c-VC | 2.03 (1.34–3.06)† | 1.50 (0.98–2.31) | 1.16 (0.74–1.84) | 2.47 (1.62–3.76)* | 1.82 (1.17–2.84)† | 1.41 (0.88–2.26) | |
Composite renal outcome n = 183 | FG-SD | 1.87 (1.29–2.71)† | 1.52 (1.00–2.31) | 1.32 (0.82–2.13) | 2.18 (1.50–3.17)* | 1.88 (1.23–2.87)† | 1.66 (1.03–2.67)‡ |
FG-VC | 1.69 (1.17–2.45)† | 1.49 (0.99–2.22) | 1.39 (0.91–2.12) | 1.84 (1.28–2.66)† | 1.66 (1.12–2.51)‡ | 1.60 (1.05–1.43)‡ | |
HbA1c-SD | 1.52 (1.06–2.17)‡ | 1.23 (0.84–1.81) | 1.00 (0.62–1.59) | 1.68 (1.18–2.39)† | 1.38 (0.94–2.02) | 1.14 (0.72–1.81) | |
HbA1c-VC | 1.42 (1.00–2.02)‡ | 1.22 (0.85–1.76) | 1.06 (0.72–1.58) | 1.56 (1.10–2.21)‡ | 1.35 (0.93–1.94) | 1.16 (0.79–1.72) | |
Microalbuminuria (incident) n = 89 | FG-SD | 1.66 (0.98–2.81) | 1.67 (0.93–2.98) | 1.60 (0.81–3.13) | 1.70 (1.00–2.90)‡ | 1.78 (0.98–3.22) | 1.64 (0.81–3.33) |
FG-VC | 1.32 (0.78–2.25) | 1.37 (0.77–2.42) | 1.31 (0.73–2.37) | 1.63 (0.96–2.78) | 1.85 (1.03–3.30)‡ | 1.80 (0.98–3.30) | |
HbA1c-SD | 1.10 (0.66–1.83) | 1.04 (0.60–1.81) | 0.80 (0.40–1.60) | 1.31 (0.79–2.18) | 1.28 (0.74–2.22) | 1.06 (0.54–2.11) | |
HbA1c-VC | 1.09 (0.65–1.81) | 1.05 (0.62–1.79) | 0.90 (0.50–1.63) | 1.32 (0.79–2.19) | 1.27 (0.74–2.19) | 1.09 (0.59–2.01) | |
Renal failure n = 91 | FG-SD | 2.70 (1.54–4.72)* | 1.70 (0.90–3.20) | 1.36 (0.67–2.77) | 3.63 (2.05–6.45)* | 2.14 (1.13–4.07)‡ | 1.75 (0.86–3.54) |
FG-VC | 2.56 (1.46–4.50)* | 1.86 (1.01–3.44)‡ | 1.63 (0.86–3.08) | 2.67 (1.56–4.59)* | 1.71 (0.95–3.09) | 1.57 (0.85–2.88) | |
HbA1c-SD | 3.40 (1.95–5.92)* | 2.34 (1.29–4.24)† | 2.12 (1.05–4.27)‡ | 3.12 (1.82–5.37)* | 2.13 (1.19–3.81)‡ | 1.78 (0.91–3.49) | |
HbA1c-VC | 2.43 (1.43–4.11)* | 1.91 (1.10–3.30)‡ | 1.66 (0.92–2.98) | 2.38 (1.42–4.01)* | 1.78 (1.03–3.08)‡ | 1.50 (0.84–2.67) | |
Peripheral neuropathy (incident or worsening) n = 96 | FG-SD | 2.50 (1.35–4.62)† | 1.45 (0.70–3.00) | 1.05 (0.46–2.41) | 2.82 (1.54–5.13)* | 1.73 (0.85–3.50) | 1.35 (0.60–3.03) |
FG-VC | 3.45 (1.77–6.72)* | 2.52 (1.17–5.39)‡ | 2.02 (0.91–4.45) | 3.60 (1.91–6.79)* | 2.82 (1.36–5.87)† | 2.33 (1.09–4.97)‡ | |
HbA1c-SD | 2.07 (1.16–3.77)‡ | 1.35 (0.69–2.68) | 0.76 (0.33–1.75) | 2.14 (1.18–3.90)‡ | 1.39 (0.70–2.77) | 0.79 (0.34–1.79) | |
HbA1c-VC | 1.82 (1.00–3.34)‡ | 1.34 (0.69–2.62) | 0.97 (0.47–2.01) | 2.38 (1.29–4.39)† | 1.63 (0.83–3.22) | 1.20 (0.57–2.50) | |
Peripheral neuropathy (incident) n = 42 | FG-SD | 2.04 (0.90–4.62) | 1.46 (0.54–3.95) | 0.99 (0.31–3.16) | 1.78 (0.80–3.97) | 1.15 (0.44–2.99) | 0.73 (0.24–2.25) |
FG-VC | 2.56 (1.07–6.13)‡ | 2.13 (0.78–5.81) | 1.80 (0.64–5.07) | 2.46 (1.05–5.78)‡ | 2.18 (0.83–5.72) | 1.88 (0.69–5.13) | |
HbA1c-SD | 2.17 (0.98–4.79) | 1.55 (0.62–3.85) | 1.07 (0.35–3.33) | 2.21 (1.00–4.89)‡ | 1.59 (0.64–3.94) | 1.15 (0.37–3.52) | |
HbA1c-VC | 2.78 (1.16–6.67)‡ | 2.14 (0.82–5.58) | 1.73 (0.61–4.94) | 3.06 (1.28–7.23)‡ | 2.22 (0.86–5.75) | 1.85 (0.66–5.18) |