Background
Methods
Study design
Exposures
Outcomes: cardiovascular and renal events and mortality
Baseline covariates
Data analysis
Results
Factor | Full cohort with complete case | Propensity score-matched cohort | ||||||
---|---|---|---|---|---|---|---|---|
Total (N = 11,293) | MM group (N = 7493) | Control group (N = 3800) | P value | Total (N = 6800) | MM group (N = 3400) | Control group (N = 3400) | P value | |
Socio-demographic (%, n) | ||||||||
Age (mean ± SD, n), years | 62.05 ± 10.83 (11,293) | 61.70 ± 10.75 (7493) | 62.75 ± 10.97 (3800) | <0.001* | 62.57 ± 10.78 (6800) | 62.64 ± 10.58 (3400) | 62.51 ± 10.98 (3400) | 0.621 |
Gender | 0.728 | 0.711 | ||||||
Female | 59.51 % (6721) | 59.63 % (4468) | 59.29 % (2253) | 59.31 % (4033) | 59.09 % (2009) | 59.53 % (2024) | ||
Male | 40.49 % (4572) | 40.37 % (3025) | 40.71 % (1547) | 40.69 % (2767) | 40.91 % (1391) | 40.47 % (1376) | ||
Smoking status | <0.001* | 0.878 | ||||||
Non-smoker | 92.69 % (10,468) | 91.82 % (6880) | 94.42 % (3588) | 94.04 % (6395) | 94.09 % (3199) | 94.00 % (3196) | ||
Smoker | 7.31 % (825) | 8.18 % (613) | 5.58 % (212) | 5.96 % (405) | 5.91 % (201) | 6.00 % (204) | ||
Alcohol status | 0.990 | 0.634 | ||||||
Non-drinker | 84.77 % (9573) | 84.77 % (6352) | 84.76 % (3221) | 85.03 % (5782) | 85.24 % (2898) | 84.82 % (2884) | ||
Drinker | 15.23 % (1720) | 15.23 % (1141) | 15.24 % (579) | 14.97 % (1018) | 14.76 % (502) | 15.18 % (516) | ||
Educational level | 0.235 | 0.672 | ||||||
No formal education/primary | 60.23 % (6802) | 59.84 % (4484) | 61.00 % (2318) | 61.04 % (4151) | 61.29 % (2084) | 60.79 % (2067) | ||
Secondary/tertiary | 39.77 % (4491) | 40.16 % (3009) | 39.00 % (1482) | 38.96 % (2649) | 38.71 % (1316) | 39.21 % (1333) | ||
Clinical parameters (Mean ± SD) | ||||||||
HbA1c, % | 6.83 ± 0.96 (11,293) | 6.99 ± 1.05 (7493) | 6.52 ± 0.64 (3800) | <0.001* | 6.57 ± 0.64 (6800) | 6.57 ± 0.67 (3400) | 6.58 ± 0.62 (3400) | 0.351 |
SBP, mmHg | 133.17 ± 16.91 (11,293) | 132.92 ± 17.02 (7493) | 133.67 ± 16.69 (3800) | 0.026* | 133.41 ± 16.77 (6800) | 133.28 ± 16.92 (3400) | 133.54 ± 16.62 (3400) | 0.512 |
DBP, mmHg | 74.94 ± 10.04 (11,293) | 74.98 ± 10.08 (7493) | 74.84 ± 9.98 (3800) | 0.479 | 74.75 ± 9.97 (6800) | 74.68 ± 10.00 (3400) | 74.83 ± 9.95 (3400) | 0.530 |
LDL-C, mmol/L | 3.25 ± 0.84 (11,293) | 3.18 ± 0.82 (7493) | 3.40 ± 0.87 (3800) | <0.001* | 3.34 ± 0.84 (6800) | 3.32 ± 0.83 (3400) | 3.35 ± 0.85 (3400) | 0.106 |
TC/HDL-C Ratio | 4.36 ± 1.26 (11,293) | 4.31 ± 1.13 (7493) | 4.45 ± 1.46 (3800) | <0.001* | 4.39 ± 1.16 (6800) | 4.38 ± 1.13 (3400) | 4.41 ± 1.18 (3400) | 0.327 |
Triglyceride, mmol/L | 1.65 ± 0.89 (11,293) | 1.68 ± 0.91 (7493) | 1.59 ± 0.85 (3800) | <0.001* | 1.60 ± 0.83 (6800) | 1.60 ± 0.78 (3400) | 1.60 ± 0.87 (3400) | 0.914 |
BMI, kg/m2
| 25.63 ± 3.91 (11,293) | 25.69 ± 3.89 (7493) | 25.51 ± 3.94 (3800) | 0.018* | 25.59 ± 3.85 (6800) | 25.56 ± 3.72 (3400) | 25.61 ± 3.98 (3400) | 0.665 |
Stage of CKD (%, n) | <0.001* | 0.711 | ||||||
Stage 1 | 35.74 % (4036) | 37.89 % (2839) | 31.50 % (1197) | 32.85 % (2234) | 32.62 % (1109) | 33.09 % (1125) | ||
Stage 2 | 55.98 % (6322) | 54.16 % (4058) | 59.58 % (2264) | 58.71 % (3992) | 59.15 % (2011) | 58.26 % (1981) | ||
Stage 3 | 8.28 % (935) | 7.95 % (596) | 8.92 % (339) | 8.44 % (574) | 8.24 % (280) | 8.65 % (294) | ||
Disease characteristics (%, n) | ||||||||
Duration of DM | <0.001* | 0.652 | ||||||
<5 years | 63.91 % (7217) | 59.72 % (4475) | 72.16 % (2742) | 70.03 % (4762) | 70.06 % (2382) | 70.00 % (2380) | ||
5–10 years | 23.84 % (2692) | 26.37 % (1976) | 18.84 % (716) | 20.50 % (1394) | 20.76 % (706) | 20.24 % (688) | ||
>10 years | 12.26 % (1384) | 13.91 % (1042) | 9.00 % (342) | 9.47 % (644) | 9.18 % (312) | 9.76 % (332) | ||
Hypertension | <0.001* | 0.669 | ||||||
No | 28.30 % (3196) | 31.59 % (2367) | 21.82 % (829) | 23.81 % (1619) | 24.03 % (817) | 23.59 % (802) | ||
Yes | 71.70 % (8097) | 68.41 % (5126) | 78.18 % (2971) | 76.19 % (5181) | 75.97 % (2583) | 76.41 % (2598) | ||
Treatment modalities (%, n) | ||||||||
Use of anti-hypertensive drugs | <0.001* | 0.956 | ||||||
No | 29.33 % (3312) | 31.06 % (2327) | 25.92 % (985) | 26.41 % (1796) | 26.38 % (897) | 26.44 % (899) | ||
Yes | 70.67 % (7981) | 68.94 % (5166) | 74.08 % (2815) | 73.59 % (5004) | 73.62 % (2503) | 73.56 % (2501) | ||
Use of lipid-lowering agents | 0.032* | 0.699 | ||||||
No | 95.71 % (10809) | 95.42 % (7150) | 96.29 % (3659) | 96.32 % (6550) | 96.41 % (3278) | 96.24 % (3272) | ||
Yes | 4.29 % (484) | 4.58 % (343) | 3.71 % (141) | 3.68 % (250) | 3.59 % (122) | 3.76 % (128) |
Clinical parameters (Mean ± SD) | Full cohort with complete case | Propensity score-matched cohort | ||||||
---|---|---|---|---|---|---|---|---|
MM group paired diff.a (N = 7493) | Control group paired diff.a (N = 3800) | Diff. in diff. (MM group—control group) | P value | MM group paired diff.a (N = 3400) | Control group paired diff.a (N = 3400) | Diff. in diff. (MM group—control group) | P value | |
HbA1c, % | −0.04 ± 1.08 | 0.29 ± 0.68 | −0.32 | <0.001* | 0.19 ± 0.79 | 0.28 ± 0.69 | −0.09 | <0.001* |
SBP, mmHg | −2.86 ± 19.33 | −1.91 ± 19.04 | −0.95 | 0.013* | −3.07 ± 19.40 | −1.95 ± 18.95 | −1.12 | 0.016* |
DBP, mmHg | −2.20 ± 10.64 | −1.42 ± 10.16 | −0.78 | <0.001* | −2.25 ± 10.54 | −1.30 ± 10.15 | −0.95 | <0.001* |
LDL-C, mmol/L | −0.58 ± 0.90 | −0.48 ± 0.89 | −0.10 | <0.001* | −0.71 ± 0.92 | −0.44 ± 0.87 | −0.27 | <0.001* |
TC/HDL-C ratio | −0.69 ± 1.04 | −0.60 ± 1.22 | −0.09 | <0.001* | −0.78 ± 1.07 | −0.56 ± 1.01 | −0.23 | <0.001* |
Triglyceride, mmol/L | −0.21 ± 0.84 | −0.14 ± 0.75 | −0.07 | <0.001* | −0.18 ± 0.73 | −0.14 ± 0.77 | −0.03 | 0.059 |
BMI, kg/m2
| −0.30 ± 1.55 | −0.05 ± 1.46 | −0.25 | <0.001* | −0.19 ± 1.54 | −0.08 ± 1.43 | −0.11 | 0.002* |
Stage of CKD (%, n/N) | Full cohort with complete case | Propensity score-matched cohort | ||||
---|---|---|---|---|---|---|
MM group | Control group | P value | MM group | Control group | P value | |
Stage 1 (baseline) to stage 2 or above (post) | 21.98 % (624/2839) | 21.72 % (260/1197) | 0.856 | 23.26 % (258/1109) | 21.07 % (237/1125) | 0.211 |
Stage 2 (baseline) to stage 3 or above (post) | 10.62 % (431/4058) | 6.89 % (156/2 264) | <0.001* | 11.09 % (223/2011) | 6.66 % (132/1981) | <0.001* |
Stage 3 (baseline) to stage 4 or above (post) | 10.74 % (64/596) | 9.73 % (33/339) | 0.629 | 11.43 % (32/280) | 9.18 % (27/294) | 0.376 |
Total | 14.93 % (1119/7493) | 11.82 % (449/3800) | <0.001* | 15.09 % (513/3400) | 11.65 % (396/3400) | <0.001* |
Event | Cumulative incidence | Incidence rate (cases/1000 person-years) | Person-years | Median follow-up periods (months) | ||
---|---|---|---|---|---|---|
No. of event | Rate (%) | Estimate | 95 % CIa
| |||
Full cohort (N = 11,293) | ||||||
All-cause mortality | 397 | 3.52 | 8.713 | (7.877–9.614) | 45,561.5 | 60.5 |
CVD | 610 | 5.40 | 13.527 | (12.474–14.644) | 45,095.8 | 58.5 |
CHD | 294 | 2.60 | 6.482 | (5.763–7.267) | 45,353.5 | 59.5 |
Stroke | 266 | 2.36 | 5.865 | (5.182–6.614) | 45,351.9 | 59.5 |
Heart failure | 139 | 1.23 | 3.055 | (2.569–3.608) | 45,493.0 | 60.5 |
Severe CKD | 333 | 2.95 | 5.266 | (4.716–5.864) | 63,230.1 | 60.5 |
MM group (N = 7493) | ||||||
All-cause Mortality | 240 | 3.20 | 7.591 | (6.661–8.615) | 31,615.0 | 62.5 |
CVD | 382 | 5.10 | 12.204 | (11.011–13.492) | 31,300.8 | 61.5 |
CHD | 176 | 2.35 | 5.591 | (4.796–6.481) | 31,477.2 | 61.5 |
Stroke | 170 | 2.27 | 5.403 | (4.621–6.279) | 31,466.3 | 61.5 |
Heart failure | 85 | 1.13 | 2.692 | (2.150–3.328) | 31,580.7 | 62.5 |
Severe CKD | 230 | 3.07 | 7.275 | (6.365–8.278) | 31,615.0 | 62.5 |
Control group (N = 3800) | ||||||
All-cause Mortality | 157 | 4.13 | 11.257 | (9.565–13.162) | 13,946.5 | 45.5 |
CVD | 228 | 6.00 | 16.528 | (14.452–18.818) | 13,795.0 | 44.5 |
CHD | 118 | 3.11 | 8.504 | (7.039–10.184) | 13,876.3 | 45 |
Stroke | 96 | 2.53 | 6.914 | (5.600–8.443) | 13,885.6 | 44.5 |
Heart failure | 54 | 1.42 | 3.881 | (2.916–5.064) | 13,912.3 | 45.5 |
Severe CKD | 103 | 2.71 | 7.385 | (6.028–8.957) | 13,946.5 | 45.5 |
Propensity score-matched cohort (N = 6800) | ||||||
All-cause mortality | 249 | 3.66 | 9.104 | (8.009–10.308) | 27,349.6 | 60.5 |
CVD | 366 | 5.38 | 13.527 | (12.177–14.987) | 27,056.3 | 58.5 |
CHD | 183 | 2.69 | 6.724 | (5.785–7.772) | 27,217.4 | 59.5 |
Stroke | 162 | 2.38 | 5.951 | (5.070–6.942) | 27,221.0 | 59.5 |
Heart failure | 77 | 1.13 | 2.821 | (2.226–3.525) | 27,298.1 | 60.5 |
Severe CKD | 197 | 2.90 | 7.203 | (6.232–8.282) | 27,349.6 | 60.5 |
MM group (N = 3400) | ||||||
All-cause mortality | 113 | 3.32 | 7.493 | (6.175–9.008) | 15,081.4 | 62.5 |
CVD | 169 | 4.97 | 11.330 | (9.686–13.173) | 14,915.8 | 62.5 |
CHD | 81 | 2.38 | 5.398 | (4.287–6.710) | 15,004.7 | 62.5 |
Stroke | 76 | 2.24 | 5.065 | (3.990–6.339) | 15,006.4 | 62.5 |
Heart failure | 34 | 1.00 | 2.257 | (1.563–3.154) | 15,062.0 | 62.5 |
Severe CKD | 112 | 3.29 | 7.426 | (6.115–8.936) | 15,081.4 | 62.5 |
Control group (N = 3400) | ||||||
All-cause mortality | 136 | 4.00 | 11.086 | (9.301–13.113) | 12,268.2 | 44.5 |
CVD | 197 | 5.79 | 16.227 | (14.040–18.658) | 12,140.6 | 43.5 |
CHD | 102 | 3.00 | 8.352 | (6.810–10.139) | 12,212.8 | 43.5 |
Stroke | 86 | 2.53 | 7.041 | (5.632–8.695) | 12,214.6 | 43.5 |
Heart failure | 43 | 1.26 | 3.514 | (2.543–4.734) | 12,236.1 | 43.5 |
Severe CKD | 85 | 2.50 | 6.929 | (5.534–8.567) | 12,268.2 | 44.5 |
MM group comparing with control group | Harrell’s C-statistic | |||
---|---|---|---|---|
HRa
| 95 % CI | P value | ||
Full cohort (N = 11,293) | ||||
All-cause mortality | 0.725 | (0.584–0.901) | 0.004* | 0.806 (0.783–0.828) |
CVD | 0.726 | (0.609–0.866) | <0.001* | 0.731 (0.711–0.752) |
CHD | 0.670 | (0.521–0.862) | 0.002* | 0.727 (0.698–0.756) |
Stroke | 0.750 | (0.573–0.982) | 0.036* | 0.734 (0.704–0.765) |
Heart failure | 0.795 | (0.551–1.147) | 0.221 | 0.872 (0.844–0.899) |
Chronic kidney disease (eGFR <30 ml/min/1.73 m2) | 1.076 | (0.838–1.381) | 0.565 | 0.848 (0.827–0.870) |
Propensity score-matched cohort (N = 6800) | ||||
All-cause mortality | 0.705 | (0.547–0.908) | 0.007* | 0.809 (0.783–0.836) |
CVD | 0.684 | (0.556–0.842) | <0.001* | 0.731 (0.705–0.756) |
CHD | 0.645 | (0.480–0.866) | 0.004* | 0.720 (0.683–0.758) |
Stroke | 0.698 | (0.511–0.954) | 0.024* | 0.754 (0.719–0.790) |
Heart failure | 0.688 | (0.435–1.086) | 0.109 | 0.865 (0.825–0.906) |
Chronic kidney disease (eGFR <30 ml/min/1.73 m2) | 1.163 | (0.874–1.549) | 0.300 | 0.854 (0.826–0.881) |