Journal of Southern Medical University ›› 2026, Vol. 46 ›› Issue (7): 1634-1647.doi: 10.12122/j.issn.1673-4254.2026.07.17
Buffering effect of intensive lipid lowering on mortality risk in type 2 diabetic patients with chronic kidney disease and challenging glycemic management: a cohort study based on dual metabolic trajectories
Xiaolong WANG(
), Jian YANG, Shuang LIANG, Zheyi DONG()
- Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100853, China
-
Received:2026-01-29Online:2026-07-20Published:2026-07-20 -
Contact:Zheyi DONG E-mail:450391715@qq.com;shengdai26@163.com
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Xiaolong WANG, Jian YANG, Shuang LIANG, Zheyi DONG. Buffering effect of intensive lipid lowering on mortality risk in type 2 diabetic patients with chronic kidney disease and challenging glycemic management: a cohort study based on dual metabolic trajectories[J]. Journal of Southern Medical University, 2026, 46(7): 1634-1647.
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URL: https://www.j-smu.com/EN/10.12122/j.issn.1673-4254.2026.07.17
Fig.1 Trajectories of low-density lipoprotein.
Fig.1 Trajectories of low-density lipoprotein.
Tab.2 Baseline and endpoint characteristics of latent class trajectory groups for LDL-C and HbA1c
| Trajectory cohort | Number of patients [n (%)] | Mean indicator values | ||
|---|---|---|---|---|
| Baseline | Endpoint | Overall | ||
| HbA1c | ||||
| Good control | 3378 (42.3) | 5.50 | 4.88 | 5.11 |
| Moderatel improvement | 3254 (40.7) | 7.12 | 6.16 | 6.64 |
| Poor control | 1359 (17.0) | 8.96 | 8.27 | 8.74 |
| LDL-C | ||||
| Deep control | 3970 (49.7) | 1.82 | 1.58 | 1.65 |
| Standard control | 3231 (40.4) | 2.59 | 2.25 | 2.41 |
| High-level regression | 790 (9.9) | 3.88 | 3.04 | 3.54 |
Tab.2 Baseline and endpoint characteristics of latent class trajectory groups for LDL-C and HbA1c
| Trajectory cohort | Number of patients [n (%)] | Mean indicator values | ||
|---|---|---|---|---|
| Baseline | Endpoint | Overall | ||
| HbA1c | ||||
| Good control | 3378 (42.3) | 5.50 | 4.88 | 5.11 |
| Moderatel improvement | 3254 (40.7) | 7.12 | 6.16 | 6.64 |
| Poor control | 1359 (17.0) | 8.96 | 8.27 | 8.74 |
| LDL-C | ||||
| Deep control | 3970 (49.7) | 1.82 | 1.58 | 1.65 |
| Standard control | 3231 (40.4) | 2.59 | 2.25 | 2.41 |
| High-level regression | 790 (9.9) | 3.88 | 3.04 | 3.54 |
Fig.2 Trajectories of glycated hemoglobin.
Fig.2 Trajectories of glycated hemoglobin.
Tab.3 Baseline characteristics of T2DM patients with CKD stratified by survival status
| Item | Survival (n=7586) | Death (n=405) | Total (n=7991) | P |
|---|---|---|---|---|
| Age (year) | 58.21 (50.47, 64.55) | 65.46 (58.89, 71.69) | 58.58 (50.83, 65.04) | <0.001 |
| Male [n (%)] | 4300(56.7) | 240 (59.3) | 4540 (56.8) | 0.333 |
| BMI (kg/m2) | 25.78 (23.67, 28.37) | 25.51 (23.51, 28.58) | 25.78 (23.66, 28.38) | 0.431 |
| SBP (mmHg) | 130.00 (122.00, 140.00) | 130.00 (126.00, 140.00) | 130.00 (122.00, 140.00) | 0.002 |
| DBP (mmHg) | 80.00 (76.00, 85.00) | 80.00 (78.00, 86.00) | 80.00 (76.00, 85.00) | 0.247 |
| Laboratory tests | ||||
| Hemoglobin (g/L) | 139.00 (127.00, 152.00) | 126.00 (112.00, 141.00) | 139.00 (126.00, 151.00) | <0.001 |
| White blood cells (10⁹/L) | 6.79 (5.68, 8.12) | 7.00 (5.93, 8.53) | 6.79 (5.69, 8.14) | 0.017 |
| Neutrophils (10⁹/L) | 4.14 (3.28, 5.27) | 4.59 (3.61, 5.89) | 4.15 (3.30, 5.30) | <0.001 |
| Lymphocytes (10⁹/L) | 1.92 (1.51, 2.38) | 1.68 (1.26, 2.12) | 1.90 (1.50, 2.37) | <0.001 |
| Platelets (10⁹/L) | 226.00 (189.00, 270.00) | 210.00 (169.00, 258.00) | 226.00 (187.70, 269.00) | <0.001 |
| ALT (U/L) | 19.70 (14.00, 29.60) | 15.90 (11.40, 23.00) | 19.50 (14.00, 29.10) | <0.001 |
| AST (U/L) | 18.90 (15.00, 24.50) | 16.60 (13.50, 22.00) | 18.70 (15.00, 24.30) | <0.001 |
| Total protein (g/L) | 69.80 (64.50, 74.50) | 66.30 (60.60, 71.30) | 69.60 (64.20, 74.40) | <0.001 |
| Albumin (g/L) | 42.20 (38.70, 45.30) | 37.90 (34.10, 42.00) | 42.00 (38.50, 45.10) | <0.001 |
| Direct bilirubin (μmol/L) | 2.90 (2.00, 4.19) | 2.55 (1.60, 3.50) | 2.90 (1.98, 4.13) | <0.001 |
| Total bilirubin (μmol/L) | 7.90 (5.74, 10.70) | 5.90 (4.20, 8.65) | 7.85 (5.63, 10.61) | <0.001 |
| Total cholesterol (mmol/L) | 5.12 (4.31, 6.04) | 5.09 (4.20, 6.18) | 5.12 (4.30, 6.05) | 0.922 |
| Triglycerides (mmol/L) | 1.78 (1.23, 2.71) | 1.77 (1.21, 2.60) | 1.78 (1.23, 2.70) | 0.464 |
| HDL-C (mmol/L) | 1.13 (0.96, 1.35) | 1.09 (0.91, 1.33) | 1.13 (0.95, 1.35) | 0.001 |
| LDL-C( mmol/L) | 2.15 (1.70, 2.80) | 2.29 (1.74, 3.13) | 2.16 (1.70, 2.81) | 0.009 |
| Glucose (mmol/L) | 8.55 (6.84, 11.43) | 8.67 (6.44, 11.88) | 8.57 (6.83, 11.46) | 0.934 |
| Blood urea nitrogen (mmol/L) | 5.90 (4.73, 7.50) | 7.60 (5.89, 10.60) | 5.96 (4.76, 7.61) | <0.001 |
| Uric acid (μmol/L) | 335.00 (275.00, 410.00) | 352.00 (283.10, 445.90) | 336.00 (275.00, 411.00) | <0.001 |
| Serum creatinine (μmol/L) | 70.90 (57.00, 92.00) | 100.40 (74.00, 148.00) | 71.80 (57.30, 94.00) | <0.001 |
| eGFR [mL·min-1·(1.73 m²)-1] | 93.21 (71.11, 104.60) | 60.73 (38.36, 85.72) | 92.40 (68.84, 104.09) | <0.001 |
| INR | 0.94 (0.89, 1.00) | 0.96 (0.90, 1.03) | 0.94 (0.89, 1.00) | <0.001 |
| D-dimer (μg/mL) | 0.36 (0.22, 0.60) | 0.61 (0.33, 1.11) | 0.37 (0.22, 0.63) | <0.001 |
| Phosphorus (mmol/L) | 1.18 (1.06, 1.31) | 1.19 (1.05, 1.37) | 1.18 (1.06, 1.32) | 0.251 |
| Potassium (mmol/L) | 4.14 (3.86, 4.43) | 4.20 (3.85, 4.60) | 4.14 (3.86, 4.44) | 0.013 |
| Sodium (mmol/L) | 140.08 (138.00, 142.00) | 140.00 (137.40, 142.10) | 140.07 (138.00, 142.00) | 0.250 |
| Calcium (mmol/L) | 2.29 (2.19, 2.38) | 2.18 (2.05, 2.30) | 2.28 (2.18, 2.38) | <0.001 |
| 24-hour UTP (g/24 h) | 0.24 (0.11, 0.83) | 0.95 (0.26, 4.03) | 0.25 (0.11, 0.94) | <0.001 |
| CKD stage [n (%)] | <0.001 | |||
| G1 | 4237 (55.8) | 81 (20.0) | 4318 (54.0) | |
| G2 | 2057 (27.1) | 123 (30.4) | 2180 (27.3) | |
| G3 | 1063 (14.0) | 131 (32.3) | 1194 (14.9) | |
| G4 | 163 (2.1) | 46 (11.4) | 209 (2.6) | |
| G5 | 66 (0.9) | 24 (5.9) | 90 (1.1) | |
| Comorbidities | ||||
| Hypertension [n (%)] | 4629 (61.0) | 279 (68.9) | 4908 (61.4) | 0.002 |
| Duration of hypertension (year) | 0.84 (0.00, 3.69) | 0.75 (0.00, 3.19) | 0.84 (0.00, 3.64) | 0.332 |
| Duration of diabetes (year) | 2.43 (0.41, 5.12) | 2.06 (0.46, 4.76) | 2.40 (0.41, 5.09) | 0.215 |
| Dyslipidemia [n (%)] | 3208 (42.3) | 150 (37.0) | 3358 (42.0) | 0.042 |
Tab.3 Baseline characteristics of T2DM patients with CKD stratified by survival status
| Item | Survival (n=7586) | Death (n=405) | Total (n=7991) | P |
|---|---|---|---|---|
| Age (year) | 58.21 (50.47, 64.55) | 65.46 (58.89, 71.69) | 58.58 (50.83, 65.04) | <0.001 |
| Male [n (%)] | 4300(56.7) | 240 (59.3) | 4540 (56.8) | 0.333 |
| BMI (kg/m2) | 25.78 (23.67, 28.37) | 25.51 (23.51, 28.58) | 25.78 (23.66, 28.38) | 0.431 |
| SBP (mmHg) | 130.00 (122.00, 140.00) | 130.00 (126.00, 140.00) | 130.00 (122.00, 140.00) | 0.002 |
| DBP (mmHg) | 80.00 (76.00, 85.00) | 80.00 (78.00, 86.00) | 80.00 (76.00, 85.00) | 0.247 |
| Laboratory tests | ||||
| Hemoglobin (g/L) | 139.00 (127.00, 152.00) | 126.00 (112.00, 141.00) | 139.00 (126.00, 151.00) | <0.001 |
| White blood cells (10⁹/L) | 6.79 (5.68, 8.12) | 7.00 (5.93, 8.53) | 6.79 (5.69, 8.14) | 0.017 |
| Neutrophils (10⁹/L) | 4.14 (3.28, 5.27) | 4.59 (3.61, 5.89) | 4.15 (3.30, 5.30) | <0.001 |
| Lymphocytes (10⁹/L) | 1.92 (1.51, 2.38) | 1.68 (1.26, 2.12) | 1.90 (1.50, 2.37) | <0.001 |
| Platelets (10⁹/L) | 226.00 (189.00, 270.00) | 210.00 (169.00, 258.00) | 226.00 (187.70, 269.00) | <0.001 |
| ALT (U/L) | 19.70 (14.00, 29.60) | 15.90 (11.40, 23.00) | 19.50 (14.00, 29.10) | <0.001 |
| AST (U/L) | 18.90 (15.00, 24.50) | 16.60 (13.50, 22.00) | 18.70 (15.00, 24.30) | <0.001 |
| Total protein (g/L) | 69.80 (64.50, 74.50) | 66.30 (60.60, 71.30) | 69.60 (64.20, 74.40) | <0.001 |
| Albumin (g/L) | 42.20 (38.70, 45.30) | 37.90 (34.10, 42.00) | 42.00 (38.50, 45.10) | <0.001 |
| Direct bilirubin (μmol/L) | 2.90 (2.00, 4.19) | 2.55 (1.60, 3.50) | 2.90 (1.98, 4.13) | <0.001 |
| Total bilirubin (μmol/L) | 7.90 (5.74, 10.70) | 5.90 (4.20, 8.65) | 7.85 (5.63, 10.61) | <0.001 |
| Total cholesterol (mmol/L) | 5.12 (4.31, 6.04) | 5.09 (4.20, 6.18) | 5.12 (4.30, 6.05) | 0.922 |
| Triglycerides (mmol/L) | 1.78 (1.23, 2.71) | 1.77 (1.21, 2.60) | 1.78 (1.23, 2.70) | 0.464 |
| HDL-C (mmol/L) | 1.13 (0.96, 1.35) | 1.09 (0.91, 1.33) | 1.13 (0.95, 1.35) | 0.001 |
| LDL-C( mmol/L) | 2.15 (1.70, 2.80) | 2.29 (1.74, 3.13) | 2.16 (1.70, 2.81) | 0.009 |
| Glucose (mmol/L) | 8.55 (6.84, 11.43) | 8.67 (6.44, 11.88) | 8.57 (6.83, 11.46) | 0.934 |
| Blood urea nitrogen (mmol/L) | 5.90 (4.73, 7.50) | 7.60 (5.89, 10.60) | 5.96 (4.76, 7.61) | <0.001 |
| Uric acid (μmol/L) | 335.00 (275.00, 410.00) | 352.00 (283.10, 445.90) | 336.00 (275.00, 411.00) | <0.001 |
| Serum creatinine (μmol/L) | 70.90 (57.00, 92.00) | 100.40 (74.00, 148.00) | 71.80 (57.30, 94.00) | <0.001 |
| eGFR [mL·min-1·(1.73 m²)-1] | 93.21 (71.11, 104.60) | 60.73 (38.36, 85.72) | 92.40 (68.84, 104.09) | <0.001 |
| INR | 0.94 (0.89, 1.00) | 0.96 (0.90, 1.03) | 0.94 (0.89, 1.00) | <0.001 |
| D-dimer (μg/mL) | 0.36 (0.22, 0.60) | 0.61 (0.33, 1.11) | 0.37 (0.22, 0.63) | <0.001 |
| Phosphorus (mmol/L) | 1.18 (1.06, 1.31) | 1.19 (1.05, 1.37) | 1.18 (1.06, 1.32) | 0.251 |
| Potassium (mmol/L) | 4.14 (3.86, 4.43) | 4.20 (3.85, 4.60) | 4.14 (3.86, 4.44) | 0.013 |
| Sodium (mmol/L) | 140.08 (138.00, 142.00) | 140.00 (137.40, 142.10) | 140.07 (138.00, 142.00) | 0.250 |
| Calcium (mmol/L) | 2.29 (2.19, 2.38) | 2.18 (2.05, 2.30) | 2.28 (2.18, 2.38) | <0.001 |
| 24-hour UTP (g/24 h) | 0.24 (0.11, 0.83) | 0.95 (0.26, 4.03) | 0.25 (0.11, 0.94) | <0.001 |
| CKD stage [n (%)] | <0.001 | |||
| G1 | 4237 (55.8) | 81 (20.0) | 4318 (54.0) | |
| G2 | 2057 (27.1) | 123 (30.4) | 2180 (27.3) | |
| G3 | 1063 (14.0) | 131 (32.3) | 1194 (14.9) | |
| G4 | 163 (2.1) | 46 (11.4) | 209 (2.6) | |
| G5 | 66 (0.9) | 24 (5.9) | 90 (1.1) | |
| Comorbidities | ||||
| Hypertension [n (%)] | 4629 (61.0) | 279 (68.9) | 4908 (61.4) | 0.002 |
| Duration of hypertension (year) | 0.84 (0.00, 3.69) | 0.75 (0.00, 3.19) | 0.84 (0.00, 3.64) | 0.332 |
| Duration of diabetes (year) | 2.43 (0.41, 5.12) | 2.06 (0.46, 4.76) | 2.40 (0.41, 5.09) | 0.215 |
| Dyslipidemia [n (%)] | 3208 (42.3) | 150 (37.0) | 3358 (42.0) | 0.042 |
Fig.3 Kaplan-Meier survival analysis of LDL trajectories and all-cause mortality.
Fig.3 Kaplan-Meier survival analysis of LDL trajectories and all-cause mortality.
Fig.4 Kaplan-Meier survival analysis of HbA1c trajectories and all-cause mortality.
Fig.4 Kaplan-Meier survival analysis of HbA1c trajectories and all-cause mortality.
Fig.5 Multidimensional flow Sankey diagram of the evolution from LDL-C and HbA1c trajectories to clinical outcomes.
Fig.5 Multidimensional flow Sankey diagram of the evolution from LDL-C and HbA1c trajectories to clinical outcomes.
Fig.6 Heatmap of cross-distribution and mortality rates for LDL-C and HbA1c dual trajectories.
Fig.6 Heatmap of cross-distribution and mortality rates for LDL-C and HbA1c dual trajectories.
Fig.8 Feature selection based on the LASSOalgorithm. A: Selection of the tuning parameter(λ) for the LASSO model using 5-fold crossvalidationbased on the minimum criterion. Theoptimal λ value was 0.001793. B: LASSOcoefficient profiles of clinical features. C:LASSO variable importance ranking plot,illustrating the relative weight distribution ofthe absolute values of the coefficients for eachfeature in the model.
Fig.8 Feature selection based on the LASSOalgorithm. A: Selection of the tuning parameter(λ) for the LASSO model using 5-fold crossvalidationbased on the minimum criterion. Theoptimal λ value was 0.001793. B: LASSOcoefficient profiles of clinical features. C:LASSO variable importance ranking plot,illustrating the relative weight distribution ofthe absolute values of the coefficients for eachfeature in the model.
Fig.7 Nomenclature system for the cross-grouping of LDL-C and HbA1c dual trajectories.
Fig.7 Nomenclature system for the cross-grouping of LDL-C and HbA1c dual trajectories.
Tab.4 Multivariate Cox regression analysis of risk factors for all-cause mortality in T2DM patients with CKD
| Risk factor | Model 1 | Model 2 | Model 3 | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
| Lipid optimal glucose optimal | 1.0 (Reference) | 1.0 (Reference) | 1.0 (Reference) | |||
| Lipid optimal glucose moderate | 1.840 (1.269-2.668) | 0.001 | 1.239 (0.847-1.814) | 0.270 | 1.160 (0.792-1.700) | 0.445 |
| Lipid optimal glucose poor | 2.302 (1.492-3.552) | <0.001 | 1.394 (0.890-2.184) | 0.146 | 1.177 (0.748-1.852) | 0.480 |
| Lipid moderate glucose optimal | 0.891 (0.566-1.402) | 0.616 | 1.061 (0.667-1.686) | 0.803 | 1.002 (0.630-1.593) | 0.994 |
| Lipid moderate glucose moderate | 1.813 (1.248-2.634) | 0.002 | 1.506 (1.023-2.218) | 0.038 | 1.454 (0.987-2.142) | 0.058 |
| Lipid moderate glucose poor | 3.392 (2.292-5.018) | <0.001 | 2.619 (1.745-3.933) | <0.001 | 2.343 (1.554-3.533) | <0.001 |
| Lipid poor glucose optimal | 1.989 (1.049-3.772) | 0.035 | 2.147 (1.104-4.173) | 0.024 | 2.015 (1.036-3.918) | 0.039 |
| Lipid poor glucose moderate | 2.471 (1.535-3.979) | <0.001 | 2.162 (1.287-3.631) | 0.004 | 2.142 (1.273-3.606) | 0.004 |
| Lipid poor glucose poor | 5.457 (3.467-8.591) | <0.001 | 5.551 (3.323-9.273) | <0.001 | 5.550 (3.322-9.274) | <0.001 |
| Age (year) | 1.061 (1.048-1.074) | <0.001 | 1.060 (1.047-1.073) | <0.001 | ||
| Hypertension duration (year) | 1.036 (0.989-1.085) | 0.140 | 1.017 (0.969-1.067) | 0.492 | ||
| MI/Stroke | 1.672 (1.339-2.090) | <0.001 | 1.589 (1.270-1.988) | <0.001 | ||
| DBP (mmHg) | 1.015 (1.004-1.027) | 0.010 | 1.011 (1.000-1.023) | 0.049 | ||
| Platelets (10⁹/L) | 0.998 (0.997-1.000) | 0.021 | 0.998 (0.997-1.000) | 0.031 | ||
| Neutrophils (10⁹/L) | 1.058 (1.016-1.101) | 0.006 | 1.051 (1.010-1.095) | 0.015 | ||
| Hemoglobin (g/L) | 0.994 (0.989-1.000) | 0.059 | 0.996 (0.991-1.002) | 0.226 | ||
| INR | 1.244 (0.627-2.469) | 0.532 | 1.379 (0.706-2.692) | 0.347 | ||
| Albumin (g/L) | 0.909 (0.887-0.932) | <0.001 | 0.916 (0.893-0.940) | <0.001 | ||
| Total protein (g/L) | 1.038 (1.021-1.055) | <0.001 | 1.042 (1.025-1.060) | <0.001 | ||
| Direct bilirubin (μmol/L) | 1.004 (0.983-1.025) | 0.730 | 1.010 (0.988-1.032) | 0.376 | ||
| Indirect bilirubin (μmol/L) | 0.999 (0.972-1.027) | 0.962 | 0.996 (0.970-1.022) | 0.740 | ||
| HDL-C (mmol/L) | 0.678 (0.481-0.954) | 0.026 | 0.734 (0.522-1.033) | 0.076 | ||
| Potassium (mmol/L) | 0.852 (0.698-1.039) | 0.113 | 0.862 (0.708-1.050) | 0.140 | ||
| Sodium (mmol/L) | 0.987 (0.964-1.011) | 0.282 | 0.993 (0.969-1.018) | 0.573 | ||
| Calcium (mmol/L) | 0.905 (0.617-1.327) | 0.609 | 0.882 (0.597-1.303) | 0.528 | ||
| Blood urea nitrogen (mmol/L) | 1.027 (1.001-1.054) | 0.042 | 1.024 (0.997-1.052) | 0.077 | ||
| Serum creatinine (μmol/L) | 1.000 (0.998-1.001) | 0.807 | 1.000 (0.998-1.002) | 0.819 | ||
| 24-hour UTP (g/24 h) | 1.124 (1.088-1.160) | <0.001 | 1.107 (1.071-1.144) | <0.001 | ||
| Glucose (mmol/L) | 1.048 (1.026-1.072) | <0.001 | 1.046 (1.023-1.071) | <0.001 | ||
| eGFR (mL/min/1.73 m²) | 0.981 (0.976-0.987) | <0.001 | 0.984 (0.978-0.991) | <0.001 | ||
| Proton pump inhibitors | 1.068 (0.854-1.337) | 0.563 | ||||
| β-blockers | 1.131 (0.912-1.404) | 0.262 | ||||
| Calcium channel blockers | 1.345 (1.056-1.713) | 0.017 | ||||
| Diuretics | 1.715 (1.352-2.175) | <0.001 | ||||
| Biguanides | 0.898 (0.715-1.128) | 0.354 | ||||
| CPM | 1.112 (0.856-1.445) | 0.426 | ||||
| ARB/ACEI | 1.123 (0.884-1.426) | 0.342 | ||||
| DPP4 inhibitors | 1.135 (0.833-1.547) | 0.423 | ||||
| SGLT2 inhibitors | 1.064 (0.592-1.912) | 0.836 | ||||
| Insulin | 1.346 (0.953-1.901) | 0.092 | ||||
Tab.4 Multivariate Cox regression analysis of risk factors for all-cause mortality in T2DM patients with CKD
| Risk factor | Model 1 | Model 2 | Model 3 | |||
|---|---|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | HR (95% CI) | P | |
| Lipid optimal glucose optimal | 1.0 (Reference) | 1.0 (Reference) | 1.0 (Reference) | |||
| Lipid optimal glucose moderate | 1.840 (1.269-2.668) | 0.001 | 1.239 (0.847-1.814) | 0.270 | 1.160 (0.792-1.700) | 0.445 |
| Lipid optimal glucose poor | 2.302 (1.492-3.552) | <0.001 | 1.394 (0.890-2.184) | 0.146 | 1.177 (0.748-1.852) | 0.480 |
| Lipid moderate glucose optimal | 0.891 (0.566-1.402) | 0.616 | 1.061 (0.667-1.686) | 0.803 | 1.002 (0.630-1.593) | 0.994 |
| Lipid moderate glucose moderate | 1.813 (1.248-2.634) | 0.002 | 1.506 (1.023-2.218) | 0.038 | 1.454 (0.987-2.142) | 0.058 |
| Lipid moderate glucose poor | 3.392 (2.292-5.018) | <0.001 | 2.619 (1.745-3.933) | <0.001 | 2.343 (1.554-3.533) | <0.001 |
| Lipid poor glucose optimal | 1.989 (1.049-3.772) | 0.035 | 2.147 (1.104-4.173) | 0.024 | 2.015 (1.036-3.918) | 0.039 |
| Lipid poor glucose moderate | 2.471 (1.535-3.979) | <0.001 | 2.162 (1.287-3.631) | 0.004 | 2.142 (1.273-3.606) | 0.004 |
| Lipid poor glucose poor | 5.457 (3.467-8.591) | <0.001 | 5.551 (3.323-9.273) | <0.001 | 5.550 (3.322-9.274) | <0.001 |
| Age (year) | 1.061 (1.048-1.074) | <0.001 | 1.060 (1.047-1.073) | <0.001 | ||
| Hypertension duration (year) | 1.036 (0.989-1.085) | 0.140 | 1.017 (0.969-1.067) | 0.492 | ||
| MI/Stroke | 1.672 (1.339-2.090) | <0.001 | 1.589 (1.270-1.988) | <0.001 | ||
| DBP (mmHg) | 1.015 (1.004-1.027) | 0.010 | 1.011 (1.000-1.023) | 0.049 | ||
| Platelets (10⁹/L) | 0.998 (0.997-1.000) | 0.021 | 0.998 (0.997-1.000) | 0.031 | ||
| Neutrophils (10⁹/L) | 1.058 (1.016-1.101) | 0.006 | 1.051 (1.010-1.095) | 0.015 | ||
| Hemoglobin (g/L) | 0.994 (0.989-1.000) | 0.059 | 0.996 (0.991-1.002) | 0.226 | ||
| INR | 1.244 (0.627-2.469) | 0.532 | 1.379 (0.706-2.692) | 0.347 | ||
| Albumin (g/L) | 0.909 (0.887-0.932) | <0.001 | 0.916 (0.893-0.940) | <0.001 | ||
| Total protein (g/L) | 1.038 (1.021-1.055) | <0.001 | 1.042 (1.025-1.060) | <0.001 | ||
| Direct bilirubin (μmol/L) | 1.004 (0.983-1.025) | 0.730 | 1.010 (0.988-1.032) | 0.376 | ||
| Indirect bilirubin (μmol/L) | 0.999 (0.972-1.027) | 0.962 | 0.996 (0.970-1.022) | 0.740 | ||
| HDL-C (mmol/L) | 0.678 (0.481-0.954) | 0.026 | 0.734 (0.522-1.033) | 0.076 | ||
| Potassium (mmol/L) | 0.852 (0.698-1.039) | 0.113 | 0.862 (0.708-1.050) | 0.140 | ||
| Sodium (mmol/L) | 0.987 (0.964-1.011) | 0.282 | 0.993 (0.969-1.018) | 0.573 | ||
| Calcium (mmol/L) | 0.905 (0.617-1.327) | 0.609 | 0.882 (0.597-1.303) | 0.528 | ||
| Blood urea nitrogen (mmol/L) | 1.027 (1.001-1.054) | 0.042 | 1.024 (0.997-1.052) | 0.077 | ||
| Serum creatinine (μmol/L) | 1.000 (0.998-1.001) | 0.807 | 1.000 (0.998-1.002) | 0.819 | ||
| 24-hour UTP (g/24 h) | 1.124 (1.088-1.160) | <0.001 | 1.107 (1.071-1.144) | <0.001 | ||
| Glucose (mmol/L) | 1.048 (1.026-1.072) | <0.001 | 1.046 (1.023-1.071) | <0.001 | ||
| eGFR (mL/min/1.73 m²) | 0.981 (0.976-0.987) | <0.001 | 0.984 (0.978-0.991) | <0.001 | ||
| Proton pump inhibitors | 1.068 (0.854-1.337) | 0.563 | ||||
| β-blockers | 1.131 (0.912-1.404) | 0.262 | ||||
| Calcium channel blockers | 1.345 (1.056-1.713) | 0.017 | ||||
| Diuretics | 1.715 (1.352-2.175) | <0.001 | ||||
| Biguanides | 0.898 (0.715-1.128) | 0.354 | ||||
| CPM | 1.112 (0.856-1.445) | 0.426 | ||||
| ARB/ACEI | 1.123 (0.884-1.426) | 0.342 | ||||
| DPP4 inhibitors | 1.135 (0.833-1.547) | 0.423 | ||||
| SGLT2 inhibitors | 1.064 (0.592-1.912) | 0.836 | ||||
| Insulin | 1.346 (0.953-1.901) | 0.092 | ||||
Fig.9 Main effects and interaction effects of dual metabolic trajectories on mortality risk (with intensive control as the reference). The multivariate Cox regression model adjusted for age, duration of hypertension, stroke history, diastolic blood pressure, laboratory parameters (platelets, neutrophils, hemoglobin, INR, albumin, total protein, direct/indirect bilirubin, HDL-C, potassium, sodium, calcium, BUN, serum creatinine, 24-hour UTP, glucose, eGFR), and medications (PPIs, β-blockers, CCBs, diuretics, biguanides, CPM, RAS inhibitors, DPP-4 inhibitors, SGLT-2 inhibitors, insulin).
Fig.9 Main effects and interaction effects of dual metabolic trajectories on mortality risk (with intensive control as the reference). The multivariate Cox regression model adjusted for age, duration of hypertension, stroke history, diastolic blood pressure, laboratory parameters (platelets, neutrophils, hemoglobin, INR, albumin, total protein, direct/indirect bilirubin, HDL-C, potassium, sodium, calcium, BUN, serum creatinine, 24-hour UTP, glucose, eGFR), and medications (PPIs, β-blockers, CCBs, diuretics, biguanides, CPM, RAS inhibitors, DPP-4 inhibitors, SGLT-2 inhibitors, insulin).
Fig.10 Main effects and interaction effects of dual metabolic trajectories on mortality risk (with standard control as the reference). The multivariate Cox regression model adjusted for age, duration of hypertension, stroke history, diastolic blood pressure, laboratory parameters (platelets, neutrophils, hemoglobin, INR, albumin, total protein, direct/indirect bilirubin, HDL-C, potassium, sodium, calcium, BUN, serum creatinine, 24-hour UTP, glucose, eGFR), and medications (PPIs, β-blockers, CCBs, diuretics, biguanides, CPM, RAS inhibitors, DPP-4 inhibitors, SGLT-2 inhibitors, insulin).
Fig.10 Main effects and interaction effects of dual metabolic trajectories on mortality risk (with standard control as the reference). The multivariate Cox regression model adjusted for age, duration of hypertension, stroke history, diastolic blood pressure, laboratory parameters (platelets, neutrophils, hemoglobin, INR, albumin, total protein, direct/indirect bilirubin, HDL-C, potassium, sodium, calcium, BUN, serum creatinine, 24-hour UTP, glucose, eGFR), and medications (PPIs, β-blockers, CCBs, diuretics, biguanides, CPM, RAS inhibitors, DPP-4 inhibitors, SGLT-2 inhibitors, insulin).
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