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Department of Internal Medicine, University Hospital Clementino Fraga Filho, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Copyright © 2023 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: C.R.L.C., N.C.L., G.F.S. Acquisition, analysis, or interpretation of data: C.R.L.C., N.C.L., G.F.S. Drafting the work or revising: C.R.L.C., N.C.L., G.F.S. Final approval of the manuscript: C.R.L.C., N.C.L., G.F.S.
Characteristic | All patients (n=651) | Weight loss ≥5% (n=125) | Weight loss 0% to <5% (n=180) | Weight gain (n=346) | P value | |
---|---|---|---|---|---|---|
Age, yr | 59.9±9.5 | 60.0±10.1 | 59.9±9.8 | 59.9±9.2 | 0.990 | |
Male sex, % | 38.1 | 31.2 | 39.4 | 39.9 | 0.210 | |
Body mass index, kg/m2 | 29.7±4.9 | 30.9±4.8a | 29.9±5.1 | 29.1±4.7 | 0.002 | |
Abdominal circumference, cm | 102±11 | 105±11a | 102±12 | 101±11 | 0.003 | |
Smoking, current/past, % | 43.8 | 40.0 | 39.4 | 47.4 | 0.141 | |
Physical activity, % active | 34.4 | 35.2 | 31.8 | 35.4 | 0.710 | |
Diabetes duration, yr | 8 (3–15) | 5 (2–12)b | 7 (3–12) | 10 (4–18) | <0.001 | |
Chronic diabetic complication, % | ||||||
Cerebrovascular disease | 8.4 | 8.8 | 8.3 | 8.4 | 0.990 | |
Coronary artery disease | 14.9 | 11.2 | 15.6 | 15.9 | 0.432 | |
Peripheral artery disease | 16.3 | 12.0 | 16.8 | 17.6 | 0.341 | |
Retinopathy | 31.9 | 26.4 | 27.0 | 36.3 | 0.038 | |
Nephropathy | 30.8 | 23.8 | 31.4 | 32.9 | 0.170 | |
Peripheral neuropathy | 28.1 | 21.1 | 27.0 | 31.3 | 0.092 | |
Diabetes treatment, % | ||||||
Metformin | 88.0 | 84.8 | 88.3 | 89.0 | 0.461 | |
Sulfonylureas | 42.5 | 46.4 | 50.6a | 37.0 | 0.007 | |
Insulin | 47.5 | 32.8b | 38.9b | 57.2 | <0.001 | |
Other medicationsc | 5.3 | 5.7 | 5.1 | 5.2 | 0.971 | |
Dyslipidemia, % | 87.1 | 82.4 | 88.3 | 88.2 | 0.220 | |
Statin use | 77.1 | 70.4 | 78.3 | 78.9 | 0.141 | |
Arterial hypertension, % | 86.3 | 87.2 | 85.6 | 86.4 | 0.921 | |
Number of antihypertensive drugs | 3 (1–3) | 2 (1–3) | 3 (1–4) | 3 (1–3) | 0.601 | |
ACE inhibitors/AR blockers, % | 81.0 | 80.8 | 78.3 | 82.4 | 0.531 | |
Diuretics, % | 61.4 | 62.4 | 60.6 | 61.6 | 0.951 | |
Calcium channel blockers, % | 28.1 | 25.6 | 29.4 | 28.3 | 0.760 | |
Beta-blockers, % | 45.5 | 42.4 | 48.3 | 45.1 | 0.580 | |
Mean 2-year SBP, mm Hg | 140±18 | 139±19 | 141±18 | 141±17 | 0.711 | |
Mean 2-year DBP, mm Hg | 79±9 | 79±9 | 79±9 | 79±9 | 0.990 | |
Laboratory variables | ||||||
Mean fasting glycemia, mmol/L | 8.2±2.8 | 7.6±2.8 | 8.4±2.9 | 8.2±2.8 | 0.028 | |
Mean HbA1c, % | 7.7±1.4 | 7.2±1.4b | 7.7±1.4 | 7.9±1.4 | <0.001 | |
Mean HbA1c, mmol/mol | 61±15.3 | 55±15.3 | 61±15.3 | 63±15.3 | ||
Mean triacylglycerol, mmol/L | 1.9±1.4 | 1.6±0.9a | 2.0±1.3 | 1.9±1.6 | 0.004 | |
Mean HDL-C, mmol/L | 1.1±0.3 | 1.1±0.3 | 1.2±0.3 | 1.1±0.2 | 0.941 | |
Mean LDL-C, mmol/L | 2.7±0.8 | 2.7±0.9 | 2.7±0.7 | 2.7±0.8 | 0.920 | |
eGFR, mL/min/1.73 m2 | 80±18 | 81±17 | 82±18 | 79±17 | 0.151 | |
Albuminuria, mg/day | 13 (7–40) | 11 (7–24) | 15 (7–40) | 13 (7–50) | 0.350 |
Values are expressed as mean±standard deviation, percentage, or median (interquartile range).
ACE, angiotensin-converting enzyme; AR, angiotensin II receptor; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate.
Post hoc comparisons among subgroups were performed against the reference subgroup (weight gain) with the Bonferroni correction for multiple comparisons
a P<0.01;
b P<0.001;
c Other antidiabetic medications in use were acarbose, dipeptidyl peptidase 4 inhibitors, and thiazolidinediones—no individual was using glucagon-like peptide-1 agonists or sodium-glucose cotransporter 2 inhibitors.
Outcomes incidence | All patients (n=651) | Weight loss ≥5% (n=125) | Weight loss 0% to <5% (n=180) | Weight gain (n=346) | P value |
---|---|---|---|---|---|
Total cardiovascular events | 188 (31.6) | 19 (15.3)a | 53 (33.7) | 116 (37.0) | 0.001 |
Major adverse cardiovascular events | 150 (24.3) | 17 (13.6)b | 43 (26.3) | 90 (27.4) | 0.023 |
Cardiovascular mortality | 106 (16.5) | 13 (10.3) | 33 (19.2) | 60 (17.4) | 0.121 |
Model 1 was adjusted for age, sex, baseline body mass index, smoking status, diabetes duration, presence of macrovascular and microvascular complications, use of insulin and statins, and number of antihypertensive drugs. Model 2 was further adjusted for the potential mediating covariates between weight loss during the initial 2-year period and outcomes: regular physical activity, and mean systolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.
HR, hazard ratio; CI, confidence interval.
HRs were adjusted for age, sex, baseline body mass index, smoking status, diabetes duration, presence of macrovascular and microvascular complications, use of insulin and statins, number of antihypertensive drugs, and mean systolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol during the 2-year period of weight change (model 2 in Table 2).
HR, hazard ratio; CI, confidence interval.
Characteristic | All patients (n=651) | Weight loss ≥5% (n=125) | Weight loss 0% to <5% (n=180) | Weight gain (n=346) | P value | |
---|---|---|---|---|---|---|
Age, yr | 59.9±9.5 | 60.0±10.1 | 59.9±9.8 | 59.9±9.2 | 0.990 | |
Male sex, % | 38.1 | 31.2 | 39.4 | 39.9 | 0.210 | |
Body mass index, kg/m2 | 29.7±4.9 | 30.9±4.8 |
29.9±5.1 | 29.1±4.7 | 0.002 | |
Abdominal circumference, cm | 102±11 | 105±11 |
102±12 | 101±11 | 0.003 | |
Smoking, current/past, % | 43.8 | 40.0 | 39.4 | 47.4 | 0.141 | |
Physical activity, % active | 34.4 | 35.2 | 31.8 | 35.4 | 0.710 | |
Diabetes duration, yr | 8 (3–15) | 5 (2–12) |
7 (3–12) | 10 (4–18) | <0.001 | |
Chronic diabetic complication, % | ||||||
Cerebrovascular disease | 8.4 | 8.8 | 8.3 | 8.4 | 0.990 | |
Coronary artery disease | 14.9 | 11.2 | 15.6 | 15.9 | 0.432 | |
Peripheral artery disease | 16.3 | 12.0 | 16.8 | 17.6 | 0.341 | |
Retinopathy | 31.9 | 26.4 | 27.0 | 36.3 | 0.038 | |
Nephropathy | 30.8 | 23.8 | 31.4 | 32.9 | 0.170 | |
Peripheral neuropathy | 28.1 | 21.1 | 27.0 | 31.3 | 0.092 | |
Diabetes treatment, % | ||||||
Metformin | 88.0 | 84.8 | 88.3 | 89.0 | 0.461 | |
Sulfonylureas | 42.5 | 46.4 | 50.6 |
37.0 | 0.007 | |
Insulin | 47.5 | 32.8 |
38.9 |
57.2 | <0.001 | |
Other medications |
5.3 | 5.7 | 5.1 | 5.2 | 0.971 | |
Dyslipidemia, % | 87.1 | 82.4 | 88.3 | 88.2 | 0.220 | |
Statin use | 77.1 | 70.4 | 78.3 | 78.9 | 0.141 | |
Arterial hypertension, % | 86.3 | 87.2 | 85.6 | 86.4 | 0.921 | |
Number of antihypertensive drugs | 3 (1–3) | 2 (1–3) | 3 (1–4) | 3 (1–3) | 0.601 | |
ACE inhibitors/AR blockers, % | 81.0 | 80.8 | 78.3 | 82.4 | 0.531 | |
Diuretics, % | 61.4 | 62.4 | 60.6 | 61.6 | 0.951 | |
Calcium channel blockers, % | 28.1 | 25.6 | 29.4 | 28.3 | 0.760 | |
Beta-blockers, % | 45.5 | 42.4 | 48.3 | 45.1 | 0.580 | |
Mean 2-year SBP, mm Hg | 140±18 | 139±19 | 141±18 | 141±17 | 0.711 | |
Mean 2-year DBP, mm Hg | 79±9 | 79±9 | 79±9 | 79±9 | 0.990 | |
Laboratory variables | ||||||
Mean fasting glycemia, mmol/L | 8.2±2.8 | 7.6±2.8 | 8.4±2.9 | 8.2±2.8 | 0.028 | |
Mean HbA1c, % | 7.7±1.4 | 7.2±1.4 |
7.7±1.4 | 7.9±1.4 | <0.001 | |
Mean HbA1c, mmol/mol | 61±15.3 | 55±15.3 | 61±15.3 | 63±15.3 | ||
Mean triacylglycerol, mmol/L | 1.9±1.4 | 1.6±0.9 |
2.0±1.3 | 1.9±1.6 | 0.004 | |
Mean HDL-C, mmol/L | 1.1±0.3 | 1.1±0.3 | 1.2±0.3 | 1.1±0.2 | 0.941 | |
Mean LDL-C, mmol/L | 2.7±0.8 | 2.7±0.9 | 2.7±0.7 | 2.7±0.8 | 0.920 | |
eGFR, mL/min/1.73 m2 | 80±18 | 81±17 | 82±18 | 79±17 | 0.151 | |
Albuminuria, mg/day | 13 (7–40) | 11 (7–24) | 15 (7–40) | 13 (7–50) | 0.350 |
Outcomes incidence | All patients (n=651) | Weight loss ≥5% (n=125) | Weight loss 0% to <5% (n=180) | Weight gain (n=346) | P value |
---|---|---|---|---|---|
Total cardiovascular events | 188 (31.6) | 19 (15.3) |
53 (33.7) | 116 (37.0) | 0.001 |
Major adverse cardiovascular events | 150 (24.3) | 17 (13.6) |
43 (26.3) | 90 (27.4) | 0.023 |
Cardiovascular mortality | 106 (16.5) | 13 (10.3) | 33 (19.2) | 60 (17.4) | 0.121 |
Outcomes | Model 1 |
Model 2 |
|||
---|---|---|---|---|---|
HR (95% CI) | P value | HR (95% CI) | P value | ||
Total cardiovascular events (n=188) | |||||
Weight loss ≥5% | 0.54 (0.33–0.89) | 0.016 | 0.52 (0.32–0.86) | 0.011 | |
Weight loss 0% to <5% | 1.08 (0.77–1.52) | 0.640 | 1.12 (0.80–1.56) | 0.520 | |
Weight gain | 1.0 (Ref) | - | 1.0 (Ref) | - | |
Major adverse cardiovascular events (n=150) | |||||
Weight loss ≥5% | 0.68 (0.40–1.16) | 0.160 | 0.66 (0.39–1.14) | 0.140 | |
Weight loss 0% to <5% | 1.21 (0.83–1.77) | 0.321 | 1.22 (0.83–1.78) | 0.312 | |
Weight gain | 1.0 (Ref) | - | 1.0 (Ref) | - | |
Cardiovascular mortality (n=106) | |||||
Weight loss ≥5% | 0.83 (0.44–1.55) | 0.550 | 0.85 (0.45–1.59) | 0.600 | |
Weight loss 0% to <5% | 1.39 (0.89–2.17) | 0.151 | 1.39 (0.89–2.18) | 0.151 | |
Weight gain | 1.0 (Ref) | - | 1.0 (Ref) | - |
Outcomes | Regular physical activity during the initial 2-year period |
P for interaction | ||||
---|---|---|---|---|---|---|
Physically active (n=224) |
Sedentary (n=427) |
|||||
HR (95% CI) | P value | HR (95% CI) | P value | |||
Total cardiovascular events (n=51/137) | ||||||
Weight loss ≥5% | 0.20 (0.06–0.60) | 0.004 | 0.66 (0.37–1.18) | 0.161 | 0.073 | |
Weight loss 0% to <5% | 0.82 (0.42–1.61) | 0.570 | 1.16 (0.78–1.74) | 0.470 | 0.570 | |
Weight gain | 1.0 (Ref) | - | 1.0 (Ref) | - | ||
Major adverse cardiovascular events (n=43/107) | ||||||
Weight loss ≥5% | 0.21 (0.07–0.69) | 0.010 | 0.83 (0.44–1.56) | 0.570 | 0.097 | |
Weight loss 0% to <5% | 0.82 (0.38–1.74) | 0.601 | 1.31 (0.83–2.07) | 0.241 | 0.410 | |
Weight gain | 1.0 (Ref) | - | 1.0 (Ref) | - | ||
Cardiovascular mortality (n=28/78) | ||||||
Weight loss ≥5% | 0.28 (0.07–1.13) | 0.073 | 1.10 (0.53–2.30) | 0.801 | 0.101 | |
Weight loss 0% to <5% | 0.46 (0.16–1.29) | 0.140 | 1.89 (1.12–3.20) | 0.018 | 0.016 | |
Weight gain | 1.0 (Ref) | - | 1.0 (Ref) | - |
Values are expressed as mean±standard deviation, percentage, or median (interquartile range). ACE, angiotensin-converting enzyme; AR, angiotensin II receptor; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate. Other antidiabetic medications in use were acarbose, dipeptidyl peptidase 4 inhibitors, and thiazolidinediones—no individual was using glucagon-like peptide-1 agonists or sodium-glucose cotransporter 2 inhibitors.
Values are expressed as number (incidence rate per 1,000 person-years of follow-up).
Model 1 was adjusted for age, sex, baseline body mass index, smoking status, diabetes duration, presence of macrovascular and microvascular complications, use of insulin and statins, and number of antihypertensive drugs. Model 2 was further adjusted for the potential mediating covariates between weight loss during the initial 2-year period and outcomes: regular physical activity, and mean systolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. HR, hazard ratio; CI, confidence interval.
HRs were adjusted for age, sex, baseline body mass index, smoking status, diabetes duration, presence of macrovascular and microvascular complications, use of insulin and statins, number of antihypertensive drugs, and mean systolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol during the 2-year period of weight change (model 2 in Table 2). HR, hazard ratio; CI, confidence interval.