Sıra | DOSYA ADI | Format | Bağlantı |
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01. | Tanaka Associations Online Indirect | pptx | Sunumu İndir |
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Serum total bilirubin concentration is negatively associated with increasing severity in patients with type 2 diabetes mellitus Masami Tanaka, Takeshi Nishimura, Risa Sekioka, Hiroshi Itoh Department of Internal Medicine, School of Medicine, Keio UniversityTokyo, Japan3
Aims• Serum bilirubin concentration is associated with diabetic retinopathy in patients with type 2 diabetes. • This study investigated the relationships between serum bilirubin concentration and the severity of diabetic retinopathy. • The importance of bilirubin was compared with the factors which were previously shown to be associated with the incidence of diabetic retinopathy (duration of diabetes, body mass index, systolic blood pressure, and HbA1c). 4
Methods• A total of 674 patients with type 2 diabetes are investigated in this cross-sectional study. • Serum total bilirubin concentrations are compared between patients with and without diabetic retinopathy, and according to the severity of the retinopathy. • Multivariate analyses are performed to evaluate the association of retinopathy with total bilirubin concentration, duration of diabetes, body mass index, systolic blood pressure, and HbA1c. 5
Patient demographic and laboratory data• N 674• Age (years) 64.7 ± 13.9• Sex (men/women) 446/228• Duration of diabetes (years) 13.9 ± 10.9• BMI (kg/m2) 25.5 ± 6.3• HbA1c (%) 9.13 ± 2.16• Total bilirubin (mg/dL) 0.74 ± 0.36• AST (IU/L) 26.8 ± 17.0• ALT (IU/L) 26.8 ± 20.1• eGFR (mL min −1 1.73 m −2) 61.7 ± 31.6• Smoking, n (%) 324 (48.1)• Hypertension, n (%) 498 (73.9)• Dyslipidaemia, n (%) 520 (77.2)• Diabetic retinopathy, n (%) 279 (41.4)• NDR/SDR/PPDR/PDR, n (%) 395 (58.6)/132 (19.6)/43 (6.4)/104 (21.8)• Diabetic nephropathy, n (%) 323 (47.9)• Cerebrovascular disease, n (%) 101 (15.0)• Cardiovascular disease, n (%)128 (19.0)6NDR, no diabetic retinopathy SDR, simple DRPPDR, preproliferative DR PDR, proliferative DR
Result 1: Serum total bilirubin concentration of patients with and without retinopathySekioka R, Tanaka, M, et al. Serum total bilirubin concentration is negatively associated with increasing severity of retinopathy in patients with type 2 diabetes mellitusJournal of Diabetes and its Complications, Volume 29, Issue 2, 2015, 218–221** p < 0.001
Result 2: Serum total bilirubin concentration of patients with NDR, SDR, and PPDR + PDRSekioka R, Tanaka, M, et al. Serum total bilirubin concentration is negatively associated with increasing severity of retinopathy in patients with type 2 diabetes mellitusJournal of Diabetes and its Complications, Volume 29, Issue 2, 2015, 218–221** p < 0.001, * p < 0.05NDR, no diabetic retinopathy; SDR, simple diabetic retinopathy; PPDR, preproliferative diabetic retinopathy PDR, proliferative diabetic retinopathy
Wald Odds ratio 95%CI pSex (Female = 1, Male = 0)2.620 1.419 0.929–2.168 0.106Age 0.327 0.995 0.980–1.011 0.568BMI 0.295 0.992 0.962–1.022 0.587Duration of diabetes 57.419 1.079 1.058–1.100 0.000Systolic blood pressure 8.100 1.012 1.004–1.021 0.004HbA1c 0.002 1.002 0.917–1.095 0.961Total bilirubin 18.112 0.262 0.142–0.486 0.000Smoking 1.005 1.225 0.824–1.822 0.316Result 3: Multivariate logistic regression analysis of diabetic retinopathyCI : confidence interval
Summary of results Total bilirubin concentration is lower in type 2 diabetic patient▶s with retinopathy.Total bilirubin concentration decreases with increasing severit▶y of diabetic retinopathy. Patients with retinopathy have high blood pressure and long di▶abetes duration.10
ADA2015 Boston Low serum total bilirubin concentration in patients with type 1 or type 2 diabetes mellitus complicated by vascular complication Masami Tanaka, Takeshi Nishimura, Risa Sekioka, Hiroshi ItohDiscussion• It is already shown that bilirubin concentration is lower in patients with type 1 and 2 diabetes with vascular complications.
1) 131 patients with type 1 DM serum TBC is compared between patients with and without retinopathy/nephropathy, and among groups stratified according to the severity of retinopathy/nephropathy. 2) 293 patients with type 2 DM TBC is compared between patients with and without diabetic microangiopathy, and between patients with and without macroangiopathy (cerebral infarction, coronary artery disease, and peripheral arterial disease).12
Comparison of serum total bilirubin concentration according to severity of diabetic retinopathy and nephropathyMA Severity n Total bilirubin (mg/dl) J-T, p valueR NDR 82 0.8 (0.6-1.0) <0.001SDR 24 0.6 (0.5-0.775)PPDR+PDR 25 0.5 (0.4-0.75)N Without nephropathy 88 0.8 (0.6-1.0) <0.001Microalbuminuria 12 0.75 (0.525-1.0)Macroalbuminuria and/or renal failure including dialysis31 0.5 (0.4-0.7)Values are expressed as number or median (interquartile range).Abbreviation: MA, Microangiopathy; R, Retinopathy; N, Nephropathy; J-T, Jonckheere-Terpstra test; NDR, no diabetic retinopathy; SDR, simple DR; PPDR, preproliferative DR; PDR, proliferative DR. Results: T1DM-113
Logistic-regression analysis of diabetic retinopathy and nephropathy Odds ratio 95%CI p valueGender(Female = 1, Male = 0)0.474 0.176-1.278 0.140Age 1.061 1.025-1.099 0.001Duration of diabetes 1.011 0.972-1.051 0.593HbA1c 1.074 0.813-1.418 0.616Systolic blood pressure 1.020 0.993-1.048 0.142Total bilirubin 0.017 0.002-0.158 0.000Smoking 0.818 0.316-2.118 0.679Nephropathy Odds ratio 95%CI p valueGender (Female = 1, Male = 0)0.879 0.347-2.228 0.786Age 1.007 0.976-1.038 0.672Duration of diabetes 1.067 1.022-1.114 0.003HbA1c 1.064 0.813-1.394 0.650Systolic blood pressure 1.025 0.998-1.053 0.067Total bilirubin 0.047 0.007-0.310 0.001Smoking 0.538 0.209-1.380 0.197RetinopathyResults: T1DM-214
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Diabetic micro/macro angiopathy and serum total bilirubin concentration Total bilirubin concentration (mg/dL(1.21.00.80.60.40.2 0Retinopathy ((( (((p=0.00290.79±0.320.69±0.24p=0.01400.78±0.290.70±0.28Nephropathy ((( (((p=0.0330.80±0.280.72±0.29Neuropathy ((( (((Results: T2DM-1Total bilirubin concentration (mg/dL(1.21.00.80.60.40.2 0Stroke ((( (((p<0.00010.78±0.300.59±0.20p=0.00100.77±0.300.65±0.24CAD ((( (((p<0.00010.77±0.300.56±0.16PAD ((( (((n=167 n=124 n=174 n=119 n=87 n=204n=251 n=41 n=236 n=56 n=266 n=26CAD: Coronary artery disease, PAD: Peripheral artery disease16
Characteristics Odds ratio PTBC 0.652 0.49BMI 1.05 0.24Age 1.02 0.35Gender 0.788 0.57Duration of diabetes 1.18 0.0000HbA1c 1.01 0.94Smoking 1.60 0.29Alcohol 1.06 0.90LDL-C 0.999 0.88HDL-C 0.993 0.59TG 1.00 0.32SBP 1.01 0.63Logistic regression analysis examining the effect of various factors on micro/macro angiopathyCharacteristics Odds ratio PTBC 0.1051 0.0004BMI 1.0567 0.0851Age 1.0512 0.0022Gender 1.1601 0.6896Duration of diabetes 1.0359 0.0482HbA1c 0.8849 0.2088Smoking 1.5366 0.2523Alcohol 1.6685 0.1799LDL-C 0.9906 0.0297HDL-C 0.9978 0.8419TG 1.0010 0.1597SBP 1.0049 0.5311Microangiopathy MacroangiopathyResults: T2DM-2TBC: total bilirubin concentration, SBP: systolic blood pressure 17
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Correlation between serum bilirubin concentration and estimated glomerular filtration rate (eGFR) in patients with type 1 diabetesNishimura T, Tanaka M, et al Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitusJournal of Diabetes and its Complications, 2015, Available online 9 July 2015http://dx.doi.org/10.1016/j.jdiacomp.2015.07.007(b) Indirect bilirubin(a) Total bilirubin
Correlation between serum bilirubin concentration and log(urinary albumin excretion) in patients with type 1 diabetesNishimura T, Tanaka M, et al Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitusJournal of Diabetes and its Complications, 2015, Available online 9 July 2015http://dx.doi.org/10.1016/j.jdiacomp.2015.07.007(b) Indirect bilirubin(a) Total bilirubin
Estimated SE t value p valueTotal bilirubin Total bilirubin level (mg/dL) 0.160 5.490 1.837 0.069Duration of diabetes (years) –0.110 0.176 –1.252 0.213BMI (kg/m2) –0.116 0.592 –1.318 0.190HbA1c (%) 0.099 1.332 1.122 0.264Use of ARB or ACEI (yes = 1, no = 0) –0.290 4.611 –3.285 0.001Systolic blood pressure (mmHg) –0.006 0.105 –0.069 0.945Indirect bilirubin Indirect bilirubin level (mg/dL) 0.174 5.752 2.012 0.047Duration of diabetes (years) –0.108 0.175 –1.234 0.220BMI (kg/m2) –0.113 0.591 –1.280 0.203HbA1c (%) 0.095 1.324 1.085 0.280Use of ARB or ACEI (yes = 1, no = 0) –0.288 4.599 –3.279 0.001Systolic blood pressure (mmHg) –0.004 0.104 –0.041 0.968“Estimated” refers to the estimated value of the standardized regression coefficient. Abbreviations: SE, standard error; BMI; body mass index; HbA1c, haemoglobin A1c; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockerFactors contributing to the estimated glomerular filtration rateNishimura T, Tanaka M, et al Serum bilirubin concentration is associated with eGFR and urinary albumin excretion in patients with type 1 diabetes mellitusJournal of Diabetes and its Complications, 2015, Available online 9 July 2015http://dx.doi.org/10.1016/j.jdiacomp.2015.07.007
Estimated SE t value p valueTotal bilirubin Total bilirubin level (mg/dL) –0.186 0.169 –2.095 0.038Sex (male = 1, female = 0) 0.052 0.123 0.586 0.559Age (years) 0.233 0.004 2.699 0.009Duration of diabetes (years) 0.111 0.005 1.271 0.206BMI (kg/m2) 0.009 0.017 0.107 0.915HbA1c (%) 0.222 0.039 2.617 0.010Use of ARB or ACEI (yes = 1, no = 0) 0.230 0.137 2.661 0.009Systolic blood pressure (mmHg) 0.110 0.003 1.223 0.224Indirect bilirubin Indirect bilirubin level (mg/dL) –0.196 0.177 –2.242 0.027Sex (male = 1, female = 0) 0.050 0.121 0.576 0.566Age (years) 0.231 0.004 2.651 0.009Duration of diabetes (years) 0.110 0.005 1.260 0.210BMI (kg/m2) 0.006 0.017 0.068 0.946HbA1c (%) 0.226 0.039 2.682 0.008Use of ARB or ACEI (yes = 1, no = 0) 0.230 0.137 2.668 0.009Systolic blood pressure (mmHg) 0.107 0.003 1.199 0.233Factors contributing to urinary albumin excretion“Estimated” refers to the estimated value of the standardized regression coefficient. Abbreviations: SE, standard error; BMI, body mass index; HbA1c, haemoglobin A1c; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blockerNishimura T, Tanaka M, et alJournal of Diabetes and its Complications, 2015, Available online 9 July 2015http://dx.doi.org/10.1016/j.jdiacomp.2015.07.007
Serum bilirubin concentration is negatively associated with micro/macro vascular complications in both type 1 and type 2 diabetes.
Bilirubin 1) Antioxidant properties by scavenging reactive oxygen species,2) Anti-inflammatory properties by inhibiting the TNFα-related induction of endothelial adhesion molecules (E-selectin, VCAM-1, ICAM-1)
Conclusion• Bilirubin might function protectively against vascular complications in both type 1 and type 2 DM patients.25
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