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Erschienen in: Diabetologia 9/2017

10.06.2017 | Article

Urinary liver-type fatty acid binding protein is an independent predictor of stroke and mortality in individuals with type 1 diabetes

verfasst von: Nicolae M. Panduru, Carol Forsblom, Markku Saraheimo, Lena M. Thorn, Daniel Gordin, Nina Elonen, Valma Harjusalo, Angelika Bierhaus, Per M. Humpert, Per-Henrik Groop, on behalf of the FinnDiane Study Group

Erschienen in: Diabetologia | Ausgabe 9/2017

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Abstract

Aims/hypothesis

In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether urinary L-FABP also predicts cardiovascular outcomes and mortality.

Methods

We tested our hypothesis in a Finnish cohort of 2329 individuals with type 1 diabetes and a median follow-up of 14.1 years. The L-FABP to creatinine ratio was determined from baseline urine samples. The predictive value of urinary L-FABP was evaluated using Cox regression models, while its added predictive benefit for cardiovascular outcomes and mortality was evaluated using a panel of statistical indexes.

Results

Urinary L-FABP predicted incident stroke independently of traditional risk factors (HR 1.33 [95% CI 1.20, 1.49]) and after further adjustment for eGFR (HR 1.28 [95% CI 1.14, 1.44]) or AER (HR 1.24 [95% CI 1.06, 1.44]). In addition, it predicted mortality independently of traditional risk factors (HR 1.34 [95% CI 1.24, 1.45]), and after adjustment for eGFR (HR 1.29 [95% CI 1.18, 1.39]) or AER (HR 1.22 [95% CI 1.09, 1.36]). Urinary L-FABP was as good a predictor as eGFR or AER, and improved the AUC for both outcomes on top of traditional risk factors, with no reclassification benefit (integrated discrimination improvement/net reclassification improvement) for stroke or mortality when AER or eGFR were added to traditional risk factors. However, urinary L-FABP was not a predictor of other cardiovascular endpoints (coronary artery disease, peripheral vascular disease and overall CVD events) when adjusted for the AER.

Conclusions/interpretation

Urinary L-FABP is an independent predictor of stroke and mortality in individuals with type 1 diabetes.
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Literatur
1.
Zurück zum Zitat Laing SP, Swerdlow AJ, Slater SD et al (2003) Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 46:760–765CrossRefPubMed Laing SP, Swerdlow AJ, Slater SD et al (2003) Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia 46:760–765CrossRefPubMed
2.
Zurück zum Zitat Laing SP, Swerdlow AJ, Carpenter LM et al (2003) Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 34:418–421CrossRefPubMed Laing SP, Swerdlow AJ, Carpenter LM et al (2003) Mortality from cerebrovascular disease in a cohort of 23 000 patients with insulin-treated diabetes. Stroke 34:418–421CrossRefPubMed
3.
Zurück zum Zitat Maftei O, Pena AS, Sullivan T et al (2014) Early atherosclerosis relates to urinary albumin excretion and cardiovascular risk factors in adolescents with type 1 diabetes: Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT). Diabetes Care 37:3069–3075CrossRefPubMed Maftei O, Pena AS, Sullivan T et al (2014) Early atherosclerosis relates to urinary albumin excretion and cardiovascular risk factors in adolescents with type 1 diabetes: Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT). Diabetes Care 37:3069–3075CrossRefPubMed
4.
Zurück zum Zitat Groop PH, Thomas MC, Moran JL et al (2009) The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes 58:1651–1658CrossRefPubMedPubMedCentral Groop PH, Thomas MC, Moran JL et al (2009) The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes 58:1651–1658CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Forsblom C, Harjutsalo V, Thorn LM et al (2011) Competing-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol 22:537–544CrossRefPubMedPubMedCentral Forsblom C, Harjutsalo V, Thorn LM et al (2011) Competing-risk analysis of ESRD and death among patients with type 1 diabetes and macroalbuminuria. J Am Soc Nephrol 22:537–544CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Thorn LM, Forsblom C, Waden J et al (2009) Metabolic syndrome as a risk factor for cardiovascular disease, mortality, and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 32:950–952CrossRefPubMedPubMedCentral Thorn LM, Forsblom C, Waden J et al (2009) Metabolic syndrome as a risk factor for cardiovascular disease, mortality, and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 32:950–952CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat McKenna K, Thompson C (1997) Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. Scott Med J 42:99–104CrossRefPubMed McKenna K, Thompson C (1997) Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. Scott Med J 42:99–104CrossRefPubMed
8.
Zurück zum Zitat Viberti GC (1991) Diabetic renal disease in type 1 diabetes: aetiology and prevention. Diabet Med 8 Spec No:S38–S42CrossRefPubMed Viberti GC (1991) Diabetic renal disease in type 1 diabetes: aetiology and prevention. Diabet Med 8 Spec No:S38–S42CrossRefPubMed
9.
Zurück zum Zitat Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno Hypothesis. Diabetologia 32:219–226 Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno Hypothesis. Diabetologia 32:219–226
10.
Zurück zum Zitat Panduru NM, Forsblom C, Saraheimo M et al (2013) Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 36:2077–2083CrossRefPubMedPubMedCentral Panduru NM, Forsblom C, Saraheimo M et al (2013) Urinary liver-type fatty acid-binding protein and progression of diabetic nephropathy in type 1 diabetes. Diabetes Care 36:2077–2083CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Makowski L, Hotamisligil GS (2005) The role of fatty acid binding proteins in metabolic syndrome and atherosclerosis. Curr Opin Lipidol 16:543–548CrossRefPubMedPubMedCentral Makowski L, Hotamisligil GS (2005) The role of fatty acid binding proteins in metabolic syndrome and atherosclerosis. Curr Opin Lipidol 16:543–548CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Furuhashi M, Hotamisligil GS (2008) Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 7:489–503CrossRefPubMedPubMedCentral Furuhashi M, Hotamisligil GS (2008) Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov 7:489–503CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Kamijo-Ikemori A, Sugaya T, Kimura K (2006) Urinary fatty acid binding protein in renal disease. Clin Chim Acta 374:1–7CrossRefPubMed Kamijo-Ikemori A, Sugaya T, Kimura K (2006) Urinary fatty acid binding protein in renal disease. Clin Chim Acta 374:1–7CrossRefPubMed
14.
Zurück zum Zitat Matsui K, Kamijo-Ikemorif A, Sugaya T, Yasuda T, Kimura K (2011) Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity. Am J Pathol 178:1021–1032CrossRefPubMedPubMedCentral Matsui K, Kamijo-Ikemorif A, Sugaya T, Yasuda T, Kimura K (2011) Renal liver-type fatty acid binding protein (L-FABP) attenuates acute kidney injury in aristolochic acid nephrotoxicity. Am J Pathol 178:1021–1032CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Yamamoto T, Noiri E, Ono Y et al (2007) Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 18:2894–2902CrossRefPubMed Yamamoto T, Noiri E, Ono Y et al (2007) Renal L-type fatty acid-binding protein in acute ischemic injury. J Am Soc Nephrol 18:2894–2902CrossRefPubMed
16.
Zurück zum Zitat Matsui K, Kamijo-Ikemori A, Imai N et al (2016) Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of ESRD and CVD in patients with CKD. Clin Exp Nephrol 20:195–203CrossRefPubMed Matsui K, Kamijo-Ikemori A, Imai N et al (2016) Clinical significance of urinary liver-type fatty acid-binding protein as a predictor of ESRD and CVD in patients with CKD. Clin Exp Nephrol 20:195–203CrossRefPubMed
17.
Zurück zum Zitat Ishimitsu T, Ohta S, Saito M et al (2005) Urinary excretion of liver fatty acid-binding protein in health-check participants. Clin Exp Nephrol 9:34–39CrossRefPubMed Ishimitsu T, Ohta S, Saito M et al (2005) Urinary excretion of liver fatty acid-binding protein in health-check participants. Clin Exp Nephrol 9:34–39CrossRefPubMed
18.
Zurück zum Zitat Nielsen SE, Sugaya T, Hovind P, Baba T, Parving HH, Rossing P (2010) Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients. Diabetes Care 33:1320–1324CrossRefPubMedPubMedCentral Nielsen SE, Sugaya T, Hovind P, Baba T, Parving HH, Rossing P (2010) Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients. Diabetes Care 33:1320–1324CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Araki S, Haneda M, Koya D et al (2013) Predictive effects of urinary liver-type fatty acid-binding protein for deteriorating renal function and incidence of cardiovascular disease in type 2 diabetic patients without advanced nephropathy. Diabetes Care 36:1248–1253CrossRefPubMedPubMedCentral Araki S, Haneda M, Koya D et al (2013) Predictive effects of urinary liver-type fatty acid-binding protein for deteriorating renal function and incidence of cardiovascular disease in type 2 diabetic patients without advanced nephropathy. Diabetes Care 36:1248–1253CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Thorn LM, Forsblom C, Fagerudd J et al (2005) Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). Diabetes Care 28:2019–2024CrossRefPubMed Thorn LM, Forsblom C, Fagerudd J et al (2005) Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). Diabetes Care 28:2019–2024CrossRefPubMed
21.
Zurück zum Zitat Stevens LA, Coresh J, Schmid CH et al (2008) Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51:395–406CrossRefPubMedPubMedCentral Stevens LA, Coresh J, Schmid CH et al (2008) Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51:395–406CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Sund R (2012) Quality of the Finnish Hospital Discharge Register: a systematic review. Scand J Public Health 40:505–515CrossRefPubMed Sund R (2012) Quality of the Finnish Hospital Discharge Register: a systematic review. Scand J Public Health 40:505–515CrossRefPubMed
23.
Zurück zum Zitat Gordin D, Forsblom C, Panduru NM et al (2014) Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes. Diabetes Care 37:2593–2600CrossRefPubMed Gordin D, Forsblom C, Panduru NM et al (2014) Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes. Diabetes Care 37:2593–2600CrossRefPubMed
24.
Zurück zum Zitat Delong ER, Delong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845CrossRefPubMed Delong ER, Delong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845CrossRefPubMed
25.
Zurück zum Zitat Pencina MJ, D’Agostino RB Sr, D’Agostino R Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172 discussion 207–212CrossRefPubMed Pencina MJ, D’Agostino RB Sr, D’Agostino R Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27:157–172 discussion 207–212CrossRefPubMed
26.
Zurück zum Zitat Pencina MJ, D’Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21CrossRefPubMed Pencina MJ, D’Agostino RB Sr, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30:11–21CrossRefPubMed
27.
Zurück zum Zitat Greenland P, Smith SC Jr, Grundy SM (2001) Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation 104:1863–1867CrossRefPubMed Greenland P, Smith SC Jr, Grundy SM (2001) Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and noninvasive cardiovascular tests. Circulation 104:1863–1867CrossRefPubMed
28.
Zurück zum Zitat Yamada Y, Kato K, Oguri M et al (2008) Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med 21:801–808PubMed Yamada Y, Kato K, Oguri M et al (2008) Association of genetic variants with atherothrombotic cerebral infarction in Japanese individuals with metabolic syndrome. Int J Mol Med 21:801–808PubMed
29.
Zurück zum Zitat Fukuda Y, Miura S, Zhang B et al (2009) Significance of urinary liver-fatty acid-binding protein in cardiac catheterization in patients with coronary artery disease. Intern Med 48:1731–1737CrossRefPubMed Fukuda Y, Miura S, Zhang B et al (2009) Significance of urinary liver-fatty acid-binding protein in cardiac catheterization in patients with coronary artery disease. Intern Med 48:1731–1737CrossRefPubMed
30.
Zurück zum Zitat Matsumori R, Shimada K, Kiyanagi T et al (2012) Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome. J Cardiol 60:168–173CrossRefPubMed Matsumori R, Shimada K, Kiyanagi T et al (2012) Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome. J Cardiol 60:168–173CrossRefPubMed
31.
Zurück zum Zitat Pluznick J (2014) A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes 5:202–207CrossRefPubMed Pluznick J (2014) A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes 5:202–207CrossRefPubMed
32.
Zurück zum Zitat Kamijo A, Sugaya T, Hikawa A et al (2004) Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules. Am J Pathol 165:1243–1255CrossRefPubMedPubMedCentral Kamijo A, Sugaya T, Hikawa A et al (2004) Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules. Am J Pathol 165:1243–1255CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Nosadini R, Tonolo G (2011) Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes. Nutr Metab Cardiovasc Dis 21:79–85CrossRefPubMed Nosadini R, Tonolo G (2011) Role of oxidized low density lipoproteins and free fatty acids in the pathogenesis of glomerulopathy and tubulointerstitial lesions in type 2 diabetes. Nutr Metab Cardiovasc Dis 21:79–85CrossRefPubMed
34.
Zurück zum Zitat Inoue T, Ikeda H, Nakamura T et al (2011) Potential benefit of statin therapy for dyslipidemia with chronic kidney disease: Fluvastatin Renal Evaluation Trial (FRET). Intern Med 50:1273–1278CrossRefPubMed Inoue T, Ikeda H, Nakamura T et al (2011) Potential benefit of statin therapy for dyslipidemia with chronic kidney disease: Fluvastatin Renal Evaluation Trial (FRET). Intern Med 50:1273–1278CrossRefPubMed
35.
Zurück zum Zitat Agarwal A, Balla J, Balla G, Croatt AJ, Vercellotti GM, Nath KA (1996) Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL. Am J Phys 271:F814–F823 Agarwal A, Balla J, Balla G, Croatt AJ, Vercellotti GM, Nath KA (1996) Renal tubular epithelial cells mimic endothelial cells upon exposure to oxidized LDL. Am J Phys 271:F814–F823
36.
Zurück zum Zitat Pelsers MM, Hanhoff T, Van Der Voort D et al (2004) Brain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility. Clin Chem 50:1568–1575CrossRefPubMed Pelsers MM, Hanhoff T, Van Der Voort D et al (2004) Brain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility. Clin Chem 50:1568–1575CrossRefPubMed
37.
Zurück zum Zitat Wunderlich MT, Hanhoff T, Goertler M et al (2005) Release of brain-type and heart-type fatty acid-binding proteins in serum after acute ischaemic stroke. J Neurol 252:718–724CrossRefPubMed Wunderlich MT, Hanhoff T, Goertler M et al (2005) Release of brain-type and heart-type fatty acid-binding proteins in serum after acute ischaemic stroke. J Neurol 252:718–724CrossRefPubMed
Metadaten
Titel
Urinary liver-type fatty acid binding protein is an independent predictor of stroke and mortality in individuals with type 1 diabetes
verfasst von
Nicolae M. Panduru
Carol Forsblom
Markku Saraheimo
Lena M. Thorn
Daniel Gordin
Nina Elonen
Valma Harjusalo
Angelika Bierhaus
Per M. Humpert
Per-Henrik Groop
on behalf of the FinnDiane Study Group
Publikationsdatum
10.06.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 9/2017
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4328-x

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