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Published in: Diabetology & Metabolic Syndrome 1/2017

Open Access 01-12-2017 | Research

Soluble plasma proteins ST2 and CD163 as early biomarkers of nephropathy in Swedish patients with diabetes, 15–34 years of age: a prospective cohort study

Authors: My Samuelsson, Jonatan Dereke, Maria K. Svensson, Mona Landin-Olsson, Magnus Hillman, on the behalf of the DISS Study group

Published in: Diabetology & Metabolic Syndrome | Issue 1/2017

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Abstract

Background

The aim of this study was to investigate plasma levels of sST2 and sCD163 to determine whether they at an early stage could predict development of diabetic nephropathy and/or diabetic retinopathy in patients at clinical onset.

Methods

Patients diagnosed with diabetes mellitus at age 15–34 years between 1987 and 1988 (n = 220) were included. Data such as BMI, smoking, HbA1c and islet cell antibodies were collected at time of diagnosis. Within the 10 year follow-up period, 112 patients (51%) developed following diabetes related complications; retinopathy (n = 91), nephropathy (n = 12) or both (n = 9). Plasma concentrations of sST2 and sCD163 were measured at time of diagnosis and levels compared between different complication groups.

Results

Plasma levels of sST2 were significantly higher in patients who later developed nephropathy (n = 21; 1012 [773–1493] pg/ml) compared to those who did not (n = 199; 723 [449–1084] pg/ml; p = 0.006). A tendency for higher plasma levels of sCD163 was observed but not statistically significant (p = 0.058).

Conclusions

sST2 and sCD163 show promise as potential biomarkers for the development of nephropathy already at clinical onset. sST2 and/or sCD163 could possibly be part of a biomarker panel aimed to find patients at high risk of developing nephropathy. Both markers need to be investigated in a larger prospective study.
Literature
1.
go back to reference Dcct Edic research group. Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: long-term follow-up of the Diabetes control and complications trial and epidemiology of diabetes interventions and complications study. Lancet Diabetes Endocrinol. 2014;2(10):793–800.CrossRef Dcct Edic research group. Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: long-term follow-up of the Diabetes control and complications trial and epidemiology of diabetes interventions and complications study. Lancet Diabetes Endocrinol. 2014;2(10):793–800.CrossRef
2.
go back to reference Hata J, Arima H, Rothwell PM, Woodward M, Zoungas S, Anderson C, Patel A, Neal B, Glasziou P, Hamet P, et al. Effects of visit-to-visit variability in systolic blood pressure on macrovascular and microvascular complications in patients with type 2 diabetes mellitus: the ADVANCE trial. Circulation. 2013;128(12):1325–34.CrossRefPubMed Hata J, Arima H, Rothwell PM, Woodward M, Zoungas S, Anderson C, Patel A, Neal B, Glasziou P, Hamet P, et al. Effects of visit-to-visit variability in systolic blood pressure on macrovascular and microvascular complications in patients with type 2 diabetes mellitus: the ADVANCE trial. Circulation. 2013;128(12):1325–34.CrossRefPubMed
3.
go back to reference Selvarajah S, Uiterwaal CS, Haniff J, van der Graaf Y, Visseren FL, Bots ML, Group Ss. Renal impairment and all-cause mortality in cardiovascular disease: effect modification by type 2 diabetes mellitus. Eur J Clin Investig. 2013;43(2):198–207.CrossRef Selvarajah S, Uiterwaal CS, Haniff J, van der Graaf Y, Visseren FL, Bots ML, Group Ss. Renal impairment and all-cause mortality in cardiovascular disease: effect modification by type 2 diabetes mellitus. Eur J Clin Investig. 2013;43(2):198–207.CrossRef
4.
go back to reference Ismail-Beigi F, Craven TE, O’Connor PJ, Karl D, Calles-Escandon J, Hramiak I, Genuth S, Cushman WC, Gerstein HC, Probstfield JL, et al. Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients. Kidney Int. 2012;81(6):586–94.CrossRefPubMed Ismail-Beigi F, Craven TE, O’Connor PJ, Karl D, Calles-Escandon J, Hramiak I, Genuth S, Cushman WC, Gerstein HC, Probstfield JL, et al. Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients. Kidney Int. 2012;81(6):586–94.CrossRefPubMed
5.
go back to reference Beulens JW, Patel A, Vingerling JR, Cruickshank JK, Hughes AD, Stanton A, Lu J, Thom SM, Grobbee DE, Stolk RP, et al. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia. 2009;52(10):2027–36.CrossRefPubMed Beulens JW, Patel A, Vingerling JR, Cruickshank JK, Hughes AD, Stanton A, Lu J, Thom SM, Grobbee DE, Stolk RP, et al. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia. 2009;52(10):2027–36.CrossRefPubMed
7.
go back to reference Gansevoort RT, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Chronic Kidney Disease Prognosis C. Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int. 2011;80(1):93–104.CrossRefPubMedPubMedCentral Gansevoort RT, Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Chronic Kidney Disease Prognosis C. Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int. 2011;80(1):93–104.CrossRefPubMedPubMedCentral
8.
go back to reference Svensson MK, Cederholm J, Eliasson B, Zethelius B, Gudbjornsdottir S, Swedish National Diabetes R. Albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register. Diabetes Vasc Dis Res. 2013;10(6):520–9.CrossRef Svensson MK, Cederholm J, Eliasson B, Zethelius B, Gudbjornsdottir S, Swedish National Diabetes R. Albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register. Diabetes Vasc Dis Res. 2013;10(6):520–9.CrossRef
9.
go back to reference Bjornstad P, Cherney DZ, Snell-Bergeon JK, Pyle L, Rewers M, Johnson RJ, Maahs DM. Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with type 1 diabetes. Nephrol Dial Transplant. 2015;30(10):1706–11.CrossRefPubMedPubMedCentral Bjornstad P, Cherney DZ, Snell-Bergeon JK, Pyle L, Rewers M, Johnson RJ, Maahs DM. Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with type 1 diabetes. Nephrol Dial Transplant. 2015;30(10):1706–11.CrossRefPubMedPubMedCentral
10.
12.
go back to reference Kern EF, Erhard P, Sun W, Genuth S, Weiss MF. Early urinary markers of diabetic kidney disease: a nested case-control study from the diabetes control and complications trial (DCCT). Am J Kidney Dis. 2010;55(5):824–34.CrossRefPubMedPubMedCentral Kern EF, Erhard P, Sun W, Genuth S, Weiss MF. Early urinary markers of diabetic kidney disease: a nested case-control study from the diabetes control and complications trial (DCCT). Am J Kidney Dis. 2010;55(5):824–34.CrossRefPubMedPubMedCentral
13.
go back to reference Nielsen SE, Sugaya T, Hovind P, Baba T, Parving HH, Rossing P. Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients. Diabetes Care. 2010;33(6):1320–4.CrossRefPubMedPubMedCentral Nielsen SE, Sugaya T, Hovind P, Baba T, Parving HH, Rossing P. Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients. Diabetes Care. 2010;33(6):1320–4.CrossRefPubMedPubMedCentral
14.
go back to reference Ahsan H. Diabetic retinopathy–biomolecules and multiple pathophysiology. Diabetes Metab Syndr. 2015;9(1):51–4.CrossRefPubMed Ahsan H. Diabetic retinopathy–biomolecules and multiple pathophysiology. Diabetes Metab Syndr. 2015;9(1):51–4.CrossRefPubMed
15.
go back to reference Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2:17.CrossRef Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2:17.CrossRef
16.
go back to reference Milovanovic M, Volarevic V, Radosavljevic G, Jovanovic I, Pejnovic N, Arsenijevic N, Lukic ML. IL-33/ST2 axis in inflammation and immunopathology. Immunol Res. 2012;52(1–2):89–99.CrossRefPubMed Milovanovic M, Volarevic V, Radosavljevic G, Jovanovic I, Pejnovic N, Arsenijevic N, Lukic ML. IL-33/ST2 axis in inflammation and immunopathology. Immunol Res. 2012;52(1–2):89–99.CrossRefPubMed
17.
go back to reference Bandara G, Beaven MA, Olivera A, Gilfillan AM, Metcalfe DD. Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33. Eur J Immunol. 2015;45(11):3034–44.CrossRefPubMedPubMedCentral Bandara G, Beaven MA, Olivera A, Gilfillan AM, Metcalfe DD. Activated mast cells synthesize and release soluble ST2-a decoy receptor for IL-33. Eur J Immunol. 2015;45(11):3034–44.CrossRefPubMedPubMedCentral
18.
go back to reference Miller AM, Purves D, McConnachie A, Asquith DL, Batty GD, Burns H, Cavanagh J, Ford I, McLean JS, Packard CJ, et al. Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes? PLoS ONE. 2012;7(10):e47830.CrossRefPubMedPubMedCentral Miller AM, Purves D, McConnachie A, Asquith DL, Batty GD, Burns H, Cavanagh J, Ford I, McLean JS, Packard CJ, et al. Soluble ST2 associates with diabetes but not established cardiovascular risk factors: a new inflammatory pathway of relevance to diabetes? PLoS ONE. 2012;7(10):e47830.CrossRefPubMedPubMedCentral
19.
go back to reference Fousteris E, Melidonis A, Panoutsopoulos G, Tzirogiannis K, Foussas S, Theodosis-Georgilas A, Tzerefos S, Matsagos S, Boutati E, Economopoulos T, et al. Toll/interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction. Cardiovasc Diabetol. 2011;10:101.CrossRefPubMedPubMedCentral Fousteris E, Melidonis A, Panoutsopoulos G, Tzirogiannis K, Foussas S, Theodosis-Georgilas A, Tzerefos S, Matsagos S, Boutati E, Economopoulos T, et al. Toll/interleukin-1 receptor member ST2 exhibits higher soluble levels in type 2 diabetes, especially when accompanied with left ventricular diastolic dysfunction. Cardiovasc Diabetol. 2011;10:101.CrossRefPubMedPubMedCentral
20.
go back to reference Dieplinger B, Egger M, Haltmayer M, Kleber ME, Scharnagl H, Silbernagel G, de Boer RA, Maerz W, Mueller T. Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study. Clin Chem. 2014;60(3):530–40.CrossRefPubMed Dieplinger B, Egger M, Haltmayer M, Kleber ME, Scharnagl H, Silbernagel G, de Boer RA, Maerz W, Mueller T. Increased soluble ST2 predicts long-term mortality in patients with stable coronary artery disease: results from the Ludwigshafen risk and cardiovascular health study. Clin Chem. 2014;60(3):530–40.CrossRefPubMed
21.
go back to reference Vilchez JA, Perez-Cuellar M, Marin F, Gallego P, Manzano-Fernandez S, Valdes M, Vicente V, Noguera-Velasco JA, Lip GY, Ordonez-Llanos J, et al. sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation. Eur J Clin Investig. 2015;45(9):899–905.CrossRef Vilchez JA, Perez-Cuellar M, Marin F, Gallego P, Manzano-Fernandez S, Valdes M, Vicente V, Noguera-Velasco JA, Lip GY, Ordonez-Llanos J, et al. sST2 levels are associated with all-cause mortality in anticoagulated patients with atrial fibrillation. Eur J Clin Investig. 2015;45(9):899–905.CrossRef
22.
go back to reference Miller WL, Saenger AK, Grill DE, Slusser JP, Bayes-Genis A, Jaffe AS. Prognostic value of serial measurements of soluble suppression of tumorigenicity 2 and galectin-3 in ambulatory patients with chronic heart failure. J Cardiac Fail. 2016;22(4):249–55.CrossRef Miller WL, Saenger AK, Grill DE, Slusser JP, Bayes-Genis A, Jaffe AS. Prognostic value of serial measurements of soluble suppression of tumorigenicity 2 and galectin-3 in ambulatory patients with chronic heart failure. J Cardiac Fail. 2016;22(4):249–55.CrossRef
23.
24.
go back to reference Parkner T, Sørensen LP, Nielsen AR, Fischer CP, Bibby BM, Nielsen S, Pedersen BK, Moller HJ. Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia. 2012;55(6):1856–62.CrossRefPubMed Parkner T, Sørensen LP, Nielsen AR, Fischer CP, Bibby BM, Nielsen S, Pedersen BK, Moller HJ. Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia. 2012;55(6):1856–62.CrossRefPubMed
25.
go back to reference Fjeldborg K, Christiansen T, Bennetzen M, Moller HJ, Pedersen SB, Richelsen B. The macrophage-specific serum marker, soluble CD163, is increased in obesity and reduced after dietary-induced weight loss. Obesity (Silver Spring, Md). 2013;21(12):2437–43.CrossRef Fjeldborg K, Christiansen T, Bennetzen M, Moller HJ, Pedersen SB, Richelsen B. The macrophage-specific serum marker, soluble CD163, is increased in obesity and reduced after dietary-induced weight loss. Obesity (Silver Spring, Md). 2013;21(12):2437–43.CrossRef
27.
go back to reference Akahori H, Karmali V, Polavarapu R, Lyle AN, Weiss D, Shin E, Husain A, Naqvi N, Van Dam R, Habib A, et al. CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury. Nat Commun. 2015;6:7792.CrossRefPubMedPubMedCentral Akahori H, Karmali V, Polavarapu R, Lyle AN, Weiss D, Shin E, Husain A, Naqvi N, Van Dam R, Habib A, et al. CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury. Nat Commun. 2015;6:7792.CrossRefPubMedPubMedCentral
28.
go back to reference Abu El-Asrar AM, De Hertogh G, Nawaz MI, Siddiquei MM, Van den Eynde K, Mohammad G, Opdenakker G, Geboes K. The tumor necrosis factor superfamily members TWEAK, TNFSF15 and fibroblast growth factor-inducible protein 14 are upregulated in proliferative diabetic retinopathy. Ophthalmic Res. 2015;53(3):122–30.CrossRefPubMed Abu El-Asrar AM, De Hertogh G, Nawaz MI, Siddiquei MM, Van den Eynde K, Mohammad G, Opdenakker G, Geboes K. The tumor necrosis factor superfamily members TWEAK, TNFSF15 and fibroblast growth factor-inducible protein 14 are upregulated in proliferative diabetic retinopathy. Ophthalmic Res. 2015;53(3):122–30.CrossRefPubMed
29.
go back to reference Moller HJ, Frikke-Schmidt R, Moestrup SK, Nordestgaard BG, Tybjaerg-Hansen A. Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clin Chem. 2011;57(2):291–7.CrossRefPubMed Moller HJ, Frikke-Schmidt R, Moestrup SK, Nordestgaard BG, Tybjaerg-Hansen A. Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clin Chem. 2011;57(2):291–7.CrossRefPubMed
30.
go back to reference Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1985; 727:1–113. Diabetes mellitus. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1985; 727:1–113.
31.
go back to reference Svensson M, Sundkvist G, Arnqvist HJ, Bjork E, Blohme G, Bolinder J, Henricsson M, Nystrom L, Torffvit O, Waernbaum I, et al. Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS). Diabetes Care. 2003;26(10):2903–9.CrossRefPubMed Svensson M, Sundkvist G, Arnqvist HJ, Bjork E, Blohme G, Bolinder J, Henricsson M, Nystrom L, Torffvit O, Waernbaum I, et al. Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS). Diabetes Care. 2003;26(10):2903–9.CrossRefPubMed
32.
go back to reference Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32(Suppl 2):64–78.CrossRefPubMed Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32(Suppl 2):64–78.CrossRefPubMed
33.
go back to reference Weir RA, Miller AM, Murphy GE, Clements S, Steedman T, Connell JM, McInnes IB, Dargie HJ, McMurray JJ. Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction. J Am Coll Cardiol. 2010;55(3):243–50.CrossRefPubMed Weir RA, Miller AM, Murphy GE, Clements S, Steedman T, Connell JM, McInnes IB, Dargie HJ, McMurray JJ. Serum soluble ST2: a potential novel mediator in left ventricular and infarct remodeling after acute myocardial infarction. J Am Coll Cardiol. 2010;55(3):243–50.CrossRefPubMed
34.
go back to reference Nordwall M, Abrahamsson M, Dhir M, Fredrikson M, Ludvigsson J, Arnqvist HJ. Impact of HbA1c, followed from onset of type 1 diabetes, on the development of severe retinopathy and nephropathy: the VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care. 2015;38(2):308–15.CrossRefPubMed Nordwall M, Abrahamsson M, Dhir M, Fredrikson M, Ludvigsson J, Arnqvist HJ. Impact of HbA1c, followed from onset of type 1 diabetes, on the development of severe retinopathy and nephropathy: the VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care. 2015;38(2):308–15.CrossRefPubMed
35.
go back to reference Chavers BM, Mauer SM, Ramsay RC, Steffes MW. Relationship between retinal and glomerular lesions in IDDM patients. Diabetes. 1994;43(3):441–6.CrossRefPubMed Chavers BM, Mauer SM, Ramsay RC, Steffes MW. Relationship between retinal and glomerular lesions in IDDM patients. Diabetes. 1994;43(3):441–6.CrossRefPubMed
36.
go back to reference Lovestam-Adrian M, Agardh E, Agardh CD. The incidence of nephropathy in type 1 diabetic patients with proliferative retinopathy: a 10-year follow-up study. Diabetes Res Clin Pract. 1998;39(1):11–7.CrossRefPubMed Lovestam-Adrian M, Agardh E, Agardh CD. The incidence of nephropathy in type 1 diabetic patients with proliferative retinopathy: a 10-year follow-up study. Diabetes Res Clin Pract. 1998;39(1):11–7.CrossRefPubMed
37.
go back to reference Tannus LR, Drummond KR, Clemente EL, da Matta Mde F, Gomes MB, Brazilian Type 1 Diabetes Study G. Predictors of cardiovascular autonomic neuropathy in patients with type 1 diabetes. Front Endocrinol. 2014;5:191.CrossRef Tannus LR, Drummond KR, Clemente EL, da Matta Mde F, Gomes MB, Brazilian Type 1 Diabetes Study G. Predictors of cardiovascular autonomic neuropathy in patients with type 1 diabetes. Front Endocrinol. 2014;5:191.CrossRef
38.
go back to reference Nathan DM, McGee P, Steffes MW, Lachin JM, Group DER. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes. 2014;63(1):282–90.CrossRefPubMed Nathan DM, McGee P, Steffes MW, Lachin JM, Group DER. Relationship of glycated albumin to blood glucose and HbA1c values and to retinopathy, nephropathy, and cardiovascular outcomes in the DCCT/EDIC study. Diabetes. 2014;63(1):282–90.CrossRefPubMed
39.
go back to reference Parikh R, Mathai A, Parikh S, Chandra Sekhar G, Thomas R. Understanding and using sensitivity, specificity and predictive values. Indian J Ophthalmol. 2008;56(1):45–50.CrossRefPubMedPubMedCentral Parikh R, Mathai A, Parikh S, Chandra Sekhar G, Thomas R. Understanding and using sensitivity, specificity and predictive values. Indian J Ophthalmol. 2008;56(1):45–50.CrossRefPubMedPubMedCentral
40.
go back to reference Llauradó G, González-Clemente J-M, Maymó-Masip E, Subías D, Vendrell J, Chacón MR. Serum levels of TWEAK and scavenger receptor CD163 in type 1 diabetes mellitus: relationship with cardiovascular risk factors. A case-control study. PLoS ONE. 2012;7(8):e43919.CrossRefPubMedPubMedCentral Llauradó G, González-Clemente J-M, Maymó-Masip E, Subías D, Vendrell J, Chacón MR. Serum levels of TWEAK and scavenger receptor CD163 in type 1 diabetes mellitus: relationship with cardiovascular risk factors. A case-control study. PLoS ONE. 2012;7(8):e43919.CrossRefPubMedPubMedCentral
41.
go back to reference Al-Daghri NM, Al-Attas OS, Bindahman LS, Alokail MS, Alkharfy KM, Draz HM, Yakout S, McTernan PG, Sabico S, Chrousos GP. Soluble CD163 is associated with body mass index and blood pressure in hypertensive obese Saudi patients. Eur J Clin Investig. 2012;42(11):1221–6.CrossRef Al-Daghri NM, Al-Attas OS, Bindahman LS, Alokail MS, Alkharfy KM, Draz HM, Yakout S, McTernan PG, Sabico S, Chrousos GP. Soluble CD163 is associated with body mass index and blood pressure in hypertensive obese Saudi patients. Eur J Clin Investig. 2012;42(11):1221–6.CrossRef
Metadata
Title
Soluble plasma proteins ST2 and CD163 as early biomarkers of nephropathy in Swedish patients with diabetes, 15–34 years of age: a prospective cohort study
Authors
My Samuelsson
Jonatan Dereke
Maria K. Svensson
Mona Landin-Olsson
Magnus Hillman
on the behalf of the DISS Study group
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2017
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-017-0240-2

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