Skip to main content
Top
Published in: Journal of Endocrinological Investigation 5/2015

01-05-2015 | Original Article

Increased levels of galectin-3 were associated with prediabetes and diabetes: new risk factor?

Authors: H. Yilmaz, M. Cakmak, O. Inan, T. Darcin, A. Akcay

Published in: Journal of Endocrinological Investigation | Issue 5/2015

Login to get access

Abstract

Purpose

Galectin-3 (Gal-3) is a marker of cardiac fibrosis and predicts incident heart failure. Gal-3-deficient mice are resistant to multiple low-dose streptozotocin-induced diabetes. Recent experimental studies suggested an important role for Gal-3 in the regulation of adiposity, metaflammation and type 2 diabetes. This study aimed to examine the relationship between Gal-3 and newly diagnosed prediabetes and diabetes.

Methods

Gal-3 concentrations were measured in 118 participants and 56 age- and sex-matched healthy controls. All subjects underwent a 75-g oral glucose tolerance test and were stratified into normal, prediabetic, and diabetes mellitus subgroups. DM was defined as a plasma glucose level ≥126 mg/dL in the fasting state or ≥200 mg/dL in the second hour after glucose loading. Impaired fasting glucose was defined as an FPG level of 100–125 mg/dL, and impaired glucose tolerance was defined as a 2-h plasma glucose level of 140–199 mg/dL.

Results

Sixty-one patients had prediabetes (Group 1), 57 had diabetes (Group 2), and 56 had neither diabetes nor prediabetes (Group 3). Gal-3 levels correlated with FPG (r = 0.787, P < 0.01), 2hPG (r = 0.833, P < 0.01), CRP (r = 0.501, P < 0.01), and HOMA-IR (r = 0.518, P < 0.01). Gal-3 levels were higher in Group 2 than in Groups 1 and 3 [1,053.9 (358.1) and 744.1 (119.3) vs. 481.7 (175.4) pg/mL; P < 0.001]. Gal-3 is an independent predictor of diabetes in multivariate logistic analysis. In ROC analysis, a Gal-3 cutoff value of 803.55 pg/mL diagnoses diabetes with a sensitivity of 80.7 % and a specificity of 85.5 % (AUC = 0.912).

Conclusions

Gal-3 is a promising biomarker for detecting prediabetes and diabetes.
Literature
1.
go back to reference Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, Larson MG, Levy D (2012) Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol 60(14):1249–1256CrossRefPubMedCentralPubMed Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, Larson MG, Levy D (2012) Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol 60(14):1249–1256CrossRefPubMedCentralPubMed
2.
go back to reference de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJ, van der Harst P (2012) The fibrosis marker galectin-3 and outcome in the general population. J Intern Med 272(1):55–64CrossRefPubMed de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJ, van der Harst P (2012) The fibrosis marker galectin-3 and outcome in the general population. J Intern Med 272(1):55–64CrossRefPubMed
3.
go back to reference van der Velde AR, Gullestad L, Ueland T, Aukrust P, Guo Y, Adourian A, Muntendam P, van Veldhuisen DJ, de Boer RA (2013) Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH. Circ Heart Fail 6(2):219–226CrossRefPubMed van der Velde AR, Gullestad L, Ueland T, Aukrust P, Guo Y, Adourian A, Muntendam P, van Veldhuisen DJ, de Boer RA (2013) Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH. Circ Heart Fail 6(2):219–226CrossRefPubMed
4.
5.
go back to reference Barrow H, Rhodes JM, Yu LG (2013) Simultaneous determination of serum galectin-3 and -4 levels detects metastases in colorectal cancer patients. Cell Oncol (Dordr) 36(1):9–13CrossRef Barrow H, Rhodes JM, Yu LG (2013) Simultaneous determination of serum galectin-3 and -4 levels detects metastases in colorectal cancer patients. Cell Oncol (Dordr) 36(1):9–13CrossRef
6.
go back to reference Vereecken P, Awada A, Suciu S, Castro G, Morandini R, Litynska A, Lienard D, Ezzedine K, Ghanem G, Heenen M (2009) Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage III and stage IV melanoma patients. Melanoma Res 19(5):316–320CrossRefPubMed Vereecken P, Awada A, Suciu S, Castro G, Morandini R, Litynska A, Lienard D, Ezzedine K, Ghanem G, Heenen M (2009) Evaluation of the prognostic significance of serum galectin-3 in American Joint Committee on Cancer stage III and stage IV melanoma patients. Melanoma Res 19(5):316–320CrossRefPubMed
7.
go back to reference McCullough PA, Olobatoke A, Vanhecke TE (2011) Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med 12(4):200–210PubMed McCullough PA, Olobatoke A, Vanhecke TE (2011) Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med 12(4):200–210PubMed
8.
go back to reference Mensah-Brown EP, Al Rabesi Z, Shahin A, Al Shamsi M, Arsenijevic N, Hsu DK, Liu FT, Lukic ML (2009) Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice. Clin Immunol 130(1):83–88CrossRefPubMed Mensah-Brown EP, Al Rabesi Z, Shahin A, Al Shamsi M, Arsenijevic N, Hsu DK, Liu FT, Lukic ML (2009) Targeted disruption of the galectin-3 gene results in decreased susceptibility to multiple low dose streptozotocin-induced diabetes in mice. Clin Immunol 130(1):83–88CrossRefPubMed
10.
go back to reference Pejnovic NN, Pantic JM, Jovanovic IP, Radosavljevic GD, Milovanovic MZ, Nikolic IG, Zdravkovic NS, Djukic AL, Arsenijevic NN, Lukic ML (2013) Galectin-3 deficiency accelerates high-fat diet-induced obesity and amplifies inflammation in adipose tissue and pancreatic islets. Diabetes 62(6):1932–1944CrossRefPubMedCentralPubMed Pejnovic NN, Pantic JM, Jovanovic IP, Radosavljevic GD, Milovanovic MZ, Nikolic IG, Zdravkovic NS, Djukic AL, Arsenijevic NN, Lukic ML (2013) Galectin-3 deficiency accelerates high-fat diet-induced obesity and amplifies inflammation in adipose tissue and pancreatic islets. Diabetes 62(6):1932–1944CrossRefPubMedCentralPubMed
11.
go back to reference Saksida T, Nikolic I, Vujicic M, Nilsson UJ, Leffler H, Lukic ML, Stojanovic I, Stosic-Grujicic S (2013) Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro. J Cell Physiol 228(7):1568–1576CrossRefPubMed Saksida T, Nikolic I, Vujicic M, Nilsson UJ, Leffler H, Lukic ML, Stojanovic I, Stosic-Grujicic S (2013) Galectin-3 deficiency protects pancreatic islet cells from cytokine-triggered apoptosis in vitro. J Cell Physiol 228(7):1568–1576CrossRefPubMed
12.
go back to reference Darrow AL, Shohet RV, Maresh JG (2011) Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3. Physiol Genom 43:1144–1152CrossRef Darrow AL, Shohet RV, Maresh JG (2011) Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3. Physiol Genom 43:1144–1152CrossRef
13.
go back to reference Karlsen AE, Størling ZM, Sparre T, Larsen MR, Mahmood A, Størling J, Roepstorff P, Wrzesinski K, Larsen PM, Fey S, Nielsen K, Heding P, Ricordi C, Johannesen J, Kristiansen OP, Christensen UB, Kockum I, Luthman H, Nerup J, Pociot F (2006) Immune-mediated beta-cell destruction in vitro and in vivo—a pivotal role for galectin-3. Biochem Biophys Res Commun 344:406–415CrossRefPubMed Karlsen AE, Størling ZM, Sparre T, Larsen MR, Mahmood A, Størling J, Roepstorff P, Wrzesinski K, Larsen PM, Fey S, Nielsen K, Heding P, Ricordi C, Johannesen J, Kristiansen OP, Christensen UB, Kockum I, Luthman H, Nerup J, Pociot F (2006) Immune-mediated beta-cell destruction in vitro and in vivo—a pivotal role for galectin-3. Biochem Biophys Res Commun 344:406–415CrossRefPubMed
14.
go back to reference Pugliese G, Iacobini C, Ricci C, Blasetti Fantauzzi C, Menini S (2014) Galectin-3 in diabetic patients. Clin Chem Lab Med 52(10):1413–1423CrossRefPubMed Pugliese G, Iacobini C, Ricci C, Blasetti Fantauzzi C, Menini S (2014) Galectin-3 in diabetic patients. Clin Chem Lab Med 52(10):1413–1423CrossRefPubMed
15.
go back to reference Weigert J, Neumeier M, Wanninger J, Bauer S, Farkas S, Scherer MN, Schnitzbauer A, Schäffler A, Aslanidis C, Schölmerich J, Buechler C (2010) serum galectin-3 is elevated in obesity and negatively correlates with glycosylated hemoglobin in type 2 diabetes. J Clin Endocrinol Metab 95(3):1404–1411CrossRefPubMed Weigert J, Neumeier M, Wanninger J, Bauer S, Farkas S, Scherer MN, Schnitzbauer A, Schäffler A, Aslanidis C, Schölmerich J, Buechler C (2010) serum galectin-3 is elevated in obesity and negatively correlates with glycosylated hemoglobin in type 2 diabetes. J Clin Endocrinol Metab 95(3):1404–1411CrossRefPubMed
16.
go back to reference Yilmaz H, Celik HT, Ozdemir O, Kalkan D, Namuslu M, Abusoglu S, Atalay CR, Yigitoglu R (2014) Serum galectin-3 levels in women with PCOS. J Endocrinol Invest 37(2):181–187CrossRefPubMed Yilmaz H, Celik HT, Ozdemir O, Kalkan D, Namuslu M, Abusoglu S, Atalay CR, Yigitoglu R (2014) Serum galectin-3 levels in women with PCOS. J Endocrinol Invest 37(2):181–187CrossRefPubMed
17.
go back to reference American Diabetes Association (2014) Standards of medical care in diabetes–2014. Diabetes Care 37(Suppl 1):S14–S80CrossRef American Diabetes Association (2014) Standards of medical care in diabetes–2014. Diabetes Care 37(Suppl 1):S14–S80CrossRef
18.
go back to reference Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27:1487–1495CrossRefPubMed Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27:1487–1495CrossRefPubMed
19.
go back to reference Henderson NC, Sethi T (2009) The regulation of inflammation by galectin-3. Immunol Rev 230(1):160–171CrossRefPubMed Henderson NC, Sethi T (2009) The regulation of inflammation by galectin-3. Immunol Rev 230(1):160–171CrossRefPubMed
20.
go back to reference ten Oever J, Giamarellos-Bourboulis EJ, van de Veerdonk FL, Stelma FF, Simon A, Janssen M, Johnson M, Pachot A, Kullberg BJ, Joosten LA, Netea MG (2013) Circulating galectin-3 in infections and non-infectious inflammatory diseases. Eur J Clin Microbiol Infect Dis 32(12):1605–1610CrossRefPubMed ten Oever J, Giamarellos-Bourboulis EJ, van de Veerdonk FL, Stelma FF, Simon A, Janssen M, Johnson M, Pachot A, Kullberg BJ, Joosten LA, Netea MG (2013) Circulating galectin-3 in infections and non-infectious inflammatory diseases. Eur J Clin Microbiol Infect Dis 32(12):1605–1610CrossRefPubMed
22.
go back to reference Dehghan A, Kardys I, de Maat MPM, Uitterlinden AG, Sijbrands EJG, Bootsma AH, Stijnen T, Hofman A, Schram MT, Witteman JCM (2007) Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56:872–878CrossRefPubMed Dehghan A, Kardys I, de Maat MPM, Uitterlinden AG, Sijbrands EJG, Bootsma AH, Stijnen T, Hofman A, Schram MT, Witteman JCM (2007) Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56:872–878CrossRefPubMed
23.
go back to reference Liu S, Tinker L, Song Y, Rifai N, Bonds DE, Cook NR, Heiss G, Howard BV, Hotamisligil GS, Hu FB, Kuller LH, Manson JE (2007) A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. Arch Intern Med 167:1676–1685CrossRefPubMed Liu S, Tinker L, Song Y, Rifai N, Bonds DE, Cook NR, Heiss G, Howard BV, Hotamisligil GS, Hu FB, Kuller LH, Manson JE (2007) A prospective study of inflammatory cytokines and diabetes mellitus in a multiethnic cohort of postmenopausal women. Arch Intern Med 167:1676–1685CrossRefPubMed
24.
go back to reference Thorand B, Baumert J, Kolb H, Meisinger C, Chambless L, Koenig W, Herder C (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30:854–860CrossRefPubMed Thorand B, Baumert J, Kolb H, Meisinger C, Chambless L, Koenig W, Herder C (2007) Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002. Diabetes Care 30:854–860CrossRefPubMed
25.
go back to reference Lee CC, Adler AI, Sandhu MS, Sharp SJ, Forouhi NG, Erqou S, Luben R, Bingham S, Khaw KT, Wareham NJ (2009) Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52(6):1040–1047CrossRefPubMed Lee CC, Adler AI, Sandhu MS, Sharp SJ, Forouhi NG, Erqou S, Luben R, Bingham S, Khaw KT, Wareham NJ (2009) Association of C-reactive protein with type 2 diabetes: prospective analysis and meta-analysis. Diabetologia 52(6):1040–1047CrossRefPubMed
26.
go back to reference Lee CC, Lorenzo C, Haffner SM, Wagenknecht LE, Festa A, Goodarzi MO, Stefanovski D, Olson NC, Norris JM, Rewers MJ, Hanley AJ (2013) The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia 56(1):112–120CrossRefPubMedCentralPubMed Lee CC, Lorenzo C, Haffner SM, Wagenknecht LE, Festa A, Goodarzi MO, Stefanovski D, Olson NC, Norris JM, Rewers MJ, Hanley AJ (2013) The association of inflammatory and fibrinolytic proteins with 5 year change in insulin clearance: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia 56(1):112–120CrossRefPubMedCentralPubMed
27.
go back to reference Brunner EJ, Kivimäki M, Witte DR, Lawlor DA, Smith GD, Cooper JA, Miller M, Lowe GD, Rumley A, Casas JP, Shah T, Humphries SE, Hingorani AD, Marmot MG, Timpson NJ, Kumari M (2008) Inflammation, insulin resistance, and diabetes—Mendelian randomization using CRP haplotypes points upstream. PLoS Med 5(8):e155. doi:10.1371/journal.pmed.0050155 CrossRefPubMedCentralPubMed Brunner EJ, Kivimäki M, Witte DR, Lawlor DA, Smith GD, Cooper JA, Miller M, Lowe GD, Rumley A, Casas JP, Shah T, Humphries SE, Hingorani AD, Marmot MG, Timpson NJ, Kumari M (2008) Inflammation, insulin resistance, and diabetes—Mendelian randomization using CRP haplotypes points upstream. PLoS Med 5(8):e155. doi:10.​1371/​journal.​pmed.​0050155 CrossRefPubMedCentralPubMed
28.
go back to reference de Rn P, Peila R, Ding J et al (2006) Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study. Diabetes Care 29:1902–1908CrossRef de Rn P, Peila R, Ding J et al (2006) Diabetes, hyperglycemia, and inflammation in older individuals: the health, aging and body composition study. Diabetes Care 29:1902–1908CrossRef
29.
go back to reference Doi Y, Kiyohara Y, Kubo M et al (2005) Relationship between C-reactive protein and glucose levels in community-dwelling subjects without diabetes: the Hisayama Study. Diabetes Care 28:1211–1213CrossRefPubMed Doi Y, Kiyohara Y, Kubo M et al (2005) Relationship between C-reactive protein and glucose levels in community-dwelling subjects without diabetes: the Hisayama Study. Diabetes Care 28:1211–1213CrossRefPubMed
30.
go back to reference Lin J, Zhang M, Song F, Qin J, Wang R, Yao P, Ying C, Hu FB, Liu L (2009) Association between C-reactive protein and pre-diabetic status in a Chinese Han clinical population. Diabetes Metab Res Rev 25:219–223CrossRefPubMed Lin J, Zhang M, Song F, Qin J, Wang R, Yao P, Ying C, Hu FB, Liu L (2009) Association between C-reactive protein and pre-diabetic status in a Chinese Han clinical population. Diabetes Metab Res Rev 25:219–223CrossRefPubMed
31.
go back to reference Sabanayagam C, Shankar A, Lim SC, Lee J, Tai ES, Wong TY (2011) Serum C-reactive protein level and prediabetes in two Asian populations. Diabetologia 54(4):767–775CrossRefPubMed Sabanayagam C, Shankar A, Lim SC, Lee J, Tai ES, Wong TY (2011) Serum C-reactive protein level and prediabetes in two Asian populations. Diabetologia 54(4):767–775CrossRefPubMed
32.
go back to reference Rhodes DH, Pini M, Castellanos KJ, Montero-Melendez T, Cooper D, et al. (2012) Adipose tissue specific modulation of galectin expression in lean and obese mice: evidence for regulatory function. Obesity (in press) Rhodes DH, Pini M, Castellanos KJ, Montero-Melendez T, Cooper D, et al. (2012) Adipose tissue specific modulation of galectin expression in lean and obese mice: evidence for regulatory function. Obesity (in press)
33.
go back to reference Kiwaki K, Novak CM, Hsu DK, Liu F-T, Levine JA (2007) Galectin-3 stimulates preadipocyte proliferation and is up-regulated in growing adipose tissue. Obesity 15:32–39CrossRefPubMed Kiwaki K, Novak CM, Hsu DK, Liu F-T, Levine JA (2007) Galectin-3 stimulates preadipocyte proliferation and is up-regulated in growing adipose tissue. Obesity 15:32–39CrossRefPubMed
Metadata
Title
Increased levels of galectin-3 were associated with prediabetes and diabetes: new risk factor?
Authors
H. Yilmaz
M. Cakmak
O. Inan
T. Darcin
A. Akcay
Publication date
01-05-2015
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 5/2015
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-014-0222-2

Other articles of this Issue 5/2015

Journal of Endocrinological Investigation 5/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.