Skip to main content
Erschienen in: Journal of Endocrinological Investigation 12/2014

01.12.2014 | Original Article

Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial

verfasst von: A. Esteghamati, S. Rezvani, E. Khajeh, M. Ebadi, M. Nakhjavani, S. Noshad

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 12/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Metformin and pioglitazone are believed to exert their long-term benefits by means of amelioration of chronic low-grade inflammation, a key event in development of diabetes and its long-term complications. The present trial was designed to investigate the comparative efficacy of the two anti-diabetes medications on serum concentrations of YKL-40, a novel marker of inflammation.

Methods

In a parallel-group, open-label, randomized trial setting (ClinicalTrials.gov Identifier No. NCT01521624), 84 newly diagnosed, medication-naïve type 2 diabetes patients were assigned to metformin 1,000 mg daily (n = 42) or pioglitazone 30 mg daily (n = 42). Serum concentrations of YKL-40, along with highly sensitive C-reactive protein, indices of glycemic control and lipid profile were measured at baseline and after 3 months.

Results

In the analyzed sample (metformin = 40, pioglitazone = 42), both medications were equally effective with regard to control of hyperglycemia, and hsCRP reduction (p > 0.05). However, metformin caused a significant decline in weight (p = 0.005), BMI (p = 0.004), and total cholesterol levels (p = 0.028) of the patients. Metformin also significantly reduced YKL-40 concentrations after 3 months (1.90 ± 17 vs. 1.66 ± 0.15 µg/L, p = 0.019). The amount of change in the pioglitazone arm did not reach statistical significance (2.18 ± 0.14 vs. 2.25 ± 0.16 µg/L, p = 0.687). When compared, metformin was significantly more effective than pioglitazone with respect to YKL-40 reduction in both univariate (p = 0.020, effect size = 6.7 %) and multivariate models (p = 0.047, effect size = 5.7 %).

Conclusions

Metformin is more effective in reduction of YKL-40 concentration in short term and the effect seems to be independent of degree of glycemic control, or hsCRP reduction.
Literatur
1.
Zurück zum Zitat Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. New Eng J Med 339:229–234. doi:10.1056/NEJM199807233390404 PubMedCrossRef Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. New Eng J Med 339:229–234. doi:10.​1056/​NEJM199807233390​404 PubMedCrossRef
2.
Zurück zum Zitat Pyorala K, Laakso M, Uusitupa M (1987) Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 3:463–524PubMedCrossRef Pyorala K, Laakso M, Uusitupa M (1987) Diabetes and atherosclerosis: an epidemiologic view. Diabetes Metab Rev 3:463–524PubMedCrossRef
7.
Zurück zum Zitat Gustafson B (2010) Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 17:332–341PubMedCrossRef Gustafson B (2010) Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb 17:332–341PubMedCrossRef
8.
Zurück zum Zitat Stern MP (1995) Diabetes and cardiovascular disease. The “common soil” hypothesis. Diabetes 44:369–374PubMedCrossRef Stern MP (1995) Diabetes and cardiovascular disease. The “common soil” hypothesis. Diabetes 44:369–374PubMedCrossRef
10.
Zurück zum Zitat Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137PubMedCrossRef Festa A, D’Agostino R Jr, Tracy RP, Haffner SM (2002) Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51:1131–1137PubMedCrossRef
11.
Zurück zum Zitat Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27:813–823PubMedCrossRef Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27:813–823PubMedCrossRef
12.
Zurück zum Zitat Rathcke C, Vestergaard H (2006) YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm Res 55:221–227PubMedCrossRef Rathcke C, Vestergaard H (2006) YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm Res 55:221–227PubMedCrossRef
14.
Zurück zum Zitat Nøjgaard C, Høst NB, Christensen IJ, Poulsen SH, Egstrup K, Price PA, Johansen JS (2008) Serum levels of YKL-40 increases in patients with acute myocardial infarction. Coron Artery Dis 19:257–263PubMedCrossRef Nøjgaard C, Høst NB, Christensen IJ, Poulsen SH, Egstrup K, Price PA, Johansen JS (2008) Serum levels of YKL-40 increases in patients with acute myocardial infarction. Coron Artery Dis 19:257–263PubMedCrossRef
15.
Zurück zum Zitat Chu NV, Kong APS, Kim DD, Armstrong D, Baxi S, Deutsch R, Caulfield M, Mudaliar SR, Reitz R, Henry RR, Reaven PD (2002) Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care 25:542–549. doi:10.2337/diacare.25.3.542 PubMedCrossRef Chu NV, Kong APS, Kim DD, Armstrong D, Baxi S, Deutsch R, Caulfield M, Mudaliar SR, Reitz R, Henry RR, Reaven PD (2002) Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes. Diabetes Care 25:542–549. doi:10.​2337/​diacare.​25.​3.​542 PubMedCrossRef
16.
Zurück zum Zitat Satoh N, Ogawa Y, Usui T, Tagami T, Kono S, Uesugi H, Sugiyama H, Sugawara A, Yamada K, Shimatsu A, Kuzuya H, Nakao K (2003) Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 26:2493–2499. doi:10.2337/diacare.26.9.2493 PubMedCrossRef Satoh N, Ogawa Y, Usui T, Tagami T, Kono S, Uesugi H, Sugiyama H, Sugawara A, Yamada K, Shimatsu A, Kuzuya H, Nakao K (2003) Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care 26:2493–2499. doi:10.​2337/​diacare.​26.​9.​2493 PubMedCrossRef
18.
Zurück zum Zitat Cohen J (1988) Statistical power analysis for the behavioral sciences. L. Erlbaum Associates, Hillsdale Cohen J (1988) Statistical power analysis for the behavioral sciences. L. Erlbaum Associates, Hillsdale
19.
Zurück zum Zitat Volck B, Price PA, Johansen JS, Sørensen O, Benfield TL, Nielsen HJ, Calafat J, Borregaard N (1998) YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc Assoc Am Phys 110:351PubMed Volck B, Price PA, Johansen JS, Sørensen O, Benfield TL, Nielsen HJ, Calafat J, Borregaard N (1998) YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc Assoc Am Phys 110:351PubMed
20.
Zurück zum Zitat Rehli M, Krause S, Andreesen R (1997) Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 43:221–225PubMedCrossRef Rehli M, Krause S, Andreesen R (1997) Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 43:221–225PubMedCrossRef
21.
Zurück zum Zitat Recklies AD, White C, Ling H (2002) The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem J 365:119–126. doi:10.1042/bj20020075 PubMedCentralPubMedCrossRef Recklies AD, White C, Ling H (2002) The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates proliferation of human connective-tissue cells and activates both extracellular signal-regulated kinase- and protein kinase B-mediated signalling pathways. Biochem J 365:119–126. doi:10.​1042/​bj20020075 PubMedCentralPubMedCrossRef
22.
24.
Zurück zum Zitat Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H (2009) YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care 32:323–328. doi:10.2337/dc08-1144 PubMedCentralPubMedCrossRef Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H (2009) YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care 32:323–328. doi:10.​2337/​dc08-1144 PubMedCentralPubMedCrossRef
25.
Zurück zum Zitat Wang Y, Ripa RS, Johansen JS, Gabrielsen A, Steinbrüchel DA, Friis T, Bindslev L, Haack-Sørensen M, Jørgensen E, Kastrup J (2008) YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease. Scand Cardiovasc J 42:295–302PubMedCrossRef Wang Y, Ripa RS, Johansen JS, Gabrielsen A, Steinbrüchel DA, Friis T, Bindslev L, Haack-Sørensen M, Jørgensen E, Kastrup J (2008) YKL-40 a new biomarker in patients with acute coronary syndrome or stable coronary artery disease. Scand Cardiovasc J 42:295–302PubMedCrossRef
26.
Zurück zum Zitat Kastrup J, Johansen JS, Winkel P, Hansen JF, Hildebrandt P, Jensen GB, Jespersen CM, Kjøller E, Kolmos HJ, Lind I (2009) High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease. Eur Heart J 30:1066–1072PubMedCrossRef Kastrup J, Johansen JS, Winkel P, Hansen JF, Hildebrandt P, Jensen GB, Jespersen CM, Kjøller E, Kolmos HJ, Lind I (2009) High serum YKL-40 concentration is associated with cardiovascular and all-cause mortality in patients with stable coronary artery disease. Eur Heart J 30:1066–1072PubMedCrossRef
27.
Zurück zum Zitat Boot RG, van Achterberg TAE, van Aken BE, Renkema GH, Jacobs MJHM, Aerts JMFG, de Vries CJM (1999) Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler Thromb Vasc Biol 19:687–694. doi:10.1161/01.atv.19.3.687 PubMedCrossRef Boot RG, van Achterberg TAE, van Aken BE, Renkema GH, Jacobs MJHM, Aerts JMFG, de Vries CJM (1999) Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler Thromb Vasc Biol 19:687–694. doi:10.​1161/​01.​atv.​19.​3.​687 PubMedCrossRef
29.
Zurück zum Zitat Rathcke CN, Raymond I, Kistorp C, Hildebrandt P, Faber J, Vestergaard H (2010) Low grade inflammation as measured by levels of YKL-40: Association with an increased overall and cardiovascular mortality rate in an elderly population. Int J Cardiol 143:35–42. doi:10.1016/j.ijcard.2009.01.043 PubMedCrossRef Rathcke CN, Raymond I, Kistorp C, Hildebrandt P, Faber J, Vestergaard H (2010) Low grade inflammation as measured by levels of YKL-40: Association with an increased overall and cardiovascular mortality rate in an elderly population. Int J Cardiol 143:35–42. doi:10.​1016/​j.​ijcard.​2009.​01.​043 PubMedCrossRef
30.
Zurück zum Zitat Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the american diabetes association (ADA) and the european association for the study of diabetes (EASD). Diabetes Care 35:1364–1379. doi:10.2337/dc12-0413 PubMedCentralPubMedCrossRef Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR (2012) Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the american diabetes association (ADA) and the european association for the study of diabetes (EASD). Diabetes Care 35:1364–1379. doi:10.​2337/​dc12-0413 PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366:1279–1289. doi:10.1016/s0140-6736(05)67528-9 PubMedCrossRef Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366:1279–1289. doi:10.​1016/​s0140-6736(05)67528-9 PubMedCrossRef
32.
Zurück zum Zitat Belcher G, Matthews D (2000) Safety and tolerability of pioglitazone. Exp Clin Endocr Diabetes 108:S267–S273CrossRef Belcher G, Matthews D (2000) Safety and tolerability of pioglitazone. Exp Clin Endocr Diabetes 108:S267–S273CrossRef
33.
Zurück zum Zitat Hempen M, Kopp HP, Elhenicky M, Hobaus C, Brix JM, Koppensteiner R, Schernthaner G, Schernthaner GH (2009) YKL-40 is elevated in morbidly obese patients and declines after weight loss. Obes Surg 19:1557–1563. doi:10.1007/s11695-009-9917-4 PubMedCrossRef Hempen M, Kopp HP, Elhenicky M, Hobaus C, Brix JM, Koppensteiner R, Schernthaner G, Schernthaner GH (2009) YKL-40 is elevated in morbidly obese patients and declines after weight loss. Obes Surg 19:1557–1563. doi:10.​1007/​s11695-009-9917-4 PubMedCrossRef
34.
Zurück zum Zitat Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Rotellar F, Valenti V, Silva C, Gil MJ, Salvador J, Fruhbeck G (2011) Increased circulating and visceral adipose tissue expression levels of YKL-40 in obesity-associated type 2 diabetes are related to inflammation: impact of conventional weight loss and gastric bypass. J Clin Endocr Metab 96:200–209. doi:10.1210/jc.2010-0994 PubMedCrossRef Catalan V, Gomez-Ambrosi J, Rodriguez A, Ramirez B, Rotellar F, Valenti V, Silva C, Gil MJ, Salvador J, Fruhbeck G (2011) Increased circulating and visceral adipose tissue expression levels of YKL-40 in obesity-associated type 2 diabetes are related to inflammation: impact of conventional weight loss and gastric bypass. J Clin Endocr Metab 96:200–209. doi:10.​1210/​jc.​2010-0994 PubMedCrossRef
35.
Metadaten
Titel
Comparative effects of metformin and pioglitazone on YKL-40 in type 2 diabetes: a randomized clinical trial
verfasst von
A. Esteghamati
S. Rezvani
E. Khajeh
M. Ebadi
M. Nakhjavani
S. Noshad
Publikationsdatum
01.12.2014
Verlag
Springer International Publishing
Erschienen in
Journal of Endocrinological Investigation / Ausgabe 12/2014
Elektronische ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-014-0154-x

Weitere Artikel der Ausgabe 12/2014

Journal of Endocrinological Investigation 12/2014 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

29.05.2024 Herzinfarkt Nachrichten

Bei Menschen mit Typ-2-Diabetes sind die Chancen, einen Myokardinfarkt zu überleben, in den letzten 15 Jahren deutlich gestiegen – nicht jedoch bei Betroffenen mit Typ 1.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.