Subscribe to RSS
DOI: 10.1055/s-0035-1569287
Relationship of Serum Adiponectin Levels and Metformin Therapy in Patients with Type 2 Diabetes
Publication History
received 02 February 2015
accepted 18 November 2015
Publication Date:
25 January 2016 (online)
Abstract
We performed this meta-analysis to investigate and determine the role of metformin on serum adiponectin levels in Type 2 diabetes (T2DM) patients. Embase, Web of Science, Cochrane Library PubMed, and China National Knowledge Infrastructure (CNKI) were thoroughly searched. Eligible human studies assessing the association between serum adiponectin levels and metformin in patients were included, and data were extracted and then analyzed with STATA 12.0 statistical software. Eighteen cohort studies conducted among Asians and Caucasians from 2004 to 2013 were recruited. Post-treatment serum adiponectin level (mmol/l) was higher than pre-treatment levels in T2DM patients (SMD=0.19, 95% CI=0.09–0.30, p<0.001). Country-subgroup analysis showed that serum adiponectin levels in T2DM patients increased after the treatment of metformin in Italy (SMD=0.34, 95% CI=0.09–0.59, p=0.008). Further detection method and follow-up time subgroup analyses implied a positive association of metformin with serum adiponectin level in T2DM patients by using all ELISA, PETIA, and RIA in both<12 weeks and≥12 weeks subgroups (all p<0.05). The present meta-analysis provides compelling evidence that metformin may increase serum adiponectin levels when treating T2DM. Further studies should be promoted to explore the combined efficacy of metformin with other antidiabetic drugs, or developing new predictors with antidiabetic efficacy.
-
References
- 1 American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2006; 29 (Suppl. 01) S43-S48
- 2 Idf Diabetes Atlas G. Update of mortality attributable to diabetes for the IDF Diabetes Atlas: Estimates for the year 2013. Diabetes Res Clin Pract. 2015 109. 461-465
- 3 Guariguata L. Contribute data to the 6th edition of the IDF Diabetes Atlas. Diabetes Res Clin Pract 2013; 100: 280-281
- 4 Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. American Diabetes A, European Association for Study of D. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193-203
- 5 Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diab Vasc Dis Res 2008; 5: 157-167
- 6 Lehman DM, Lorenzo C, Hernandez J, Wang CP. Statin use as a moderator of metformin effect on risk for prostate cancer among type 2 diabetic patients. Diabetes Care 2012; 35: 1002-1007
- 7 Fox MM, Phoenix KN, Kopsiaftis SG, Claffey KP. AMP-Activated Protein Kinase alpha 2 Isoform Suppression in Primary Breast Cancer Alters AMPK Growth Control and Apoptotic Signaling. Genes Cancer 2013; 4: 3-14
- 8 Boyle JG, Logan PJ, Jones GC, Small M, Sattar N, Connell JM, Cleland SJ, Salt IP. AMP-activated protein kinase is activated in adipose tissue of individuals with type 2 diabetes treated with metformin: a randomised glycaemia-controlled crossover study. Diabetologia 2011; 54: 1799-1809
- 9 Doogue MP, Begg EJ, Moore MP, Lunt H, Pemberton CJ, Zhang M. Metformin increases plasma ghrelin in Type 2 diabetes. Br J Clin Pharmacol 2009; 68: 875-882
- 10 Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005; 26: 439-451
- 11 Chandran M, Phillips SA, Ciaraldi T, Henry RR. Adiponectin: more than just another fat cell hormone?. Diabetes Care 2003; 26: 2442-2450
- 12 Diez JJ, Iglesias P. The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol 2003; 148: 293-300
- 13 Xu A, Chan KW, Hoo RL, Wang Y, Tan KC, Zhang J, Chen B, Lam MC, Tse C, Cooper GJ, Lam KS. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem 2005; 280: 18073-18080
- 14 Jalovaara K, Santaniemi M, Timonen M, Jokelainen J, Kesaniemi YA, Ukkola O, Keinanen-Kiukaanniemi S, Rajala U. Low serum adiponectin level as a predictor of impaired glucose regulation and type 2 diabetes mellitus in a middle-aged Finnish population. Metabolism 2008; 57: 1130-1134
- 15 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946
- 16 Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001; 7: 947-953
- 17 Zulian A, Cancello R, Girola A, Gilardini L, Alberti L, Croci M, Micheletto G, Danelli P, Invitti C. In vitro and in vivo effects of metformin on human adipose tissue adiponectin. Obes Facts 2011; 4: 27-33
- 18 Tamura Y, Watada H, Sato F, Kumashiro N, Sakurai Y, Hirose T, Tanaka Y, Kawamori R. Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects. Diabetes Obes Metab 2008; 10: 733-738
- 19 Esteghamati A, Mousavizadeh M, Noshad S, Zandieh A, Zarei H, Nakhjavani M. Gender-dependent effects of metformin on vaspin and adiponectin in type 2 diabetes patients: a randomized clinical trial. Horm Metab Res 2013; 45: 319-325
- 20 Miazgowski T, Dziwura-Ogonowska J, Safranow K, Iskierska K, Widecka K. Changes in adiponectin level and fat distribution in patients with type 2 diabetes. Eur J Clin Invest 2014; 44: 192-199
- 21 Hanefeld M, Pfutzner A, Forst T, Kleine I, Fuchs W. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study. Cardiovasc Diabetol 2011; 10: 65
- 22 Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-605
- 23 Zintzaras E, Ioannidis JP. Heterogeneity testing in meta-analysis of genome searches. Genet Epidemiol 2005; 28: 123-137
- 24 Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA 2006; 295: 676-680
- 25 Zintzaras E, Ioannidis JP. HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics 2005; 21: 3672-3673
- 26 Jung HS, Youn BS, Cho YM, Yu KY, Park HJ, Shin CS, Kim SY, Lee HK, Park KS. The effects of rosiglitazone and metformin on the plasma concentrations of resistin in patients with type 2 diabetes mellitus. Metabolism 2005; 54: 314-320
- 27 Araki T, Emoto M, Teramura M, Yokoyama H, Mori K, Hatsuda S, Maeno T, Shinohara K, Koyama H, Shoji T, Inaba M, Nishizawa Y. Effect of adiponectin on carotid arterial stiffness in type 2 diabetic patients treated with pioglitazone and metformin. Metabolism 2006; 55: 996-1001
- 28 Derosa G, Salvadeo SA, D’Angelo A, Fogari E, Ragonesi PD, Ciccarelli L, Piccinni MN, Ferrari I, Gravina A, Maffioli P, Cicero AF. Rosiglitazone therapy improves insulin resistance parameters in overweight and obese diabetic patients intolerant to metformin. Arch Med Res 2008; 39: 412-419
- 29 Erdem G, Dogru T, Tasci I, Bozoglu E, Muhsiroglu O, Tapan S, Ercin CN, Sonmez A. The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus. Diabetes Res Clin Pract 2008; 82: 214-218
- 30 Eriksson A, Attvall S, Bonnier M, Eriksson JW, Rosander B, Karlsson FA. Short-term effects of metformin in type 2 diabetes. Diabetes Obes Metab 2007; 9: 483-489
- 31 Fan H, Pan Q, Xu Y, Yang X. Exenatide improves type 2 diabetes concomitant with non-alcoholic fatty liver disease. Arq Bras Endocrinol Metabol 2013; 57: 702-708
- 32 Goldberg R, Temprosa M, Otvos J, Brunzell J, Marcovina S, Mather K, Arakaki R, Watson K, Horton E, Barrett-Connor E. Lifestyle and metformin treatment favorably influence lipoprotein subfraction distribution in the Diabetes Prevention Program. J Clin Endocrinol Metab 2013; 98: 3989-3998
- 33 Kadoglou NP, Kapelouzou A, Tsanikidis H, Vitta I, Liapis CD, Sailer N. Effects of rosiglitazone/metformin fixed-dose combination therapy and metformin monotherapy on serum vaspin, adiponectin and IL-6 levels in drug-naive patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2011; 119: 63-68
- 34 Kim HJ, Kang ES, Kim DJ, Kim SH, Ahn CW, Cha BS, Nam M, Chung CH, Lee KW, Nam CM, Lee HC. Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin-18 is an independent factor for the improvement of homeostasis model assessment-beta in type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66: 282-289
- 35 Miazgowski T, Dziwura-Ogonowska J, Safranow K, Iskierska K, Widecka K. Changes in adiponectin level and fat distribution in patients with type 2 diabetes. Eur J Clin Invest 2014; 44: 192-199
- 36 Ohira M, Miyashita Y, Ebisuno M, Saiki A, Endo K, Koide N, Oyama T, Murano T, Watanabe H, Shirai K. Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients. Diabetes Res Clin Pract 2007; 78: 34-41
- 37 Putz DM, Goldner WS, Bar RS, Haynes WG, Sivitz WI. Adiponectin and C-reactive protein in obesity, type 2 diabetes, and monodrug therapy. Metabolism 2004; 53: 1454-1461
- 38 Sharma PK, Bhansali A, Sialy R, Malhotra S, Pandhi P. Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2006; 65: 722-728
- 39 Teranishi T, Ohara T, Maeda K, Zenibayashi M, Kouyama K, Hirota Y, Kawamitsu H, Fujii M, Sugimura K, Kasuga M. Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus. Metabolism 2007; 56: 1418-1424
- 40 Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 2004; 53: 2169-2176
- 41 Wang H, Ni Y, Yang S, Li H, Li X, Feng B. The effects of gliclazide, metformin, and acarbose on body composition in patients with newly diagnosed type 2 diabetes mellitus. Curr Ther Res Clin Exp 2013; 75: 88-92
- 42 Shin L, Bregman H, Breeze JL, Noyes N, Frazier JA. Metformin for weight control in pediatric patients on atypical antipsychotic medication. J Child Adolesc Psychopharmacol 2009; 19: 275-279
- 43 Diabetes Prevention Program Research G. Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. Diabetes Care 2012; 35: 731-737
- 44 Kirino Y, Sei M, Kawazoe K, Minakuchi K, Sato Y. Plasma dipeptidyl peptidase 4 activity correlates with body mass index and the plasma adiponectin concentration in healthy young people. Endocr J 2012; 59: 949-953
- 45 Singh S, Akhtar N, Ahmad J. Plasma adiponectin levels in women with polycystic ovary syndrome: impact of metformin treatment in a case-control study. Diabetes Metab Syndr 2012; 6: 207-211