Subscribe to RSS
DOI: 10.1055/s-0042-119788
Growth Hormone Treatment Increases Plasma Irisin Concentration in Patients with Turner Syndrome
Publication History
received 03 August 2016
accepted 17 October 2016
Publication Date:
07 December 2016 (online)
![](https://www.thieme-connect.de/media/hmr/201702/lookinside/thumbnails/2016-08-0259_10-1055-s-0042-119788-1.jpg)
Abstract
Irisin (Ir) deficiency may be a contributing factor in metabolic disease. This study aimed to investigate the effect of supraphysiological doses of recombinant human growth hormone (rhGH) on Ir plasma concentration in relation to metabolic disorders, including obesity and other components of metabolic syndrome. We studied 36 girls with Turner syndrome (mean age 8.2 years) treated with rhGH (0.05 mg/kg/day). Anthropometric data and fasting blood levels [e. g., Ir, insulin, glucose, glycated hemoglobin (HbA1c), IGF-1, IGFBP-3, cholesterol, insulin resistance (HOMA-IR), and β-cell function (HOMA-β)] were analyzed prior to and following rhGH therapy [mean (SD) follow-up of 1.47 (0.89) years]. Insulin sensitivity (Matsuda index) was calculated before and after the glucose load. Following rhGH therapy, an increase in IGF-1 [mean (SD) of 119.40 (62.47) ng/ml to 439.08 (209.91) ng/ml, p=0.000], Ir [2.10 (1.03) μg/ml to 2.48 (0.78) μg/ml, p=0.036], HOMA-IR [median (IQR) of 0.64 (0.45–1.30) to 0.92 (0.67–2.36), p=0.0206], and HOMA-β values [45.00 (27.69–72.00) to 81.53 (51.43–132.00), p=0.0447] were observed. Multiple regression analysis yielded no associations between Ir and metabolic and hormonal parameters before rhGH treatment; however, on rhGH, the model (R2=0.56, adjusted R2=0.45) showed positive associations between Ir and IGF-1 standard deviation score and HbA1c, and negative associations between Ir and fasting blood glucose, HDL-cholesterol, and triglycerides. Despite manifestation of insulin resistance, rhGH application had a positive effect on Ir regulation, and restored physiological conditions of lipid and glucose metabolism.
Key words
irisin - growth hormone - insulin resistance - metabolic syndrome - HOMA-IR - beta-cell function* The authors equally contributed to the paper.
-
References
- 1 Lv J, Pan Y, Li X, Cheng D, Ju H, Tian J, Shi H, Zhang Y. Study on the distribution and elimination of the new hormone irisin in vivo: new discoveries regarding irisin. Horm Metab Res 2015; 47: 591-595
- 2 Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic Peroxisome Proliferator-activated Receptor ? (PPAR?) Activation of Epididymally Derived White Adipocyte Cultures Reveals a Population of Thermogenically Competent, UCP1-containing Adipocytes Molecularly Distinct from Classic Brown Adipocytes. J Biol Chem 2010; 285: 7153-7164
- 3 Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang A-H, Khandekar M, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerback S, Schrauwen P, Spiegelman BM. Beige Adipocytes are a Distinct Type of Thermogenic Fat Cell in Mouse and Human. Cell 2012; 150: 366-376
- 4 Huh JY, Panagiotou G, Mougios V, Brinkoetter M, Vamvini MT, Schneider BE, Mantzoros CS. FNDC5 and irisin in humans: I. Predictors of circulating concentrations in serum and plasma and II. mRNA expression and circulating concentrations in response to weight loss and exercise. Metabolism 2012; 61: 1725-1738
- 5 McMillan AC, White MD. Induction of thermogenesis in brown and beige adipose tissues: molecular markers, mild cold exposure and novel therapies. Curr Opin Endocrinol Diabetes Obes 2015; 22: 347-352
- 6 Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998; 92: 829-839
- 7 Kraemer RR, Shockett P, Webb ND, Shah U, Castracane VD. A Transient Elevated Irisin Blood Concentration in Response to Prolonged, Moderate Aerobic Exercise in Young Men and Women. Horm Metab Res Horm Stoffwechselforschung Horm Metab 2014; 46: 150-154
- 8 Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Boström EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Højlund K, Gygi SP, Spiegelman BM. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012; 481: 463-468
- 9 Jóźków P, Medraś M. Growth hormone and IGF-1 as doping agents in competitive sport. Endokrynol Pol 2009; 60: 389-394
- 10 Reinehr T, Lindberg A, Koltowska-Häggström M, Ranke M. Is growth hormone treatment in children associated with weight gain? Longitudinal analysis of KIGS data. Clin Endocrinol (Oxf) 2014; 81: 721-726
- 11 Meazza C, Elsedfy HH, Pagani S, Bozzola E, El Kholy M, Bozzola M. Metabolic parameters and adipokine profile in growth hormone deficient (GHD) children before and after 12-month GH treatment. Horm Metab Res Horm Stoffwechselforschung Horm Métabolisme 2014; 46: 219-223
- 12 Srinivasa S, Suresh C, Mottla J, Hamarneh SR, Irazoqui JE, Frontera W, Torriani M, Stanley T, Makimura H. FNDC5 relates to skeletal muscle IGF-I and mitochondrial function and gene expression in obese men with reduced growth hormone. Growth Horm IGF Res 2016; 26: 36-41
- 13 Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, Muroya K, Binder G, Kirsch S, Winkelmann M, Nordsiek G, Heinrich U, Breuning MH, Ranke MB, Rosenthal A, Ogata T, Rappold GA. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet 1997; 16: 54-63
- 14 Bakalov VK, Cooley MM, Quon MJ, Luo ML, Yanovski JA, Nelson LM, Sullivan G, Bondy CA. Impaired insulin secretion in the Turner metabolic syndrome. J Clin Endocrinol Metab 2004; 89: 3516-3520
- 15 Landin-Wilhelmsen K, Bryman I, Wilhelmsen L. Cardiac malformations and hypertension, but not metabolic risk factors, are common in Turner syndrome. J Clin Endocrinol Metab 2001; 86: 4166-4170
- 16 Lichiardopol C, Moţa M, Braicu D, Militaru C, Mixich F. Diabetes mellitus and Turner syndrome. Romanian J Intern Med Rev Roum Médecine Interne 2007; 45: 299-304
- 17 Caprio S, Boulware S, Diamond M, Sherwin RS, Carpenter TO, Rubin K, Amiel S, Press M, Tamborlane WV. Insulin resistance: an early metabolic defect of Turner’s syndrome. J Clin Endocrinol Metab 1991; 72: 832-836
- 18 Hazem A, Elamin MB, Bancos I, Malaga G, Prutsky G, Domecq JP, Elraiyah TA, Elnour NOA, Prevost Y, Almandoz JP, Zeballos-Palacios C, Velasquez ER, Erwin PJ, Natt N, Montori VM, Murad MH. Therapy in Endocrine Disease: Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis. Eur J Endocrinol 2012; 166: 13-20
- 19 Darendeliler F, Aycan Z, Cetinkaya E, Vidilisan S, Bas F, Bideci A, Demirel F, Darcan S, Buyukgebiz A, Yildiz M, Berberoglu M, Arslanoglu I, Bundak R. Effects of growth hormone on growth, insulin resistance and related hormones (ghrelin, leptin and adiponectin) in Turner syndrome. Horm Res 2007; 68: 1-7
- 20 Schweizer R, Martin DD, Schönau E, Ranke MB. Muscle function improves during growth hormone therapy in short children born small for gestational age: results of a peripheral quantitative computed tomography study on body composition. J Clin Endocrinol Metab 2008; 93: 2978-2983
- 21 Wikiera B, Bieniasz J, Barg E, Głab E, Noczyńska A. Lipoprotein a (Lp(a)) in patients with Turner’s syndrome. Pediatr Endocrinol Diabetes Metab 2010; 16: 29-32
- 22 Wooten N, Bakalov VK, Hill S, Bondy CA. Reduced abdominal adiposity and improved glucose tolerance in growth hormone-treated girls with Turner syndrome. J Clin Endocrinol Metab 2008; 93: 2109-2114
- 23 Blüher S, Panagiotou G, Petroff D, Markert J, Wagner A, Klemm T, Filippaios A, Keller A, Mantzoros CS. Effects of a 1-year exercise and lifestyle intervention on irisin, adipokines, and inflammatory markers in obese children. Obes Silver Spring Md 2014; 22: 1701-1708
- 24 Palacios-González B, Vadillo-Ortega F, Polo-Oteyza E, Sánchez T, Ancira-Moreno M, Romero-Hidalgo S, Meráz N, Antuna-Puente B. Irisin levels before and after physical activity among school-age children with different BMI: a direct relation with leptin. Obes Silver Spring Md 2015; 23: 729-732
- 25 Reinehr T, Elfers C, Lass N, Roth CL. Irisinand Its Relation to Insulin Resistance and Puberty in Obese Children: A Longitudinal Analysis. J Clin Endocrinol Metab 2015; 100: 2123-2130
- 26 Al-Daghri NM, Alkharfy KM, Rahman S, Amer OE, Vinodson B, Sabico S, Piya MK, Harte AL, McTernan PG, Alokail MS, Chrousos GP. Irisin as a predictor of glucose metabolism in children: sexually dimorphic effects. Eur J Clin Invest 2014; 44: 119-124
- 27 Zybek-Kocik A, Sawicka-Gutaj N, Wrotkowska E, Sowiński J, Ruchała M. Time-dependent irisin concentration changes in patients affected by overt hypothyroidism. Endokrynol Pol 2016; DOI: 10.5603/EP.a2016.0030.
- 28 Ruchala M, Zybek A, Szczepanek-Parulska E. Serum irisin levels and thyroid function-newly discovered association. Peptides 2014; 60: 51-55
- 29 Elsheikh M, Dunger DB, Conway GS, Wass JaH. Turner’s Syndrome in Adulthood. Endocr Rev 2002; 23: 120-140
- 30 Clement-Jones M, Schiller S, Rao E, Blaschke RJ, Zuniga A, Zeller R, Robson SC, Binder G, Glass I, Strachan T, Lindsay S, Rappold GA. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet 2000; 9: 695-702
- 31 Wikiera B, Mulak M, Koltowska-Haggstrom M, Noczynska A. The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype. Clin Endocrinol (Oxf) 2015; 83: 842-848
- 32 Zhong Q, Layman LC. Genetic considerations in the patient with Turner syndrome-45,X with or without mosaicism. Fertil Steril 2012; 98: 775-779
- 33 Pena-Bello L, Pértega-Diaz S, Sangiao-Alvarellos S, Outeiriño-Blanco E, Eiras-Leal R, Varela-Rodriguez B, Juiz-Valiña P, Pérez-Fontán M, Cordido M, Cordido F. Circulating Levels of Irisin in Hypopituitary and Normal Subjects. PloS One 2016; 11: e0160364
- 34 Irzyniec TJ, Jeż W. The influence of hormonal replacement and growth hormone treatment on the lipids in Turner syndrome. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 2014; 30: 250-253
- 35 Hee Park K, Zaichenko L, Brinkoetter M, Thakkar B, Sahin-Efe A, Joung KE, Tsoukas MA, Geladari EV, Huh JY, Dincer F, Davis CR, Crowell JA, Mantzoros CS. Circulating irisin in relation to insulin resistance and the metabolic syndrome. J Clin Endocrinol Metab 2013; 98: 4899-4907
- 36 Stengel A, Hofmann T, Goebel-Stengel M, Elbelt U, Kobelt P, Klapp BF. Circulating levels of irisin in patients with anorexia nervosa and different stages of obesity–correlation with body mass index. Peptides 2013; 39: 125-130
- 37 Pukajło K, Łaczmański Ł, Kolackov K, Kuliczkowska-Płaksej J, Bolanowski M, Milewicz A, Daroszewski J. Irisin plasma concentration in PCOS and healthy subjects is related to body fat content and android fat distribution. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol 2015; 1-5
- 38 Choi Y-K, Kim M-K, Bae KH, Seo H-A, Jeong J-Y, Lee W-K, Kim J-G, Lee I-K, Park K-G. Serum irisin levels in new-onset type 2 diabetes. Diabetes Res Clin Pract 2013; 100: 96-101
- 39 Liu J-J, Wong MDS, Toy WC, Tan CSH, Liu S, Ng XW, Tavintharan S, Sum CF, Lim SC. Lower circulating irisin is associated with type 2 diabetes mellitus. J Diabetes Complicat 2013; 27: 365-369
- 40 Moreno-Navarrete JM, Ortega F, Serrano M, Guerra E, Pardo G, Tinahones F, Ricart W, Fernández-Real JM. Irisin is expressed and produced by human muscle and adipose tissue in association with obesity and insulin resistance. J Clin Endocrinol Metab 2013; 98: E769-E778
- 41 Sanchis-Gomar F, Alis R, Pareja-Galeano H, Romagnoli M, Perez-Quilis C. Inconsistency in circulating irisin levels: what is really happening?. Horm Metab Res Horm 2014; 46: 591-596