title: Insulin-like growth factor 1 predicts post-load hypoglycemia following bariatric surgery: a prospective cohort study.
abstract: Postprandial hypoglycemia is a complication following gastric bypass surgery, which frequently remains undetected. Severe hypoglycemic episodes, however, put patients at risk, e.g., for syncope. A major cause of hypoglycemia following gastric bypass is hyperinsulinemic nesidioblastosis. Since pancreatic islets in nesidioblastosis overexpress insulin-like growth factor 1 (IGF-1) receptor α and administration of recombinant IGF-1 provokes hypoglycemia, our main objective was to investigate the occurrence of post-load hypoglycemia one year after bariatric surgery and its relation to pre- and post-operative IGF-1 serum concentrations. We evaluated metabolic parameters including 2 h 75 g oral glucose tolerance test (OGTT) and measured IGF-1 serum concentration in thirty-six non-diabetic patients (29 f/7 m), aged 41.3±2.0 y with a median (IQR) BMI of 30.9 kg/m2 (27.5-34.3 kg/m2), who underwent elective bariatric surgery (predominantly gastric bypass, 83%) at our hospital. Post-load hypoglycemia as defined by a 2 h glucose concentration <60 mg/dl was detected in 50% of patients. Serum insulin and C-peptide concentration during the OGTT and HOMA-IR (homeostatic model assessment-insulin resistance) were similar in hypoglycemic and euglycemic patients. Strikingly, pre- and post-operative serum IGF-1 concentrations were significantly higher in hypoglycemic patients (p = 0.012 and p = 0.007 respectively). IGF-1 serum concentration before surgery negatively correlated with 2 h glucose concentration during the OGTT (rho = -0.58, p = 0.0003). Finally, IGF-1 serum concentrations before and after surgery significantly predicted post-load hypoglycemia with odds ratios of 1.28 (95%CI:1.03-1.55, p = 0.029) and 1.18 (95%CI:1.03-1.33, p = 0.015), respectively, for each 10 ng/ml increment. IGF-1 serum concentration could be a valuable biomarker to identify patients at risk for hypoglycemia following bariatric surgery independently of a diagnostic OGTT. Thus, IGF-1 testing could help to prevent a significant complication of gastric bypass surgery.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy, Medical University Vienna, Vienna, Austria.
authors.forename: Bianca K
authors.initials: BK
authors.lastname: Itariu
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy, Medical University Vienna, Vienna, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine III, Medical University Vienna, Vienna, Austria; Christian Doppler Laboratory for Cardio-Metabolic Immunotherapy, Medical University Vienna, Vienna, Austria.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
mesh_terms: D000328:Adult; D050110:Bariatric Surgery / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000209:etiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D012306:Risk
chemical_list: D015415:Biomarkers; D007334:Insulin-Like Growth Factor I
references.citation: Int J Obes (Lond). 2007 Aug;31(8):1248-61
references.pmid: 17356530
references.citation: J Clin Endocrinol Metab. 2007 Mar;92(3):902-10
references.pmid: 17192294
references.citation: J Gastrointest Surg. 2006 Sep-Oct;10(8):1116-9
references.pmid: 16966030
references.citation: Diabetes Care. 2012 Apr;35(4):768-73
references.pmid: 22374641
references.citation: Obes Surg. 2013 May;23(5):594-601
references.pmid: 23179244
references.citation: Diabetes Care. 1999 Sep;22(9):1462-70
references.pmid: 10480510
references.citation: Ann Intern Med. 2008 Oct 7;149(7):461-71, W83-8
references.pmid: 18838726
references.citation: BMC Gastroenterol. 2006 Nov 02;6:33
references.pmid: 17081293
references.citation: Diabetologia. 2005 Nov;48(11):2236-40
references.pmid: 16195867
references.citation: Obes Surg. 2008 Dec;18(12):1618-21
references.pmid: 18566871
references.citation: PLoS One. 2013;8(1):e54634
references.pmid: 23372745
references.citation: J Gastrointest Surg. 2011 Oct;15(10):1879-88
references.pmid: 21671112
references.citation: Obes Surg. 2013 Apr;23(4):427-36
references.pmid: 23338049
references.citation: Obesity (Silver Spring). 2013 Apr;21(4):665-72
references.pmid: 23404774
references.citation: Int J Obes (Lond). 2006 Nov;30(11):1623-31
references.pmid: 16552400
references.citation: Obes Surg. 2009 Nov;19(11):1550-6
references.pmid: 19557485
references.citation: N Engl J Med. 2005 Jul 21;353(3):249-54
references.pmid: 16034010
references.citation: Mol Cell Biochem. 2011 Feb;348(1-2):33-42
references.pmid: 21076856
references.citation: Am J Clin Nutr. 2012 Nov;96(5):1137-49
references.pmid: 23034965
references.citation: J Biol Chem. 1978 Apr 25;253(8):2769-76
references.pmid: 632300
references.citation: Horm Res. 2004;62 Suppl 1:77-82
references.pmid: 15761237
references.citation: N Engl J Med. 2007 Aug 23;357(8):753-61
references.pmid: 17715409
references.citation: Int J Obes (Lond). 2009 Jan;33(1):46-53
references.pmid: 19002144
references.citation: J Diabetes Sci Technol. 2012 Sep 01;6(5):1107-13
references.pmid: 23063037
references.citation: Obes Surg. 2012 Jun;22(6):910-7
references.pmid: 22246393
references.citation: BMC Med. 2013 Jan 10;11:8
references.pmid: 23302153
references.citation: PLoS One. 2013 Oct 16;8(10):e77326
references.pmid: 24146977
references.citation: Diabetologia. 2010 Nov;53(11):2276-9
references.pmid: 20730413
references.citation: Diabetes Care. 2000 Feb;23(2):163-70
references.pmid: 10868825
references.citation: J Clin Endocrinol Metab. 2007 Dec;92(12):4678-85
references.pmid: 17895322
references.citation: Diabetes Care. 2005 Jan;28(1):120-5
references.pmid: 15616244
references.citation: Mol Pathol. 2001 Oct;54(5):311-6
references.pmid: 11577173
references.citation: Diabetes. 1965 Aug;14:526-8
references.pmid: 14334844
references.citation: Lancet Oncol. 2010 Jun;11(6):530-42
references.pmid: 20472501
references.citation: Ann Surg. 2014 Apr;259(4):687-93
references.pmid: 23787216
references.citation: Diabetes. 2001 May;50(5):1110-8
references.pmid: 11334415
references.citation: Surg Endosc. 2011 Jun;25(6):1926-32
references.pmid: 21184112
references.citation: Endocr J. 2010;57(4):325-30
references.pmid: 20081321
references.citation: World J Gastroenterol. 2004 Jan 15;10(2):255-9
references.pmid: 14716834
references.citation: J Clin Endocrinol Metab. 1999 Dec;84(12):4397-404
references.pmid: 10599694
references.citation: Diabet Med. 2006 May;23(5):469-80
references.pmid: 16681555
references.citation: Eur J Endocrinol. 2013 Oct 08;169(5):695-703
references.pmid: 23946276
references.citation: Diabetes Care. 2012 Dec;35(12):2580-7
references.pmid: 22923664
references.citation: Int J Obes (Lond). 2008 Nov;32(11):1640-6
references.pmid: 18794895
references.citation: Diabetologia. 2010 Nov;53(11):2307-11
references.pmid: 20495972
references.citation: Diabetologia. 1985 Jul;28(7):412-9
references.pmid: 3899825
references.citation: Mod Pathol. 2009 Feb;22(2):239-45
references.pmid: 18931647