title: Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease.
abstract: BACKGROUND
  Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has a wide range of effects on glucose metabolism and cardiovascular function (e.g., improving insulin sensitivity, reduction in appetite, modulation of heart rate, blood pressure and myocardial contractility). Metabolic syndrome (MetS) is associated with an increased risk of developing atherosclerotic cardiovascular diseases. Novel glycemic control drugs, the dipeptidyl-peptidase-4 (DPP-4) inhibitors, work by inhibiting the inactivation of incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In spite of good effects of these drugs in diabetic patients, circulating levels of incretins and their role in MetS are largely unknown.
  
  
  METHODS
  To examine relationships between incretin hormones and MetS risk factors, we measured circulating levels of incretins in obese high-risk patients for cardiovascular disease. Fasting serum GLP-1 and GIP levels were measured by ELISA. We performed a cross-sectional analysis of metabolic variables in the fasting state in two subject groups: with MetS (n = 60) and pre-MetS (n = 37).
  
  
  RESULTS
  Fasting levels of Serum GLP -1 in the peripheral circulation were significantly increased correlated with the accumulation of MetS risk factors components (r = 0. 470, P < 0.001). There was a significant interaction between circulating GLP-1 and GIP, serum high-density lipoprotein cholesterol, triglyceride, and serum uric acid concentrations but not waist circumference, fasting glucose, HbA1c, or presence of diabetes.
  
  
  CONCLUSIONS
  Circulating levels of GLP-1 in relation to the accumulation in MetS factors suggested that MetS patients with elevated levels of GLP-1 are high-risk patients for cardiovascular disease, independent with the presence of diabetes.
authors.affiliation: Department of Rehabilitation, Kitasato University School of Allied Health Sciences, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0373, Japan. myamaoka@med.kitasato-u.ac.jp
authors.forename: Minako
authors.initials: M
authors.lastname: Yamaoka-Tojo
authors.forename: Taiki
authors.initials: T
authors.lastname: Tojo
authors.forename: Naonobu
authors.initials: N
authors.lastname: Takahira
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Matsunaga
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Aoyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Masuda
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000097:blood; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D006442:Glycated Hemoglobin; D006801:Humans; D007333:Insulin Resistance; D007564:Japan; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D014527:Uric Acid / Q000097:blood; D055105:Waist Circumference
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D014280:Triglycerides; D014527:Uric Acid; C517652:hemoglobin A1c protein, human
references.citation: J Clin Endocrinol Metab. 2001 Aug;86(8):3717-23
references.pmid: 11502801
references.citation: Curr Opin Lipidol. 1996 Jun;7(3):167-71
references.pmid: 8818515
references.citation: J Pharmacol Exp Ther. 2006 Jun;317(3):1106-13
references.pmid: 16489128
references.citation: Am J Med. 2008 May;121(5):426-32
references.pmid: 18456039
references.citation: Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):629-36
references.pmid: 18174459
references.citation: Gastroenterology. 2007 May;132(6):2131-57
references.pmid: 17498508
references.citation: Circulation. 2005 Oct 25;112(17):2735-52
references.pmid: 16157765
references.citation: Am J Med. 2009 Jun;122(6 Suppl):S37-50
references.pmid: 19464427
references.citation: Circulation. 2007 Mar 20;115(11):1345-53
references.pmid: 17339551
references.citation: Ann Surg. 2006 Jan;243(1):108-14
references.pmid: 16371744
references.citation: Drugs. 2008;68(15):2131-62
references.pmid: 18840004
references.citation: Neuroimage. 2007 Apr 1;35(2):511-7
references.pmid: 17317222
references.citation: J Clin Endocrinol Metab. 2009 Jul;94(7):2558-64
references.pmid: 19366852
references.citation: Rev Diabet Stud. 2006 Winter;3(4):208-16
references.pmid: 17487346
references.citation: Acta Psychiatr Scand. 2009 Jan;119(1):4-14
references.pmid: 19133915
references.citation: Endocr Rev. 2008 Dec;29(7):777-822
references.pmid: 18971485
references.citation: Am J Cardiol. 2007 Sep 1;100(5):824-9
references.pmid: 17719327
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14843-7
references.pmid: 10611300
references.citation: Lancet. 2009 Nov 7;374(9701):1570-1
references.pmid: 19853907
references.citation: J Clin Invest. 2007 Jan;117(1):143-52
references.pmid: 17187081
references.citation: Br J Pharmacol. 2009 Aug;157(8):1340-51
references.pmid: 19681866
references.citation: J Clin Endocrinol Metab. 2007 Feb;92(2):399-404
references.pmid: 17284640
references.citation: JAMA. 2008 Mar 12;299(10):1185-7
references.pmid: 18334695
references.citation: Cardiovasc Drugs Ther. 2007 Aug;21(4):253-6
references.pmid: 17541736
references.citation: Br J Surg. 2006 Feb;93(2):210-5
references.pmid: 16392104
references.citation: Mol Endocrinol. 2006 Jul;20(7):1644-51
references.pmid: 16469773
references.citation: Lancet. 1987 Dec 5;2(8571):1300-4
references.pmid: 2890903
references.citation: J Clin Invest. 1995 Jan;95(1):417-21
references.pmid: 7814643
references.citation: Nature. 1996 Jan 4;379(6560):69-72
references.pmid: 8538742
references.citation: Cardiovasc Diabetol. 2009 Jul 20;8:38
references.pmid: 19619327
references.citation: Chin Med J (Engl). 2008 Nov 5;121(21):2134-8
references.pmid: 19080172
references.citation: Am J Hypertens. 2007 Jan;20(1):83-9
references.pmid: 17198917
references.citation: J Clin Endocrinol Metab. 2007 Dec;92(12):4678-85
references.pmid: 17895322
references.citation: Physiol Rev. 2007 Oct;87(4):1409-39
references.pmid: 17928588
references.citation: J Clin Endocrinol Metab. 1986 Aug;63(2):492-8
references.pmid: 3522621
references.citation: N Engl J Med. 1996 Feb 8;334(6):374-81
references.pmid: 8538710
references.citation: Circulation. 2004 Mar 2;109(8):962-5
references.pmid: 14981009
references.citation: Diabetes. 2001 Mar;50(3):609-13
references.pmid: 11246881
references.citation: JAMA. 2002 Dec 4;288(21):2709-16
references.pmid: 12460094
references.citation: Circulation. 2008 May 6;117(18):2340-50
references.pmid: 18427132
references.citation: Obes Surg. 2005 Apr;15(4):474-81
references.pmid: 15946424
references.citation: Nat Med. 2002 Jul;8(7):738-42
references.pmid: 12068290
references.citation: Diabetes. 2009 Apr;58(4):975-83
references.pmid: 19151200
references.citation: J Atheroscler Thromb. 2006 Aug;13(4):202-8
references.pmid: 16908953
references.citation: Diabetes. 2005 Jan;54(1):146-51
references.pmid: 15616022
references.citation: Diabetologia. 1985 Jul;28(7):412-9
references.pmid: 3899825
references.citation: J Clin Invest. 1996 Jan 1;97(1):92-103
references.pmid: 8550855