Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2010

Open Access 01-12-2010 | Original investigation

Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease

Authors: Minako Yamaoka-Tojo, Taiki Tojo, Naonobu Takahira, Atsuhiko Matsunaga, Naoyoshi Aoyama, Takashi Masuda, Tohru Izumi

Published in: Cardiovascular Diabetology | Issue 1/2010

Login to get access

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.

Conclusion

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.
Appendix
Available only for authorised users
Literature
1.
Grundy SM: Metabolic syndrome pandemic. Arteriosclerosis, thrombosis, and vascular biology. 2008, 28 (4): 629-636. 10.1161/ATVBAHA.107.151092.CrossRefPubMed
2.
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC, Spertus JA, Costa F: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005, 112 (17): 2735-2752. 10.1161/CIRCULATIONAHA.105.169404.CrossRefPubMed
3.
Grundy SM: Metabolic syndrome: a multiplex cardiovascular risk factor. The Journal of clinical endocrinology and metabolism. 2007, 92 (2): 399-404. 10.1210/jc.2006-0513.CrossRefPubMed
4.
Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, Van Pelt RE, Wang H, Eckel RH: The metabolic syndrome. Endocrine reviews. 2008, 29 (7): 777-822. 10.1210/er.2008-0024.CrossRefPubMed
5.
Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002, 288 (21): 2709-2716. 10.1001/jama.288.21.2709.CrossRefPubMed
6.
Reaven GM, Lithell H, Landsberg L: Hypertension and associated metabolic abnormalities--the role of insulin resistance and the sympathoadrenal system. The New England journal of medicine. 1996, 334 (6): 374-381. 10.1056/NEJM199602083340607.CrossRefPubMed
7.
Wang TJ, Larson MG, Keyes MJ, Levy D, Benjamin EJ, Vasan RS: Association of plasma natriuretic peptide levels with metabolic risk factors in ambulatory individuals. Circulation. 2007, 115 (11): 1345-1353. 10.1161/CIRCULATIONAHA.106.655142.CrossRefPubMed
8.
Austin MA, Edwards KL: Small, dense low density lipoproteins, the insulin resistance syndrome and noninsulin-dependent diabetes. Current opinion in lipidology. 1996, 7 (3): 167-171. 10.1097/00041433-199606000-00010.CrossRefPubMed
9.
Coutinho Tde A, Turner ST, Peyser PA, Bielak LF, Sheedy PF, Kullo IJ: Associations of serum uric acid with markers of inflammation, metabolic syndrome, and subclinical coronary atherosclerosis. American journal of hypertension. 2007, 20 (1): 83-89. 10.1016/j.amjhyper.2006.06.015.CrossRefPubMed
10.
Servais A, Giral P, Bernard M, Bruckert E, Deray G, Isnard Bagnis C: Is serum cystatin-C a reliable marker for metabolic syndrome?. The American journal of medicine. 2008, 121 (5): 426-432. 10.1016/j.amjmed.2008.01.040.CrossRefPubMed
11.
Saleem U, Khaleghi M, Morgenthaler NG, Bergmann A, Struck J, Mosley TH, Kullo IJ: Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. The Journal of clinical endocrinology and metabolism. 2009, 94 (7): 2558-2564. 10.1210/jc.2008-2278.PubMedCentralCrossRefPubMed
12.
Wang Z, Wang RM, Owji AA, Smith DM, Ghatei MA, Bloom SR: Glucagon-like peptide-1 is a physiological incretin in rat. The Journal of clinical investigation. 1995, 95 (1): 417-421. 10.1172/JCI117671.PubMedCentralCrossRefPubMed
13.
Turton MD, O'Shea D, Gunn I, Beak SA, Edwards CM, Meeran K, Choi SJ, Taylor GM, Heath MM, Lambert PD, Wilding JP, Smith DM, Ghatei MA, Herbert J, Bloom SR: A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996, 379 (6560): 69-72. 10.1038/379069a0.CrossRefPubMed
14.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28 (7): 412-419. 10.1007/BF00280883.CrossRefPubMed
15.
Arai H, Yamamoto A, Matsuzawa Y, Saito Y, Yamada N, Oikawa S, Mabuchi H, Teramoto T, Sasaki J, Nakaya N, Itakura H, Ishikawa Y, Ouchi Y, Horibe H, Shirahashi N, Kita T: Prevalence of metabolic syndrome in the general Japanese population in 2000. Journal of atherosclerosis and thrombosis. 2006, 13 (4): 202-208.CrossRefPubMed
16.
Kreymann B, Williams G, Ghatei MA, Bloom SR: Glucagon-like peptide-17-36: a physiological incretin in man. Lancet. 1987, 2 (8571): 1300-1304. 10.1016/S0140-6736(87)91194-9.CrossRefPubMed
17.
Holst JJ: The physiology of glucagon-like peptide 1. Physiological reviews. 2007, 87 (4): 1409-1439. 10.1152/physrev.00034.2006.CrossRefPubMed
18.
Baggio LL, Drucker DJ: Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007, 132 (6): 2131-2157. 10.1053/j.gastro.2007.03.054.CrossRefPubMed
19.
Bray GA: Gastrointestinal hormones and weight management. Lancet. 2009, 374 (9701): 1606-16. 10.1016/S0140-6736(09)61560-9.CrossRef
20.
Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001, 50 (3): 609-613. 10.2337/diabetes.50.3.609.CrossRefPubMed
21.
Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, Kubota A, Fujimoto S, Kajikawa M, Kuroe A, Tsuda K, Hashimoto H, Yamashita T, Jomori T, Tashiro F, Miyazaki J, Seino Y: Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proceedings of the National Academy of Sciences of the United States of America. 1999, 96 (26): 14843-14847. 10.1073/pnas.96.26.14843.PubMedCentralCrossRefPubMed
22.
Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y: Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nature medicine. 2002, 8 (7): 738-742. 10.1038/nm727.CrossRefPubMed
23.
Tsukiyama K, Yamada Y, Yamada C, Harada N, Kawasaki Y, Ogura M, Bessho K, Li M, Amizuka N, Sato M, Udagawa N, Takahashi N, Tanaka K, Oiso Y, Seino Y: Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Molecular endocrinology (Baltimore, Md). 2006, 20 (7): 1644-1651. 10.1210/me.2005-0187.CrossRef
24.
Hansotia T, Maida A, Flock G, Yamada Y, Tsukiyama K, Seino Y, Drucker DJ: Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure. The Journal of clinical investigation. 2007, 117 (1): 143-152. 10.1172/JCI25483.PubMedCentralCrossRefPubMed
25.
Grieve DJ, Cassidy RS, Green BD: Emerging cardiovascular actions of the incretin hormone glucagon-like peptide-1: potential therapeutic benefits beyond glycaemic control?. British journal of pharmacology. 2009, 157 (8): 1340-1351. 10.1111/j.1476-5381.2009.00376.x.PubMedCentralCrossRefPubMed
26.
Nikolaidis LA, Mankad S, Sokos GG, Miske G, Shah A, Elahi D, Shannon RP: Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004, 109 (8): 962-965. 10.1161/01.CIR.0000120505.91348.58.CrossRefPubMed
27.
Sokos GG, Bolukoglu H, German J, Hentosz T, Magovern GJ, Maher TD, Dean DA, Bailey SH, Marrone G, Benckart DH, Elahi D, Shannon RP: Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting. The American journal of cardiology. 2007, 100 (5): 824-829. 10.1016/j.amjcard.2007.05.022.CrossRefPubMed
28.
Bose AK, Mocanu MM, Carr RD, Brand CL, Yellon DM: Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury. Diabetes. 2005, 54 (1): 146-151. 10.2337/diabetes.54.1.146.CrossRefPubMed
29.
Bose AK, Mocanu MM, Carr RD, Yellon DM: Myocardial ischaemia-reperfusion injury is attenuated by intact glucagon like peptide-1 (GLP-1) in the in vitro rat heart and may involve the p70s6K pathway. Cardiovascular drugs and therapy/sponsored by the International Society of Cardiovascular Pharmacotherapy. 2007, 21 (4): 253-256.CrossRefPubMed
30.
Zhao T, Parikh P, Bhashyam S, Bolukoglu H, Poornima I, Shen YT, Shannon RP: Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts. The Journal of pharmacology and experimental therapeutics. 2006, 317 (3): 1106-1113. 10.1124/jpet.106.100982.CrossRefPubMed
31.
Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M: Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008, 117 (18): 2340-2350. 10.1161/CIRCULATIONAHA.107.739938.CrossRefPubMed
32.
Xie Y, Wang SX, Sha WW, Zhou X, Wang WL, Han LP, Li DQ, Yu DM: Effects and mechanism of glucagon-like peptide-1 on injury of rats cardiomyocytes induced by hypoxia-reoxygenation. Chinese medical journal. 2008, 121 (21): 2134-2138.PubMed
33.
Noyan-Ashraf MH, Momen MA, Ban K, Sadi AM, Zhou YQ, Riazi AM, Baggio LL, Henkelman RM, Husain M, Drucker DJ: GLP-1R agonist liraglutide activates cytoprotective pathways and improves outcomes after experimental myocardial infarction in mice. Diabetes. 2009, 58 (4): 975-983. 10.2337/db08-1193.PubMedCentralCrossRefPubMed
34.
Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, Creutzfeldt W: Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. The Journal of clinical endocrinology and metabolism. 1986, 63 (2): 492-498. 10.1210/jcem-63-2-492.CrossRefPubMed
35.
Toft-Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ: Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. The Journal of clinical endocrinology and metabolism. 2001, 86 (8): 3717-3723. 10.1210/jc.86.8.3717.CrossRefPubMed
36.
Schirra J, Katschinski M, Weidmann C, Schafer T, Wank U, Arnold R, Goke B: Gastric emptying and release of incretin hormones after glucose ingestion in humans. The Journal of clinical investigation. 1996, 97 (1): 92-103. 10.1172/JCI118411.PubMedCentralCrossRefPubMed
37.
Borg CM, le Roux CW, Ghatei MA, Bloom SR, Patel AG, Aylwin SJ: Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. The British journal of surgery. 2006, 93 (2): 210-215. 10.1002/bjs.5227.CrossRefPubMed
38.
Goldfine AB, Mun EC, Devine E, Bernier R, Baz-Hecht M, Jones DB, Schneider BE, Holst JJ, Patti ME: Patients with neuroglycopenia after gastric bypass surgery have exaggerated incretin and insulin secretory responses to a mixed meal. The Journal of clinical endocrinology and metabolism. 2007, 92 (12): 4678-4685. 10.1210/jc.2007-0918.CrossRefPubMed
39.
le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, Shurey S, Ghatei MA, Patel AG, Bloom SR: Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Annals of surgery. 2006, 243 (1): 108-114. 10.1097/01.sla.0000183349.16877.84.CrossRefPubMed
40.
Wickremesekera K, Miller G, Naotunne TD, Knowles G, Stubbs RS: Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course study. Obesity surgery. 2005, 15 (4): 474-481. 10.1381/0960892053723402.CrossRefPubMed
41.
Fisman EZ, Tenenbaum A: A cardiologic approach to non-insulin antidiabetic pharmacotherapy in patients with heart disease. Cardiovascular diabetology. 2009, 8: 38-10.1186/1475-2840-8-38.PubMedCentralCrossRefPubMed
42.
Gallwitz B: The fate of Beta-cells in type 2 diabetes and the possible role of pharmacological interventions. Rev Diabet Stud. 2006, 3 (4): 208-216. 10.1900/RDS.2006.3.208.PubMedCentralCrossRefPubMed
43.
Kendall DM, Cuddihy RM, Bergenstal RM: Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. The American journal of medicine. 2009, 122 (6 Suppl): S37-50. 10.1016/j.amjmed.2009.03.015.CrossRefPubMed
44.
Unger RH: Reinventing type 2 diabetes: pathogenesis, treatment, and prevention. JAMA. 2008, 299 (10): 1185-1187. 10.1001/jama.299.10.1185.CrossRefPubMed
45.
Krentz AJ, Patel MB, Bailey CJ: New drugs for type 2 diabetes mellitus: what is their place in therapy?. Drugs. 2008, 68 (15): 2131-2162. 10.2165/00003495-200868150-00005.CrossRefPubMed
46.
Meyer JM, Stahl SM: The metabolic syndrome and schizophrenia. Acta psychiatrica Scandinavica. 2009, 119 (1): 4-14. 10.1111/j.1600-0447.2008.01317.x.CrossRefPubMed
47.
Pannacciulli N, Le DS, Salbe AD, Chen K, Reiman EM, Tataranni PA, Krakoff J: Postprandial glucagon-like peptide-1 (GLP-1) response is positively associated with changes in neuronal activity of brain areas implicated in satiety and food intake regulation in humans. NeuroImage. 2007, 35 (2): 511-517. 10.1016/j.neuroimage.2006.12.035.PubMedCentralCrossRefPubMed
Metadata
Title
Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease
Authors
Minako Yamaoka-Tojo
Taiki Tojo
Naonobu Takahira
Atsuhiko Matsunaga
Naoyoshi Aoyama
Takashi Masuda
Tohru Izumi
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2010
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-9-17

Other articles of this Issue 1/2010

Cardiovascular Diabetology 1/2010 Go to the issue

Original investigation

Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study)

Original investigation

Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol

Original investigation

Nocturnal blood pressure fall as predictor of diabetic nephropathy in hypertensive patients with type 2 diabetes

Original investigation

Age- and sex-specific prevalence and ten-year risk for cardiovascular disease of all 16 risk factor combinations of the metabolic syndrome - A cross-sectional study

Study protocol

The Chronic CARe for diAbeTes study (CARAT): a cluster randomized controlled trial

Original investigation

Uncoupling protein 2 G(-866)A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients C-reactive protein in type 2 diabetic patients
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits