Circulating Leptin Levels Are Not Associated with Cardiovascular Morbidity and Mortality in Women with Diabetes: a Prospective Cohort Study

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2007 Mar 21

PMID 17372717

Citations 16

Authors

A M Brennan

T Y Li

I Kelesidis

A Gavrila

F B Hu

C S Mantzoros

Affiliations

Soon will be listed here.

Abstract

Aims/hypothesis: Leptin, an adipocyte-secreted hormone, plays an important role in regulating neuroendocrine and immune function as well as insulin resistance and metabolism. Our objective was to examine the relationship between leptin levels and cardiovascular morbidity and overall mortality in women with type 2 diabetes.

Subjects And Methods: This prospective cohort study included 1,194 women with a confirmed diagnosis of type 2 diabetes, who provided a blood sample at baseline in 1989-1990. Participants were followed for 12 years for the development of health outcomes including cardiovascular disease (CVD) events as well as total mortality.

Results: There were 218 new CVD events and 228 deaths from all causes. Cox proportional hazards analysis was used to estimate the relative risks (RRs) for each quintile level of leptin compared with the lowest quintile. Leptin levels were positively associated with several CVD risk factors including BMI and inflammatory markers, but were not independently associated with the incidence of CVD or total mortality in women with diabetes. The multivariate RRs (95% CIs) for CVD across the quintiles of leptin were 0.96 (0.61-1.53), 0.99 (0.61-1.61), 1.04 (0.63-1.71), 1.02 (0.59-1.75) (p for trend = 0.83).

Conclusions/interpretation: Although circulating leptin levels are associated with obesity and inflammatory markers, they are not significantly related to the risk of CVD or mortality in women with diabetes.

Citing Articles

Association of Low Leptin with Poor 3-Month Prognosis in Ischemic Stroke Patients with Type 2 Diabetes.

Zou Y, Ling Hu , Zou W, Li H Clin Interv Aging. 2020; 15:2353-2361.

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The role of adipokines as prognostic factors of one-year mortality in hip fracture patients.

Gulin T, Kruljac I, Kirigin Bilos L, Gulin M, Grgurevic M, Borojevic M Osteoporos Int. 2017; 28(8):2475-2483.

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Beneficial effects of leptin treatment in a setting of cardiac dysfunction induced by transverse aortic constriction in mouse.

Gomez-Hurtado N, Dominguez-Rodriguez A, Mateo P, Fernandez-Velasco M, Val-Blasco A, Aizpun R J Physiol. 2017; 595(13):4227-4243.

PMID: 28374413 PMC: 5491865. DOI: 10.1113/JP274030.

The Association of Serum Leptin with Mortality in Older Adults.

Mishra S, Harris T, Hsueh W, Hue T, Leak T, Li R PLoS One. 2015; 10(10):e0140763.

PMID: 26473487 PMC: 4608587. DOI: 10.1371/journal.pone.0140763.

Serum Leptin Levels and the Risk of Stroke: The Framingham Study.

Saber H, Himali J, Shoamanesh A, Beiser A, Pikula A, Harris T Stroke. 2015; 46(10):2881-5.

PMID: 26337973 PMC: 4589501. DOI: 10.1161/STROKEAHA.115.009463.

References

Shai I, Rosner B, Shahar D, Vardi H, Azrad A, Kanfi A . Dietary evaluation and attenuation of relative risk: multiple comparisons between blood and urinary biomarkers, food frequency, and 24-hour recall questionnaires: the DEARR study. J Nutr. 2005; 135(3):573-9. DOI: 10.1093/jn/135.3.573. View

Ma Z, Gingerich R, Santiago J, Klein S, Smith C, Landt M . Radioimmunoassay of leptin in human plasma. Clin Chem. 1996; 42(6 Pt 1):942-6. View

Gomez-Ambrosi J, Salvador J, Silva C, Rotellar F, Gil M, Cienfuegos J . Leptin therapy does not affect inflammatory markers. J Clin Endocrinol Metab. 2005; 90(6):3803. DOI: 10.1210/jc.2005-0558. View

Lee J, Chan J, Sourlas E, Raptopoulos V, Mantzoros C . Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab. 2006; 91(7):2605-11. DOI: 10.1210/jc.2005-1545. View

Howard J, Lord G, Matarese G, Vendetti S, Ghatei M, Ritter M . Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest. 1999; 104(8):1051-9. PMC: 408574. DOI: 10.1172/JCI6762. View

Manson J, Colditz G, Stampfer M, Willett W, Krolewski A, Rosner B . A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med. 1991; 151(6):1141-7. View

Gomez-Ambrosi J, Salvador J, Paramo J, Orbe J, de Irala J, Diez-Caballero A . Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors. Clin Biochem. 2002; 35(4):315-20. DOI: 10.1016/s0009-9120(02)00320-x. View

Hu F, Meigs J, Li T, Rifai N, Manson J . Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004; 53(3):693-700. DOI: 10.2337/diabetes.53.3.693. View

Soderberg S, Ahren B, Stegmayr B, Johnson O, Wiklund P, Weinehall L . Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke. 1999; 30(2):328-37. DOI: 10.1161/01.str.30.2.328. View

10.

Farooqi I, Matarese G, Lord G, Keogh J, Lawrence E, Agwu C . Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002; 110(8):1093-103. PMC: 150795. DOI: 10.1172/JCI15693. View

11.

van Dielen F, Vant Veer C, Schols A, Soeters P, Buurman W, Greve J . Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. Int J Obes Relat Metab Disord. 2002; 25(12):1759-66. DOI: 10.1038/sj.ijo.0801825. View

12.

Considine R, Sinha M, Heiman M, Kriauciunas A, STEPHENS T, Nyce M . Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334(5):292-5. DOI: 10.1056/NEJM199602013340503. View

13.

Chan J, Bullen J, Stoyneva V, DePaoli A, Addy C, Mantzoros C . Recombinant methionyl human leptin administration to achieve high physiologic or pharmacologic leptin levels does not alter circulating inflammatory marker levels in humans with leptin sufficiency or excess. J Clin Endocrinol Metab. 2004; 90(3):1618-24. DOI: 10.1210/jc.2004-1921. View

14.

Shamsuzzaman A, Winnicki M, Wolk R, Svatikova A, Phillips B, Davison D . Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation. 2004; 109(18):2181-5. DOI: 10.1161/01.CIR.0000127960.28627.75. View

15.

Wallace A, McMahon A, Packard C, Kelly A, Shepherd J, Gaw A . Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001; 104(25):3052-6. DOI: 10.1161/hc5001.101061. View

16.

Soderberg S, Ahren B, Jansson J, Johnson O, Hallmans G, Asplund K . Leptin is associated with increased risk of myocardial infarction. J Intern Med. 1999; 246(4):409-18. DOI: 10.1046/j.1365-2796.1999.00571.x. View

17.

Couillard C, Lamarche B, Mauriege P, Cantin B, Dagenais G, Moorjani S . Leptinemia is not a risk factor for ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Diabetes Care. 1998; 21(5):782-6. DOI: 10.2337/diacare.21.5.782. View

18.

Mantzoros C, Li T, Manson J, Meigs J, Hu F . Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab. 2005; 90(8):4542-8. DOI: 10.1210/jc.2005-0372. View

19.

Soderberg S, Stegmayr B, Stenlund H, Sjostrom L, Agren A, Johansson L . Leptin, but not adiponectin, predicts stroke in males. J Intern Med. 2004; 256(2):128-36. DOI: 10.1111/j.1365-2796.2004.01351.x. View

20.

Tanasescu M, Cho E, Manson J, Hu F . Dietary fat and cholesterol and the risk of cardiovascular disease among women with type 2 diabetes. Am J Clin Nutr. 2004; 79(6):999-1005. DOI: 10.1093/ajcn/79.6.999. View