Skip to main content
Erschienen in: Diabetologia 6/2007

01.06.2007 | Article

Circulating leptin levels are not associated with cardiovascular morbidity and mortality in women with diabetes: a prospective cohort study

verfasst von: A. M. Brennan, T. Y. Li, I. Kelesidis, A. Gavrila, F. B. Hu, C. S. Mantzoros

Erschienen in: Diabetologia | Ausgabe 6/2007

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Howard JK, Lord GM, Matarese G et al (1999) Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest 104:1051–1059PubMedCrossRef Howard JK, Lord GM, Matarese G et al (1999) Leptin protects mice from starvation-induced lymphoid atrophy and increases thymic cellularity in ob/ob mice. J Clin Invest 104:1051–1059PubMedCrossRef
2.
Zurück zum Zitat Farooqi IS, Matarese G, Lord GM et al (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110:1093–1103PubMedCrossRef Farooqi IS, Matarese G, Lord GM et al (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110:1093–1103PubMedCrossRef
3.
Zurück zum Zitat Chan JL, Moschos SJ, Bullen J et al (2005) Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency. J Clin Endocrinol Metab 90:1625–1631PubMedCrossRef Chan JL, Moschos SJ, Bullen J et al (2005) Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency. J Clin Endocrinol Metab 90:1625–1631PubMedCrossRef
4.
Zurück zum Zitat Welt CK, Chan JL, Bullen J et al (2004) Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 351:987–997PubMedCrossRef Welt CK, Chan JL, Bullen J et al (2004) Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 351:987–997PubMedCrossRef
5.
Zurück zum Zitat Considine RV, Sinha MK, Heiman ML et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295PubMedCrossRef Considine RV, Sinha MK, Heiman ML et al (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295PubMedCrossRef
6.
Zurück zum Zitat Shamsuzzaman AS, Winnicki M, Wolk R et al (2004) Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 109:2181–2185PubMedCrossRef Shamsuzzaman AS, Winnicki M, Wolk R et al (2004) Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation 109:2181–2185PubMedCrossRef
7.
Zurück zum Zitat van Dielen FM, van’t Veer C, Schols AM, Soeters PB, Buurman WA, Greve JW (2001) Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. Int J Obes Relat Metab Disord 25:1759–1766PubMedCrossRef van Dielen FM, van’t Veer C, Schols AM, Soeters PB, Buurman WA, Greve JW (2001) Increased leptin concentrations correlate with increased concentrations of inflammatory markers in morbidly obese individuals. Int J Obes Relat Metab Disord 25:1759–1766PubMedCrossRef
8.
Zurück zum Zitat Gomez-Ambrosi J, Salvador J, Paramo JA et al (2002) Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors. Clin Biochem 35:315–320PubMedCrossRef Gomez-Ambrosi J, Salvador J, Paramo JA et al (2002) Involvement of leptin in the association between percentage of body fat and cardiovascular risk factors. Clin Biochem 35:315–320PubMedCrossRef
9.
Zurück zum Zitat Gomez-Ambrosi J, Salvador J, Silva C et al (2005) Leptin therapy does not affect inflammatory markers. J Clin Endocrinol Metab 90:3803PubMedCrossRef Gomez-Ambrosi J, Salvador J, Silva C et al (2005) Leptin therapy does not affect inflammatory markers. J Clin Endocrinol Metab 90:3803PubMedCrossRef
10.
Zurück zum Zitat Canavan B, Salem RO, Schurgin S et al (2005) Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation. J Clin Endocrinol Metab 90:5779–5785PubMedCrossRef Canavan B, Salem RO, Schurgin S et al (2005) Effects of physiological leptin administration on markers of inflammation, platelet activation, and platelet aggregation during caloric deprivation. J Clin Endocrinol Metab 90:5779–5785PubMedCrossRef
11.
Zurück zum Zitat Chan JL, Bullen J, Stoyneva V, DePaoli AM, Addy C, Mantzoros CS (2005) 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 90:1618–1624PubMedCrossRef Chan JL, Bullen J, Stoyneva V, DePaoli AM, Addy C, Mantzoros CS (2005) 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 90:1618–1624PubMedCrossRef
12.
Zurück zum Zitat Wallace AM, McMahon AD, Packard CJ et al (2001) Plasma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 104:3052–3056PubMed Wallace AM, McMahon AD, Packard CJ et al (2001) Plasma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 104:3052–3056PubMed
13.
Zurück zum Zitat Soderberg S, Ahren B, Jansson JH et al (1999) Leptin is associated with increased risk of myocardial infarction. J Intern Med 246:409–418PubMedCrossRef Soderberg S, Ahren B, Jansson JH et al (1999) Leptin is associated with increased risk of myocardial infarction. J Intern Med 246:409–418PubMedCrossRef
14.
Zurück zum Zitat Soderberg S, Ahren B, Stegmayr B et al (1999) Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 30:328–337PubMed Soderberg S, Ahren B, Stegmayr B et al (1999) Leptin is a risk marker for first-ever hemorrhagic stroke in a population-based cohort. Stroke 30:328–337PubMed
15.
Zurück zum Zitat Soderberg S, Stegmayr B, Stenlund H et al (2004) Leptin, but not adiponectin, predicts stroke in males. J Intern Med 256:128–136PubMedCrossRef Soderberg S, Stegmayr B, Stenlund H et al (2004) Leptin, but not adiponectin, predicts stroke in males. J Intern Med 256:128–136PubMedCrossRef
16.
Zurück zum Zitat Couillard C, Lamarche B, Mauriege P et al (1998) Leptinemia is not a risk factor for ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Diabetes Care 21:782–786PubMedCrossRef Couillard C, Lamarche B, Mauriege P et al (1998) Leptinemia is not a risk factor for ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Diabetes Care 21:782–786PubMedCrossRef
17.
Zurück zum Zitat Piemonti L, Calori G, Mercalli A et al (2003) Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality. Diabetes Care 26:2883–2889PubMedCrossRef Piemonti L, Calori G, Mercalli A et al (2003) Fasting plasma leptin, tumor necrosis factor-alpha receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women: impact on cardiovascular mortality. Diabetes Care 26:2883–2889PubMedCrossRef
18.
Zurück zum Zitat Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB (2005) 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 90:4542–4548PubMedCrossRef Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB (2005) 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 90:4542–4548PubMedCrossRef
19.
Zurück zum Zitat Manson JE, Colditz GA, Stampfer MJ et al (1991) A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 151:1141–1147PubMedCrossRef Manson JE, Colditz GA, Stampfer MJ et al (1991) A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med 151:1141–1147PubMedCrossRef
20.
Zurück zum Zitat Shai I, Schulze MB, Manson JE, Stampfer MJ, Rifai N, Hu FB (2005) A prospective study of lipoprotein(a) and risk of coronary heart disease among women with type 2 diabetes. Diabetologia 48:1469–1476PubMedCrossRef Shai I, Schulze MB, Manson JE, Stampfer MJ, Rifai N, Hu FB (2005) A prospective study of lipoprotein(a) and risk of coronary heart disease among women with type 2 diabetes. Diabetologia 48:1469–1476PubMedCrossRef
21.
Zurück zum Zitat Tanasescu M, Cho E, Manson JE, Hu FB (2004) Dietary fat and cholesterol and the risk of cardiovascular disease among women with type 2 diabetes. Am J Clin Nutr 79:999–1005PubMed Tanasescu M, Cho E, Manson JE, Hu FB (2004) Dietary fat and cholesterol and the risk of cardiovascular disease among women with type 2 diabetes. Am J Clin Nutr 79:999–1005PubMed
22.
Zurück zum Zitat Gavrila A, Chan JL, Yiannakouris N et al (2003) Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab 88:4823–4831PubMedCrossRef Gavrila A, Chan JL, Yiannakouris N et al (2003) Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab 88:4823–4831PubMedCrossRef
23.
Zurück zum Zitat Ma Z, Gingerich RL, Santiago JV, Klein S, Smith CH, Landt M (1996) Radioimmunoassay of leptin in human plasma. Clin Chem 42:942–946PubMed Ma Z, Gingerich RL, Santiago JV, Klein S, Smith CH, Landt M (1996) Radioimmunoassay of leptin in human plasma. Clin Chem 42:942–946PubMed
24.
Zurück zum Zitat Hu FB, Meigs JB, Li TY, Rifai N, Manson JE (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53:693–700PubMedCrossRef Hu FB, Meigs JB, Li TY, Rifai N, Manson JE (2004) Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53:693–700PubMedCrossRef
25.
Zurück zum Zitat Shai I, Rosner BA, Shahar DR et al (2005) 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 135:573–579PubMed Shai I, Rosner BA, Shahar DR et al (2005) 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 135:573–579PubMed
26.
Zurück zum Zitat Oral EA, Simha V, Ruiz E et al (2002) Leptin-replacement therapy for lipodystrophy. N Engl J Med 346:570–578PubMedCrossRef Oral EA, Simha V, Ruiz E et al (2002) Leptin-replacement therapy for lipodystrophy. N Engl J Med 346:570–578PubMedCrossRef
27.
Zurück zum Zitat Javor ED, Cochran EK, Musso C, Young JR, DePaoli AM, Gorden P (2005) Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes 54:1994–2002PubMedCrossRef Javor ED, Cochran EK, Musso C, Young JR, DePaoli AM, Gorden P (2005) Long-term efficacy of leptin replacement in patients with generalized lipodystrophy. Diabetes 54:1994–2002PubMedCrossRef
28.
Zurück zum Zitat Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS (2006) 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 91:2605–2611PubMedCrossRef Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS (2006) 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 91:2605–2611PubMedCrossRef
Metadaten
Titel
Circulating leptin levels are not associated with cardiovascular morbidity and mortality in women with diabetes: a prospective cohort study
verfasst von
A. M. Brennan
T. Y. Li
I. Kelesidis
A. Gavrila
F. B. Hu
C. S. Mantzoros
Publikationsdatum
01.06.2007
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 6/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0635-y

Weitere Artikel der Ausgabe 6/2007

Diabetologia 6/2007 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Blutdrucksenkung könnte Uterusmyome verhindern

Frauen mit unbehandelter oder neu auftretender Hypertonie haben ein deutlich erhöhtes Risiko für Uterusmyome. Eine Therapie mit Antihypertensiva geht hingegen mit einer verringerten Inzidenz der gutartigen Tumoren einher.

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.