Fasting plasma leptin, tumor necrosis factor-α receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women impact on cardiovascular mortality

Lorenzo Piemonti, Giliola Calori, Alessia Mercalli, Guido Lattuada, Paolo Monti, Maria Paola Garancini, Federica Costantino, Giacomo Ruotolo, Livio Luzi, Gianluca Perseghin

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - Leptin and tumor necrosis factor (TNF)-α are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis. RESEARCH DESIGN AND METHODS - In this study, fasting plasma leptin, soluble TNF-α receptor 2 (TNF-α-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 ± 12 years, BMI 30.1 ± 6.6 kg/m2), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality. RESULTS - At baseline, leptin and TNF-α-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes (P <0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P <0.02). CONCLUSIONS - In middle-aged women, MCP-1/CCL2, leptin, and TNF-α-R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF-α-R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.

Original languageEnglish
Pages (from-to)2883-2889
Number of pages7
JournalDiabetes Care
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 1 2003

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Receptors, Tumor Necrosis Factor, Type II
Leptin
Monocytes
Fasting
Glucose
Cardiovascular Diseases
Mortality
Population
Atherosclerosis
Proteins
Tumor Necrosis Factor-alpha
Type 2 Diabetes Mellitus
Multivariate Analysis
Biomarkers
Insulin
Glucose Intolerance
Chemokines
Insulin Resistance
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Fasting plasma leptin, tumor necrosis factor-α receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women impact on cardiovascular mortality. / Piemonti, Lorenzo; Calori, Giliola; Mercalli, Alessia; Lattuada, Guido; Monti, Paolo; Garancini, Maria Paola; Costantino, Federica; Ruotolo, Giacomo; Luzi, Livio; Perseghin, Gianluca.

In: Diabetes Care, Vol. 26, No. 10, 01.10.2003, p. 2883-2889.

Research output: Contribution to journalArticle

Piemonti, Lorenzo ; Calori, Giliola ; Mercalli, Alessia ; Lattuada, Guido ; Monti, Paolo ; Garancini, Maria Paola ; Costantino, Federica ; Ruotolo, Giacomo ; Luzi, Livio ; Perseghin, Gianluca. / Fasting plasma leptin, tumor necrosis factor-α receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women impact on cardiovascular mortality. In: Diabetes Care. 2003 ; Vol. 26, No. 10. pp. 2883-2889.
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T1 - Fasting plasma leptin, tumor necrosis factor-α receptor 2, and monocyte chemoattracting protein 1 concentration in a population of glucose-tolerant and glucose-intolerant women impact on cardiovascular mortality

AU - Piemonti, Lorenzo

AU - Calori, Giliola

AU - Mercalli, Alessia

AU - Lattuada, Guido

AU - Monti, Paolo

AU - Garancini, Maria Paola

AU - Costantino, Federica

AU - Ruotolo, Giacomo

AU - Luzi, Livio

AU - Perseghin, Gianluca

PY - 2003/10/1

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N2 - OBJECTIVE - Leptin and tumor necrosis factor (TNF)-α are associated with insulin resistance and cardiovascular disease. In vitro studies suggested that these effects may be mediated via overproduction of monocyte chemoattracting protein (MCP)-1/CCL2, which is a chemokine involved in the pathogenesis of atherosclerosis. RESEARCH DESIGN AND METHODS - In this study, fasting plasma leptin, soluble TNF-α receptor 2 (TNF-α-R2), and MCP-1/CCL2 concentrations were measured in 207 middle-aged women (age 61 ± 12 years, BMI 30.1 ± 6.6 kg/m2), including 53 patients with type 2 diabetes, 42 with impaired glucose tolerance, and 112 with normal glucose tolerance, to assess cross-sectionally their relationship with markers of atherosclerosis and, longitudinally over 7 years, whether their circulating levels were associated with cardiovascular disease (CVD) mortality. RESULTS - At baseline, leptin and TNF-α-R2 were not different among groups; meanwhile, MCP-1/CCL2 was increased in type 2 diabetes (P <0.05). All showed significant associations with biochemical risk markers of atherosclerosis. In a univariate analysis, age, fasting insulin, leptin, and MCP-1/CCL2 were associated with CVD mortality at 7 years. When a multivariate analysis was performed, only age, leptin, and insulin retained an independent association with CVD mortality, with leptin showing a protective effect (hazard ratio 0.88; P <0.02). CONCLUSIONS - In middle-aged women, MCP-1/CCL2, leptin, and TNF-α-R2 were all related to biochemical risk markers of atherosclerosis. MCP-1/CCL2 concentration was the only one to be increased in type 2 diabetes with respect to nondiabetic women and the only one to be associated with increased risk of CVD mortality after a 7-year follow-up period in the univariate analysis. In the multivariate analysis, neither MCP-1/CCL2 nor TNF-α-R2 was associated with CVD mortality, and inspection of the data showed that leptin, in both the univariate and multivariate analysis, was associated with a protective effect.

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