Dataset Information

Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes.

ABSTRACT:

Objective

Atherosclerosis is prevalent in diabetic patients, but there is little information on the localization of nonesterified fatty acids (NEFAs) within the plaque and their relationship with inflammation. We sought to characterize the NEFA composition and location in human diabetic atheroma plaques by metabolomic analysis and imaging and to address their relationship with inflammation activity.

Research design and methods

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for metabolomic analysis imaging of frozen carotid atheroma plaques. Carotid endarterectomy specimens were used for conventional immunohistochemistry, laser-capture microdissection quantitative PCR, and in situ Southwestern hybridization. Biological actions of linoleic acid were studied in cultured vascular smooth muscle cells (VSMCs).

Results

TOF-SIMS imaging evidenced a significant increase in the quantity of several NEFA in diabetic versus nondiabetic atheroma plaques. Higher levels of NEFA were also found in diabetic sera. The presence of LPL mRNA in NEFA-rich areas of the atheroma plaque, as well as the lack of correlation between serum and plaque NEFA, suggests a local origin for plaque NEFA. The pattern of distribution of plaque NEFA is similar to that of MCP-1, LPL, and activated NF-kappaB. Diabetic endarterectomy specimens showed higher numbers of infiltrating macrophages and T-lymphocytes-a finding that associated with higher NEFA levels. Finally, linoleic acid activates NF-kappaB and upregulates NF-kappaB-mediated LPL and MCP-1 expression in cultured VSMC.

Discussion

There is an increased presence of NEFA in diabetic plaque neointima. NEFA levels are higher in diabetic atheroma plaques than in nondiabetic subjects. We hypothesize that NEFA may be produced locally and contribute to local inflammation.

SUBMITTER: Mas S

PROVIDER: S-EPMC2874689 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes.

Mas Sebastián S Martínez-Pinna Roxana R Martín-Ventura Jose Luis JL Pérez Raul R Gomez-Garre Dulcenombre D Ortiz Alberto A Fernandez-Cruz Arturo A Vivanco Fernando F Egido Jesús J

Diabetes 20100303 6

<h4>Objective</h4>Atherosclerosis is prevalent in diabetic patients, but there is little information on the localization of nonesterified fatty acids (NEFAs) within the plaque and their relationship with inflammation. We sought to characterize the NEFA composition and location in human diabetic atheroma plaques by metabolomic analysis and imaging and to address their relationship with inflammation activity.<h4>Research design and methods</h4>Time-of-flight secondary ion mass spectrometry (TOF-SI ...[more]

PMID: 20200316

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Project description:BackgroundIt has been suggested that liraglutide could have an impact on glucose and lipid metabolism disorder and adhesion molecule activation, which may play important roles in the vascular damage of diabetes. In this study, we examined the effects of liraglutide versus metformin on non-esterified free fatty acids, beta-cell insulin secretion, and adhesion molecule levels in patients with recent-onset type 2 diabetes mellitus.MethodsIn this study, 60 patients newly diagnosed with type 2 diabetes mellitus (mean age 33.97 ± 5.67 years) were randomly assigned to receive once-daily subcutaneous liraglutide or oral metformin. Before the study and after the 8-week treatment period, a 75 g oral glucose tolerance test was performed. Plasma glucose, lipids and lipoprotein, plasma insulin, glycaemic and insulin responses, non-esterified free fatty acids (NEFA), and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were evaluated.ResultsAfter 8 weeks, 120 min of NEFA (155 ± 125 vs 99 ± 73 µmol/L, P = 0.026) and the levels of sVCAM-1 (465 ± 136 vs 382 ± 131 ng/ml, P = 0.013) significantly decreased, while the early phase insulin secretion index (24.94 [7.78, 38.89] vs. 31.13 [17.67, 59.09], P = 0.031), fasting plasma insulin (104 [51, 123] vs 113 [54, 171] mIU/L, P = 0.015), 60 min plasma insulin (326 [165, 441] vs 471 [334, 717] mIU/L, P = 0.005), 120 min plasma insulin (401 [193, 560] vs 500 [367, 960] mIU/L, P = 0.047), and insulin area under the curve (AUCins) (648 [321, 742] vs 738 [451, 1118] mIU/L, P = 0.005) remarkably increased for patients in the liraglutide treatment group. The levels of sVCAM-1 dramatically decreased after 8 weeks of liraglutide treatment (503 ± 182 vs 382 ± 131 ng/ml, P = 0.046) compared to that of the metformin treatment group. At the same time, the differences before and after liraglutide treatment in 120 min of NEFA (- 32 [- 96, - 5] vs 5 [- 35, 38] µmol/L, P = 0.033) and AUCins (738 [451, 1118] vs 594 [357, 1216] mIU/L, P = 0.014) were remarkably enhanced compared to that of the metformin therapy. Nevertheless, there were no significant differences in fasting NEFA after liraglutide or metformin treatment. The reduction of 120 min NEFA (ΔNEFA) was positively correlated with the decrease of sVCAM-1 (ΔsVCAM-1) after 8 weeks of liraglutide treatment (r = 0.523, P = 0.003).ConclusionsOur results demonstrate that liraglutide administration is more effective than metformin in reducing 120 min NEFA and suppressing sVCAM-1 levels for recent-onset type 2 diabetes mellitus. We suggest that this outcome may be because liraglutide is associated with potentiating insulin secretion capacity, inhibiting vascular inflammatory cytokines, and antagonizing atherosclerosis.

Dataset Information

Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes.

Objective

Research design and methods

Results

Discussion

Publications

Local non-esterified fatty acids correlate with inflammation in atheroma plaques of patients with type 2 diabetes.

Similar Datasets

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