The effect of pioglitazone treatment on 15-epi-lipoxin A 4 levels in patients with type 2 diabetes

Absalon D. Gutierrez, Padma Sathyanarayana, Somasekhar Konduru, Yumei Ye, Yochai Birnbaum, Mandeep Bajaj

Research output: Contribution to journalArticle

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Abstract

Objectives: Arachidonic acid-derived eicosanoids (lipoxins and 15-epilipoxins) have a major role in resolution of inflammation. 15-epi-lipoxin A 4 (15-epi-LXA 4) is a lipid mediator with strong anti-inflammatory and inflammation-resolving effects. We examined the effect of pioglitazone therapy on plasma 15-epi-LXA 4 in patients with type 2 diabetes (T2DM). Methods: T2DM patients (Age = 56 ± 2 y, BMI = 33 ± 1.8, HbA1c = 7.8 ± 0.3%) not on thiazolidinedione therapy for at least 12 months were randomized to receive either pioglitazone 15 mg/daily for two months (PIO 15) or pioglitazone 15 mg/day for one month followed by a dose escalation to 30 mg/day for an additional one month (PIO 30). Results: PIO 15 increased plasma 15-epi-LXA 4 levels (0.63 ± 0.06-1.05 ± 0.08 ng/mL, p < 0.01) and adiponectin levels (6.4 ± 0.3-10.1 ± 0.7 μg/mL, p < 0.001) and decreased fasting plasma glucose (125 ± 8-106 ± 9 mg/dL, p < 0.05), free fatty acids (FFA) (414 ± 46-320 ± 38 μmol/l, p < 0.05) and HOMA-IR (5.3 ± 0.4 to 4.0 ± 0.4, p < 0.05). Body weight (Δ = 0.2 kg) and HbA1c (7.4 ± 0.2-7.1 ± 0.2%) did not change significantly. PIO 30 treated patients had similar increase in plasma 15-epi-LXA 4 (0.64 ± 0.10-1.08 ± 0.09 ng/mL, p < 0.01), and decrease in plasma FFA (423 ± 42-317 ± 40 μmol/l, p < 0.05) despite a greater increase in plasma adiponectin (6.5 ± 0.4-15.5 ± 0.7 ug/mL, p < 0.001) and a greater reduction in HbA1c (8.7 ± 0.5-7.4 ± 0.3%, p < 0.01), FPG (159 ± 16-120 ± 10 mg/dL, p < 0.01), and HOMA-IR (6.6 ± 0.8-4.4 ± 0.4, p < 0.005). Furthermore, PIO 30 treated patients had a significant increase in body weight (Δ = 1.7 kg, p < 0.02). Conclusion: In T2DM, low dose pioglitazone (15 mg/day) increases 15-epi-LXA 4 and adiponectin levels in the absence of significant changes in body weight. Dose escalation of pioglitazone to 30 mg/day is associated with a similar increase in 15-epi-LXA 4 despite a greater increase in plasma adiponectin concentrations.

Original languageEnglish (US)
Pages (from-to)204-208
Number of pages5
JournalAtherosclerosis
Volume223
Issue number1
DOIs
StatePublished - Jul 2012

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pioglitazone
Lipoxins
Type 2 Diabetes Mellitus
Adiponectin
Nonesterified Fatty Acids
Therapeutics
Body Weight
Inflammation
Body Weight Changes
Eicosanoids
Arachidonic Acid
Fasting
Anti-Inflammatory Agents

Keywords

  • 15-Epi-lipoxin A
  • Adiponectin
  • Inflammation
  • Insulin resistance
  • Pioglitazone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The effect of pioglitazone treatment on 15-epi-lipoxin A 4 levels in patients with type 2 diabetes. / Gutierrez, Absalon D.; Sathyanarayana, Padma; Konduru, Somasekhar; Ye, Yumei; Birnbaum, Yochai; Bajaj, Mandeep.

In: Atherosclerosis, Vol. 223, No. 1, 07.2012, p. 204-208.

Research output: Contribution to journalArticle

Gutierrez, Absalon D. ; Sathyanarayana, Padma ; Konduru, Somasekhar ; Ye, Yumei ; Birnbaum, Yochai ; Bajaj, Mandeep. / The effect of pioglitazone treatment on 15-epi-lipoxin A 4 levels in patients with type 2 diabetes. In: Atherosclerosis. 2012 ; Vol. 223, No. 1. pp. 204-208.
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abstract = "Objectives: Arachidonic acid-derived eicosanoids (lipoxins and 15-epilipoxins) have a major role in resolution of inflammation. 15-epi-lipoxin A 4 (15-epi-LXA 4) is a lipid mediator with strong anti-inflammatory and inflammation-resolving effects. We examined the effect of pioglitazone therapy on plasma 15-epi-LXA 4 in patients with type 2 diabetes (T2DM). Methods: T2DM patients (Age = 56 ± 2 y, BMI = 33 ± 1.8, HbA1c = 7.8 ± 0.3{\%}) not on thiazolidinedione therapy for at least 12 months were randomized to receive either pioglitazone 15 mg/daily for two months (PIO 15) or pioglitazone 15 mg/day for one month followed by a dose escalation to 30 mg/day for an additional one month (PIO 30). Results: PIO 15 increased plasma 15-epi-LXA 4 levels (0.63 ± 0.06-1.05 ± 0.08 ng/mL, p < 0.01) and adiponectin levels (6.4 ± 0.3-10.1 ± 0.7 μg/mL, p < 0.001) and decreased fasting plasma glucose (125 ± 8-106 ± 9 mg/dL, p < 0.05), free fatty acids (FFA) (414 ± 46-320 ± 38 μmol/l, p < 0.05) and HOMA-IR (5.3 ± 0.4 to 4.0 ± 0.4, p < 0.05). Body weight (Δ = 0.2 kg) and HbA1c (7.4 ± 0.2-7.1 ± 0.2{\%}) did not change significantly. PIO 30 treated patients had similar increase in plasma 15-epi-LXA 4 (0.64 ± 0.10-1.08 ± 0.09 ng/mL, p < 0.01), and decrease in plasma FFA (423 ± 42-317 ± 40 μmol/l, p < 0.05) despite a greater increase in plasma adiponectin (6.5 ± 0.4-15.5 ± 0.7 ug/mL, p < 0.001) and a greater reduction in HbA1c (8.7 ± 0.5-7.4 ± 0.3{\%}, p < 0.01), FPG (159 ± 16-120 ± 10 mg/dL, p < 0.01), and HOMA-IR (6.6 ± 0.8-4.4 ± 0.4, p < 0.005). Furthermore, PIO 30 treated patients had a significant increase in body weight (Δ = 1.7 kg, p < 0.02). Conclusion: In T2DM, low dose pioglitazone (15 mg/day) increases 15-epi-LXA 4 and adiponectin levels in the absence of significant changes in body weight. Dose escalation of pioglitazone to 30 mg/day is associated with a similar increase in 15-epi-LXA 4 despite a greater increase in plasma adiponectin concentrations.",
keywords = "15-Epi-lipoxin A, Adiponectin, Inflammation, Insulin resistance, Pioglitazone",
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TY - JOUR

T1 - The effect of pioglitazone treatment on 15-epi-lipoxin A 4 levels in patients with type 2 diabetes

AU - Gutierrez, Absalon D.

AU - Sathyanarayana, Padma

AU - Konduru, Somasekhar

AU - Ye, Yumei

AU - Birnbaum, Yochai

AU - Bajaj, Mandeep

PY - 2012/7

Y1 - 2012/7

N2 - Objectives: Arachidonic acid-derived eicosanoids (lipoxins and 15-epilipoxins) have a major role in resolution of inflammation. 15-epi-lipoxin A 4 (15-epi-LXA 4) is a lipid mediator with strong anti-inflammatory and inflammation-resolving effects. We examined the effect of pioglitazone therapy on plasma 15-epi-LXA 4 in patients with type 2 diabetes (T2DM). Methods: T2DM patients (Age = 56 ± 2 y, BMI = 33 ± 1.8, HbA1c = 7.8 ± 0.3%) not on thiazolidinedione therapy for at least 12 months were randomized to receive either pioglitazone 15 mg/daily for two months (PIO 15) or pioglitazone 15 mg/day for one month followed by a dose escalation to 30 mg/day for an additional one month (PIO 30). Results: PIO 15 increased plasma 15-epi-LXA 4 levels (0.63 ± 0.06-1.05 ± 0.08 ng/mL, p < 0.01) and adiponectin levels (6.4 ± 0.3-10.1 ± 0.7 μg/mL, p < 0.001) and decreased fasting plasma glucose (125 ± 8-106 ± 9 mg/dL, p < 0.05), free fatty acids (FFA) (414 ± 46-320 ± 38 μmol/l, p < 0.05) and HOMA-IR (5.3 ± 0.4 to 4.0 ± 0.4, p < 0.05). Body weight (Δ = 0.2 kg) and HbA1c (7.4 ± 0.2-7.1 ± 0.2%) did not change significantly. PIO 30 treated patients had similar increase in plasma 15-epi-LXA 4 (0.64 ± 0.10-1.08 ± 0.09 ng/mL, p < 0.01), and decrease in plasma FFA (423 ± 42-317 ± 40 μmol/l, p < 0.05) despite a greater increase in plasma adiponectin (6.5 ± 0.4-15.5 ± 0.7 ug/mL, p < 0.001) and a greater reduction in HbA1c (8.7 ± 0.5-7.4 ± 0.3%, p < 0.01), FPG (159 ± 16-120 ± 10 mg/dL, p < 0.01), and HOMA-IR (6.6 ± 0.8-4.4 ± 0.4, p < 0.005). Furthermore, PIO 30 treated patients had a significant increase in body weight (Δ = 1.7 kg, p < 0.02). Conclusion: In T2DM, low dose pioglitazone (15 mg/day) increases 15-epi-LXA 4 and adiponectin levels in the absence of significant changes in body weight. Dose escalation of pioglitazone to 30 mg/day is associated with a similar increase in 15-epi-LXA 4 despite a greater increase in plasma adiponectin concentrations.

AB - Objectives: Arachidonic acid-derived eicosanoids (lipoxins and 15-epilipoxins) have a major role in resolution of inflammation. 15-epi-lipoxin A 4 (15-epi-LXA 4) is a lipid mediator with strong anti-inflammatory and inflammation-resolving effects. We examined the effect of pioglitazone therapy on plasma 15-epi-LXA 4 in patients with type 2 diabetes (T2DM). Methods: T2DM patients (Age = 56 ± 2 y, BMI = 33 ± 1.8, HbA1c = 7.8 ± 0.3%) not on thiazolidinedione therapy for at least 12 months were randomized to receive either pioglitazone 15 mg/daily for two months (PIO 15) or pioglitazone 15 mg/day for one month followed by a dose escalation to 30 mg/day for an additional one month (PIO 30). Results: PIO 15 increased plasma 15-epi-LXA 4 levels (0.63 ± 0.06-1.05 ± 0.08 ng/mL, p < 0.01) and adiponectin levels (6.4 ± 0.3-10.1 ± 0.7 μg/mL, p < 0.001) and decreased fasting plasma glucose (125 ± 8-106 ± 9 mg/dL, p < 0.05), free fatty acids (FFA) (414 ± 46-320 ± 38 μmol/l, p < 0.05) and HOMA-IR (5.3 ± 0.4 to 4.0 ± 0.4, p < 0.05). Body weight (Δ = 0.2 kg) and HbA1c (7.4 ± 0.2-7.1 ± 0.2%) did not change significantly. PIO 30 treated patients had similar increase in plasma 15-epi-LXA 4 (0.64 ± 0.10-1.08 ± 0.09 ng/mL, p < 0.01), and decrease in plasma FFA (423 ± 42-317 ± 40 μmol/l, p < 0.05) despite a greater increase in plasma adiponectin (6.5 ± 0.4-15.5 ± 0.7 ug/mL, p < 0.001) and a greater reduction in HbA1c (8.7 ± 0.5-7.4 ± 0.3%, p < 0.01), FPG (159 ± 16-120 ± 10 mg/dL, p < 0.01), and HOMA-IR (6.6 ± 0.8-4.4 ± 0.4, p < 0.005). Furthermore, PIO 30 treated patients had a significant increase in body weight (Δ = 1.7 kg, p < 0.02). Conclusion: In T2DM, low dose pioglitazone (15 mg/day) increases 15-epi-LXA 4 and adiponectin levels in the absence of significant changes in body weight. Dose escalation of pioglitazone to 30 mg/day is associated with a similar increase in 15-epi-LXA 4 despite a greater increase in plasma adiponectin concentrations.

KW - 15-Epi-lipoxin A

KW - Adiponectin

KW - Inflammation

KW - Insulin resistance

KW - Pioglitazone

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