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
N1 - Funding Information:
Dr. Bajaj has received research grants from Takeda, Amylin, Eli Lilly, Bristol-Myers Squibb, and Astra Zenica; honoraria for speaking from Takeda, Eli Lilly, Boehringer Ingelheim, and Sanofi-Aventis; and has served as a consultant to Takeda and Sanofi-Aventis. Dr. Birnbaum has received research grants from Merck, Takeda, Amylin, and Eli Lilly. All other authors have reported that they have no relationships to disclose.
Funding Information:
The study was funded by a grant from Takeda Pharmaceuticals U.S.A., Inc. (previously known as Takeda Pharmaceuticals North America). Dr. AD Gutierrez was supported by a Molecular Medicine Scholars Training Grant ( NIH T-32 HL-66991 ) Additional support was from Diabetes and Endocrinology Research Center DERC ( NIH P30 DK-079638 ).
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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U2 - 10.1016/j.atherosclerosis.2012.04.016
DO - 10.1016/j.atherosclerosis.2012.04.016
M3 - Article
C2 - 22687642
AN - SCOPUS:84863097684
SN - 0021-9150
VL - 223
SP - 204
EP - 208
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -