The effect of pioglitazone treatment on 15-epi-lipoxin A4 levels in patients with type 2 diabetes.
OBJECTIVE
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).


CONCLUSIONS
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.
Baylor College of Medicine, Houston, TX, USA.
Absalon D
AD
Gutierrez
Padma
P
Sathyanarayana
Somasekhar
S
Konduru
Yumei
Y
Ye
Yochai
Y
Birnbaum
Mandeep
M
Bajaj
D052242:Adiponectin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D044045:Lipoxins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D013781:Texas; D045162:Thiazolidinediones / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D044045:Lipoxins; D000077205:Pioglitazone; D045162:Thiazolidinediones; C499918:ADIPOQ protein, human; C517652:hemoglobin A1c protein, human; C040527:lipoxin A4