Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are heightened in obese patients.
J Investig Med
; 61(8): 1152-60, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-24141239
ABSTRACT
OBJECTIVE:
The American Diabetes Association has called for further research on how patients' demographics should determine drug choices for individuals with type 2 diabetes mellitus (T2DM). Here, using in-depth physiology studies, we investigate whether obese patients with T2DM are likely to benefit from thiazolidinediones, medications with a known adverse effect of weight gain. MATERIALS ANDMETHODS:
Eleven obese and 7 nonobese individuals with T2DM participated in this randomized, placebo-controlled, double-blind, crossover study. Each subject underwent a pair of "stepped" pancreatic clamp studies with subcutaneous adipose tissue biopsies after 21 days of pioglitazone (45 mg) or placebo.RESULTS:
Obese subjects demonstrated significant decreases in insulin resistance and many adipose inflammatory parameters with pioglitazone relative to placebo. Specifically, significant improvements in glucose infusion rates, suppression of hepatic glucose production, and whole fat expression of certain inflammatory markers (IL-6, IL-1B, and inducible nitric oxide synthase) were observed in the obese subjects but not in the nonobese subjects. Additionally, adipose tissue from the obese subjects demonstrated reduced infiltration of macrophages, dendritic cells, and neutrophils as well as increased expression of factors associated with fat "browning" (peroxisome proliferator-activated receptor gamma coactivator-1α and uncoupling protein-1).CONCLUSIONS:
These findings support the efficacy of pioglitazone to improve insulin resistance and reduce adipose tissue inflammation in obese patients with T2DM.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Mediadores da Inflamação
/
Tiazolidinedionas
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Diabetes Mellitus Tipo 2
/
Anti-Inflamatórios
/
Obesidade
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Investig Med
Assunto da revista:
MEDICINA
Ano de publicação:
2013
Tipo de documento:
Article