PMID- 24141239
OWN - NLM
STAT- MEDLINE
DCOM- 20140714
LR  - 20211021
IS  - 1708-8267 (Electronic)
IS  - 1081-5589 (Print)
IS  - 1081-5589 (Linking)
VI  - 61
IP  - 8
DP  - 2013 Dec
TI  - Insulin sensitizing and anti-inflammatory effects of thiazolidinediones are 
      heightened in obese patients.
PG  - 1152-60
LID - 10.2310/JIM.0000000000000017 [doi]
AB  - 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 AND METHODS: 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-1alpha 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.
FAU - Esterson, Yonah B
AU  - Esterson YB
AD  - From the *Division of Endocrinology, Department of Medicine, and daggerDiabetes 
      Research and Training Center, Albert Einstein College of Medicine, Bronx, NY.
FAU - Zhang, Kehao
AU  - Zhang K
FAU - Koppaka, Sudha
AU  - Koppaka S
FAU - Kehlenbrink, Sylvia
AU  - Kehlenbrink S
FAU - Kishore, Preeti
AU  - Kishore P
FAU - Raghavan, Pooja
AU  - Raghavan P
FAU - Maginley, Sylvan Roger
AU  - Maginley SR
FAU - Carey, Michelle
AU  - Carey M
FAU - Hawkins, Meredith
AU  - Hawkins M
LA  - eng
GR  - R56 DK069861/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000086/TR/NCATS NIH HHS/United States
GR  - DK-48321/DK/NIDDK NIH HHS/United States
GR  - KL2 TR000088/TR/NCATS NIH HHS/United States
GR  - TL1RR000087/RR/NCRR NIH HHS/United States
GR  - R01 DK048321/DK/NIDDK NIH HHS/United States
GR  - KL2TR000088/TR/NCATS NIH HHS/United States
GR  - TL1 TR000087/TR/NCATS NIH HHS/United States
GR  - R01 DK069861/DK/NIDDK NIH HHS/United States
GR  - P60 DK020541/DK/NIDDK NIH HHS/United States
GR  - R37 DK048321/DK/NIDDK NIH HHS/United States
GR  - UL1TR000086/TR/NCATS NIH HHS/United States
GR  - DK-069861/DK/NIDDK NIH HHS/United States
GR  - RR 12248/RR/NCRR NIH HHS/United States
GR  - UL1 TR001073/TR/NCATS NIH HHS/United States
GR  - P30 DK020541/DK/NIDDK NIH HHS/United States
GR  - DK-20541/DK/NIDDK NIH HHS/United States
GR  - M01 RR012248/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Investig Med
JT  - Journal of investigative medicine : the official publication of the American 
      Federation for Clinical Research
JID - 9501229
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Thiazolidinediones)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Inflammation Mediators/*blood
MH  - Insulin Resistance/*physiology
MH  - Male
MH  - Middle Aged
MH  - Obesity/*blood/drug therapy
MH  - Pioglitazone
MH  - Thiazolidinediones/*therapeutic use
MH  - Treatment Outcome
PMC - PMC3933072
MID - NIHMS542244
EDAT- 2013/10/22 06:00
MHDA- 2014/07/16 06:00
PMCR- 2014/12/01
CRDT- 2013/10/22 06:00
PHST- 2013/10/22 06:00 [entrez]
PHST- 2013/10/22 06:00 [pubmed]
PHST- 2014/07/16 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - 10.2310/JIM.0000000000000017 [doi]
PST - ppublish
SO  - J Investig Med. 2013 Dec;61(8):1152-60. doi: 10.2310/JIM.0000000000000017.