Baseline adiponectin levels do not influence the response to pioglitazone in ACT NOW.
OBJECTIVE
Plasma adiponectin levels are reduced in type 2 diabetes mellitus (T2DM) and other insulin-resistant states. We examined whether plasma adiponectin levels at baseline and after pioglitazone treatment in impaired glucose tolerance (IGT) subjects were associated with improved insulin sensitivity (SI) and glucose tolerance status.


METHODS
A total of 602 high-risk IGT subjects in ACT NOW were randomized to receive pioglitazone or placebo with a median follow-up of 2.4 years.


RESULTS
Pioglitazone reduced IGT conversion to diabetes by 72% in association with improved β-cell function by 64% (insulin secretion/insulin resistance index) and increased tissue sensitivity by 88% (Matsuda index). In pioglitazone-treated subjects, plasma adiponectin concentration increased threefold from 13 ± 0.5 to 38 ± 2.5 μg/mL (P < 0.001) and was strongly correlated with the improvement in SI (r = 0.436, P < 0.001) and modestly correlated with glucose area under the curve during oral glucose tolerance test (r = 0.238, P < 0.005) and insulin secretion/insulin resistance index (r = 0.306, P < 0.005). The increase in adiponectin was a strong predictor of reversion to normal glucose tolerance and prevention of T2DM. In the placebo group, plasma adiponectin did not change and was not correlated with changes in glucose levels. There was an inverse association between baseline plasma adiponectin concentration and progression to diabetes in the placebo group but not in the pioglitazone group.


CONCLUSIONS
Baseline adiponectin does not predict the response to pioglitazone. The increase in plasma adiponectin concentration after pioglitazone therapy in IGT subjects is strongly related to improved glucose tolerance status and enhanced tissue sensitivity to insulin.
Texas Diabetes Institute and University of Texas Health Science Center and Audie L. Murphy Hospital, South Texas VA Health Care System, San Antonio, TX.
Devjit
D
Tripathy
Division of Endocrinology and Metabolism, Georgetown University, Washington, DC.
Stephen C
SC
Clement
Phoenix VA Health Care System, Phoenix, AZCollege of Nursing and Health Innovation, Arizona State University, Phoenix, AZ.
Dawn C
DC
Schwenke
State University of New York Health Science Center at Brooklyn, Brooklyn, NY.
MaryAnn
M
Banerji
Pennington Biomedical Research Center/Louisiana State University, Baton Rouge, LA.
George A
GA
Bray
University of Southern California Keck School of Medicine, Los Angeles, CA.
Thomas A
TA
Buchanan
University of Texas Health Science Center, San Antonio, TX, and Cardiometabolic Risk Unit, Institute of Clinical Physiology, Pisa, Italy.
Amalia
A
Gastaldelli
VA San Diego Healthcare System and University of California, San Diego, San Diego, CA.
Robert R
RR
Henry
Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Memphis, TN.
Abbas E
AE
Kitabchi
VA San Diego Healthcare System and University of California, San Diego, San Diego, CA.
Sunder
S
Mudaliar
Medstar Research Institute, Hyattsville, MD.
Robert E
RE
Ratner
Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Memphis, TN.
Frankie B
FB
Stentz
Texas Diabetes Institute and University of Texas Health Science Center and Audie L. Murphy Hospital, South Texas VA Health Care System, San Antonio, TX.
Nicolas
N
Musi
Phoenix VA Health Care System, Phoenix, AZ.
Peter D
PD
Reaven
Texas Diabetes Institute and University of Texas Health Science Center and Audie L. Murphy Hospital, South Texas VA Health Care System, San Antonio, TX albarado@uthscsa.edu.
Ralph A
RA
DeFronzo
D052242:Adiponectin / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D052242:Adiponectin; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone