Effects of pioglitazone and metformin on plasma adiponectin in newly detected type 2 diabetes mellitus.
OBJECTIVE
This prospective study evaluates the effect of insulin sensitizers, pioglitazone (PGZ) and metformin (MET) on plasma adiponectin and leptin levels in subjects newly diagnosed with type 2 diabetes mellitus (T2DM).


METHODS
Double blind, randomized, active control, dose escalation study of 12 weeks treatment duration.


METHODS
Thirty apparently healthy, treatment-naive T2DM patients diagnosed within the past 6 months.


METHODS
Plasma adiponectin and leptin levels were estimated by enzyme-linked immunosorbent assay (ELISA), and insulin resistance by the homeostasis model of assessment (HOMA-IR).


RESULTS
Baseline plasma levels of adiponectin were lower in diabetic (n = 30) subjects than matched controls (n = 10, 6.6 +/- 1.1 vs 10.4 +/- 4.2 microg/ml, P = 0.021). The 12-week treatment with PGZ significantly increased adiponectin concentrations (6.6 +/- 1.1-17.9 +/- 7.4 microg/ml, P < 0.001) with no alteration in the MET treated group (6.8 +/- 1.5-6.7 +/- 2.8 microg/ml, P = 0.9). A significant decrease in plasma leptin levels was observed in the MET treated group (32.0 +/- 28.9-21.4 +/- 23.3 ng/ml, P = 0.024) but not in the PGZ treated group (23.9 +/- 24.1-22.4 +/- 25.4 ng/ml, P = 0.69). The alterations in plasma adiponectin and leptin levels were not associated with any change in body mass index (BMI). PGZ therapy improved insulin sensitivity to a greater degree (P = 0.007 and P = 0.001 for fasting plasma insulin (FPI) and HOMA-IR, respectively) than MET (P = 0.75 and P = 0.02 for FPI and HOMA-IR, respectively) but this improvement was not significantly different from that of MET at the end of 12 weeks (P = 0.146 and P = 0.09 for FPI and HOMA-IR, respectively). However, improvement in insulin sensitivity with PGZ was not commensurate with the increase in adiponectin. Better control of postbreakfast plasma glucose (PBPG) as well as decrease in serum triglycerides (TGs) were also seen with PGZ (PBPG, P < 0.001; TGs, P = 0.013). The rest of the parameters were comparable. Adverse reactions reported were minor and did not result in treatment discontinuation.


CONCLUSIONS
Pioglitazone therapy appears to be better in achieving glycaemic control and increasing plasma adiponectin and insulin sensitivity in newly detected type 2 diabetics.
Sharma
Pramod Kumar
PK
Department of Pharmacology, PGIMER, Chandigarh, India.
Bhansali
Anil
A
Sialy
Ravinder
R
Malhotra
Samir
S
Pandhi
Promila
P
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D019518:Postprandial Period; D011446:Prospective Studies; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D014280:Triglycerides; D008687:Metformin; D000077205:Pioglitazone