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Pioglitazone may increase adiponectin diabetes prevention in patients with IGT
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In high-risk patients with impaired glucose tolerance, the marked threefold increase in plasma adiponectin seen after treatment with pioglitazone appears to be linked to the prevention of type 2 diabetes, according to recent findings.
Moreover, the study found that baseline adiponectin levels are not predictive of the response to pioglitazone.
In the study, researchers evaluated 602 patients with IGT and followed them for a mean of 2.4 years. All participants underwent a baseline 2-hour oral glucose tolerance test after an overnight fast, with plasma samples acquired every 15 minutes for 2 hours. These samples were assayed to determine concentrations of glucose, insulin and free fatty acids. The participants were then randomly assigned to placebo or pioglitazone (30 mg daily). After 1 month, pioglitazone dosage was increased to 45 mg daily. Glucose measurements were repeated at the end of the study (2 years after completion of enrollment), at time of dropout or loss to follow-up, or at time of conversion to type 2 diabetes.
The researchers found that pioglitazone decreased the conversion of IGT to diabetes by 72% in connection with improved beta-cell function by 64% and yielded an 88% increase in tissue sensitivity.
In the pioglitazone group, the concentration of plasma adiponectin increased threefold, from 13 mcg/mL to 38 mcg/mL (P<.001), and was strongly correlated with the improvement in insulin sensitivity (P<.001) and moderately correlated with glucose area under the curve during OGTT (P<.005) and insulin secretion/insulin resistance index (P<.005). The increase in adiponectin was highly predictive of a return to normal glucose tolerance and avoidance of type 2 diabetes. Baseline plasma adiponectin was inversely related to diabetes progression in the placebo group, but not in the pioglitazone group.
“The completely novel observation of the current study is that the increase in plasma adiponectin concentration after pioglitazone treatment correlates strongly with the prevention of type 2 diabetes and reversion to normal glucose tolerance in high-risk individuals with [IGT],” the researchers wrote. “The potential success of failure of a specific medication or lifestyle intervention may be related to how effectively the therapy corrects the underlying pathophysiologic defect responsible for the low plasma adiponectin level.”
Disclosure: This study was supported by grants from the University of Tennessee, the University of Southern California and the South Texas Veterans Health Care System. The researchers also reported financial ties to Boehringer Ingelheim, Bristol-Myers Squibb, HDL Diagnostics, Merck, Novartis, Roche, Sanofi and Takeda Pharmaceuticals North America. Please see the study for a full list of financial disclosures.
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