Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population
| Autor: | Sudha S. Shankar, MD, R. Ravi Shankar, MD, Radha A. Railkar, PhD, Chan R. Beals, MD, PhD, Helmut O. Steinberg, MD, David E. Kelley, MD |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Current Therapeutic Research, Vol 77, Iss C, Pp 83-89 (2015) |
| Druh dokumentu: | article |
| ISSN: | 0011-393X 1879-0313 |
| DOI: | 10.1016/j.curtheres.2015.08.001 |
| Popis: | Background: Insulin resistance heightens the risk for type 2 diabetes mellitus and cardiovascular disease. Amelioration of insulin resistance may reduce this risk. The thiazolidinedone class of insulin sensitizers improves insulin action in individuals with insulin-resistant diabetes and nondiabetic individuals. However, there are few reports on the time of onset of such effects independent of reversal of glucotoxicity. Objective: The goal of our study was to test whether the thiazolidinedione pioglitazone has prominent early metabolic effects that can be detected in an obese, nondiabetic, insulin-resistant population. Methods: We conducted a randomized, double-blind, placebo-controlled, parallel-group trial in men with nondiabetic insulin resistance using a hyperinsulinemic euglycemic clamp technique (at low and high doses of insulin at 10 and 40 mU/m2/min, respectively). The patients were given 30 mg daily oral pioglitazone or placebo for 28 days. Patients underwent a baseline clamp before initiation of treatment, and again at 14 and 28 days of treatment. Results: Compared with placebo, under high-dose hyperinsulinemia, pioglitazone led to significant increases in glucose disposal rates (GDR) of 1.29 mg/kg/min (90% CI, 0.43–2.15; 39%; P=0.008) that were detectable at 2 weeks of treatment and persisted at 4 weeks of treatment. Under low-dose hyperinsulinemia, significant increases in GDR of 0.40 mg/kg/min (90% CI, 0.17–0.62; 95%; P=0.003) were observed at 4 weeks of treatment. These responses were accompanied by robust suppression of free fatty acids under hyperinsulinemic conditions, and by significant increases in circulating basal total adiponectin at 2 and 4 weeks of treatment. Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712. |
| Databáze: | Directory of Open Access Journals |
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