Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action (DAPA MITO)
The purpose of this study is to examine the effect of the chronic treatment of type 2 diabetes (T2DM) with dapagliflozin on: (1) mitochondrial gene function/expression and insulin signaling/action and (2) oral glucose tolerance and beta cell function. Dapagliflozin is a potent, highly specific inhibitor of renal glucose transport [SGLT2].
Multiple Mitochondrial Dysfunctions Syndrome
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||Regulation of Hepatic and Peripheral Glucose Metabolism: Protocol IVA. Effect of Plasma Glucose Reduction by Selective SLGT2 Inhibition on Mitochondrial Dysfunction and Impaired Insulin Signaling/Sensitivity in T2DM|
- Change in Insulin Sensitivity [ Time Frame: baseline, two weeks ] [ Designated as safety issue: No ]The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline.
- Change in Mitochondrial Function [ Time Frame: baseline, two weeks ] [ Designated as safety issue: No ]The change in mitochondrial function/gene expression at two weeks compared to baseline.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Placebo Comparator: Placebo
this arm is control
Patients are treated with placebo
Treatment arm, 10 mg per day for 2 weeks
"Glucotoxicity" has been implicated as a cause of insulin resistance and impaired beta cell function in T2DM. Abundant support for the glucotoxicity hypothesis has been provided by in vivo and in vitro studies in animals, but a rigorous test of this hypothesis in man is lacking. The investigators propose to test the glucotoxicity hypothesis by chronically reducing the plasma glucose in type 2 diabetic subjects (T2DM) with an inhibitor of renal glucose transport, dapaglifozin, and examining the effect of restoration of normoglycemia on mitochondrial function and insulin signaling/sensitivity. Lastly, the investigators will test the "glucolipotoxicity" hypothesis, which states that the toxic effects of elevated plasma FFA on insulin sensitive tissues (i.e., muscle) are magnified in the presence of concurrent hyperglycemia. Thus, high glucose levels increase malonyl CoA, which inhibits CPT I, leading to accumulation of FACoA/DAG, which impair mitochondrial function and inhibit insulin action.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01439854
|Contact: Aurora Merovci||210-567 4686|
|Contact: Carolina Solis||210-567-4686|
|United States, Texas|
|Diabetes Division, UTHSCSA||Recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: Irma 210-567-4686|
|Principal Investigator:||Ralph DeFronzo, MD||The University of Texas Health Science Center at San Antonio|