Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action

Not Applicable

Completed

• Conditions: Insulin Sensitivity; Multiple Mitochondrial Dysfunctions Syndrome
• Interventions: Drug: Placebo; Drug: Dapagliflozin

• Registration Number: NCT01439854
• Lead Sponsor: The University of Texas Health Science Center at San Antonio

Brief Summary

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 \[SGLT2\].

Detailed Description

"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.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-08-03
• Study First Submitted QC: 2011-09-22
• Study First Posted: 2011-09-23
• Primary Completion: 2018-06-30
• Study Completion: 2018-06-30
• Status Verified: 2018-07
• Results First Submitted: 2019-09-16
• Results First Submitted QC: 2019-10-10
• Last Update Submitted: 2019-10-10
• Results First Posted: 2019-10-29
• Last Update Posted: 2019-10-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• T2DM
• Drug Naive Or On Oral Therapy

Exclusion Criteria

• Insulin Treatment
• Major Organ Disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	this arm is control
Dapagliflozin	Dapagliflozin	Interventional arm

Primary Outcome Measures

Name	Time	Method
Change in Insulin Sensitivity	baseline, two weeks	The change in insulin sensitivity and total glucose disposal measured at two weeks with the insulin clamp compared to baseline. This is measured using TGD (whole body tissue glucose disposal)/SSPI (steady state plasma insulin concentration) ratio

Secondary Outcome Measures

Name	Time	Method
Change in Mitochondrial Function	baseline, two weeks	The change in mitochondrial function/gene expression at two weeks compared to baseline. This was measured by energy expenditure.

Trial Locations

Locations (1)

Diabetes Division, UTHSCSA; 🇺🇸 San Antonio, Texas, United States