Study of Dapagliflozin on Mitochondrial Dysfunction and Impaired Insulin Signaling/Action (DAPA MITO)

The University of Texas System (UT)

Status: Completed

Conditions: Multiple Mitochondrial Dysfunctions Syndrome; Insulin Sensitivity

Treatments: Drug: Placebo; Drug: Dapagliflozin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01439854

R01DK024092 (U.S. NIH Grant/Contract)

5 R01 DK024092-27/NIH Prot IV

Details and patient eligibility

About

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].

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• T2DM
• Drug Naive Or On Oral Therapy

Exclusion criteria

• Insulin Treatment
• Major Organ Disease

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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18 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

this arm is control

Treatment:

Drug: Placebo

Dapagliflozin

Experimental group

Description:

Interventional arm

Treatment:

Drug: Dapagliflozin