Dapagliflozin on cholesterol metabolism in DM2: dissecting its effect on dyslipidemia by using stable isotope based cholesterol and glucose fluxes

Completed

Conditions: cholesterol
diabetes mellitus
10018424

Registration Number: NL-OMON43515

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

-Male or postmenopauzal female patients with type 2 diabetes mellitus(HbA1C *6.5% - <8.5%)
-At least 12 weeks of stable dose metformin treatment, FPG<13.2 mmol/l
-LDL cholesterol >2.5 mmol/l
-Willing to switch used statin to rosuvastatin 10mg once daily for 9 weeks
-18-75 years of age
-Ability to provide informed consent

Exclusion Criteria

-History of cardiovascular event
-Smoking
-exogenous insulin use
-Creatinin clearance < 60ml/min
-Alcohol abuse (>4 units/day)
-AST or ALT elevation (>2.5x upper limit)
-Contraindication to MR scanning (i.e. pacemaker, metallic foreign body, claustrophobia)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>effect of 5 weeks dapagliflozin 10mg on top of rosuvastatin treatment on LDL de<br /><br>novo lipogenesis compared to rosuvastatin 10mg therapy only or no medication</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Effect of 5 weeks dapagliflozin 10mg on:<br /><br>-Change in VLDL secretion and clearance (as determined by 2H3 Leucine<br /><br>enrichment) and relation to plasma CETP, PLTP and HDL subfractions<br /><br>- (dietary) Triglyceride fluxes (as determined by 1,2,3,4-13C16 * palmitate<br /><br>to measure FFA remnant uptake).<br /><br>- hepatic and peripheral insulin sensitivity (2 step Hyperinsulinemic<br /><br>normoglycemic clamp with 2H2enriched glucose:) and energy expenditure<br /><br>including carbohydrate oxidation and fatty acid oxidation rates in breathing air<br /><br>- liver fat content (MRI liver)<br /><br>-change in fecal microbiome composition<br /><br>-cholesterol and bile salt excretion</p><br>