Renal Function Disorder, Glucose Metabolism Disorders
Conditions
Brief summary
In this open clinical trial, 30 subjects with inadequately controlled T2D and eligible, as per good clinical practice, for therapy with SGLT-2 inhibitor, will be randomized to receive a SGLT-2 inhibitor vs other oral-antidiabetic drugs (OADs) therapy for 3 months. Measures will be performed at baseline, after 2 days, after one month and at the end of the study protocol, as per good clinical practice
Detailed description
* Total concentrations of MEHP, MEOHP and MEHHP will be quantified, in the laboratories of the Institute of Clinical Physiology, National Research Council, Pisa, in a spot morning urine sample by ultra-HPLC coupled with electrospray ionization/quadrupole time-of-flight mass spectrometry (Agilent UHPLC 1290 infinity coupled to an Agilent 6540 MS-QTOF, Santa Clara, CA) using stable isotope labeled substrates, i.e. MEHP (ring-1,2-13C2, dicarboxyl-13C2), MEHHP, MEHHP 13C4, MEOHP and MEOHP 13C4 that will be purchased from Cambridge Isotope Laboratories (Tewksbury, MA). * Urinary creatinine concentrations will be measured to adjust urinary concentrations of DEHP metabolite (Beckman Coulter AU400, Brea, CA), thus minimizing the influence of urine volume. * Serum and urinary inflammatory markers and adipocytokines will be quantitatively determined using sandwich enzyme-linked immunosorbent assays kits according to the manufacturer's instructions. Optical density will be measured using a microplate reader. * Serum and urinary markers of oxidative stress will be measured by gold standard techniques. In detail, MDA will be quantified by TBARS reactive substances measured by optical density; GSH-Px by a specific assay kit according to the manufacturer's instruction; SOD activity will be determined using a specific SOD kit; urinary 8-isoprostane concentration will be measured by a specific affinity sorbent. (Cayman Chemical, Ann Harbor, MI, USA) according to the manufacturer's instructions. * To analyze mitochondrial DNA we will apply a triplex design previously reported to amplify mitochondria loci located within the MinorArc and MajorArc, respectively. To assess nuclear DNA, we will use RNase P Copy Number Reference. * The phthalates-free diet will be self-administered by the individuals under intervention, following a set of instruction and rules provided by the physicians based on the current literature data.
Interventions
DRUGDapagliflozin 10 MG
SGLT2-inhibitor: Diabetic oral drug with diuretic properties
Best known thiazide class diuretic.
Sponsors
University of Pisa
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Individuals of both sex; * Age between 18 and 85 years; * T2D * T2D duration \> 6 months * BMI ≤ 40 Kg/m2, * HbA1c \> 48 mmol/mol * Eligible for SGLT-2i therapy
Exclusion criteria
* age \>85 years, * eGFR \<60 ml/min/1.73 m2, * occurring acute complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Phthalates concentration | Changes between baseline and 1 month | Exposure to phthalates assessed through urinary concentration of phthalates metabolites spot and 24-hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting glucose | 1 and 3 months | Fasting glucose measured in a fasting morning blood sample |
| Glycated Haemoglobin | 1 and 3 months | HbA1c in a fasting measured in a morning blood sample |
| Renal function | 1 and 3 months | Using creatinine measured in a fasting morning blood sample and estimated by eGFR (calculated with the CDK-EPI formula) |
| Macrovascular events | 1 and 3 months | Number of participants with MACE events (Stroke, Acute Myocardial Infarction, Unstable Angina, Revascularization) |
| Albumin excretion | 1 and 3 months | Measured by urinary albumin/creatinine ratio |
Countries
Italy
Outcome results
None listed