1. Pre-clinical diabetic cardiomyopathy in type 2 diabetes mellitus
Conditions
Interventions
Study 1 and 2:
The intervention group of 25 patients injects Liraglutide (Victoza®) once daily
subcutaneously, the control group of 25 patients injects Liraglutide-Placebo
subcutaneously once daily.
Sponsors
Leids Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Study 1 - Informed consent - Age > 18 years and 25 kg/m2 - DM2 treated with metformin, metformin + SU derivative, metformin + SU derivative + insulin, or metformin + insulin for at least 3 months in the maximum tolerable dosage - HbA1c >=7% and 60 ml/min - Normal sitting blood pressure 18 years and 23 kg/m2 - DM2 treated with metformin and/or SU derivative and/or insulin for at least 3 months in stable dosage - HbA1c >= 6.5% and 30 ml/min;Study 1 healthy controls - No Hindustani Surinamese descent Study 2 healthy controls - Hindustani Surinamese descent (based on self-identified ethnicity and self-reported origin of the mother, the father and the mother*s and father's ancestors. Both parents and the mother*s and father's ancestors should be South Asian for inclusion)
Exclusion criteria
Exclusion criteria: Study 1 and study 2: - Use of thiazolidinediones (TZD), GLP-1 analogues, DPP-IV inhibitors, fibrates, prednisone, cytostatic or antiretroviral therapy within 6 months prior to the study - Hereditary lipoprotein disease - Psychiatric disorders and / or use of antipsychotic or antidepressant drugs at present or in the past - Hepatic disease (AST/ALT > 2 times reference values) - Endocrine disease other than diabetes mellitus type 2 - Any significant chronic disease (e.g. inflammatory bowel disease) - Any significant abnormal laboratory results found during the medical screening procedure - Gastrointestinal surgery (e.g. gastric bypass) - Pregnant woman or a woman who is breast-feeding - Female of child-bearing potential intending to become pregnant or is not using adequate contraceptive methods while sexually active - Allergy to intravenous contrast - Known or suspected hypersensitivity to trial products or related products - Chronic pancreatitis or previous acute pancreatitis - Personal history or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia type 2 - Claustrophobia - Metal implants or other contraindications for MRI - Recent participation in other research projects within the last 3 months or participation in 2 or more projects in one year;Study 1: - History or presence of cardiovascular disease;Study 2: - Uncontrolled treated or untreated hypertension (systolic blood pressue > 180 mmHg and/or diastolic blood pressure > 110 mmHg) - Acute coronary or cerebrovascular event within 30 days prior to study - Congestive heart failure NYHA III-IV;Exclusion criteria healthy controls study 1 and study 2: - Known acute or chronic disease based on history (which is of influence on primary or secondary outcome measures, at the discretion of the investigator) and physical examination and standard laboratory tests (blood counts, fasting blood glucose, lipids, eGFR, liver enzymes, and electrocardiogram) - Chronic use of any drug (which is of influence on primary or secondary outcome measures, at the discretion of the investigator), and impaired glucose tolerance (as excluded by a 75-g oral glucose tolerance test) - Pregnant woman or a woman who is breast-feeding - Female of child-bearing potential intending to become pregnant or is not using adequate contraceptive methods while sexually active - Allergy to intravenous contrast - Claustrophobia - Metal implants or other contraindications for MRI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Study 1 and 2: Heart function: - Systolic function: stroke volume, ejection fraction, cardiac output, cardiac index, peak ejection rate - Diastolic function: early peak filling rate (E), early deceleration peak (E dec peak), atrial peak filling rate (A), E/A ratio, peak mitral annulus longitudinal motion (Ea), MR estimate of LV filling pressure (E/Ea). | — |
Secondary
| Measure | Time frame |
|---|---|
| Study 1 and 2: - Heart dimensions: End diastolic volume, end-systolic volume, LV mass, LV mass index, LVMI/EDVI, percentage scar tissue - Aorta and carotid vessel wall imaging: total vessel wall area, average vessel wall thickness, minimum vessel wall thickness, maximum vessel wall thickness, vascular distensibility; carotid artery intima media thickness (IMT) by ultrasound. - Body fat distribution: Adipose tissue distribution, visceral and subcutaneous fat volume at level of L4-L5 vertebra, total fat distribution including BAT, epicardial fat volume, Magnetic Resonance Spectroscopy of the heart, liver and kidney triglyceride content - Glycemic control: HBA1C and fasting blood glucose level | — |
Countries
Netherlands
Outcome results
None listed