UnknownNot Applicable

Lipid and Glycogen Metabolism in Patients With Impaired Glucose Tolerance and Calcium Sensing Receptor Mutations

Austria90 participantsStarted 2013-07

Plain-language summary

Background: Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure, in part due to diabetic cardiomyopathy. However, the association between intracellular lipid accumulation and (myocardial) functional impairment is likely more complex than originally imagined. Recent studies suggest that not fat per se, but the content of saturated or unsaturated fatty acids might predict the development of cardiac steatosis and myocardial dysfunction. In addition skeletal muscle and hepatic glycogen metabolism is impaired in patients with diabetes mellitus. Data from animal experiments suggest a relevant role of myocardial glycogen stores in ischemic preconditioning. Due to methodological limitations so far data on myocardial glycogen stores and myocardial lipid composition in humans are missing. Hypothesis: In addition to total ectopic lipid deposition in the myocardium, myocardial lipid composition, i.e. the relative abundance of saturated and unsaturated fatty acids, and impaired myocardial glycogen metabolism may play an important role in the development cardiac lipotoxicity leading to diabetic cardiomyopathy. Pancreatic endocrine function and myocardial morphology and function is altered in patients with heterozygote inactivating mutations of the CaSR-gene / FHH. Aims: * Metabolic virtual biopsy of the myocardium for identification of specific patterns of intracellular lipid composition and myocardial glycogen metabolism as possible critical determinants of metabolic cardiomyopathy * Characterization of the metabolic interplay between the myocardium, skeletal muscle, liver and adipose tissues in different stages of development of type 2 diabetes compared to patients with calcium sensing receptor mutation Methods: * 1H/13C and 31P magnetic resonance spectroscopy and imaging for measurements of myocardial, skeletal and liver lipid and glycogen content, abdominal adipose tissue distribution and composition, ATP synthesis and myocardial functional parameters * Mixed meal tolerance tests to trace the postprandial partitioning of substrates between insulin sensitive tissues (myocardium, skeletal muscle, liver, adipose tissue). * Hyperinsulinemic-hyperglycemic glucose clamp (HHC) with enrichment of the infused glucose with the stable isotope \[1-13C\]glucose to trace the incorporation of circulating glucose into myocardial glycogen in healthy insulin sensitive volunteers, prediabetic insulin resistant volunteers with impaired glucose tolerance, healthy subjects, patients suffering from type 2 diabetes mellitus, patients suffering from type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor.

Who can participate

Age range

18 Years – 90 Years

Sex

ALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria for Type 2 DM patients: * HbA1c: 7.0-8.0 %, * m/f, * age \<90, * no insulin therapy, * normal liver function (transaminase \<2 x than normal), * no late diabetic complication (prolif. retinopathy, neuropathy, creatinin \<1.5 mg/dl), * female premenopausal patients: follicular = 1. phase of menstrual cycle, * no evidence of coronary artery disease (ECG, patient history, symptoms). Exclusion criteria for healthy controls: * age \<18 / \>90a, * dyslipidaemia (serum total cholesterol \> 220 mg/dl, triglycerides \> 150 mg/dl, LDL cholesterol \> 130 mg/dl), * arterial hypertension, * cardiovascular diseases, * thyroid disorders, * bleeding disorders, * medication potentially affecting glucose or lipid metabolism. Inclusion criteria for the CaSR collective: • genetically characterized heterozygote mutation in the CaSR gene General exclusion criteria are: * metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation \[heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt-spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips), embolization coil, or any metal fragments or shrapnel in the body\]. * BMI \> 3…

Questions worth asking your doctor

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1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

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Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

change in myocardial glycogen content

Timeframe: at baseline and during the third hour of the hyperglycemic clamp/ in the morning and at 5 p.m. after a meal tolerance test

Trial details

NCT IDNCT02023489

SponsorMedical University of Vienna

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2017-12

Contact for this trial

Peter Wolf, MD

00436646499456 peter.wolf@meduniwien.ac.at

View on ClinicalTrials.gov More Type 2 Diabetes Mellitus trials