Type 2 Diabetes MellitusRISC_7TNCT02023489
Lipid and Glycogen Metabolism in Patients With Impaired Glucose Tolerance and Calcium Sensing Receptor Mutations
A study testing 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Meal Tolerance Test and Hyperglycemic-hyperinsulinemic clamp in people with Type 2 Diabetes Mellitus and Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), run by Medical University of Vienna at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus, Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Familiar Hypocalcuric Hypercalcemia
- What is being tested?
- 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Meal Tolerance Test and Hyperglycemic-hyperinsulinemic clamp
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteAustria
- Study dates
- Jul 2013to Jul 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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),
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- female premenopausal patients: follicular = 1. phase of menstrual cycle,
- no evidence of coronary artery disease (ECG, patient history, symptoms).
- 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 > 35 kg/m2
- tendency toward claustrophobia
- severe thyroid or liver disorders
- any acute illness within 2 weeks prior the study
- donation of blood within 30 days prior the study
- pregnancy
- malignancies, autoimmune disease
- AIDS, HIV, infectious hepatitis
- Plasma transaminases elevated > 3 fold
- Clinically relevant anemia
- Neurological disease
- Blood coagulation disorder
- severe dyslipidemia (serum triglycerides > 400 mg/dl, cholesterol > 300 mg/dl)
- arterial hypertension (RR > 180/100 mm Hg)
- clinical relevant cardiovascular diseases
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University Of Vienna, Department of Internal Medicine III
Vienna, State of Vienna, 1090
Michael Krebs, Prof. MD, michael.krebs@meduniwien.ac.at
Michael Krebs, Prof. MD
About this study
Official title: Myocardial Lipid and Glycogen Metabolism & Cardiac Function in Patients With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus and Calcium Sensing Receptor Mutations - A Cross Sectional Magnetic Resonance Spectroscopy and Imaging Study
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.
Read more
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.
Read the detailed description
Background:
- Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure, in part due to diabetic cardiomyopathy. Ectopic intracellular lipid accumulation and impaired glycogen metabolism in skeletal muscle and liver and are closely associated with metabolic impairment in insulin resistant subjects and patients with diabetes mellitus. Recent evidence suggests that increased myocardial lipid accumulation might contribute to the development of myocardial dysfunction by direct toxic effects (lipotoxicity). 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 carbohydrates stored as glycogen in muscle cells serve as readily available energy supply for contracting muscle. 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.
- Heterozygote inherited inactivating mutations in Calcium Sensing Receptor (CaSR)-gene leads to familiar hypocalciuric hypercalcemia (FHH), specified by mildly elevated plasma Ca and parathyroid hormone concentrations, whereas urine Ca excretion is inadequately low. However, in addition to the parathyroid gland CaSR is expressed in various tissues including the endocrine pancreas and the heart. So far it is unknown whether the endocrine function of the pancreas or myocardial morphology and/or function is altered in patients with FHH.
- Altered hepatic energy metabolism might play an important role in the development of type 2 diabetes. Additionally, the lack of insulin delivery to the liver via the portal vein in type 1 diabetes might alter liver ATP synthesis. Therefore we aim to investigate hepatic energy metabolism non invasively with MRS.
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.
Hepatic and cardiac lipid and energy metabolism is altered in T1DM.
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 (MRS) and imaging (MRI) 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, type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor.
Relevance:
Despite intensive treatment of cardiovascular risk factors, heart diseases are still the main cause of death in diabetic patients. Thus, elucidation of mechanisms that link impaired lipid and/or glycogen metabolism and energy homeostasis to the development of heart failure appears to be crucial for the development of novel treatment strategies. Additionally, hepatic steatosis plays a challenging, emerging role in the treatment of liver disease, wherefore further insight in hepatic energy metabolism in various endocrine disease is urgently needed.
- Conditions
- Type 2 Diabetes Mellitus, Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Familiar Hypocalcuric Hypercalcemia, Healthy Volunteers, Type 1 Diabetes Mellitus
- Being tested
- 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Meal Tolerance Test, Hyperglycemic-hyperinsulinemic clamp
- Medical subject headings
- Diabetes Mellitus, Type 2, Prediabetic State, Insulin Resistance, Glucose Intolerance, Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1H/ 13C and 31P Magnetic Resonance SpectroscopyDevice
Study participants will be studied in the fasting state after an overnight fast of at least 10 h. Participants will arrive at the MR-Centre in the morning of the study. Between 6:30 and 10:00 a.m., 1H MRI (3T) will be performed for the assessment abdominal adipose tissue distribution and composition as well as myocardial functional parameters. 1H/13C MRS examinations (7T) will be performed for measurements of myocardial, skeletal muscle and liver lipid content and composition as well as glycogen content. Additionally, ATP synthesis and energy metabolism will be assessed.
Meal Tolerance TestOther
A meal tolerance test meal tolerance test according to Petersen et al. (PNAS, Vol 104, 2007) will be performed. After MRI and MRS examinations subjects will be returned at our outpatients clinic, where small polyethylene catheter will be inserted in an antecubital vein for hourly blood sampling. At 10:30 a.m. and 1:30 p.m. two liquid high carbohydrate meals of equal size containing all the required daily energy (30 kcal/kg of body weight; 55% carbohydrate, 10% protein, and 35% fat) with an additional 25% of the daily energy requirements added in the form of sucrose will be served.
At 5 p.m. subjects will be returned at the MR - Centre for postprandial 1H / 13C MRS (7T) of muscle, liver and myocardial lipid and glycogen contents. Myocardial function parameters and abdominal fat distribution will be assessed again by 1H MRI (3T).
Hyperglycemic-hyperinsulinemic clampOther
All volunteers will be admitted in the morning and basal 13C tracer enrichment will be assessed.
At 8:00a.m. (0 min) a hyperglycemic-hyperinsulinemic-pancreatic clamp test will be initiated by somatostatin (-5-300 min: 0.1 µg·kg-1·min-1, UCB Pharma, Vienna, Austria) and insulin (0 - 8 min: 80 mU·min-1·m-2 body surface area; 8 -300 min: 40 mU·min-1·m-2 body surface area) infusion. Plasma glucose will be raised and maintained at ~180 mg·dL-1 by primed (0.2 g·kg-1)-variable dextrose infusion (20%w/v) enriched with [1-13C]glucose (40%w/w). A second catheter will be placed into an antecubital vein of the other arm and blood samples for the measurement of glucose, insulin and c-peptide. Glucose concentrations will be analysed immediately every 5 minutes, employing a glucose analyser. Myocardial glycogen concentrations will be measured before the clamp (-60 - 0 min) and from 90 min to 180 min during the clamp employing 13C MRS.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetes Mellitus | Other | Not described Receives: Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy; Other: Hyperglycemic-hyperinsulinemic clamp |
| Insulin sensitive volunteers | Other | Not described Receives: Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy; Other: Meal Tolerance Test; Other: Hyperglycemic-hyperinsulinemic clamp |
| prediabetic subjects | Other | Not described Receives: Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy; Other: Meal Tolerance Test; Other: Hyperglycemic-hyperinsulinemic clamp |
| familiar hypocalciuric hypercalcemic patients | Other | Not described Receives: Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy; Other: Meal Tolerance Test |
| Type 1 diabetes mellitus | Other | Not described Receives: Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
change in myocardial glycogen content
13C magnetic resonance spectroscopy for the assessment of myocardial glycogen content: Localized 13C NMR spectra will be obtained in a 7T Magnetom MR System (Siemens Healthcare, Erlangen Germany) with a dedicated butterfly-shaped 13C (15cm)/1H(21cm) transmitter/receiver coil (Stark Contrast, Erlangen, Germany) placed over or under the thorax. Recently introduced ISIS based or 1D CSI localization schemes will be applied. Absolute glycogen concentrations will be quantified by comparing the C1 glycogen peak (100.5 ppm) integral of tissue specific spectra with that of a glycogen standard taken under identical conditions. Corrections for loading of the coil and sensitive volume of the coil will be performed.
Measured: at baseline and during the third hour of the hyperglycemic clamp/ in the morning and at 5 p.m. after a meal tolerance test
Secondary outcomes (1)
change in myocardial lipid composition
Myocardial lipid measurements will be performed using localized 1H MRS. Anatomic imaging will be used to guide water suppressed Point RESolved Spectroscopy sequence (echo time, TE= 30 ms; minimal repetition time TR= 3 s; NS=64). The volume of the interest (VOI; approx. 6 - 8 cm3) will be placed over the interventricular septum. . An additional spectrum without water suppression (NS= 2x 4) will be used as internal reference. The spectra will be processed offline using AMARES time domain line fitting as implemented jMRUI software package. The myocardial lipid content will be determined from processed spectra as a ratio of the intensities of CH2 (1.25 ppm) and CH3 (0.8-0.9 ppm) group resonances to the intensity of the water resonance from non-water suppressed spectra of the same VOI.
Measured: at baseline and during the third hour of the hyperglycemic clamp/ in the morning and at 5 p.m. after a meal tolerance test
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2017 (estimated)
- Study completionJul 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Michael Krebs, Medical University of Vienna
- Investigators
- Michael Krebs, Prof MD, Principal investigator, Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02023489
- Sponsor's protocol ID
- EK1128/2013
- Acronym
- RISC_7T
- Status last verified
- Mar 2017
- First submitted
- 18 Dec 2013
- Last updated
- 23 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myocardial Lipid and Glycogen Metabolism & Cardiac Function in Patients With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus and Calcium Sensing Receptor Mutations - A Cross Sectional Magnetic Resonance Spectroscopy and Imaging Study
- ClinicalTrials.gov ID
- NCT02023489
- Acronym / sponsor ID
- RISC_7T / EK1128/2013
- Conditions
- Type 2 Diabetes Mellitus, Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), Familiar Hypocalcuric Hypercalcemia, Healthy Volunteers, Type 1 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Jul 2018 (estimated)
- First posted
- 30 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Type 2 diabetes mellitus is a main risk factor for cardiovascular disease and heart failure, in part due to diabetic cardiomyopathy. Ectopic intracellular lipid accumulation and impaired glycogen metabolism in skeletal muscle and liver and are closely associated with metabolic impairment in insulin resistant subjects and patients with diabetes mellitus. Recent evidence suggests that increased myocardial lipid accumulation might contribute to the development of myocardial dysfunction by direct toxic effects (lipotoxicity). 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 carbohydrates stored as glycogen in muscle cells serve as readily available energy supply for contracting muscle. 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.
- Heterozygote inherited inactivating mutations in Calcium Sensing Receptor (CaSR)-gene leads to familiar hypocalciuric hypercalcemia (FHH), specified by mildly elevated plasma Ca and parathyroid hormone concentrations, whereas urine Ca excretion is inadequately low. However, in addition to the parathyroid gland CaSR is expressed in various tissues including the endocrine pancreas and the heart. So far it is unknown whether the endocrine function of the pancreas or myocardial morphology and/or function is altered in patients with FHH.
- Altered hepatic energy metabolism might play an important role in the development of type 2 diabetes. Additionally, the lack of insulin delivery to the liver via the portal vein in type 1 diabetes might alter liver ATP synthesis. Therefore we aim to investigate hepatic energy metabolism non invasively with MRS.
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.
Hepatic and cardiac lipid and energy metabolism is altered in T1DM.
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 (MRS) and imaging (MRI) 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, type 1 diabetes and patients with heterozygote mutation in calcium sensing receptor.
Relevance:
Despite intensive treatment of cardiovascular risk factors, heart diseases are still the main cause of death in diabetic patients. Thus, elucidation of mechanisms that link impaired lipid and/or glycogen metabolism and energy homeostasis to the development of heart failure appears to be crucial for the development of novel treatment strategies. Additionally, hepatic steatosis plays a challenging, emerging role in the treatment of liver disease, wherefore further insight in hepatic energy metabolism in various endocrine disease is urgently needed.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Type 2 Diabetes Mellitus | Other | Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Other: Hyperglycemic-hyperinsulinemic clamp |
| Insulin sensitive volunteers | Other | Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Other: Meal Tolerance Test, Other: Hyperglycemic-hyperinsulinemic clamp |
| prediabetic subjects | Other | Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Other: Meal Tolerance Test, Other: Hyperglycemic-hyperinsulinemic clamp |
| familiar hypocalciuric hypercalcemic patients | Other | Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Other: Meal Tolerance Test |
| Type 1 diabetes mellitus | Other | Device: 1H/ 13C and 31P Magnetic Resonance Spectroscopy |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- HbA1c: 7.0-8.0 %,
- m/f,
- age <90,
- no insulin therapy,
- normal liver function (transaminase <2 x than normal),
Key exclusion criteria (7 listed)
- 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,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1H/ 13C and 31P Magnetic Resonance SpectroscopyStudy participants will be studied in the fasting state after an overnight fast of at least 10 h. Participants will arrive at the MR-Centre in the morning of the study. Between 6:30 and 10:00 a.m., 1H MRI (3T) will be performed for the assessment abdominal adipose tissue distribution and composition as well as myocardial functional parameters. 1H/13C MRS examinations (7T) will be performed for measurements of myocardial, skeletal muscle and liver lipid content and composition as well as glycogen content. Additionally, ATP synthesis and energy metabolism will be assessed. | Device | Insulin sensitive volunteers, Type 1 diabetes mellitus, Type 2 Diabetes Mellitus, familiar hypocalciuric hypercalcemic patients, prediabetic subjects |
| Meal Tolerance TestA meal tolerance test meal tolerance test according to Petersen et al. (PNAS, Vol 104, 2007) will be performed. After MRI and MRS examinations subjects will be returned at our outpatients clinic, where small polyethylene catheter will be inserted in an antecubital vein for hourly blood sampling. At 10:30 a.m. and 1:30 p.m. two liquid high carbohydrate meals of equal size containing all the required daily energy (30 kcal/kg of body weight; 55% carbohydrate, 10% protein, and 35% fat) with an additional 25% of the daily energy requirements added in the form of sucrose will be served. At 5 p.m. subjects will be returned at the MR - Centre for postprandial 1H / 13C MRS (7T) of muscle, liver and myocardial lipid and glycogen contents. Myocardial function parameters and abdominal fat distribution will be assessed again by 1H MRI (3T). | Other | Insulin sensitive volunteers, familiar hypocalciuric hypercalcemic patients, prediabetic subjects |
| Hyperglycemic-hyperinsulinemic clampAll volunteers will be admitted in the morning and basal 13C tracer enrichment will be assessed. At 8:00a.m. (0 min) a hyperglycemic-hyperinsulinemic-pancreatic clamp test will be initiated by somatostatin (-5-300 min: 0.1 µg·kg-1·min-1, UCB Pharma, Vienna, Austria) and insulin (0 - 8 min: 80 mU·min-1·m-2 body surface area; 8 -300 min: 40 mU·min-1·m-2 body surface area) infusion. Plasma glucose will be raised and maintained at ~180 mg·dL-1 by primed (0.2 g·kg-1)-variable dextrose infusion (20%w/v) enriched with [1-13C]glucose (40%w/w). A second catheter will be placed into an antecubital vein of the other arm and blood samples for the measurement of glucose, insulin and c-peptide. Glucose concentrations will be analysed immediately every 5 minutes, employing a glucose analyser. Myocardial glycogen concentrations will be measured before the clamp (-60 - 0 min) and from 90 min to 180 min during the clamp employing 13C MRS. | Other | Insulin sensitive volunteers, Type 2 Diabetes Mellitus, prediabetic subjects |
Primary outcome
change in myocardial glycogen content
Time frame: at baseline and during the third hour of the hyperglycemic clamp/ in the morning and at 5 p.m. after a meal tolerance test
13C magnetic resonance spectroscopy for the assessment of myocardial glycogen content: Localized 13C NMR spectra will be obtained in a 7T Magnetom MR System (Siemens Healthcare, Erlangen Germany) with a dedicated butterfly-shaped 13C (15cm)/1H(21cm) transmitter/receiver coil (Stark Contrast, Erlangen, Germany) placed over or under the thorax. Recently introduced ISIS based or 1D CSI localization schemes will be applied. Absolute glycogen concentrations will be quantified by comparing the C1 glycogen peak (100.5 ppm) integral of tissue specific spectra with that of a glycogen standard taken under identical conditions. Corrections for loading of the coil and sensitive volume of the coil will be performed.
1 secondary outcome
change in myocardial lipid composition
Time frame: at baseline and during the third hour of the hyperglycemic clamp/ in the morning and at 5 p.m. after a meal tolerance test
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Krebs, Prof MD principal investigator
Medical University of Vienna, Department of Internal Medicine III, Division of Endocrinology and Metabolism
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 1H/ 13C and 31P Magnetic Resonance Spectroscopy, Meal Tolerance Test and Hyperglycemic-hyperinsulinemic clamp in people with Type 2 Diabetes Mellitus and Prediabetes (Insulin Resistance, Impaired Glucose Tolerance), run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter Wolf, MD (00436646499456, peter.wolf@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
change in myocardial glycogen content (time frame: at baseline and during the third hour of the hyperglycemic clamp/ in the morning and at 5 p.m. after a meal tolerance test). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2017.