Type 2 Diabetes Mellitus

Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)

Familiar Hypocalcuric Hypercalcemia

Healthy Volunteers

Type 1 Diabetes Mellitus

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.

1H/ 13C and 31P Magnetic Resonance Spectroscopy

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).

Meal Tolerance Test

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.

Hyperglycemic-hyperinsulinemic clamp

Medical University Of Vienna, Department of Internal Medicine III

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

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

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.

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.

Hepatic lipid content will be assessed using localized single voxel 1H MRS as published by our study-group. PRESS sequence (VOI= 3×3×3 cm3; TE= 30, 50, 70, 120 ms; NA= 4 for each TE) data acquisition will be performed during repetitive single breath holds. For intramyocellular lipid content STEAM sequence (VOI= 12x12x12 mm3; TE= 20 ms; TR= 4 sec, NA= 16) data acquisition will be performed in two volumes of interest positioned in soleus and tibialis anterior muscle.
Lipid content will be calculated from ration of summed area of methylene and methyl resonance to that of water following the individual spin-spin relaxation correction as per cent of total tissue MRS signal (water + methylene + methyl).

ATP synthesis will be assessed using 31P MRS. Patients with type 1 and type 2 diabetes, as well as pre diabetic insulin resistant subjects and insulin sensitive controls will be compared

hypercalcemia/carbohydrate

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

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