Physiologic Plasticity of Intramyocardial Lipid Storage
Condition: Lipid Metabolism
Study type: Observational

Summary: 
      The main goal of the present study was to provide a technical basis for future studies
      assessing the role of cardiac lipids. More specifically, non-invasive MR-Spectroscopy (MRS)
      techniques will be used in this study to:

        1. assess the methodological reproducibility of MRS-measurements of cardiac lipids in
           humans

        2. investigate physiological variations of cardiac lipids by measuring day-to-day changes
           under identical conditions

        3. determining diurnal variations of cardiac lipids in humans
    

Detailed description: 
      Background

      Obesity is a well known risk factor for the development of glucose intolerance, type 2
      diabetes mellitus and, consequently, diabetic complications like cardiovascular disease.
      Importantly, obesity is not only associated with lipid accumulation in adipose tissue
      (orthotopic fat deposition), but also in non-adipose tissues (ectopic fat deposition).
      Clinical studies have repetitively shown that muscular and hepatic lipid accumulation as well
      as elevated visceral adipose tissue is associated with the development of central and
      peripheral insulin resistance. In addition, recent data from animal studies show increasing
      evidence that two other organs, the heart and the pancreas, may also be involved in the
      pathophysiological processes of reduced insulin sensitivity. While reduced insulin secretion
      in the course of type 2 diabetes has been well documented, the importance of pancreatic fat
      deposition as an early step in this process has only recently been suggested based on animal
      models. Conversely, ischemic heart disease is one of the most dangerous complications of
      diabetes mellitus, its prevention thereby being a cornerstone of current diabetes management.
      Recent data suggest that changes in the lipid metabolism of the heart and associated epi- and
      myocardial lipid deposition may be earliest signs of diabetic cardiopathy.

      Magnetic-Resonance-Imaging (MRI) and -Spectroscopy (MRS) are among the most versatile methods
      for non-invasive studies of human tissue and/or metabolism in vivo and in situ. The excellent
      soft tissue contrast of MRI has already led to the implementation of this method for the
      assessment of whole body lipid accumulation, whereas MRS has successfully been applied to
      study lipid metabolism of skeletal muscle and liver. The extended application of this method
      towards heart and pancreas will allow a comprehensive investigation of orthotopic and ectopic
      fat deposition in humans and its association with the development of insulin resistance and
      diabetes mellitus.

      The methodological part of the study will focus on the physiologic plasticity of cardiac
      lipids in order to assess:

      i) methodological reproducibility ii) intra-individual physiological reproducibility by
      measuring day-to-day variations as well as variations during the day.

      Objective

      i) Adapting and optimizing the single-voxel MRS sequence that is currently used for muscle
      and liver, such that respiratory and cardiac double-triggering enables spectroscopy of the
      cardiac muscle.

      ii) Validate the methodology under different standardized physiologic conditions.

      Methods

      Cardiac lipids are determined during five independent MR-examinations distributed over two
      days separated by one or two weeks. Both days included a measurement in the morning after an
      overnight fast (>8h) and one in the afternoon (8h after breakfast, 3.5h after lunch). To
      determine methodological reproducibility, the afternoon measurement was repeated on one of
      the two days (1h break). Preparation of the volunteers included perpetuation of their normal
      diet, but restricted physical activity for two preceding days. Cardiac lipids were determined
      by single-voxel MR-Spectroscopy.
    

Intervention name(s): normal dietary behavior; Magnetic resonance spectroscopy
Intervention type(s): Other; Other
Intervention description(s): normal dietary behavior during examination days; Non-invasive diagnostic procedure
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        males between the age of 18 and 30 years with either a BMI of 18-24
      
Keywords: physiology, normal function