Lipid Metabolism Clinical Trial
Official title:
Patterns and Plasticity of Orthotopic and Ectopic Fat Deposition and Associations With Insulin Sensitivity: A Magnetic-resonance-imaging and -Spectroscopy Study in Lean and Obese Individuals: Methodological Part
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
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.
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Observational Model: Cohort, Time Perspective: Prospective
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