Ivan P.W. Teng1, Jamie X.M. Ho1, Trina Kok1, Philip Lee2, Melvin K.S. Leow3, Hong Chang Tan4, Chin Meng Khoo5, George K Radda6, and Mary C Stephenson1,5
1Clinical Imaging Research Centre, A*STAR-NUS, Singapore, Singapore, 2SBIC, A*STAR, Singapore, Singapore, 3SICS, A*STAR, Singapore, Singapore, 4Department of Endocrinology, SGH, Singapore, Singapore, 5Department of Medicine, NUS, Singapore, Singapore, 6Biomedical Research Council, A*STAR, Singapore, Singapore
Synopsis
Previous studies have
indicated differences in insulin sensitivity between lean Indian and Chinese
men. In this study we used 31P MRS and a dorsiflexion task to assess
muscle mitochondrial function, thought to be associated with insulin
sensitivity, via PCr recovery rates. No inter-ethnic group differences
were observed in measured blood parameters (HbA1c, fasting blood glucose level
and M-value) between groups. However, positive correlations were observed
between τPCr and both HbA1c and fasting blood glucose levels suggesting poorer mitochondrial function. No correlation was observed with M-value. Larger
sampling sizes are necessary for these correlations and group differences
to reach statistically-significant conclusions.Background
Lean
Chinese males are more insulin sensitive than lean Asian-Indian males, matched
for age and BMI [1,2]. The mechanisms underlying these ethnic differences in
insulin sensitivity are not clear. Mitochondrial
function may play a key role in skeletal muscle insulin sensitivity [3,4]. In
this study we used
31P MRS to examine skeletal muscle mitochondrial function at
rest and exercise state between adult Chinese and Asian-Indian males.
Methods
10
Chinese (age 28±6 years, BMI 23 ±1 kgm-2) and 7 Asian-Indian
males (age = 26±3 years, BMI = 23 ±3 kgm-2) were subjected to
MRS at their right calf muscle using a Siemens Prisma 3T system using a double
tuned flexible 31P-1H coil . A 18ch body coil was used for
acquisition of high resolution 1H images. All subjects had normal
glucose tolerance test and all underwent hyperinsulinemic euglycemic clamp for
assessment of insulin sensitivity.
T1-weighted TFE images: High resolution MR images
were acquired with the following parameters for assessment of muscle cross-sectional
area and subsequent calculation of contractile power. Muscle cross-sectional
area was analysed by region drawing in ImageJ.
31P MRS: 31P MR spectra were acquired using a
pulse-acquire sequence and the following parameters: BW = 3000, Number of data-points
= 2048. For assessment of PCr recovery
rates, individual spectra were acquired with TR=2000ms during an exercise
paradigm. Spectra were averaged in groups of 4 (8s) to improve SNR prior to
peak fitting. Data were analysed using jMRUI. 2048 data-points were truncated
and 12Hz Lorentzian line-broadening was added before phase correction. Peaks
were fitted using the AMARES algorithm in jMRUI.
Exercise: Prior to scanning, maximum voluntary
contraction (MVC) was first calculated. Ergometer pressure was set to maximum
and was decreased until the subject could perform one full compression of the
pedal. This was repeated twice more and the average value was taken. Following
positioning in the scanner and acquisition of resting 31P data, the 31P
exercise data was acquired continuously while subjects performed the exercise
protocol which sequentially involved 5 minutes resting, 3 minutes of exercise and then 8 minutes of rest. Exercise was performed at 44% of calculated MVC.
NIRS: A near infra-red spectroscopy probe (OxiplexTS) was positioned on the muscle to allow measurement of muscle oxy-haemoglobin concentration [HbO2], deoxy-haemoglobin concentration [Hb] and oxygen saturation [OS]. Mean values during exercise (taken from 1.5-2.5 minutes) and the recovery rate (from 1 minute after cessation of exercise) were calculated.
Results
Data from
four subjects were excluded from the analysis due to poor spectral quality from external noise entering the scanner. A
typical 31P spectrum is shown in Figure 1.
Group differences: Fasting blood glucose
levels and insulin sensitivity (M-value) were similar between Chinese and
Asian-Indians. No ethnic differences were seen for any of the parameters measured (τPCr,
THC, HbO2, Hb, OS).
Correlations:
τPCr versus HbA1c and τPCr versus fasting blood
glucose levels showed a trend for longer τPCr with increasing
HbA1c values and fasting blood glucose levels; however, these did not reach
significance. No correlation was seen between τPCr and M-value.
Discussion
Although
correlation between τPCr and both HbA1c and fasting
blood glucose levels showed a trend for longer τPCr with increasing HbA1c
values and fasting blood glucose levels, indicating poorer mitochondrial
function with poor blood glucose control, this did not reach significance. No correlation was observed with M-value,
another marker of blood glucose control.
However, the low sampling sizes in this study and non-significant difference
between all group measures mean we are unable to assess inter-ethnic
differences in this study.
Conclusions
In
lean Asians, mitochondrial function, as measured by τPCr, is not significantly
associated with fasting blood glucose levels or insulin sensitivity. There is
no ethnic difference in mitochondrial function.
Acknowledgements
We would
like to thank G.J. Kemp for discussions on experimental methods. This study is funded by the National University Health System (NUHS) Center Grant Seed Funding.References
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