Reduced tricarboxylic acid cycle flux in type 2 diabetes mellitus?
OBJECTIVE
Mitochondrial dysfunction has been postulated to underlie muscular fat accumulation, leading to muscular insulin sensitivity and ultimately type 2 diabetes mellitus. Here we re-interpret previously published data on [(13)C]acetate recovery in breath gas obtained during exercise in type 2 diabetic patients and control individuals.


METHODS
When infusing [(13)C]palmitate to estimate fat oxidation, part of the label is lost in exchange reactions of the tricarboxylic acid (TCA) cycle. To correct for this loss of label, an acetate recovery factor (ARF) has previously been used, assuming that 100% of the exogenously provided acetate will enter the TCA cycle. The recovery of acetate in breath gas depends on the TCA cycle activity, hence providing an indirect measure of the latter and a marker of mitochondrial function.


RESULTS
Re-evaluation of the available literature reveals that the ARF during exercise is highest in lean, healthy individuals, followed by obese individuals and type 2 diabetic patients.


CONCLUSIONS
Revisiting previously published findings on the ARF during exercise in type 2 diabetic patients reveals a reduction in muscular TCA cycle flux, reflecting mitochondrial dysfunction, in these patients. How mitochondrial dysfunction is related to type 2 diabetes mellitus-cause or consequence-requires further study.
Schrauwen
P
P
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Human Biology, Maastricht University, PO Box 616, 6200 MD, Maastricht, the Netherlands. p.schrauwen@hb.unimaas.nl
Hesselink
M K C
MK
D000328:Adult; D002952:Citric Acid Cycle / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D019308:Palmitic Acid / Q000378:metabolism; D015995:Prevalence; D012016:Reference Values
D019308:Palmitic Acid