Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications.
OBJECTIVE
We examined whether age of type 2 diabetes onset is related to mitochondrial DNA content in peripheral blood monocytes (PBMCs).


METHODS
PBMCs were isolated from 65 patients with type 2 diabetes. To minimise age as a confounder, only patients aged >or=50 years were studied. Sample mitochondrial DNA (mtDNA) content was determined by amplification of the mitochondrial gene CYT-B (also known as MT-CYB) and adjusted for single-copy nuclear control genes (36B4 [also known as RPLPO] and GAPDH).


RESULTS
Age of diabetes onset ranged from 25 to 69 years. There was a significant positive relationship between age of diabetes onset in quartiles and mtDNA content for the whole group (p = 0.02 for trend). When stratified by the presence of diabetes complications, a strong positive relationship was observed between age of diagnosis and mtDNA content for participants without diabetic complications (r = 0.7; p = 0.0002), but not for those with complications (r = -0.04; p = 0.8). Multivariate analysis confirmed age of onset and complication status as independent determinants. There was co-linearity between age of onset and disease duration, with similar relationships also seen between duration and mtDNA content.


CONCLUSIONS
An earlier age of type 2 diabetes onset is associated with a lower PBMC mtDNA content, but only in patients without diabetes complications. This may reflect a differing biology of PBMC mtDNA in those with early-onset diabetes and those who are prone to complications. PBMC mtDNA depletion may accelerate diabetes onset; however the independent effect of diabetes duration remains to be evaluated.
Wong
J
J
Diabetes Centre, Royal Prince Alfred Hospital, Level 6, West Wing, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia. jencia.wong@email.cs.nsw.gov.au
McLennan
S V
SV
Molyneaux
L
L
Min
D
D
Twigg
S M
SM
Yue
D K
DK
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D045303:Cytochromes b / Q000235:genetics; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000097:blood*; D048909:Diabetes Complications / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D004272:DNA, Mitochondrial; D045303:Cytochromes b