Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications

Diabetologia. 2009 Sep;52(9):1953-61. doi: 10.1007/s00125-009-1424-6. Epub 2009 Jul 21.

Abstract

Aims/hypothesis: 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/interpretation: 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.

MeSH terms

  • Adult
  • Age Factors
  • Age of Onset*
  • Aged
  • Cytochromes b / genetics
  • DNA Primers
  • DNA, Mitochondrial / blood*
  • Diabetes Complications / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Female
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Monocytes / cytology
  • Monocytes / physiology*
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • DNA, Mitochondrial
  • Cytochromes b