Analysis of association among clinical features and shorter leukocyte telomere length in mitochondrial diabetes with m.3243A>G mitochondrial DNA mutation

BMC Med Genet. 2015 Oct 8;16:92. doi: 10.1186/s12881-015-0238-2.


Background: Mitochondrial diabetes is a kind of rare diabetes caused by monogenic mutation in mitochondria. The study aimed to summarize the clinical phenotype profiles in mitochondrial diabetes with m.3243 A>G mitochondrial DNA mutation and to investigate the mechanism in this kind of diabetes by analyzing the relationship among clinical phenotypes and peripheral leukocyte DNA telomere length.

Methods: Fifteen patients with maternally inherited diabetes in five families were confirmed as carrying the m.3243 A>G mitochondrial DNA mutation. One hundred patients with type 2 diabetes and one hundred healthy control subjects were recruited to participate in the study. Sanger sequencing was used to detect the m.3243 A>G mitochondrial DNA mutation. The peak height G/A ratio in the sequence diagram was calculated. Real-time polymerase chain reaction (PCR) was used to measure telomere length.

Results: The patients with mitochondrial diabetes all had definite maternally inherited history, normal BMI (19.5 ± 2.36 kg/m(2)), early onset of diabetes (35.0 ± 14.6 years) and deafness. The peak height G/A ratio correlated significantly and negatively with the age at onset of diabetes (≦ 25 years, 61.6 ± 20.17%; 25-45 years, 16.59 ± 8.64%; >45 years, 6.37 ± 0.59%; p = 0.000). Telomere length was significantly shorter among patients with mitochondrial diabetes and type 2 diabetes than in the control group (1.28 ± 0.54 vs. 1.14 ± 0.43 vs. 1.63 ± 0.61; p = 0.000). However, there was no significant difference between patients with mitochondrial diabetes and those with type 2 diabetes. There was no correlation between telomere length and the peak height G/A ratio.

Conclusion: Deafness with definite maternal inheritance and normal BMI, associated with elevated blood lactic acid and encephalomyopathy, for the most part, suggest the diagnosis of mitochondrial diabetes . The peak height G/A ratio could reflect the spectrum of age at onset of the disease. Telomere length was shorter in patients with mitochondrial diabetes and those with type 2 diabetes, which suggests that the shorter telomere length is likely involved in the pathogenesis of diabetes but is not specific for this kind of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / metabolism
  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • DNA, Mitochondrial / genetics*
  • Deafness / genetics*
  • Deafness / pathology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Genetic Association Studies / methods*
  • Guanine / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Telomere / metabolism*
  • Young Adult


  • DNA, Mitochondrial
  • Guanine
  • Adenine