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

Abstract

BackgroundMitochondrial diabetes is a kind of rare diabetes caused by monogenic mutation in mitochondia. The study aimed to summarize the clinical phenotype profiles in mitochondrial diabetes withm.3243A>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.MethodsFifteen patients with maternally inherited diabetes in five families were confirmed as carrying the m.3243A>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.3243A>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.ResultsThe patients with mitochondrial diabetes all had definite maternally inherited history, normal BMI (19.5 ± 2.36 kg/m2), 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.ConclusionDeafness 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.

Longer Telomere Length and its Association with Lower Levels of C-Peptide

“…A case–control study found TL to be associated with C-peptide ( 10 ), similar results were observed in a cross-sectional study ( 13 ). However, other studies did not find a correlation between TL and C-peptide ( 11 , 12 ). C-peptide is a short polypeptide with 31-amino-acid and relates insulin’s A-chain to its B-chain in the proinsulin molecule.…”

“…However, its association with C-peptide has seldom been examined. A case–control study with 15 participants did not find a significant correlation between TL and C-peptide ( 11 ). Another study in 52 new infants of mothers with gestational diabetes and pre-gestational diabetes assessed both TL and C-peptide in this sample, but did not extensively examined their association ( 12 ).…”

Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery

“…This nutrient-induced mitochondrial dysfunction can lead to impaired respiration, lipotoxicity, oxidative species accumulation and inflammation, further exacerbating insulin resistance and type-2 diabetes [ 8 – 13 ]. Indeed, the importance of adequate mitochondrial function for metabolic health is further highlighted by the observation that mitochondrial DNA mutations often result in diabetic phenotypes [ 14 – 16 ].…”

Leukocyte telomere length and mortality risk in patients with type 2 diabetes

“…LTL determination in patients with diabetes mellitus (DM) has highlighted a significant association with the presence and number of diabetes complications [19–21]. Moreover, LTL attrition has also been described in patients with mitochondrial diabetes, suggesting its relevance in the disease [22]. Short leukocyte telomere length predicts risk of diabetes in American Indians [23].…”