Abstract
Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50–59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.
Highlights
The number of adults with type 2 diabetes mellitus (T2DM) is increasing worldwide and if the trend continues the number will rise to 693 million by 20451
Because of its close proximity with higher levels of reactive oxidative species (ROS), mitochondrial DNA is prone to oxidative stress; which may lead to mitochondrial dysfunction, characterized by lowered oxidative capacity and reduction in energy p roduction[7]
We aimed to investigate the association of mitochondrial DNA (mtDNA)-CN with both prevalent and incident T2DM events in a large population-based prospective study conducted on women
Summary
The number of adults with type 2 diabetes mellitus (T2DM) is increasing worldwide and if the trend continues the number will rise to 693 million by 20451. Mitochondrial dysfunction is associated with aging process and can affect cellular functions and thereby results in a variety of human diseases[8] such as cancer[9,10], neurodegenerative diseases[11,12], cardiovascular diseases[10,13], diabetes and metabolic s yndrome[14,15]. One of the reasons for conflicting results is suggested to be the methodology, as various analytical factors can affect the quantification of mtDNA copy number[17]. We aimed to investigate the association of mtDNA-CN with both prevalent and incident T2DM events in a large population-based prospective study conducted on women
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