Vol.:(0123456789) 1 3 Clinical and Experimental Medicine https://doi.org/10.1007/s10238-018-0495-4 ORIGINAL ARTICLE Reduced mitochondrial DNA content in lymphocytes is associated with insulin resistance and infammation in patients with impaired fasting glucose Mohamad Hafzi Abu Bakar 1  · Nany Hairunisa 2  · Hasniza Zaman Huri 2,3 Received: 27 April 2017 / Accepted: 9 March 2018 © Springer International Publishing AG, part of Springer Nature 2018 Abstract Altered mitochondrial DNA (mtDNA) is the most common denominator to numerous metabolic diseases. The present study sought to investigate the correlation between mtDNA content in lymphocytes and associated clinical risk factors for impaired fasting glucose (IFG). We included 23 healthy control and 42 IFG participants in this cross-sectional study. The measure- ments of mtDNA content in lymphocytes and pro-infammatory markers derived from both normal and diseased individuals were quantifed. Spearman partial correlation and multivariate statistical analyses were employed to evaluate the association between mtDNA content and other metabolic covariates in IFG. Reduced mtDNA content was observed in the IFG group with microvascular complications than those without complications. The IFG patients with lowest median of mtDNA content had considerably elevated hyperglycemia, insulin resistance and infammation. The adjusted partial correlation analysis showed that mtDNA content was positively correlated with HDL-cholesterol and IL-10 (P < 0.005 for all). Further, multiple linear regression analyses verifed that reduced mtDNA content in lymphocytes was independently associated with HOMA-IR (β = 0.027, P = 0.003), HbA1c (β = 0.652, P = 0.002), HDL-cholesterol (β = − 1.056, P = 0.021), IL-6 (β = 0.423, P = 0.002), IL-10 (β = − 1.234, P = 0.043) and TNF-α (β = 0.542, P < 0.001) after adjustment for confounding factors. Our data show that reduced mtDNA content in lymphocytes was associated with insulin resistance and infammation in individuals with IFG. Keywords mtDNA · Lymphocytes · Impaired fasting glucose · Insulin resistance · Infammation Introduction Diabetes is a global healthcare problem afecting human population worldwide. According to International Diabetes Federation (IDF), 415 million people have been diagnosed with diabetes in 2015 and the number is projected to reach 642 million in 2040. Of this global burden, it is estimated that about 90% of diabetes patients are sufered from type 2 diabetes (T2D) with a greater degree of insulin resistance. Current classifcations of individuals at risk of developing T2D are mainly based on the established factors such as blood fasting glucose, HbA1c, body mass index (BMI) and age [1]. Notably, recent estimation showed that up to 70% of individuals with prediabetes state progressively develop dia- betes in years [2]. On account of health risks, the transitions from the early symptoms of insulin resistance including impaired fasting glucose (IFG) and impaired glucose toler- ance (IGT) that precedes T2D may take several years. How- ever, the identifcation and diagnosis of prediabetes indi- viduals is not commonly employed in the clinical practice. The proposed mechanisms underpinning the develop- ment of these metabolic dysregulations are embedded in the complex networks of genetics and environmental fac- tors. A number of considerable reports have revealed that impaired mitochondrial homeostasis contributes to a broad range of T2D progressions [3]. Several defects in mitochon- drial integrity have been found in ofspring of type 2 diabetic patients, proving the degree of heritability [4]. Depletion of mitochondrial (mtDNA) content in pancreatic islet [5] and * Mohamad Hafzi Abu Bakar mhafzi88@usm.my 1 Bioprocess Technology Division, School of Industrial Technology, Universiti Sains Malaysia, 11800 Gelugor, Penang, Malaysia 2 Clinical Investigation Centre, University Malaya Medical Centre, 59100 Lembah Pantai, Kuala Lumpur, Malaysia 3 Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia