Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator.
Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention.
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA.
Louise D
LD
Zheng
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA.
Leah E
LE
Linarelli
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA.
Joseph
J
Brooke
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA.
Cayleen
C
Smith
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA.
Sarah S
SS
Wall
Department of Family and Community Medicine, Carilion Clinic, Roanoke, VA 24016, USA.
Mark H
MH
Greenawald
Department of Psychiatry, Carilion Clinic, Roanoke, VA 24014, USA.
Richard W
RW
Seidel
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA; Department of Family and Community Medicine, Carilion Clinic, Roanoke, VA 24016, USA; Department of Health Promotion, Social & Behavioral Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Paul A
PA
Estabrooks
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA; Department of Health Promotion, Social & Behavioral Health, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Fabio A
FA
Almeida
Department of Human Nutrition, Foods, and Exercise, Fralin Translational Obesity Research Center, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA 24061, USA.
Zhiyong
Z
Cheng
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D019175:DNA Methylation / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D003710:Demography; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics*; D044127:Epigenesis, Genetic; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D011236:Prediabetic State / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors
D001786:Blood Glucose; D004272:DNA, Mitochondrial; D006442:Glycated Hemoglobin