title: Insulin Resistance Is Associated With Reduced Mitochondrial Oxidative Capacity Measured by 31P-Magnetic Resonance Spectroscopy in Participants Without Diabetes From the Baltimore Longitudinal Study of Aging.
abstract: Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 participants without diabetes from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, IR, and duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as the postexercise phosphocreatine recovery time constant (τPCr) by31P-magnetic resonance spectroscopy, with higher τPCrvalues reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-h glucose measurements. IR and sensitivity were calculated using HOMA-IR and Matsuda indices. The duration and severity of hyperglycemia exposure were estimated as the number of years from prediabetes onset and the average oral glucose tolerance test (OGTT) 2-h glucose measurement over previous BLSA visits. Covariates included age, sex, body composition, physical activity, and other confounders. Higher likelihood of prediabetes, higher HOMA-IR, and lower Matsuda index were associated with longer τPCr.Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPCIn conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD.|Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Fabbri
authors.affiliation: Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Chee W
authors.initials: CW
authors.lastname: Chia
authors.affiliation: Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Spencer
authors.affiliation: Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Fishbein
authors.affiliation: Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: David A
authors.initials: DA
authors.lastname: Reiter
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Donnie
authors.initials: D
authors.lastname: Cameron
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Ariel C
authors.initials: AC
authors.lastname: Zane
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Zenobia A
authors.initials: ZA
authors.lastname: Moore
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Marta
authors.initials: M
authors.lastname: Gonzalez-Freire
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zoli
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Studenski
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Kalyani
authors.affiliation: Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD.
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.affiliation: Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD ferruccilu@mail.nih.gov.
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D011236:Prediabetic State / Q000473:pathology / Q000503:physiopathology