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
Open accessAbstract
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) by 31P-magnetic resonance spectroscopy, with higher τPCr values 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 τPC. In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.
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Impaired mitochondrial function, involving excessive ROS and reduced ATP production, is associated with visceral obesity, insulin resistance, higher circulating levels of proinflammatory markers, and loss of mobility.
“Impaired mitochondrial function, which involves excessive ROS and reduced ATP production, has been associated with visceral obesity, insulin resistance, higher circulating levels of proinflammatory markers, and loss of mobility, phenotypes that are characteristic of aging (59–64).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [59]
In the Baltimore Longitudinal Study of Aging, greater impairment of mitochondrial capacity is associated with greater insulin resistance and a higher likelihood of prediabetes.
“Data published in 2017 regarding 31P-magnetic resonance spectroscopy from individuals without diabetes mellitus in the Baltimore Longitudinal Study of Aging (BLSA) showed that a higher impairment of mitochondrial capacity is associated with greater insulin resistance and a higher likelihood of prediabetes than in participants classified as being ‘normal’ according to the American Diabetes Ass”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [138]
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- Authors
- Fabbri, E., Chia, C. W., Spencer, R. G., Fishbein, K. W., Reiter, D. A., Cameron, D., Zane, A. C., Moore, Z. A., Gonzalez-Freire, M., Zoli, M., Studenski, S. A., Kalyani, R. R., Egan, J. M., & Ferrucci, L.
- Affiliations
- National Institutes of Health (US)
- Longitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD
- University of Bologna (IT)
- Johns Hopkins University (US)
- Corresponding author
- Ferrucci, Luigi
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2016-10-13
- Volume
- 66
- Issue
- 1
- Pages
- 170-176
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC5204309
- OpenAlex
- W2531648560
- Cited by
- 76
- References
- 26
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 14 · 2017: 2 · 2016: 1
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- National Institute on Aging (03-AG-0325)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- insulin resistance, mitochondrial oxidative capacity, prediabetes, 31P NMR, HOMA-IR, Matsuda index, oral glucose tolerance test, aging, non-diabetic adults
- MeSH terms
- Aged, Aged, 80 and over, Aging, Diabetes Mellitus, Female, Glucose Tolerance Test, Humans, Insulin Resistance, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Mitochondria, Prediabetic State
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