Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects
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Aims/hypothesis Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls.Methods In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4 +/- 1 and 29.3 +/- 0.9 kg/m(2) respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic-euglycaemic clamp.Results The PCr half-time was 45% longer in diabetic patients compared with controls (27.3 +/- 3.5 vs 18.7 +/- 0.9 s, p < 0.05), whereas IMCL content was similar (1.37 +/- 0.30 vs 1.25 +/- 0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0 +/- 2.2 vs 18.9 +/- 2.3 mumol min(-1) kg(-1), p < 0.05 [all mean +/- SEM]). PCr half-time correlated positively with fasting plasma glucose (r (2) = 0.42, p < 0.01) and HbA(1c) (r (2) = 0.48, p < 0.05) in diabetic patients.Conclusions/interpretation The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.
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Using the 31P-MRS PCr recovery method, the authors previously showed approximately 40% lower mitochondrial function in type 2 diabetic patients compared with age- and BMI-matched control subjects.
“In contrast, using an alternative method to measure in vivo mitochondrial function with 31P-MRS, we recently showed an ∼40% lower mitochondrial function in type 2 diabetic patients compared with age- and BMI-matched control subjects (8).”
From Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients (2008) · cites this paper as [8]
In vivo mitochondrial function, determined as the rate of PCr recovery after exercise, is compromised in type 2 diabetic patients compared with age- and BMI-matched control subjects.
“We confirmed our previous finding (8) of compromised in vivo mitochondrial function, determined as the rate of PCr recovery after exercise in type 2 diabetic patients compared with age- and BMI-matched control subjects”
From Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients (2008) · cites this paper as [8]
Mitochondrial dysfunction has recently been implicated in the etiology of insulin resistance and type 2 diabetes, mainly based on studies of in vivo mitochondrial function.
“Mitochondrial dysfunction has recently been implicated in the etiology of insulin resistance and type 2 diabetes. This suggestion is mainly based on studies that determined in vivo mitochondrial function (6–8).”
From Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients (2008) · cites this paper as [8]
No differences in IMCL were found between BMI-matched overweight diabetic patients and control subjects in earlier findings.
“This is in line with earlier findings, in which no differences in IMCL were found between BMI-matched overweight diabetic patients and control subjects (8).”
From Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients (2008) · cites this paper as [8]
In-vivo mitochondrial function is lower in muscle of patients with type 2 diabetes compared with age-matched and BMI-matched controls.
“In-vivo mitochondrial function (measured with phosphorus-31 magnetic resonance spectroscopy) is also lower in muscle of patients with type 2 diabetes compared with age-matched and BMI-matched controls.57”
From Age-related and disease-related muscle loss: The effect of diabetes, obesity, and other diseases (2014) · cites this paper as [57]
Subjects with type 2 diabetes have decreased exercise tolerance and impaired recovery of intracellular phosphocreatinine concentration after exercise.
“Subjects with T2DM also have decreased exercise tolerance and impaired recovery of intracellular phosphocreatinine concentration following exercise [107, 108]”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [108]
Muscle mitochondria oxidative capacity is impaired in patients with overt T2DM.
“Furthermore, assessment of mitochondria function in vivo using non-invasive measurement of the phosphocreatine resynthesis rate after exercise corroborated these remarkable mitochondrial defects at the protein as well as at the transcriptional levels providing further evidence that muscle mitochondria oxidative capacity is impaired in patients with overt T2DM (Schrauwen-Hinderling et al., 2007).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Schrauwen-Hinderling et al., 2007
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“The data in the present study is gathered from clamp studies previously performed in our research center [13,14,15,16,17].”
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- Authors
- Schrauwen-Hinderling, V. B., Kooi, M. E., Hesselink, M. K. C., Jeneson, J. A. L., Backes, W. H., van Echteld, C. J. A., van Engelshoven, J. M. A., Mensink, M., & Schrauwen, P.
- Affiliations
- Maastricht University Medical Centre (NL)
- Maastricht University (NL)
- Eindhoven University of Technology (NL)
- Venue
- Diabetologia
- Published
- 2006-11-09
- Volume
- 50
- Issue
- 1
- Pages
- 113-120
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2152958952
- Cited by
- 304
- References
- 33
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 10 · 2023: 21 · 2022: 16 · 2021: 15 · 2020: 8 · 2019: 12 · 2018: 13 · 2017: 15 · 2016: 16 · 2015: 13 · 2014: 15 · 2013: 28 · 2012: 26
- FWCI
- 10.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- TU/e Research Portal (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- TU/e Research Portal (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Koninklijke Nederlandse Akademie van Wetenschappen
- Eidgenössische Technische Hochschule Zürich
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- type 2 diabetes, mitochondrial dysfunction, intramyocellular lipid, insulin resistance, skeletal muscle, obesity, insulin sensitivity, fasting blood glucose, HbA1c
- MeSH terms
- Aged, Blood Glucose, Diabetes Mellitus, Type 2, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Mitochondria, Muscle, Magnetic Resonance Spectroscopy, Obesity, Phosphocreatine, Phosphorus Isotopes, Body Mass Index, Case-Control Studies, Muscle, Skeletal, Lipid Metabolism
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