Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents.
Abstract
Insulin resistance is the best prediction factor for the clinical onset of type 2 diabetes. It was suggested that intramuscular triglyceride store may be a primary pathogenic factor for its development. To test this hypothesis, 14 young lean offspring of type 2 diabetic parents, a model of in vivo insulin resistance with increased risk to develop diabetes, and 14 healthy subjects matched for anthropomorphic parameters and life habits were studied with 1) euglycemic-hyperinsulinemic clamp to assess whole body insulin sensitivity, 2) localized 1H nuclear magnetic resonance (NMR) spectroscopy of the soleus (higher content of fiber type I, insulin sensitive) and tibialis anterior (higher content of fiber type IIb, less insulin sensitive) muscles to assess intramyocellular triglyceride content, 3) 13C NMR of the calf subcutaneous adipose tissue to assess composition in saturated/unsaturated carbons of triglyceride fatty acid chains, and 4) dual X-ray energy absorption to assess body composition. Offspring of diabetic parents, notwithstanding normal fat content and distribution, were characterized by insulin resistance and increased intramyocellular triglyceride content in the soleus (P < 0.01) but not in the tibialis anterior (P = 0.19), but showed a normal content of saturated/unsaturated carbons in the fatty acid chain of subcutaneous adipocytes. Stepwise regression analysis selected intramyocellular triglyceride soleus content and plasma free fatty acid levels as the main predictors of whole body insulin sensitivity. In conclusion, 1H and 13C NMR spectroscopy revealed intramyocellular abnormalities of lipid metabolism associated with whole body insulin resistance in subjects at high risk of developing diabetes, and might be useful tools for noninvasively monitoring these alterations in diabetes and prediabetic states.
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Previous studies by our group and others have demonstrated a strong relationship between triglyceride content in liver and muscle and insulin resistance in these tissues.
“Previous studies by our group (9, 17-20) and others (7, 21, 22) have demonstrated a strong relationship between triglyceride content in liver and muscle and insulin resistance in these tissues.”
From Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy (2002) · cites this paper as [21]
Intramyocellular lipid contributes only about 1% of total muscle fat content but has a key role in skeletal muscle insulin resistance compared with extramyocellular lipid.
“More recent studies [55, 56] using magnetic resonance spectroscopy have demonstrated that although IMCL fat content contributes only a small fraction (~1%) to the total muscle fat content, it plays a key role in the development of insulin resistance in skeletal muscle compared to EMCL.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [55]
In insulin-resistant individuals, insulin-stimulated glucose disposal correlates more strongly with intramyocellular fat content than with extramyocellular fat.
“(i) in insulin resistant individuals, insulin-stimulated glucose disposal correlates more strongly with intramyocellar fat content than with the extramtocellar fat [55, 56];”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [55]
Insulin resistance is strongly associated with increases in hepatic and/or intramyocellular lipid content.
“and that insulin resistance is strongly associated with increases in hepatic (HTG) and ∕ or intramyocellular lipid content”
From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [10]
Insulin resistance plays a major role in the pathogenesis of type 2 diabetes mellitus.
“Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM”
From Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men (2006) · cites this paper as [10]
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- Authors
- Perseghin, G., Scifo, P., De Cobelli, F., Pagliato, E., Battezzati, A., Arcelloni, C., Vanzulli, A., Testolin, G., Pozza, G., Del Maschio, A., & Luzi, L.
- Affiliations
- IRCCS Ospedale San Raffaele (IT)
- Division of Internal Medicine, Istituto Scientifico H San Raffaele, Milan, Italy. perseghin.gianluca@hsr.it
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 1999-08-01
- Volume
- 48
- Issue
- 8
- Pages
- 1600-1606
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2148562280
- Cited by
- 877
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 4 · 2023: 12 · 2022: 6 · 2021: 13 · 2020: 26 · 2019: 30 · 2018: 30 · 2017: 22 · 2016: 25 · 2015: 35 · 2014: 27 · 2013: 27 · 2012: 38
- FWCI
- 19.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- 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
- intramyocellular triglyceride, insulin resistance, type 2 diabetes risk, soleus muscle, tibialis anterior, muscle fiber type, subcutaneous adipose tissue, plasma free fatty acids, whole-body insulin sensitivity, prediabetes
- MeSH terms
- Adult, Carbon Isotopes, Diabetes Mellitus, Type 2, Female, Humans, Hyperinsulinism, Insulin Resistance, Male, Middle Aged, Magnetic Resonance Spectroscopy, Sex Characteristics, Triglycerides, Tritium, Glucose Clamp Technique, Multivariate Analysis, Muscle, Skeletal
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