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Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1 H NMR spectroscopy study
Open accessAbstract
Recent muscle biopsy studies have shown a relation between intramuscular lipid content and insulin resistance. The aim of this study was to test this relation in humans by using a novel proton nuclear magnetic resonance (1H NMR) spectroscopy technique, which enables non-invasive and rapid (approximately 45 min) determination of intramyocellular lipid (IMCL) content. Normal weight non-diabetic adults (n = 23, age 29+/-2 years. BMI = 24.1+/-0.5 kg/m2) were studied using cross-sectional analysis. Insulin sensitivity was assessed by a 2-h hyperinsulinaemic (approximately 450 pmol/l)-euglycaemic (approximately 5 mmol/l) clamp test. Intramyocellular lipid concentrations were determined by using localized 1H NMR spectroscopy of soleus muscle. Simple linear regression analysis showed an inverse correlation (r = -0.579, p = 0.0037) [corrected] between intramyocellular lipid content and M-value (100-120 min of clamp) as well as between fasting plasma non-esterified fatty acid concentration and M-value (r = -0.54, p = 0.0267). Intramyocellular lipid content was not related to BMI, age and fasting plasma concentrations of triglycerides, non-esterified fatty acids, glucose or insulin. These results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans.
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“Even small amounts of weight loss induced by a negative energy balance affects many variables pertaining to body-fat composition and lipid metabolism -variables that probably contribute to the metabolic abnormalities associated with obesity.[22][23][24][25]”
From Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease (2004) · cites this paper as [23]
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In the citing paper
“Even small amounts of weight loss induced by a negative energy balance affects many variables pertaining to body-fat composition and lipid metabolism -variables that probably contribute to the metabolic abnormalities associated with obesity.[22][23][24][25]”
From Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease (2004) · cites this paper as [23]
Experimental — accuracy not yet measuredIn the citing paper
“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 [56]
In the citing paper
“Muscle insulin resistance strongly correlates with IMCL, independent of total body fat mass and diabetes status [56], while the correlation between EMCL and insulin ressitance is not significant.”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [56]
In the citing paper
“(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 [56]
In the citing paper
“Using 1H magnetic resonance spectroscopy (MRS) to noninvasively assess IMCL content revealed that IMCL was an excellent predictor for muscle insulin resistance in sedentary individuals (Krssak et al., 1999)”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Krssak et al., 1999
In the citing paper
“and disrupt metabolism (insulin resistance, diabetes)”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Krssak et al., 1999
In the citing paper
“Myosteatosis is also linked to insulin resistance.”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Krssak et al., 1999
In the citing paper
“IMCL is a strong predictor of insulin resistance in sedentary individuals (Krssak et al., 1999) and muscle insulin resistance can be induced within 5-hours of a lipid infusion in healthy individuals (Dresner et al., 1999), and a fatty acid derived-metabolite (e.g., DAG) has been suggested to be responsible for mediating reduced insulin signaling and insulin action.”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Krssak et al., 1999
In the citing paper
“These lipids interfere with insulin signaling and represent one of the key aspects that could contribute to insulin resistance in situations of high-fat feeding or lipid infusion (Pan et al, 1997; Krssak et al, 1999; Goodpaster et al, 2000).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Krssak et al, 1999
In the citing paper
“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 [9]
In the citing paper
“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 [9]
In the citing paper
“In support of this notion, intramyocellular lipids represent a better predictor of muscle insulin resistance compared to adiposity in young, sedentary, lean subjects (Krssak et al., 1999).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Krssak et al., 1999
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Metadata
- Authors
- Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- University of Vienna (AT)
- Venue
- Diabetologia
- Published
- 1999-01-11
- Volume
- 42
- Issue
- 1
- Pages
- 113-116
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2092441434
- Semantic Scholar
- a27e69dd8a054c7932e6da0a27f4f67ad769f76a
- Cited by
- 1,264
- References
- 13
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 19 · 2023: 19 · 2022: 21 · 2021: 38 · 2020: 40 · 2019: 39 · 2018: 49 · 2017: 51 · 2016: 51 · 2015: 64 · 2014: 51 · 2013: 52 · 2012: 59
- FWCI
- 22.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Yale University
- Universität Wien
- Oesterreichische Nationalbank
- National Institutes of Health (P30 DK)
- U.S. Public Health Service
- National Institute on Aging (5 P60 AG 10469, P60AG010469)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, R01DK049230, R01 DK-49230, P30DK045735)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Keywords
- intramyocellular lipid, insulin sensitivity, insulin resistance, hyperinsulinemic-euglycemic clamp, free fatty acids, soleus muscle, whole-body insulin sensitivity
- MeSH terms
- Adult, Blood Glucose, Fasting, Fatty Acids, Nonesterified, Female, Humans, Hydrogen, Infusions, Intravenous, Insulin, Male, Magnetic Resonance Spectroscopy, Regression Analysis, Triglycerides, Glucose Clamp Technique, Muscle, Skeletal, Lipid Metabolism
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