Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Jacob, S; Machann, J; Rett, K; Brechtel, K; Volk, A; Renn, W; Maerker, E; Matthaei, S; Schick, F; Claussen, C D; Häring, H U

doi:10.2337/diabetes.48.5.1113

Cited by 643Diabetes, Cardiovascular Risks, and LipoproteinsMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

Jacob, S, Machann, J, Rett, K, Brechtel, K, Volk, A, Renn, W, Maerker, E, Matthaei, S +3 more·1999·Diabetes

DOI 10.2337/diabetes.48.5.1113

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Abstract

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

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Intramyocellular lipid excess strongly correlates with the severity of insulin resistance, even after correction for the degree of obesity, and has been observed in muscles of multiple fiber types.
“Although it remains unclear whether any of these defects play a causal role in insulin resistance, intramyocellular lipid excess strongly correlates with the severity of insulin resistance, even after correction for the degree of obesity (94), and has been observed in muscles of multiple fiber types (95).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [94]

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Authors: Jacob, S., Machann, J., Rett, K., Brechtel, K., Volk, A., Renn, W., Maerker, E., Matthaei, S., Schick, F., Claussen, C. D., & Häring, H. U.
Affiliations: University of Tübingen (DE)
ORCID: Machann, J
Rett, K
Brechtel, K
Volk, A
Schick, F
Claussen, C D
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1999-05-01
Volume: 48
Issue: 5
Pages: 1113-1119
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.48.5.1113
OpenAlex: W2133711136
Cited by: 643
References: 18
Citations by year: 2026: 4 · 2025: 10 · 2024: 4 · 2023: 11 · 2022: 7 · 2021: 12 · 2020: 19 · 2019: 15 · 2018: 21 · 2017: 22 · 2016: 25 · 2015: 27 · 2014: 20 · 2013: 28 · 2012: 27
FWCI: 15.04
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Topics: 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
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords: intramyocellular lipid, insulin resistance, type 2 diabetes, skeletal muscle, lean individuals, soleus muscle, tibialis anterior, extramyocellular lipids, muscle glucose uptake, hyperinsulinemic-euglycemic clamp, 1H NMR, first-degree relatives
MeSH terms: Adult, Blood Glucose, Body Composition, Diabetes Mellitus, Type 2, Female, Humans, Insulin, Insulin Resistance, Lipids, Male, Metabolic Clearance Rate, Magnetic Resonance Spectroscopy, Glucose Clamp Technique, Body Mass Index, Muscle, Skeletal

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Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects.

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