» Articles » PMID: 31240819

Lipotoxicity Plays a Key Role in the Development of Both Insulin Resistance and Muscle Atrophy in Patients with Type 2 Diabetes

Overview
Journal Obes Rev
Specialty Endocrinology
Date 2019 Jun 27
PMID 31240819
Citations 80
Authors
Affiliations
Soon will be listed here.
Abstract

Insulin resistance and muscle mass loss often coincide in individuals with type 2 diabetes. Most patients with type 2 diabetes are overweight, and it is well established that obesity and derangements in lipid metabolism play an important role in the development of insulin resistance in these individuals. Specifically, increased adipose tissue mass and dysfunctional adipose tissue lead to systemic lipid overflow and to low-grade inflammation via altered secretion of adipokines and cytokines. Furthermore, an increased flux of fatty acids from the adipose tissue may contribute to increased fat storage in the liver and in skeletal muscle, resulting in an altered secretion of hepatokines, mitochondrial dysfunction, and impaired insulin signalling in skeletal muscle. Recent studies suggest that obesity and lipid derangements in adipose tissue can also lead to the development of muscle atrophy, which would make insulin resistance and muscle atrophy two sides of the same coin. Unfortunately, the exact relationship between lipid accumulation, type 2 diabetes, and muscle atrophy remains largely unexplored. The aim of this review is to discuss the relationship between type 2 diabetes and muscle loss and to discuss some of the joint pathways through which lipid accumulation in organs may affect peripheral insulin sensitivity and muscle mass.

Citing Articles

Vitamin D and its receptor in skeletal muscle are associated with muscle disease manifestation, lipid metabolism and physical fitness of patients with myositis.

Vernerova L, Vokurkova M, Laiferova N, Nemec M, Spiritovic M, Mytiai O Arthritis Res Ther. 2025; 27(1):48.

PMID: 40038731 PMC: 11877867. DOI: 10.1186/s13075-025-03516-9.


Are strategies to increase muscle mass and strength as effective in people with type 2 diabetes?.

Al-Awadi A, Gray S, Al-Ozairi E Rev Endocr Metab Disord. 2025; .

PMID: 39998784 DOI: 10.1007/s11154-025-09947-8.


Feline Diabetes Is Associated with Deficits in Markers of Insulin Signaling in Peripheral Tissues.

Patra S, McMillan C, Snead E, Warren A, Cosford K, Chelikani P Int J Mol Sci. 2024; 25(23).

PMID: 39684905 PMC: 11642086. DOI: 10.3390/ijms252313195.


Advances in the Study of Denosumab Treatment for Osteoporosis and Sarcopenia in the Chinese Middle-Aged and Elderly Population.

Li S, Zou J, Ran J, Wang L, Nie G, Liu Y Int J Gen Med. 2024; 17:6089-6099.

PMID: 39678680 PMC: 11646433. DOI: 10.2147/IJGM.S494759.


Impact of Alpha-Ketoglutarate on Skeletal Muscle Health and Exercise Performance: A Narrative Review.

Xu M, Zhang Q, Liu X, Lu L, Li Z Nutrients. 2024; 16(22).

PMID: 39599754 PMC: 11597751. DOI: 10.3390/nu16223968.


References
1.
Stephens F, Chee C, Wall B, Murton A, Shannon C, van Loon L . Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men. Diabetes. 2014; 64(5):1615-20. DOI: 10.2337/db14-0961. View

2.
Breen L, Stokes K, Churchward-Venne T, Moore D, Baker S, Smith K . Two weeks of reduced activity decreases leg lean mass and induces "anabolic resistance" of myofibrillar protein synthesis in healthy elderly. J Clin Endocrinol Metab. 2013; 98(6):2604-12. DOI: 10.1210/jc.2013-1502. View

3.
Bonadonna R, Groop L, Simonson D, DeFronzo R . Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle. Am J Physiol. 1994; 266(3 Pt 1):E501-9. DOI: 10.1152/ajpendo.1994.266.3.E501. View

4.
Abbasi F, Brown Jr B, Lamendola C, McLaughlin T, Reaven G . Relationship between obesity, insulin resistance, and coronary heart disease risk. J Am Coll Cardiol. 2002; 40(5):937-43. DOI: 10.1016/s0735-1097(02)02051-x. View

5.
Kalyani R, Saudek C, Brancati F, Selvin E . Association of diabetes, comorbidities, and A1C with functional disability in older adults: results from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Diabetes Care. 2010; 33(5):1055-60. PMC: 2858174. DOI: 10.2337/dc09-1597. View