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The Link between Mitochondrial Dysfunction and Sarcopenia: An Update Focusing on the Role of Pyruvate Dehydrogenase Kinase 4
Min-Ji Kim, Ibotombi Singh Sinam, Zerwa Siddique, Jae-Han Jeon, In-Kyu Lee
Diabetes Metab J. 2023;47(2):153-163.   Published online January 12, 2023
DOI: https://doi.org/10.4093/dmj.2022.0305
  • 6,684 View
  • 460 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
Sarcopenia, defined as a progressive loss of muscle mass and function, is typified by mitochondrial dysfunction and loss of mitochondrial resilience. Sarcopenia is associated not only with aging, but also with various metabolic diseases characterized by mitochondrial dyshomeostasis. Pyruvate dehydrogenase kinases (PDKs) are mitochondrial enzymes that inhibit the pyruvate dehydrogenase complex, which controls pyruvate entry into the tricarboxylic acid cycle and the subsequent adenosine triphosphate production required for normal cellular activities. PDK4 is upregulated in mitochondrial dysfunction-related metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Increases in PDK4 are associated with perturbation of mitochondria-associated membranes and mitochondrial quality control, which are emerging as a central mechanism in the pathogenesis of metabolic disease-associated muscle atrophy. Here, we review how mitochondrial dysfunction affects sarcopenia, focusing on the role of PDK4 in mitochondrial homeostasis. We discuss the molecular mechanisms underlying the effects of PDK4 on mitochondrial dysfunction in sarcopenia and show that targeting mitochondria could be a therapeutic target for treating sarcopenia.

Citations

Citations to this article as recorded by  
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Original Article
Complication
Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis
Tianqi Zhang, Marnie Shaw, Nicolas Cherbuin
Diabetes Metab J. 2022;46(5):781-802.   Published online March 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0189
  • 8,040 View
  • 314 Download
  • 18 Web of Science
  • 26 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM.
Methods
PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression.
Results
A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration.
Conclusion
T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

Citations

Citations to this article as recorded by  
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  • Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis (Diabetes Metab J 2022;46:781-802)
    Tianqi Zhang, Marnie Shaw, Nicolas Cherbuin
    Diabetes & Metabolism Journal.2022; 46(5): 815.     CrossRef
  • Association between Type 2 Diabetes Mellitus and Brain Atrophy: A Meta-Analysis (Diabetes Metab J 2022;46:781-802)
    Se Hee Min
    Diabetes & Metabolism Journal.2022; 46(5): 813.     CrossRef
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Case Report
A Case of Failure in Insulin Pump Treatment due to Abdominal Subcutaneous Fat Atrophy and Lipohypertrophied Nodules.
Sang Youl Rhee, Suk Chon, Gwanpyo Koh, Seungjoon Oh, Jeong taek Woo, Sung Woon Kim, Jin Woo Kim, Young Seol Kim
Korean Diabetes J. 2004;28(6):547-553.   Published online December 1, 2004
  • 1,087 View
  • 24 Download
AbstractAbstract PDF
The insulin pump is an effective glycemic control device those function is analogous to the physiologic regulation of insulin in vivo. When sufficient patient education and proper selection of patients is done, the insulin pump is one of the most effective treatment modalities for diabetic patients. However, various side effects and complications might occur during its application. We report here on an unusual case of diabetic ketoacidosis that was caused by acute inflammatory colitis and insulin pump malfunction. Peculiarly, the cause of pump malfunction was far removed from its mechanical problem. We concluded that the cause of the insulin pump malfunction was due to abdominal subcutaneous fat atrophy and the lipohypertrophied nodules of the patient that developed due to the prolonged usage of the insulin pump.

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