Electron Microscopy Revealed Massive Lipid Droplets in Cardiomyocytes in a Patient with Cardiogenic Shock Following a Fulminant Type 1 Diabetes Mellitus

Abstract

A 52-year-old man with consciousness disorder following a 2-day history of general fatigue, diarrhea, vomiting and excessive thirst was admitted to our hospital. Severe hyperglycemia (1,739 mg/dL) with a slightly elevated HbA1c level (6.9%), ketonuria and low C-peptide level (0.07 ng/mL) confirmed the diagnosis of fulminant type 1 diabetes mellitus (FT1DM). Following sudden unexplained cardiogenic shock shortly after the initiation of insulin therapy with no evidence of myocardial ischemia assessed by coronary angiography, the patient was supported with percutaneous venoarterial extracorporeal membrane oxygenation. Electron microscopic analysis of the myocardium revealed massive lipid droplets without the infiltration of inflammatory cells. His left ventricular function began to recover during the following days and returned to a normal level on day 14. Currently, the impact of FT1DM on intramyocardial lipid deposition is poorly understood. However, this case suggests that even short-term exposure to high concentrations of glucose can be responsible for lipotoxicity followed by severe cardiac dysfunction.

Plin5, a New Target in Diabetic Cardiomyopathy

“…Plin5 is also named myocardial lipid droplet protein (MLDP) because it is highly expressed in the heart [ 17 – 19 ]. The increase of LDs in cardiomyocytes is the characterization of DC, which is consistent with the expression of Plin5 [ 20 , 21 ]. Plin5 can promote the accumulation of myocardial lipid and alleviate cardiac lipotoxic injury [ 22 – 26 ].…”

“…However, large lipid accumulation can also cause cardiac dysfunction. In fulminant type 1 diabetes (T1DM) patients complicated with cardiac shock, the electron microscope showed large amounts of LDs and a wide range of inflammatory cell infiltration in the myocardial cells, and cardiac ultrasound showed the heart appeared to have serious cardiac insufficiency [ 20 ]. TG accumulation can increase free radical sources, which can induce oxidative stress and trigger lipid peroxidation [ 94 ].…”

Mitochondrial Morphology and Mitophagy in Heart Diseases: Qualitative and Quantitative Analyses Using Transmission Electron Microscopy

“…Hearts from both diabetic and obese patients were the first to suggest changes in lipid content and lipotoxicity in hearts. The increased presence of LDs or cardiac steatosis has been observed through the use of TEM in diabetes (Sugawara et al, 2021 ). TEM analyses in hearts of type 2 diabetics exhibited the presence of fragmented mitochondria (Montaigne et al, 2014 ); however, the study also investigated parameters regarding mitochondrial function in the heart samples from patients with obesity, TEM analyses were not performed under these conditions, and the TEM analyses in this study were performed in right atrial tissue.…”

Zooming into lipid droplet biology through the lens of electron microscopy

“…As a general rule, room temperature (RT) EM procedures start with live, hydrated specimens and end with water-free, heavy-metal-stained, and resin-embedded material [5]. To gain a general understanding of LD sizes, numbers, and the immediate cellular context of surrounding organelles, conventional transmission EM (TEM) imaging of thin sections (typically of 70 nm thickness generated in an ultramicrotome by mechanical sectioning with a diamond knife) represents a good choice [13][14][15][16]. However, being 2D projections, they lack 3D volumetric information.…”