2025-06-23 杏雲堂病院
<関連情報>
糖尿病患者のインスリンボールに沈着したミクロンサイズのCu0の構造解析 Structural analysis of a micron-sized deposit of Cu0 in an insulin ball from a person with diabetes
Keiichi Iwaya,Terumasa Nagase,Tamotsu Zako,Yoshiyuki Itoh,Takashima Yoshiko,Hisae Arai,Nobumasa Nagami,Takashi Ishikawa & Haruhiko Sugimura
Communications Medicine Published:07 May 2025
DOI:https://doi.org/10.1038/s43856-025-00889-5
Abstract
Background
Protein misfolding is a hallmark of aging, resulting in diabetes and neuroendocrine disorders. Insulin preparations also form aggregates known as insulin balls. Aggregated insulin preparations usually form amyloids and are stable in subcutaneous tissue, some specimens are cytotoxic to cultured cells.
Methods
A multilayered structural analysis of the detailed morphology of 21 insulin balls was performed by connecting regions of interest along spatial axes. Gross and optical microscopic findings, Raman spectrometric analysis using formalin-fixed paraffin-embedded block specimens, matrix-assisted laser desorption/ionization-time of flight-mass spectrometry, microfocus X-ray computed tomography, scanning electron microscopy-energy dispersive X-ray spectroscopy analysis, and transmission electron microscopy analysis were performed.
Results
Here, we show the presence of 100 µm Cu0 within an insulin ball removed from a woman in her mid-40s with diabetes. The insulin ball is made of insulin lispro in an insoluble state in the lower abdominal subcutaneous adipose tissue. Transmission electron microscopy reveals fibrous structures. Microfocus X-ray computed tomography detects many spots with strong light contrast in the insulin ball. Scanning electron microscopy-energy dispersive X-ray spectroscopic analysis shows that the largest light spot is elemental metallic copper without an oxidation state (Cu0).
Conclusions
The largest amount of Cu0 found in living things is in a human. Our discovery of 100 µm Cu0 within the insulin ball supports the idea that insulin preparations from outside can disrupt the balance of metals, including Cu. In 2025, the patient continues to inject subcutaneous insulin preparations, but no new insulin balls appear.
Plain language summary
People with diabetes take insulin preparations to maintain optimal blood sugar (glucose) levels in the body. Insulin preparations can form insoluble structures in the body called “insulin balls” when repeatedly injected into the same site. We found a maximum of 100 µm-sized deposits of copper within an insulin ball in a woman in her mid-40s with diabetes. The significance of copper deposits within insulin balls should be further investigated to see if there are positive and/or negative impacts of their presence in people with diabetes.
