Public Release: 9-May-2016
New study identifies processes leading to mucormycosis infections in DKA
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed)
LOS ANGELES – Patients with diabetic ketoacidosis (DKA) face a much higher risk of succumbing to a deadly fungal infection, known as mucormycosis, than healthy patients. A new study suggests a simple treatment of sodium bicarbonate, or baking soda, could prevent the spread of mucormycosis in patients with DKA.
The study, published today in the Journal of Clinical Investigation, found sodium bicarbonate reversed the effects that promoted the spread of mucormycosis in DKA, a life-threatening condition that can affect people with diabetes. DKA occurs when the body cannot use sugar, or glucose, as a fuel source because there is no insulin or not enough insulin. Fat is used for fuel instead, triggering acids, called ketones, to accumulate in the body. In high levels, ketones are poisonous and can lead to a diabetic coma and death.
“The current guidelines for correcting acidosis of DKA patients doesn’t indicate using sodium bicarbonate until the acidosis is severe,” said Ashraf S. Ibrahim, PhD, an LA BioMed lead researcher and corresponding author of the study. “Our data strongly suggest that DKA patients suspected of having mucormycosis would benefit from adding sodium bicarbonate to the treatment regimen — regardless of whether they have severe acidosis or not — because sodium bicarbonate is likely to halt the growth of the fungus.”
The researchers identified the processes in DKA that promoted the growth of mucormycosis and suppressed the effect of the phagocytes, which are cells within the body capable of engulfing and absorbing invading microorganisms. They found fungal cell surface proteins, CotH, bind to the mammalian cell receptor, GRP78, during the invasion of host tissues.
In DKA patients, they also identified other host factors — including elevated glucose, iron and ketone bodies — that enhanced the expression of both the fungal and mammalian cell receptors in a way that promoted enhanced invasion and damage of host tissues.
In addition, the study noted that acidosis seen in DKA exerts an indirect effect by liberating iron from transferrin, which in turn augmented the expression of GRP78 and CotH, suppressed phagocyte function and enhanced growth of the fungus.
Collectively, these effects promoted rapid infection and progression of mucormycosis. Using disease models, the researchers found sodium bicarbonate reversed many of these effects and helped defeat the mucormycosis infection.
Their finding of elevated iron levels also suggested that reducing the amount of iron by the use of iron chelation, in conjunction with sodium bicarbonate treatment, would help prevent mucormycosis infections in patients with DKA. The researchers also noted that further studies are needed in well-designed clinical trials involving patients with DKA and mucormycosis infections.
The full text of the study is available at: http://www.jci.org/articles/view/82744?key=cb51a45b8d207c235e4b
Other LA BioMed researchers involved in the study were: Teclegiorgis Gebremariam, Lin Lin, Mingfu Liu, Samuel French, John E. Edwards Jr. and Scott G. Filler. Dimitrios P. Kontoyiannis from the Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M D Anderson Cancer Center, Houston, TX, also participated in the study. This work was supported by Public Health Service grants R01 AI063503 and 1R41 AI115907-01 677. Individual researchers were supported by Grant Nos. 678 UL1TR000124, R01 AI054928 and R01 AI063382.
About LA BioMed
Founded in 1952, LA BioMed is one of the country’s leading nonprofit independent biomedical research institutes. It has approximately 100 principal researchers conducting studies into improved diagnostics and treatments for cancer, inherited diseases, infectious diseases, illnesses caused by environmental factors and more. It also educates young scientists and provides community services, including prenatal counseling and childhood nutrition programs. LA BioMed is academically affiliated with the David Geffen School of Medicine at UCLA and located on the campus of Harbor-UCLA Medical Center. For more information, please visit http://www.LABioMed.org
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