Why people with diabetes are more prone to respiratory risk

For decades, it has been known that people with diabetes are at a substantially increased risk of developing severe lung disease if they become infected with viruses such as influenza, as well as with bacteria and fungi. When the COVID-19 pandemic started in early 2020, this mysterious phenomenon gained even more pressing importance: It became clear that people with diabetes were at a significantly higher risk of coming down with severe, even fatal, lung disease after developing a serious form of the virus, but no one understood why. In fact, some 35 percent of people with COVID-19 who died during the pandemic had diabetes.

Now, research conducted at the Weizmann Institute of Science and published in Nature has revealed how, in diabetics, high levels of blood sugar disrupt the function of certain lung dendritic cells, the immune cells that orchestrate a targeted immune response against pathogenic infection. “High blood sugar levels severely disrupt certain subsets of dendritic cells in the lung, preventing these gatekeepers from sending the molecular messages that activate the critically important immune response,” says Dr. Samuel Nobs, a postdoctoral fellow who was the study’s first author. “As a result, the infection rages on, uncontrolled.”

Importantly, the scientists also discovered how high sugar levels in diabetic mice disrupt the normal function of lung dendritic cells during infection. This allowed them to explore ways to prevent the harmful effects of high sugar levels in lung dendritic cells, as a means of lowering the infection’s risk in diabetic animals. “Correcting blood sugar levels, or using drugs to reverse the gene regulatory impairment induced by high sugar, enabled our team to get the dendritic cells’ function back to normal,” says Dr. Suhaib K. Abdeen, a senior intern who co-supervised the study. “This was very exciting because it means that it might be possible to block diabetes-induced susceptibility to viral lung infections and their devastating consequences.” “Our findings provide, for the first time, an explanation as to why diabetics are more susceptible to respiratory infection,” Professor Eran Elinav, who led the study, says. “Controlling sugar levels may make it possible to reduce this pronounced diabetes-associated risk. In diabetic patients whose sugar levels are not easily normalized, small molecule drugs may correct the gene alterations caused by high sugar levels, potentially alleviating or even preventing severe lung infection. Local administration of such treatments by inhalation may minimize adverse effects while enhancing effectiveness, and merits future human clinical testing.”

Sources:

ScienceDaily, December 20, 2023; see source article SP Nobs et al, Nature, 2023; 624 (7992): 645 DOI: 10.1038/s41586-023-06803-0