April 17, 2020
Question: What are some of the morphological changes associated with the diabetic lung?
Takeaway: This 1997 study in hamsters found multiple changes in the cells and structures of the diabetic lung, including increased macrophage adherence to the alveolar lumen, thickening of the alveolar endothelium, and enlargement of the extracellular matrix. These changes may explain the impairments in pulmonary function seen in diabetics.
Diabetes is associated with a variety of pulmonary defects including reduced expiratory volume (1), increased venous resistance (2) and changes to IGF-1 and ACE levels in the lungs (3). Diabetics are more susceptible to pulmonary infections (4). This 1997 hamster study sought to better understand the specific morphological changes of the lung associated with diabetes.
Hamsters were divided into three groups: those given streptozotocin (which induces diabetes), those given streptozotocin plus a high-cholesterol diet, and controls. Note that in hamsters, unlike in humans, excess cholesterol consumption induces a dramatic elevation in blood cholesterol levels. The hamsters were followed for 24 weeks.
After only six weeks of hyperglycemia, morphological changes were observed in the hamsters’ lung cells and microstructures. These changes included:
These changes were associated with narrowing or collapse of 35% of capillaries and 30% of alveoli by the 18th week. Many of these changes are similar to those previously seen in the arterial, myocardial, and retinal endothelium of diabetics (5). Similar changes were seen in the hamsters that were both diabetic and hyperlipidemic, with the speed and degree of progression generally greater in the hyperlipidemic hamsters.
Fig. 5: Compressed lung alveolar space of a 24-week-old diabetic hamster. Over a large surface, the alveolar space (A) becomes collapsed, displaying compressed surfactant, which appears as tubular myelin (t) or as a multilayered structure (s). Note the osmiophilic type I epithelial cell (ep1), whose contorted contour (arrows) is accompanied by interstitial tissue (is), as well as the presence of apparently frequent collagen bundles (arrowheads), and elastin (e). l: vascular lumen; ec: endothelial cell; ep: type I epithelial cell. (Internal scale bar=0.430 µm).
Changes to the thickness and structure of the intracellular and extracellular matrices would be expected to impair alveolar gas transport. The uneven distribution of anionic charge would be expected to impair the adherence of circulating blood cells with the capillary lumen. Taken together, the authors conclude these changes contribute to impaired pulmonary function in the diabetic lung and indicate a direct link between diabetes and loss of lung function.
Comments on Alterations of Lung Structure in Experimental Diabetes
2 Comments
And, in light of the Kohio et al study (cited below) showing that elevated tissue glucose increases the ability of influenza viruses to adhere and penetrate the endothelial cells, the possibility is raised that in the current pandemic it may be easier for SARS-CoV2 to infect the lungs of diabetics in the first place and once accomplished, with all those macrophages poised there to attack, a higher chance of overwhelming inflammatory response throughout the alveoli and the greater risk of the respiratory distress that leads to the ventilator. Certainly that's what we've seen occurring re metabolic syndrome and obesity (itself part of metabolic syndrome) driving up the risk of bad covid-19 outcomes in even those younger than 'elderly'.
(Kohio, H.P., Adamson, A.L., Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate
influenza viral infection. Virology (2013), http://dx.doi.org/10.1016/j.virol.2013.06.026i)
Exactly. There are two (maybe more, but two I can think of) axes which could explain the clearly observed phenomenon that diabetics have a higher rate of COVID morbidity and mortality than nondiabetics:
I'm slowly working my way through the data on #2, but yes, this paper and others like it suggest specific morphological changes in diabetics that could explain #1. If both were true, that would position diabetes as an extremely harmful condition, particularly if large-scale infections like COVID and like the last few flu seasons we have experienced increasingly become the norm. The questions that follow then, for me, are:
The answer to these questions should color how we think of chronic disease, and how we ought to respond to the chronic disease epidemics at an individual and a societal level in light of the infectious disease epidemics we are now seeing.