Serena Crawford

It is commonly known that having type 2 diabetes can lead to the development of various health conditions, including heart disease, neuropathy, kidney disease, and eye disease. Not as well-known is the association between type 2 diabetes and infection, according to 

published a paper on the risk of infection in older adults with type 2 diabetes

“Infections are not typically considered traditional complications of diabetes, but they are an important reason why people with diabetes end up in the hospital,” said Lipska, an associate professor of medicine (endocrinology and metabolism) at Yale School of Medicine. “Infections are also a common cause of hospitalization among older adults, and older adults with type 2 diabetes are at increased risk.”

In a Q&A, Lipska discusses the impact of type 2 diabetes on the immune system and findings from her recent research.

How does having type 2 diabetes impact the immune system?

Diabetes impacts the immune system in multiple ways. High blood sugar impairs the function of the body’s white cells, making it harder for the immune system to fight off infection. People with type 2 diabetes may also be susceptible to infection because of complications of the disease, such as neuropathy or peripheral vascular disease, in which they develop wounds on their feet. The combination of having high blood sugar and poor blood flow to the extremities makes healing difficult.

What has your research shown about the risk of infection among older adults with type 2 diabetes?

Guidelines for older adults recommend more relaxed blood sugar control than for younger adults because the risks associated with blood sugar becoming too low increase with age. Through our research, we wanted to learn whether the guidelines, which recommend keeping older people at higher blood sugar levels, increase the risk of infection. We wanted to find out if being on the higher end of the recommended range increases the risk of infection compared to being on the more tightly controlled end.

To do this, we broke up the recommended range of glycemic control from A1C levels of 6 to 7 percent, 7 to 8 percent, and 8 to 9 percent. We looked at the association between those three different ranges of glycemic control and being hospitalized for any or one of four kinds of infection—respiratory; genitourinary; skin, soft tissue, and bone; and sepsis—to see whether having A1C in these different ranges makes a difference.

We found that having A1C at the higher end of that recommended range is not associated with a significantly increased risk of hospitalization for any of those four infections. However, individuals with A1C between 8 and 9 percent had a 33 percent increased risk of having skin, soft tissue, and bone infections.

What does this mean for older people with type 2 diabetes?

In my older patients, where it doesn’t make clinical sense to control their blood sugars very tightly, I will try to hit the 7 to 8 percent, the middle range, if I can do that safely without causing undue risk to the patient. But in patients who might have low blood sugar reactions at that range or who are starting a treatment or undergoing a transition—for example, to a nursing home—that relatively small risk of skin and soft tissue and bone infection may be outweighed by the benefits of keeping their blood sugar a little bit less tightly controlled.

COVID has made us all more aware that chronic disease is interconnected with acute infectious risk. Given that diabetes raises this risk, more studies need to be done to better understand that relationship and incorporate this risk into our calculations of not only the types of medications that we use for people with diabetes but also the glycemic control levels that are optimal for individuals with respect to their health.

Section of Endocrinology and Metabolism works to improve the health of individuals with endocrine and metabolic diseases by advancing scientific knowledge; applying new information to patient care; and training the next generation of physicians and scientists to become leaders in the field. To learn more, visit

Articles

Type 2 diabetes is linked to increased infection risk, particularly in older adults, due to impaired immune function and complications like neuropathy. Research indicates that while higher A1C levels (8-9%) do not significantly increase hospitalization risk for most infections, they do elevate the risk for skin, soft tissue, and bone infections by 33%. For older patients, maintaining A1C levels between 7-8% is advisable, balancing infection risk with the dangers of hypoglycemia. Further studies are needed to refine glycemic control guidelines and medication choices considering infection risks.

In a Q&A, Kasia Lipska, MD, MHS, discusses the impact of type 2 diabetes on the immune system and findings from her recent research.

Investigating the Link Between Type 2 Diabetes and Infection

, researches the effects of mitochondrial function and regulation of innate immunity on the host immune response, including aging-related immune dysregulation.

An associate professor of medicine (pulmonary), Kang came to Yale School of Medicine more than two decades ago as a visiting scholar. At the time, he was interested in learning how smoking exposure contributed to the pathobiology of chronic obstructive pulmonary disease (COPD) and asthma.

“The fact that smoking exposure impacted certain aspects of the innate immune response, especially the cytoplasmic double-stranded RNA, was against the conventional understanding at the time,” Kang said of his early research. “This led me to focus on the mitochondrial antiviral signaling protein, or MAVS.”

In a Q&A, Kang discusses the role of MAVS in host resilience, aging as a contributing factor of lung disease, and the link between viral innate immunity and aging biology.

We know that during a microbial infection, the host fights against the pathogen. However, many questions remain unanswered about host resilience. My molecule of interest, MAVS, seems to drive host resilience impairment.

MAVS is located on the outer membrane of the mitochondria and is thus ideally positioned to convey information between the cytoplasm and the mitochondria. Through MAVS, the innate immune signaling pathways are modulated and conveyed. Dissecting these innate immune signaling pathways can help us learn more about mitochondrial regulation of innate immunity.

MAVS is widely studied in viral infections and diseases, including COVID-19. However, a virus is generally not associated with the pathobiology of the diseases I study, such as idiopathic pulmonary fibrosis. Even in these non-viral disease contexts, this virus-related innate immune mechanism plays a critical role.

What have you discovered about the connection between aging and disease?

During aging, when cells are senescent and mitochondrial function deteriorates, mitochondrial nuclei contents like mitochondrial double-stranded RNA or mitochondrial DNA are released outside of the mitochondria into the cytoplasm, where they are recognized as foreigners by the cell. In other words, when these endogenous nucleic acids are located abnormally—or ectopically—they behave like viruses and stimulate the antiviral innate immune pathway, even in a nonviral context.

Aging is one of the greatest risk factors for all non-communicable chronic diseases, which are more prevalent in the aged population compared to the younger population. Diseases I study, such as COPD and idiopathic pulmonary fibrosis, are well-known age-associated lung disorders. The question is how aging hallmarks, which are observed in patients with COPD and IPF, are connected to disease pathobiology.

I am focusing on two aging hallmarks, mitochondrial dysfunction and cellular senescence, as a kind of prism through which to view fundamental biological mechanisms. We know that viral innate immunity and aging biology are married together, but why?

I am working to understand how aging-related lung disorders occur and how we can identify intervention points and potential therapeutics that promote mitochondrial function or alleviate cellular senescence. I hope to find a disease-modifying strategy for COPD and IPF. As a physician-scientist, my goal is to benefit patients.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within Yale School of Medicine’s Department of Internal Medicine. To learn more,

Min-Jong Kang's research focuses on the role of mitochondrial function and innate immunity in aging-related immune dysregulation. His work highlights the significance of the mitochondrial antiviral signaling protein (MAVS) in host resilience and its implications in non-viral diseases like COPD and idiopathic pulmonary fibrosis. Kang explores how aging and mitochondrial dysfunction contribute to these diseases, emphasizing the release of mitochondrial nucleic acids that mimic viral infections. His future research aims to identify therapeutic interventions targeting mitochondrial function and cellular senescence to modify disease progression in age-associated lung disorders.