diabetic ketoacidosis

Posted on Children's health, Diabetes

Spike in severe pediatric type 2 diabetes complication during COVID-19 pandemic

Prediabetes


According to the Centers for Disease Control and Prevention (CDC), children generally appear to be less severely impacted by COVID-19 than adults. But a new study from Children’s Hospital Los Angeles shows that the pandemic could be affecting children’s health in unexpected ways. The study reveals a surge of patients presenting with diabetic ketoacidosis, a severe complication of type 2 diabetes. Published today in Diabetes Care, these data offer additional insights into how the pandemic may be impacting the nation’s children.

Diabetic ketoacidosis, or DKA, is life-threatening. “DKA happens when insulin levels in the blood drop too low for too long,” says Lily Chao, MD, MS, Interim Medical Diabetes Director at CHLA. “Insulin helps the body utilize glucose. So when there’s not enough insulin, the body starts breaking down fat as a source of energy.”

This process, she says, causes dangerously high levels of acids in the blood. If untreated, this can lead to cerebral edema, coma, or even death. “Kids are coming in with dehydration and DKA. But DKA is preventable and reversible if we treat it early and appropriately,” says Dr. Chao, who is lead author on the paper.

Dr. Chao and her colleagues noticed back in March of 2020 that more and more patients were coming in with DKA and type 2 diabetes. “We used to see a few DKA cases in type 2 diabetes a year,” she says, “and all of a sudden we were seeing a spike, so we began keeping track. Now we have the numbers to confirm that there are more children with type 2 diabetes who present with this very serious complication of DKA.”

Yet the question remains: What is the cause of the increased incidence of Type 2 diabetes with DKA?

A year into the COVID-19 pandemic, many children are used to wearing masks and attending online classes. But other changes have affected them, too. Fewer children may be making it to the doctor’s office for their routine well-child exams, possibly due to the fear families may feel about exposure to SARS-CoV-2, the virus that causes COVID-19.

“Parents are worried about going outside of the house,” says Dr. Chao. “Some families have to take public transportation to go the pediatrician and they are hesitant to do so during the pandemic.”

This, she says, may be one of the reasons for the shift she and her colleagues have seen.

In addition to missing doctor visits, other factors may be involved, such as less physical activity during lockdown or reduced access to fresh, healthy foods. But there may also be a biological relationship between exposure to the virus and diabetes.

“There is definitely a link between COVID-19 and diabetes,” says Senta Georgia, PhD, an investigator in The Saban Research Institute of Children’s Hospital Los Angeles and senior author on the paper. Dr. Georgia runs a basic and translational research program aimed at understanding the cellular biology of diabetes and developing novel therapeutics. “We don’t know whether SARS-CoV-2 infects insulin-secreting cells in the pancreas,” she says. “There are some reports of a link between COVID-19 and diabetes in adults, but no pediatric studies have been published to date.”

As a physician scientist and a laboratory scientist, respectively, Dr. Chao and Dr. Georgia come with unique perspectives–but their objectives converge on getting answers to help children diagnosed with diabetes.

“Our work together at Children’s Hospital Los Angeles allows us to address pediatric health on multiple levels,” says Dr. Georgia. “I help Dr. Chao design her clinical studies and she works with me on our basic and translational research. So we’re coming at the problem of increased incidence of diabetes with both a clinical and a scientific perspective.”

Future translational and clinical studies may determine whether increased DKA in patients could be caused by infection with SARS-CoV-2. But for now, the data clearly point to an emerging trend toward more severe diabetes complications during the global pandemic.

The team hopes that these findings will increase vigilance. “It’s critical for pediatricians to recognize that when a child presents with symptoms of diabetes, the child needs to be evaluated right away,” says Dr. Chao. “The sooner we see these kids, the better chance we have to prevent DKA.”

Posted on Diabetes

Common diabetes drug may trigger rare complications for COVID-19 patients

Brigham physicians urge ill patients to pause SGLT2i use, especially if they suspect infection with COVID-19

Diabetes is a known risk factor for morbidity and mortality related to COVID-19. In diabetes patients, rare but severe complications, like the potentially lethal condition diabetic ketoacidosis (DKA), can arise when illness or certain conditions prevent cells from receiving enough glucose to fuel their functioning. An uptick in a particular type of DKA called euDKA at Brigham and Women’s Hospital during the COVID-19 pandemic has led researchers to hypothesize that diabetes patients on glucose-lowering drugs may be at increased risk for euDKA when they contract COVID-19. The observational case series was published in The American Association of Clinical Endocrinologists Clinical Case Reports.

EuDKA is a subset of the diabetes complication known as DKA, which occurs when the body’s cells fail to absorb enough glucose and compensate by metabolizing fats instead, creating a build-up of acids called ketones. EuDKA differs from DKA in that it is characterized by lower blood sugar levels, making it more difficult to diagnose. The U.S. Food and Drug Administration has warned that the risk of DKA and euDKA may be increased for individuals who use a popular class of diabetes drugs called sodium-glucose cotransporter 2 inhibitors (SGLT2i), which function by releasing excess glucose in the urine. Underlying nearly all euDKA cases is a state of starvation that can be triggered by illnesses that cause vomiting, diarrhea, and loss of appetite and can be compounded by the diuretic effect of SGLT2i drugs.

Brigham researchers studied five unusual euDKA cases brought to the diabetes inpatient services within the span of two months, three of which occurred in one week, at the height of the pandemic in Boston in the spring of 2020. The five cases represented a markedly heightened incidence of euDKA compared to that of the previous two years, when inpatient services saw fewer than 10 euDKA cases. All five of the recent euDKA cases were observed in COVID-19 patients who were taking SGLT2i; three patients were discharged to rehabilitation facilities, one was discharged home, and one, a 52-year-old male with acute respiratory distress syndrome, died.

“We have the background knowledge of recognizing that SGLT2 inhibitors can cause DKA and euDKA,” said corresponding author Naomi Fisher of the Division of Endocrinology, Diabetes, and Hypertension. “Our report reinforces that if patients are ill or have loss of appetite or are fasting, they should pause their medication and not resume until they are well and eating properly.”

The authors of the study also suspect that COVID-19 may particularly exacerbate euDKA risks. When the virus infects a patient, it binds to cells on the pancreas that produce insulin and may exert a toxic effect on them. Studies of the earlier SARS-CoV-1 virus found that many infected patients had increased blood sugar. “It’s been posited through other models that the virus may be preferentially destroying insulin-producing cells,” Fisher said.

Moreover, the maladaptive inflammatory response associated with COVID-19, which produces high levels of immune-response-related proteins called cytokines, may increase DKA risks. “These high levels of cytokines are also seen in DKA, so these inflammatory pathways may be interacting,” Fisher said. “It’s speculative, but there may be some synergy between them.”

Though these findings are observational, rather than the results of a randomized controlled trial, similar reports of heightened euDKA incidence have emerged from other institutions. The authors encourage patients and physicians to halt SGLT2i-use in the event of illness, which is already standard practice for the most common diabetes drug, metformin.

“Patients should continue to monitor their blood sugar, and if the illness is prolonged or if their blood sugar is very high, they can speak to their doctor about other forms of therapy,” Fisher said. “But often it’s a very short course off of the drug. We’re hopeful that with widespread patient and physician education, we will not see another cluster of euDKA cases amid the next surge in COVID-19 infections.”