Severe hypoglycemic and hyperglycemic crises that require urgent care are alarmingly common in patients with diabetes and end-stage kidney disease (ESKD) who are on dialysis and greatly exceed reports in nondialysis patients with chronic kidney disease, a new nationwide retrospective study shows.
“These are high-risk, potentially life-threatening episodes — patients can die from these crises — and it’s really important to recognize that this is not just low blood sugars, these are the most extreme cases that require external help to resolve the event — in this case emergency room care or hospitalization,” first author Rodolfo Galindo, MD, associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia told Medscape Medical News.
“So, these data represent a call for action for innovative and personalized strategies that can decrease these preventable — and in many cases iatrogenic — acute diabetes complications in this population,” Galindo and coauthors stress.
“Our results confirmed that patients with diabetes/ESKD are vulnerable to large glycemic excursions and that the current standard of care for glycemic monitoring and treatment for this population is far from optimal,” they add.
Asked by Medscape Medical News to comment on the study, Katherine Tuttle, MD, said that this is a “critically important” study that raises awareness about how common severe glycemic disorders, both hypo- and hyperglycemia are, among people with kidney failure treated by hemodialysis.
“Moreover, these data lead us to wonder about those who may not have made it to emergency care, in other words, the potential impact of such events on mortality outside the hospital,” added Tuttle, professor of medicine, University of Washington, Spokane.
“The “big issue,” she said in her email, “is the importance of identifying glycemic disorders and intervening before a crisis occurs.”
USRDS Registry
Galindo and colleagues used data from the United States Renal Data System (USRDS) registry to identify a total of 521,789 patients with diabetes and ESKD who had at least 3 months of dialysis prior to the index date and an established diagnosis of diabetes as of the index date (listed as either the primary cause of ESKD or as a comorbidity). Patients were enrolled in the registry between 2013 and 2017.
“The primary outcomes were emergency department visits or hospitalizations with a primary (first diagnosis) of severe hypoglycemic or hyperglycemic crises,” the investigators note.
Rates were reported as the number of events per 1000 person-years. The median duration of dialysis upon cohort entry was 3 months and patients were observed for a median of almost 2 years. Over the study interval, 7.9% of patients experienced at least one hypoglycemic crisis, at an overall incidence rate of 53.64 per 1000 person-years.
“These rates are three to five times higher when you compare them to other studies in patients with renal failure but not yet on dialysis,” Galindo emphasized.
Also very concerning, he added, was the incidence rate of hypoglycemic crises seen in the younger age group (patients aged 18-44 years) in which incidence rates ranged between 100 per 1000 person-years to 150 per 1000 person-years across the study interval — five times higher than incidence rates previously reported by others, he stressed (Table 1).
Women and Black patients similarly shouldered a high burden of hypoglycemic events, Galindo and colleagues point out.
Table 1. Adjusted Incidence of Hypoglycemic Crises
| Patient group | Incidence per 1000 person-years |
|---|---|
| Aged 18-44 years | 120.1 |
| Aged ≥ 75 years | 42.1 |
| Females | 56.3 |
| Males | 51.6 |
| Blacks | 60.0 |
| Non-Hispanic Whites | 54.0 |
| Hispanics | 46.3 |
Incidence rates of hypoglycemic crises actually declined between 2013 and 2017, dropping from 65.5 per 1000 person-years in 2013 to 45.1 per 1000 person-years in 2017 (P < .01).
“We are optimistic that trends are decreasing,” Galindo said, “but it was still concerning that the overall rates of hypoglycemia are the highest reported so far compared to other high-risk populations,” he added.
Hyperglycemic Crises
Far fewer patients in this nationwide study experienced at least one hyperglycemic crisis between 2013 and 2017 at 1.8% overall, for an adjusted incidence rate of 18.2 events per 1000 person-years.
Younger patients again had the highest incidence of hyperglycemic crises at 102.4 events per 1000 person-years compared with only 2.6 events per 1000 person-years among patients 75 years of age and older.
The risk of hyperglycemia among females was again higher than it was among males at 22.2 events per 1000 person-years compared with 15.4 events per 1000 person-years.
However, and in contrast to hypoglycemic crises, non-Hispanic White patients had the highest rates of hyperglycemia, at 23.1 events per 1000 person-years, compared with 19.8 events per 1000 person-years among Black patients and 10.6 events per 1000 person-years among Hispanic patients.
Similar to what was seen with incidence rates of hypoglycemic crises, the incidence of hyperglycemic crises declined between 2013 and 2017, from 21.9 events per 1000 person-years in 2013 to 15.9 events per 1000 person-years in 2017 (P < .01).
As Galindo emphasized, many of these hypo- and hyperglycemic episodes are preventable.
“We found that over 63% of patients included in our study were receiving insulin therapy and insulin therapy was associated with a 34% increased risk for hypoglycemic crises compared to non-insulin therapy,” he explained.
Of interest, insulin therapy also increased the risk of hyperglycemic crises by over 70%, again compared with other antidiabetic medications.
Episodes Are Preventable; Use of CGM Will Help
“This is why we say these episodes are preventable because using agents with a lower hypoglycemic risk [than insulin] is a better choice,” Galindo stressed. Another strategy that could help optimize glycemic control is to use continuous glucose monitoring (CGM) with predictive hypoglycemia and hyperglycemia alarms.
In a recent nationwide study conducted in France, use of CGM decreased hospitalizations for acute glycemic crises by 40%-50% in patients with type 1 or type 2 diabetes.
“Concerns about cost and insurance coverage for CGM are valid but the burden and cost of emergency room visits, or hospitalizations must also be considered,” Galindo pointed out.
“And educating patients and providers on how to prevent and treat hypoglycemia is paramount,” he stressed.
Tuttle agrees that use of CGM and medication management “to reduce the risk of hypo- and hyperglycemia are crucial areas for research that will directly impact care of patients treated by hemodialysis.”
“A multidisciplinary management team, including endocrinologists/diabetologists, pharmacists, and certified diabetes care and education specialist, and use of CGM should be incorporated in dialysis centers to help prevent these avoidable acute glycemic complications,” Galindo and colleagues conclude.
The study was supported by the NIDDK of the National Institutes of Health. Galindo has reported receiving research support to Emory University for investigator-initiated studies from Novo Nordisk, Dexcom and Eli Lilly, as well as consulting fees from Abbott Diabetes Care, Sanofi, Valeritas, Eli Lilly, Novo Nordisk, and Weight Watchers.
Diabetes Care. Published online November 5, 2021. Abstract
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