The Highest Rates of Severe Hypoglycemia Crises Are in Patients with Diabetes and End-Stage Kidney Disease, Study Finds

In patients who have diabetes and end-stage kidney disease (ESKD), the rates of severe hypoglycemia crises requiring emergency department visits or hospitalizations are the highest so far reported, according to a nationwide study recently published in Diabetes Care.

Researchers led by Rodolfo J. Galindo, MD, FACE, associate professor of medicine at Emory University School of Medicine in Atlanta, in collaboration with Rozalina McCoy, MD, MS, associate professor of medicine at Mayo Clinic, analyzed data from 521,789 adults (56.1% male, 46% white) with diabetes and ESKD from the United States Renal Data System registry, from 2013 to 2017, looking at annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1,000 person-years, adjusting for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen, and U.S. region.

The researchers found that the overall adjusted rates were 53.64 hypoglycemic crises per 1,000 person-years to 18.24 hyperglycemic crises per 1,000 years. Notably, younger patients (18–44 years of age) had the highest rates of severe hypoglycemic crises, with 120.07 events (95% CI 114.84–125.30) per 1,000 person-years, compared with 42.07 events per 1000 person-years among patients >=75 years old. These findings demonstrated the high burden of disease, vulnerability and complexity of care of young patients with diabetes on dialysis. They must “manage their diabetes and ESKD in the context of other life demands, like family, education, and employment. In addition, they are most likely to have type 1 diabetes, end-stage diabetes–related complications, and/or childhood causes of ESKD”.

The researchers also found that most patients were treated with insulin therapy, up to 63.8%, and insulin therapy was associated with a 34% increased risk for hypoglycemic crises compared to non-insulin therapy, and 40% increased risk compared to no therapy. Interestingly, compared with patients treated with insulin, patients treated with noninsulin medications had a 72% lower risk of hyperglycemic crises (IRR 0.28, 95% CI 0.25–0.32), while patients treated with lifestyle therapy had a 56% lower risk (0.46, 0.39–0.48). The study highlights that insulin therapy, considered the “safest therapy” for dialysis patients, may not be the best anti-diabetic therapy, particularly with the development of newer agents with lower hypoglycemic risk. 

Galindo and his team point out that it will be important for Endocrine Society members and others treating these patients to be aware of the burden of severe hypoglycemia. This is the highest burden of all previous reports, compared to pre-dialysis CKD, and other comorbidities, by more than three to fivefold, Galindo tells Endocrine News.

The authors write in the Discussion that the reported rates of severe hypoglycemia are higher than previous for high-risk populations, including elderly patients, elderly patients with longstanding (40 years) type 1 diabetes, patients with long-standing (15 years) type 2 diabetes treated with complex insulin regimens, and patients with diabetes and non-dialysis CKD. 

“For instance, the study by Lipska et al 2011 was a landmark study making us aware of the increasing hypoglycemia crises in the elderly, but in our study, the rates among young (18-44 ys) adults on dialysis were extremely higher (150 compared to ~20-30 events per 1000 person-years among other cohorts with high-risk comorbidities),” Galindo says.

The study exposed health disparities. Black patients were more affected by hypoglycemic crises, as well as those with a history of amputation. “In this nationwide study of patients with diabetes/ESKD, hypoglycemic crises were threefold more common than hyperglycemic crises, greatly exceeding national reports in non-dialysis patients with chronic kidney disease,” the authors conclude. “Young, Black, and female patients were disproportionately affected.”

The authors concluded that patients with diabetes on dialysis 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 made 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.”

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