Seoul, Korea—Does NAFLD increase the risk of severe hypoglycemia in T2D patients?

A new Korean cohort study of more than 1.9 million people suggests that might be the case. Patients with T2D and NAFLD without cirrhosis were found to have an estimated 26% increased risk of severe hypoglycemia after adjustment for multiple clinical covariates, according to a report in the Journal of American Medical Association (JAMA) Network Open.

The authors from Yonsei University College of Medicine suggest that being aware of the link between "NAFLD and severe hypoglycemia in adults with type 2 diabetes, independent of obesity status, could help to inform management."

Background information in the article notes that while previous research has indicated an association between liver cirrhosis and hypoglycemia, no studies have investigated the link between NAFLD and hypoglycemia in noncirrhotic populations with T2D.

The nationwide, population-based retrospective cohort study used data from the National Health Insurance System of South Korea; it included diabetes patients aged 20 years or older who had undergone a medical health examination between January 1, 2009, and December 31, 2012. Follow-up continued until December 31, 2015, with data analyses performed between January 1, 2019, and February 2, 2021.

The baseline fatty liver index (FLI) was used as a surrogate marker for NAFLD, and hospital admission and emergency department visit data with a primary diagnosis of hypoglycemia were considered severe hypoglycemia. Among the nearly 2 million T2D patients, 57.8% were male.
Results indicated that during a median interquartile range follow-up of 5.2 (4.1-6.1) years, 45,135 (2.3%) experienced one or more severe hypoglycemia events. Researchers reported that participants with severe hypoglycemia, versus those without severe hypoglycemia, were older (mean standard deviation [SD] age, 67.9 [9.9] years vs. 57.2 [12.3] years; P <.001) and had a lower mean (SD) BMI (24.2 [3.43] vs. 25.1 [3.4]; P <.001).

The study reports that patients with NAFLD tended to have less severe hypoglycemia without consideration of obesity status, but after adjustment of multiple clinical covariates, including BMI, researchers determined a J-shaped association between FLI and severe hypoglycemia (5th decile: adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.90; 9th decile: aHR, 1.02; 95% CI, 0.96-1.08; 10th decile: aHR, 1.29; 95% CI, 1.22-1.37). In addition, the estimated risk of hypoglycemia was higher in participants with NAFLD (aHR, 1.26; 95% CI, 1.22-1.30).
The association was found to be more prominent in female participants (aHR, 1.29; 95% CI, 1.23-1.36) and those who were underweight (aHR, 1.71; 95% CI, 1.02-2.88).

The authors pointed out that older age, kidney insufficiency, and insulin therapy have long been considered risk factors for hypoglycemia in patients with T2D, and the association with lower BMI has also been established.

NAFLD, meanwhile, is a major metabolic liver disease worldwide, with the current 25% prevalence anticipated to increase rapidly due to the obesity epidemic and aging populations.

"Because of its association with obesity and insulin resistance, the overall prevalence of NAFLD in patients with type 2 diabetes is reported to be 55.5%," the authors wrote. "Moreover, NAFLD is an emerging risk factor for various complications, including metabolic syndrome, cardiovascular and kidney diseases, cancers, and overall mortality." They added that the recent findings also raise concerns that it could increase several hypoglycemia incidents in diabetes patients.

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