Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), but no cirrhosis, were at a 26% higher risk of having severe hypoglycemia events, according to a study of nearly 2 million people reported in JAMA Network Open.¹ This association was particularly stronger for women and underweight individuals and independent of obesity status.

A total of 1,946,581 adults, aged ≥20 years, diagnosed with type 2 diabetes were selected from the National Health Insurance Service of South Korea database for this study; of these 1,125,187 (57.8%) were male. Researchers excluded patients with cirrhosis, carcinoma of the liver and pancreas or those who were carriers of hepatitis B or C. During a median 5.2 years, 2.3% of patients had 1 or more episodes of severe hypoglycemia based on the hospital admission and emergency department visit records. The investigators set out to examine the association between severe hypoglycemia and NAFLD among patients with type 2 diabetes using baseline fatty liver index (FLI) as a surrogate marker for NAFLD. The variables utilized in the calculation of the score include triglycerides, BMI, gamma-glutamyltransferase and waist circumference.

Based on the FLI score, the participants were categorized into three groups: Low FLI score < 30 indicative of absence of NAFLD, intermediate FLI score 30-59 and high FLI score ≥ 60 suggestive of the presence of NAFLD.  

Retrospective analysis of data showed that participants with severe hypoglycemia were likely to be older (68 years vs 57 years) and have lower BMI (mean; 24.2 vs 25.1 kg/m2) compared to those who did not have hypoglycemia. More men than women had severe hypoglycemia events; 58% vs 45%, respectively. The prevalence of HT, CKD, CVD was higher in the group with severe hypoglycemia, but less likely to smoke, drink alcohol, or be physically active.

A J-shaped association was noted between FLI and severe hypoglycemia after adjustment of multiple clinical covariates (5th decile adjusted hazard ratio [aHR], 0.86; 9th decile aHR 1.02; 10th decile aHR 1.29). The risk of severe hypoglycemia was 1.26 times higher in patients with NAFLD than those who did not have NAFLD. Patients with advanced NAFLD and FLI of ≥60, the risk of severe hypoglycemia was 38% higher versus patients with FLI <30. This association between NAFLD and hypoglycemia risk was stronger among female participants with aHR of 1.29 and those who were underweight (BMI < 18.5 kg/m2) with aHR of 1.71.

In this study, patients with NAFLD were at nearly 1.3 times greater risk of severe hypoglycemia. According to the researchers, though this association may seem insignificant when compared to the risks with insulin or sulfonylurea use, it assumes significance given that a large population of type 2 diabetes has NAFLD.

Considering that the “contribution of NAFLD to hypoglycemia risk is not negligible” as per this study, the researchers recommend that the treating physicians should be aware of this association and consider looking for NAFLD when defining the risk of hypoglycemia in patients with type 2 diabetes in addition to the established risk factors such as sulfonylureas, glinides. Women and underweight patients were more prone to develop severe hypoglycemia, as per this study enabling identification of at-risk population and institution of individualized treatment to prevent or reduce the occurrence of severe hypoglycemia.

Reference

1. Lee JY, et al. Analysis of severe hypoglycemia among adults with type 2 diabetes and nonalcoholic fatty liver disease. JAMA Netw Open. 2022 Feb 1;5(2):e220262. doi: 10.1001/jamanetworkopen.2022.0262.