Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells

Abstract

The role of inflammation has been identified in the pathogenesis of diabetic ketoacidosis (DKA). The neutrophil/lymphocyte ratio (NLR) and white blood cells (WBC) can be used to predict a systemic inflammatory response. Changes in NLR and WBC levels have never been explored in type 1 diabetes mellitus (T1DM) patients with DKA and an uninfected state. This retrospective study included a total of 644 participants. NLR and WBC were measured in the control group (n = 316) and in T1DM patients with mild-DKA (n = 92), severe-DKA (n = 52), and non-DKA (n = 184) in an uninfected state. Then, we assessed the independent predictors of DKA occurrence in T1DM patients in an uninfected state. The diagnostic performance of variables was determined by receiver operating characteristic curve analysis. Serum NLR of T1DM patients is significantly higher than that of normal controls, and if DKA occurs, NLR increases further and increases with the severity of DKA. In addition to diastolic blood pressure, blood urea nitrogen, glycated hemoglobin (HbA1c), and WBC, NLR was also independently associated with DKA in T1DM patients with an uninfected state (OR = 1.386, 95% CI: 1.127–1.705, p = 0.002). Furthermore, the diagnosis analysis showed that except for NLR and WBC, the area under the curve (AUC) of indicators with a statistical difference in patients with and without DKA were 0.747 for DKA diagnosis, and after the addition of NLR and WBC, the AUC was 0.806. The increased NLR level represents a low-cost and highly accessible predictor for DKA in T1DM patients with an uninfected state. The addition of inflammation indicators can play a statistically significant role in the prediction model of the DKA occurrence.

Neutrophil-to-Lymphocyte Ratio Adds Valuable Information Regarding the Presence of DKA in Children with New-Onset T1DM

“…Median NLR scores in our case were significantly different between groups, increasing from those without ketoacidosis (1.11; 0.80-1.80) to mild (1.58; 1.17-1.93), moderate (3.71; 1.98-4.85), and severe (5.77; 4.04-9.63) ketoacidosis groups. Our results regarding pediatric patients are consistent with a previous study addressing adults with DKA, which regards the NLR as a possible marker of the underlying severity of acute systemic inflammation in uninfected DKA patients [6]. Aside from the obvious effect of hemoconcentration on the NLR, the potential relationship between hyperglycemia and an increased NLR has been addressed in previous studies [39].…”

“…Another explanation is the fact that, in DKA, acute hyperglycemia promotes the accumulation of reactive oxygen species (ROS) which can damage peripheral blood lymphocytes' DNA. This in turn may cause the apoptosis of lymphocytes and affect their proliferation [6,43,44].…”

“…Diabetic ketoacidosis (DKA) is an acute life-threatening complication occurring mainly at the onset of type 1 diabetes mellitus [1,2], with an incidence rate that spans from 13 to 80% [3][4][5]. Being a form of systemic inflammatory state [6,7], inflammatory markers such as blood leukocytes and C-reactive protein (CRP) play a key role in the pathogenesis [8,9]. Although complete blood counts (CBCs) are a part of the routine evaluation in diabetic patients, white blood cell (WBC) fractions did not receive significant attention from diabetes specialists in the past [10].…”

Immunology of chronic low-grade inflammation: relationship with metabolic function

“…Inflammatory biomarkers such as the systemic immune-inflammatory index and the neutrophil-tolymphocyte ratio (NLR) can be used as early indicators or predictors of clinical outcomes for a variety of diabetes-associated conditions including, nephropathy (microalbuminuria) (Chollangi et al 2022, Qin et al 2022, depression (Wang et al 2021), macular oedema/retinopathy (Wan et al 2020, Elbeyli et al 2022, ketoacidosis (Cheng et al 2021), foot ulcers (Vatankhah et al 2017, Serban et al 2021, cardiovascular disease-related adverse events (Saylik & Akbulut 2022), and pregnancy outcomes in gestational diabetes (GDM) (Wang et al 2020, Pace & Vassallo 2021. Addressing the underlying subclinical metabolic inflammation in addition to achieving glucose control may thus contribute significantly towards therapeutic interventions aimed at preventing the onset of co-morbidities in diabetic patients.…”

Correlation between Neutrophil-to-Lymphocyte Ratio and Cerebral Edema in Children with Severe Diabetic Ketoacidosis

“…Furthermore, in severe DKA, vasoactive substances released by active systemic neutrophils have been noted to potentially disrupt the blood-brain barrier (BBB) [20]. DKA, recognized as a state of systemic inflammation [21,22], escalates the risk of cerebral edema [2]. The neutrophil-to-lymphocyte ratio (NLR), an established inflammatory marker associated with diabetes mellitus, stands as a pivotal indicator of inflammation in both chronic and acute diabetic complications [23][24][25].…”