Abstract Background and Aims Hemodialysis-induced hypoglycemia, a documented complication associated with adverse clinical outcomes, including mortality, is linked to factors such as impaired gluconeogenesis, inadequate nutritional status, reduced insulin clearance, glucose loss to the dialysate, and autonomic neuropathy. Glycemic variability is recognized as an independent risk factor for morbidity and mortality. This study aims to investigate the incidence of hypoglycemia during hemodialysis (HD) by exploring protocol-related factors and their impact, such as in-nutrition during HD. Additionally, the study seeks to examine the relationship between nutritional and inflammatory statuses and variations in intradialytic glycemia in both diabetic and non-diabetic patients. Method This prospective study, conducted between September and December 2023, examined the glycemic profiles of HD patients at a hospital HD program. All patients undergo hemodialysis with a dialysate containing 100 mg/dL of glucose. Plasma glucose levels were assessed at the start, 2:30 hours post-initiation, and the end of sessions. Following the 2:30-hour mark, patients received a meal (523 Kcal). Glycose variability was computed by averaging blood glucose differences across all sessions. Data collected included demographics, hemodialysis specifics, and lab results. Inflammatory and nutritional statuses were evaluated using lab tests at the study's beginning and conclusion [ferritin, protein C reactive (PCR), interleukin 6 (IL-6) and albuminemia, urea, creatinemia, cholesterol, respectively]. Anthropometric measurements and bioimpedance assessments were performed, with values averaged for better representation. Categorical variables are shown with frequencies/percentages, and continuous variables with means/standard deviations or medians/interquartile ranges for skewed distributions. The study used repeated measures ANOVA for glycemic profiles, correlation analyses for outcome influences on glycemia, and parametric/non-parametric tests for relations in diabetic and non-diabetic groups. Significance was set at p<0.05, analyzed with SPSS version 29 for Mac OS 13. Results 63 patients, 67.2% (n=43) were males, the medium age was 72.0±11.8 and 50.8% (n=32) had diabetes. Among 9072 measurements, hypoglycemia was observed in 0.07% (n=6) of diabetic patients and 0.01% (n=1) in non-diabetic individual. The initial blood glucose measurement was 139.5±260.0 mg/dL, the second was 117.05±35 mg/dL, and the third was 132.8±21.3 mg/dL. Significant differences were observed in all measurements [F (1.17, 73.58)=23.62; p<0.001]. The mean glycemic variation between the first and second measurements was 23.8±46.0 mg/dL, and for the third measurement was 5.5±71.5 mg/dL. There was no significant correlation found between glycemic and nutritional parameters neither between inflammatory parameters. In the subgroup analysis comparing diabetic and non-diabetic patients, the diabetic group demonstrated lower serum creatinine levels (6.8±2.7 mg/dL) and total cholesterol (137.4±35.6 mg/dL), coupled with a higher Charlson Index (8.2±1.7). These differences were statistically significant (p=0.055, p=0.035, p<0.001). In the subsequent analysis, no other statistically significant associations were observed. Conclusion Contrary to what is described in the literature, the studied population exhibited a very low incidence of hypoglycemic events. This underscores the importance of nutrition during HD, along with the use of a glucose-containing dialysate, as an effective preventive measure against intradialytic hypoglycemia. Careful consideration of these factors is warranted to prevent adverse health consequences for our patients. It is plausible that diabetic patients may face an elevated risk of malnutrition, necessitating heightened concern and a more proactive preventive approach.