Introdução: A permeabilidade intestinal é uma característica da barreira intestinal que realiza o controle de substâncias do meio externo para o meio interno do organismo. Estudos mostram sua associação com diversas doenças crônicas, como obesidade, doenças cardiovasculares, diabetes mellitus (DM) e doença renal crônica (DRC). Diversos marcadores têm sido estudados para avaliar a permeabilidade intestinal em diferentes patologias entre eles, a zonulina, uma proteína responsável por realizar a abertura das junções firmes ou tight junctions (do inglês), encontradas entre os enterócitos da barreira intestinal. Objetivos: Avaliar a permeabilidade intestinal, através da zonulina sérica, em indivíduos com doença renal do diabetes (DRD), e associá-los com parâmetros renais, glicêmicos, lipídicos, inflamatórios e antropométricos. Metodologia: Este é um estudo caso-controle, que incluiu quatro grupos de indivíduos: 1) controle não-DM2: sem DM2 ou DRC; 2) controle DM2: pacientes diabéticos sem função renal prejudicada; 3) DRD albuminúricos: pacientes diabéticos com albuminúria (EUA) > 30 mg/g de creatinina, mas taxa de filtração glomerular estimada (TFGe) > 60 ml/min/1,73 m3; 4) DRD avançada: pacientes diabéticos com EUA > 30 mg/g de creatinina e TFGe 30 mg/g creatinin, but estimated Glomerular Function Rate (eGFR) > 60 ml/min/1,73 m2; 4) Advanced DKD cases: diabetic patients with albuminuria (UAE) > 30 mg/g creatinin and eGFR < 60 ml/min/1,73 m2. Intestinal permeability was estimated by serum zonulin levels by ELISA. Other clinical parameters were evaluated, such as fasting glucose, glycated hemoglobin, total cholesterol, LDL-cholesterol (LDL), HDLcholesterol, triglycerides, interleukin-6, high sensitivity C-reactive protein, creatinine, albuminuria, proteinuria, body fat and handgrip strength (HGS). Results: Eighty-six patients were included in the study (18 non-DM control, 26 DM control, 20 albuminuric DKD, 22 advanced DKD). Most subjects were female and Caucasian. Diabetic patients had similar diabetes duration. In addition, most diabetic patient were hypertensive (P < 0,001), unlike the non-DM subjects. Serum zonulin was increased in control DM patients when compared to advanced DKD cases [131,3 (83,0-170,5) vs. 63,7 (45,0-106,0) μg/mL; P = 0,004]. After logarithmic transformation and adjustments for LDL, HGS and body fat, control DM group showed higher zonulin levels showing statistical difference between control DM group compared to non-DM control, albuminuric and advanced DKD (P = 0,003), indicating an impaired intestinal permeability in control DM subjects. There was a positive correlation between serum zonulin and total cholesterol (r = 0,29; P = 0,034), LDL (r = 0,26; P = 0,021), eGFR (r = 0,22; P = 0,040) e HGS (0,28; P = 0,011) and, negative correlation between zonulin and DM duration (r = -0,24; P = 0,049), body fat (r = -0,27; P = 0,014), proteinuria (r = -0,21; P = 0,048) and albuminuria (r = -0,24; P = 0,024) were observed. No correlation between zonulin and inflammatory parameters was found. Lowest zonulin levels were found in patients who presented renal function loss or started hemodialysis after 5 years of study inclusion (P = 0,007). Conclusion: Elevated serum zonulin levels suggests DM control group have an impaired intestinal permeability compared to non-DM controls. After evaluating different renal functions in diverse diabetic patients, we could observe that decreased zonulin levels seems to be related to worse renal outcomes
