Evaluation of galectin-3 levels in patients with type 2 diabetes mellitus and chronic kidney disease / Avaliação dos níveis de galectina-3 em pacientes com diabetes mellitus tipo 2 e doença renal crônica

ABSTRACT INTRODUCTION: Type 2 diabetes mellitus (T2DM) is the most common manifestation of diabetes, accounting for about 90% of diagnosed cases. The causes of T2DM are not fully understood, but its pathogenesis is possibly associated with increased adiposity and a chronic low-grade inflammatory response. The glycoprotein galectin-3 (Gal-3) is known to play an important role in the modulation of blood glucose, adiposity, and inflammation. OBJECTIVES: The aim of this study was to evaluate Gal-3 levels in patients with T2DM and chronic kidney disease (CKD), in addition to relating them with complications and comorbidities present in these patients, comparing them to a control group. MATERIAL AND METHODS: Gal-3 was evaluated in 84 selected individuals, of which 42 had clinical and laboratory diagnosis of T2DM and CKD (treated at Santa Casa Hospital in Belo Horizonte, Minas Gerais, Brazil), and 42 individuals from the local community, with no history of diabetes (control group). RESULTS AND DISCURSION: Gal-3 levels were significantly higher (p = 0.012) in the T2DM group (15.17 ± 5.54 ng/ml) when compared to the control group (12.62 ± 3.2 ng/ml). There was a tendency for higher levels of Gal-3 in diabetic patients with hypertension (15.74 ± 5.61 ng/ml) when compared to patients without this complication (10.96 ± 2.49 ng/ml) (p = 0.069) CONCLUSION: The results suggest that Gal-3 may be involved in the pathophysiology of T2DM and still be a promising biomarker associated with hypertension in this group.

RESUMEN INTRODUCCIÓN: La diabetes mellitus tipo 2 (DM2) es la forma más común de la diabetes; representa alrededor del 90% de los casos diagnosticados. Todavía no se conocen por completo las causas de la DM2, pero posiblemente su etiopatogénesis se relaciona con el aumento de adiposidad y una respuesta inflamatoria crónica de bajo grado. Se sabe que la glicoproteína galectina 3 (Gal-3) juega un papel importante en la modulación de glucemia, adiposidad e inflamación. OBJETIVOS: Evaluar los niveles de Gal-3 en pacientes con DM2 y enfermedad renal crónica, además de relacionarlos con las otras complicaciones y comorbilidades presentes en eses individuos, comparándolos con un grupo control. MATERIAL Y MÉTODO: La Gal-3 fue evaluada en 84 pacientes elegidos; entre esos, 42 poseían el diagnóstico clínico y de laboratorio de DM2 y enfermedad renal crónica (atendidos en el Hospital Santa Casa de Belo Horizonte, Minas Gerais, Brasil) y 42 eran de la comunidad local, sin historial de diabetes (grupo control). RESULTADOS Y DISCUSIÓN: Los niveles de Gal-3 fueron más altos (p = 0,012) en el grupo con DM2 (15,17 ± 5,54 ng/ml) que en el grupo control (12,62 ± 3,2 ng/ml). Hubo tendencia de mayores niveles de Gal-3 en los pacientes diabéticos con hipertensión (15,74 ± 5,61 ng/ml) que en aquellos sin esa complicación (10,96 ± 2,49 ng/ml) (p = 0,069). CONCLUSIÓN: Los resultados obtenidos apuntan que la Gal-3 puede estar involucrada en la etiología de la DM2 y aún ser un biomarcador prometedor de hipertensión en ese grupo.

RESUMO INTRODUÇÃO: O diabetes mellitus tipo 2 (DM2) é a manifestação mais comum do diabetes; representa cerca de 90% dos casos diagnosticados. As causas do DM2 ainda não foram completamente estabelecidas, mas sua patogênese está, possivelmente, relacionada com o aumento da adiposidade e uma resposta inflamatória crônica de baixo grau. Sabe-se que a glicoproteína galectina-3 (Gal-3) possui papel importante na modulação de glicemia, adiposidade e inflamação. OBJETIVOS: Avaliar os níveis de Gal-3 em pacientes com DM2 e doença renal crônica, além de relacioná-los com as demais complicações e comorbidades presentes nesses indivíduos, comparando-os com um grupo-controle. MATERIAL E MÉTODOS:: A Gal-3 foi avaliada em 84 pacientes selecionados; destes, 42 possuíam o diagnóstico clínico e laboratorial de DM2 e doença renal crônica (atendidos no Hospital Santa Casa de Belo Horizonte, Minas Gerais, Brasil), e 42 eram da comunidade local, sem histórico de diabetes (grupo-controle). RESULTADOS E DISCUSSÃO: Os níveis de Gal-3 foram significativamente mais elevados (p = 0,012) no grupo com DM2 (15,17 ± 5,54 ng/ml) quando comparados com os níveis do grupo-controle (12,62 ± 3,2 ng/ml). Houve tendência em maiores níveis de Gal-3 nos pacientes diabéticos com hipertensão (15,74 ± 5,61 ng/ml) em comparação com os pacientes sem essa complicação (10,96 ± 2,49 ng/ml) (p = 0,069). CONCLUSÃO: Os resultados obtidos sugerem que a Gal-3 pode estar envolvida na fisiopatologia do DM2 e ainda ser um promissor biomarcador associado à hipertensão nesse grupo.

Proresolving protein Annexin A1: The role in type 2 diabetes mellitus and obesity.

BACKGROUND: Annexin A1 (AnxA1) is a protein involved in inflammation resolution that might be altered in obesity-associated type 2 diabetes mellitus (DM), which is a chronic inflammatory disease. The aim of this study was to evaluate AnxA1 serum levels in individuals with and without DM stratified according to the body mass index (BMI), and the dynamic of AnxA1 expression in adipose tissue from humans with obesity and non-obesity. METHODS: Serum samples were obtained from 41 patients with DM (lean, overweight and obese) and 40 controls, and adipose tissue samples were obtained from 16 individuals with obesity (with or without DM), and 15 controls. RESULTS: DM patients showed similar AnxA1 serum levels when compared to controls. However, when the individuals were stratified according to BMI, AnxA1 levels were higher in individuals with obesity than lean or overweight, and in overweight compared to lean individuals. Moreover, AnxA1 was correlated positively with IL-6 levels. AnxA1 levels were also positively correlated with BMI, waist circumference and waist-to-hip ratio. Furthermore, higher levels of cleaved AnxA1 were observed in adipose tissue from individuals with obesity, independently of DM status. CONCLUSIONS: Enhanced levels of AnxA1 in serum of individuals with obesity suggest an attempt to counter-regulate the systemic inflammation process in this disease. However, the higher levels of cleaved AnxA1 in the adipose tissue of individuals with obesity could compromise its anti-inflammatory and proresolving actions, locally. Considering our data, AnxA1 cleavage in the adipose tissue, despite increased serum levels of this protein, and consequently the failure in inflammation resolution, suggests an important pathophysiological mechanism involved in inflammatory status observed in obesity.

Haptoglobin levels, but not Hp1-Hp2 polymorphism, are associated with polycystic ovary syndrome.

PURPOSE: Proteomic studies suggest an association between haptoglobin (Hp) and polycystic ovary syndrome (PCOS). Hp is a classic inflammatory marker and binds to the intravascular hemoglobin, avoiding the oxidative damages that can be caused by free hemoglobin. Inflammation and oxidative stress are important in the pathogenesis of the PCOS, one of the most frequent metabolic diseases in women. METHODS: To validate these proteomic studies, we developed a controlled cross-sectional study that aimed to evaluate the Hp levels and allelic and genotypic frequencies of Hp1-Hp2 polymorphism in Brazilian women with PCOS. We also investigated the correlation between Hp levels and several important parameters in PCOS as follows: body mass index (BMI), waist circumference (WC), fasting glucose, post-prandial glucose, homeostatic model assessment (HOMA), lipid accumulation product (LAP), C-reactive protein (CRP), and metabolization test of tetrazolium salts (MTTs-serum antioxidant capacity). RESULTS: Plasma Hp levels were higher in the PCOS group than in controls [8.20 (4.04) g/L; 7.98 (3.31) g/L; p = 0.018]. No significant difference was observed in the frequency of Hp1-Hp2 genotypes under additive, recessive, or dominant model of inheritance between the PCOS and the control groups. Plasma Hp levels did not differ according to the genotype. However, plasma Hp showed a negative correlation with MTT (r = - 0.383; p = 0.028), as well as a positive correlation with CRP (r = 0.361; p = 0.014) in the PCOS group. CONCLUSION: Hp1-Hp2 polymorphism is not associated with PCOS but plasma Hp could be a potential biomarker for PCOS and its complications.

The polymorphism -1131T>C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects.

BACKGROUND: Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 -1131T>C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia. METHODS: We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student-Newman-Keuls test. RESULTS: The minor allele C was more frequent in dyslipidemic subjects than controls (p=0.019) and confers an increased individual risk for dyslipidemia (OR=1.726, CI 95%=1.095-2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p=0.037; OR=2.050, CI 95%=1.042-4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p=0.046 and 0.049, respectively). CONCLUSIONS: The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 -1131T>C polymorphism is associated with dyslipidemia in male subjects.