RESUMEN
Background and Objectives: Vitamin D levels have been associated with a diversity of diseases, including obesity. Vitamin D presents a pleiotropic action, and can regulate insulin secretion and inflammatory responses. Vitamin D receptor (VDR) gene polymorphisms are involved in the gene expression regulation and have been associated with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the polymorphisms ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810), and TaqI (rs731236) in the VDR gene in people diagnosed with T2DM, and plasma 25-hydroxivitamin D levels [25(OH)D]. Materials and Methods: A total of 101 T2DM patients and 62 gender, age, and body mass index (BMI) matched non-diabetic controls were included in this study. Molecular analyzes were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma 25(OH)D levels were measured by high performance liquid chromatography. Results: The plasma 25(OH)D levels were lower in T2DM patients (17.2 (16.6) ng/mL) when compared with the control subjects (30.8 (16.2) ng/mL, p < 0.0001), independently of obesity status. We found no difference between genotypic and allelic frequencies of the VDR polymorphisms when comparing the T2DM group and control group (p > 0.05 for all), and did not show any association with plasma 25(OH)D levels. Conclusions: These results suggest that T2DM is associated with lower plasma 25(OH)D levels, which are not related to BMI and VDR gene polymorphisms.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Polimorfismo Genético/fisiología , Receptores de Calcitriol/genética , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/genética , Adulto , Anciano , Glucemia/análisis , Brasil , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/metabolismo , Ayuno/sangre , Femenino , Humanos , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/análisis , Receptores de Calcitriol/sangre , Estadísticas no Paramétricas , Vitamina D/análisis , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
This study aimed to investigate the association between vitamin D (VitD) levels, polymorphisms in VDR gene (ApaI, BsmI, FokI, and TaqI) and the polycystic ovary syndrome (PCOS) in a group of Brazilian women. A total of 100 patients with PCOS and 100 control women were included. The quantification of 25-hydroxyvitamin D (25(OH)D) was performed in high-performance liquid chromatography (HPLC). Polymorphisms on VDR gene were performed by PCR-RFLP. The BsmI AG genotype was more frequent in PCOS group, while the GG genotype was more frequent in the control group (p = .007). The frequency of the Taql CC genotype was higher in PCOS group, while the CT genotype was the most frequent in the control group (p = .021). Mean serum VitD levels were similar between the groups. However, there was a negative correlation between VitD levels and Ferriman-Gallwey score (p = .031, r = -.260) in the PCOS group. The TaqI and BsmI polymorphisms were associated with PCOS. Moreover, VitD levels are associated with the clinical hyperandrogenism. The data suggest the role of VitD in PCOS development and its complications.
Asunto(s)
Síndrome del Ovario Poliquístico/genética , Receptores de Calcitriol/genética , Vitamina D/análogos & derivados , Adulto , Glucemia/metabolismo , Brasil , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Cromatografía Líquida de Alta Presión , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hiperandrogenismo/sangre , Hiperandrogenismo/genética , Insulina/sangre , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/metabolismo , Polimorfismo Genético , Testosterona/sangre , Vitamina D/sangre , Adulto JovenRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is an inflammatory condition associated to obesity and increased oxidative stress. Haptoglobin (Hp) is an acute phase reactant that scavenges extracorpuscular hemoglobin from circulation and prevents heme-iron oxidative damage. OBJECTIVE: To assess the association between Hp levels and Hp1-Hp2 gene polymorphism and clinical and laboratory parameters in patients with T2DM. METHODS: The study sample consisted of 102 T2DM patients and 62 controls. Hp plasma levels were measured using an ELISA assay, and Hp genotyping was performed using a specific two-step allelic polymerase chain reaction. RESULTS: Hp levels were higher in T2DM patients as compared to controls (p=0.005). T2DM patients with high blood pressure had higher Hp levels than patients without this comorbidity (p=0.021). Obese T2DM patients had higher Hp levels as compared to obese controls (p=0.009) and to non-obese T2DM patients (p=0.003). The Hp1-Hp1 genotype was showed to be associated to T2DM according to additive (OR=3.038, 95% CI 1.127-8.192; p=0.036) and dominant model (OR=0.320, 95% CI 0.118-0.839; p=0.010), but Hp2 allele carriers contributed with higher Hp levels in T2DM as compared to controls. Waist circumference (p=0.002), BMI (p=0.001), and IL-6 (p=0.012), and hs-CRP (p=0.001) levels positively correlated with Hp levels in the T2DM group. CONCLUSION: These results suggest that Hp levels are influenced by Hp1-Hp2 polymorphism, obesity, inflammatory status, and high blood pressure in T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Haptoglobinas/genética , Hipertensión/sangre , Inflamación/sangre , Obesidad/sangre , Adulto , Anciano , Alelos , Biomarcadores , Glucemia/análisis , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Comorbilidad , Estudios Transversales , Citocinas/sangre , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Genotipo , Hemoglobina Glucada/análisis , Haptoglobinas/análisis , Humanos , Hipertensión/epidemiología , Inflamación/epidemiología , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Polimorfismo Genético , Circunferencia de la Cintura , Relación Cintura-CaderaRESUMEN
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with chronic lowgrade inflammation. Microparticles (MPs) are extracellular microvesicles released during apoptosis and cellular activation. The MP's pro-coagulant and pro-inflammatory activities are involved in endothelial dysfunction observed in T2DM patients. This study aimed to evaluate the circulating MPs profile in T2DM patients with diabetic kidney disease (DKD) and correlate it with clinical and laboratorial parameters. METHODS: MPs derived from platelets (PMPs), leukocytes (LMPs), endothelial cells (EMPs), and expressing tissue factor (TFMPs) were measured by flow cytometry, in plasma of 39 DKD patients and 30 non-diabetic controls. RESULTS: We observed higher PMPs, LMPs, EMPs, and TFMPs (all p<0.0001) levels in case group as compared to controls. For patients with DKD, circulating MPs levels were influenced by gender, but not by obesity status nor by T2DM onset. Fasting glucose and 25-hydroxyvitamin D levels showed correlation with circulating MPs levels in both groups. CONCLUSIONS: These results suggest that type 2 diabetes mellitus patients with DKD presented higher circulating MPs levels - PMPs, LMPs, EMPs, and TFMPs - which correlated with metabolic alterations.
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Micropartículas Derivadas de Células/química , Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Enfermedades Renales/sangre , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatías Diabéticas/diagnóstico , Femenino , Humanos , Enfermedades Renales/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
ABSTRACT Objective This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. Subjects and methods One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. Results IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. Conclusions These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Interleucina-6/genética , Factor de Necrosis Tumoral alfa/sangre , Interleucina-10/sangre , Diabetes Mellitus Tipo 2/sangre , Obesidad/sangre , Polimorfismo Genético , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Reacción en Cadena de la Polimerasa , Estudios Transversales , Factor de Necrosis Tumoral alfa/genética , Interleucina-10/genética , Diabetes Mellitus Tipo 2/genética , Frecuencia de los Genes , Genotipo , Obesidad/genéticaRESUMEN
OBJECTIVE: This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 GâA), IL-6 (-174 CâG) and IL-10 (-1082 AâG, -819 TâC and -592 AâC)] in type 2 diabetes mellitus (T2DM) and obese patients. SUBJECTS AND METHODS: One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. RESULTS: IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. CONCLUSIONS: These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Obesidad/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Anciano , Biomarcadores/sangre , Índice de Masa Corporal , Estudios de Casos y Controles , Estudios Transversales , Diabetes Mellitus Tipo 2/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Interleucina-10/genética , Interleucina-6/genética , Masculino , Persona de Mediana Edad , Obesidad/genética , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Polycystic ovary syndrome (PCOS) is the most frequent endocrinological disorder that affects women of reproductive age, leading to metabolic alterations, such as hyperandrogenism, obesity, menstrual irregularities, insulin resistance, and polycystic ovaries. The etiology remains unclear, but several genetic and environmental factors have been correlated with manifestations of this syndrome. Vitamin D plays important roles in metabolic pathways affected by PCOS, including calcium homeostasis, the insulin pathway, and sex hormone synthesis. Vitamin D concentration has been related with the severity of this disorder, and vitamin D receptor polymorphisms have been shown in some studies to have an association with some of the patterns presented by PCOS. The objective of this study is to provide an up-to-date review about vitamin D receptor polymorphisms and their association with PCOS.
Asunto(s)
Síndrome del Ovario Poliquístico/genética , Receptores de Calcitriol/genética , Femenino , Humanos , Síndrome del Ovario Poliquístico/sangre , Polimorfismo Genético , Vitamina D/sangreRESUMEN
BACKGROUND: Diabetic patients commonly present an increased risk for cardiovascular events, for which aspirin is the most frequently used medication for primary prevention. Urinary 11-dehydro thromboxane (11-dhTXB2) concentrations assess the effect of aspirin on platelets and identify patients who are at risk of cardiovascular events. The present study investigated whether or not type 2 diabetic patients who took a daily dose of 100mg of aspirin had a significant reduction in urinary 11-dhTXB2 concentrations and whether these results were associated with clinical and laboratory variables. METHODS: Eighty-one type 2 diabetic patients were enrolled in the study. Laboratory tests included the determination of lipidic profile, glycated hemoglobin, platelets count, molecular analysis for both GPIIbIIIa and COX-1 polymorphisms, and urinary 11-dhTXB2. RESULTS: Patients' median value for urinary 11-dhTXB2 before aspirin intake was 179 pg/mg of creatinine. After 15days taking aspirin, the patients presented median of 51 pg/mg of creatinine, thus revealing a significant difference between medians (p=0.00). A reduction of 95% in urinary 11-dhTXB2 concentrations could only be identified in 4 patients (5%). A BMI of ≥ 26 presented a significant association with a reduction of urinary 11-dhTXB2 concentrations (p=0.010), as shown by the multiple logistic regression model. Other clinical and laboratory variables showed no association. CONCLUSIONS: Regardless of the mechanisms related to aspirin non-responsiveness, most patients enrolled in the present study also presented a reduced or minimal response to low-dose aspirin therapy, thereby indicating a clear variability related to aspirin effectiveness. Moreover, BMI appears to be independently associated to the reduction of urinary 11-dhTXB2 concentrations in type 2 diabetic patients taking aspirin.