Metabolomic Profile of Insulin Resistance Women with Systemic Lupus Erythematosus.

The aims of this study were in systemic lupus erythematosus (SLE) patients: 1) to compare the metabolomic profile of insulin resistance (IR) with controls and 2) to correlate the metabolomic profile with other IR surrogates and SLE disease variables and vitamin levels. In this cross-sectional study, serum samples were collected from women with SLE (n=64) and gender- and age-matched controls (n=71), which were not diabetic. Serum metabolomic profiling was performed using UPLC-MS-MS (Quantse score). HOMA and QUICKI were carried out. Serum 25(OH)D concentrations were measured by chemiluminescent immunoassay. In women with SLE, the metabolomic Quantose score significantly correlated with HOMA-IR, HOMA2-IR, and QUICKI. Although concentrations of IR metabolites were not different between SLE patients and controls, fasting plasma insulin levels were higher and insulin sensitivity lower in SLE women. Interestingly, the Quantose IR score was significantly correlated with complement C3 levels (r=0.7; p=0.001). 25 (OH)D did not correlate with any metabolite or the Quantose IR index. Quantose IR may be a useful tool for IR assessment. There was a possible correlation between the metabolomic profile and complement C3 levels. The implementation of this metabolic strategy may help develop biochemical insight into metabolic disorders in SLE.

Insulin Resistance and Diabetes Mellitus in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by damage to multiple systems and a higher risk of cardiovascular disease. In addition, several studies have found that insulin resistance (IR) is more prevalent in SLE patients than controls, increasing the risk of prediabetes, type 2 diabetes mellitus (T2DM) and morbidity. The objective of this review article was to summarize the most relevant evidence about the relationship among IR, T2DM and SLE, including the effects of proinflammatory states, acute-phase proteins, pro-inflammatory cytokines, and pharmacological SLE treatment. A better understanding of the mechanisms involved in these comorbidities will allow better treatment strategies.

Insulin resistance metabolomic profile in non-diabetic women with systemic lupus erythematosus.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of insulin resistance (IR) and metabolic syndrome (MetS) than controls. OBJECTIVE: To evaluate IR in non-diabetic women with SLE by means of biomarkers using high-throughput metabolomic techniques. METHOD: Cross-sectional study in patients with SLE. A metabolomic approach was employed using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry. MetS was evaluated according to NCEP-ATP III criteria. RESULTS: Seventy patients with SLE were included, out of whom 45 (64.2%) and 27 (38.5%) had IR and MetS, respectively. Patients with IR had a higher body mass index and hypertension more often than those without IR. Chronic damage and disease activity were not related to IR. A Quantose-IR score ≥ 63 was more common in patients with MetS (81.5 vs. 53.5%; p = 0.02). Quantose-IR score was also correlated with the number of criteria for MetS (r: 0.35; p = 0.003). CONCLUSIONS: In non-diabetic women with SLE, the prevalence of IR based on Quantose-IR score was 64.2%.

INTRODUCCIÓN: En lupus eritematoso sistémico (LES) es más frecuente la prevalencia de resistencia a la insulina (RI) y síndrome metabólico (SMet) que en controles. OBJETIVO: Evaluar la RI en mujeres no diabéticas con LES mediante biomarcadores usando técnicas metabolómicas de alta resolución. MÉTODO: Estudio transversal en pacientes con LES. Se empleó un abordaje metabolómico usando cromatografía de líquidos de ultra-alta resolución con espectrometría de masa de alta resolución. El SMet fue evaluado de acuerdo con los criterios NCEP-ATP III. RESULTADOS: Se incluyeron 70 pacientes con LES. Tuvieron RI y SMet 45 (64.2%) y 27 (38.5%), respectivamente. Pacientes con RI tenían un mayor índice de masa corporal e hipertensión con mayor frecuencia que aquellas sin RI. El daño crónico y la actividad de la enfermedad no se relacionaron con RI. Un puntaje de Quantose RI ≥ 63 fue más elevado en pacientes con SMet (81.5 vs 53.5%; p = 0.02). El puntaje Quantose RI también se correlacionó con el número de criterios para SMet (r: 0.35; p = 0.003). CONCLUSIONES: En mujeres con LES no diabéticas, la prevalencia de RI basada en el puntaje de Quantose RI fue del 64.2%.

Reduced first-phase insulin secretion increases postprandial lipidemia in subjects with impaired glucose tolerance.

OBJECTIVE: It is not clear which phase of insulin secretion is more important to regulate lipoprotein lipase (LPL) activity. After a meal, insulin is released and acts as a major regulator of LPL activity. Postprandial hyperlipidemia is a common comorbidity in subjects with insulin resistance (IR). Therefore this study aimed to evaluate the role of the first-phase insulin secretion (FPIS) on postprandial lipidemia in subjects with IR and impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This is a cross-sectional, observational and comparative study. We included male and female subjects between 40 and 60 years with a body mass index (BMI) between 23 and 30 kg/m2. Then, patients were divided into three groups. Group 1 consisted of control subjects with normal glucose tolerance and preserved FPIS. Group 2 included patients with IGT and a reduced FPIS. Group 3 consisted of subjects with IGT but normal FPIS. Both groups were paired by age and BMI with subjects in the control group. Subjects underwent an intravenous glucose tolerance test to classify each case, and then a load with a mixed meal load to measure postprandial lipidemia. RESULTS: A total of 32 subjects were evaluated: 10 were control subjects, 8 subjects with IGT with a reduced FPIS and 14 subjects with IGT and preserved FPIS. After administration of a standardized meal, group 2 showed a greater glucose area under the curve (AUC) at 30 and 120 min (p=0.001, for both). This group also showed a statistically significant increase (p<0.001) in triglyceride AUC. CONCLUSIONS: A reduced FPIS is significantly and independently associated with a larger postprandial hyperlipidemia in subjects with IGT.

[Serum levels of vitamin D in systemic lupus erythematosus patients (SLE) and their relationship with disease activity: longitudinal study]. / Niveles séricos de vitamina D en pacientes con lupus eritematoso sistémico (LES) y su asociación con la actividad de la enfermedad: estudio longitudinal.

OBJECTIVE: To determine changes over time of serum levels of 25-hydroxy vitamin D (25(OH)D) in Mexican patients with SLE and their relationship with disease activity. MATERIALS AND METHODS: Longitudinal and observational study. Women with SLE were included. Serum levels of 25(OH)D were measured at baseline and after two years; the disease activity was measured with MEX-SLEDAI. Patients with initial suboptimal levels of 25(OH)D received supplements or increased doses of calcitriol. RESULTS: 105 women with SLE were included, mean age 49.4 ± 11 years. Serum levels of 25(OH)D were higher at two years (baseline 20 ± 6.8 vs. follow-up 22.7 ± 7.7; p = < 0.001). There were no differences between disease activity scores at baseline and two years (baseline 1.7 ± 1.9 vs. follow-up 1.1 ± 1.7; p = 0.7). Serum levels of 25(OH)D did not correlate with disease activity during the follow up, p = 0.7. No correlation was found between changes in MEX-SLEDAI scores and serum levels of 25(OH)D, p = 0.87. CONCLUSION: Mexican women with SLE had increased serum levels of 25(OH)D. No correlation between serum levels of 25(OH)D and disease activity was found.

Primary amenorrhea in two sisters: description of a Mexican family with 17α hydroxylase-17 lyase deficiency caused by arginine - stop mutation.

A rare cause of congental adrenal hyperplasia is 17α-hydroxylase deficiency. It results in sexual infantilism, primary amenorrhea in females, pseudohermaphroditism in males, hypertension, and hypokalemia. We studied two female siblings from a rural community in Mexico. The cause of consultation was primary amenorrhea. The proband had low levels of estrogen, progesterone and cortisol. Deoxycorticosterone and corticosterone levels were elevated. The proband was homozygous for a transversion of cytosine to thymine at exon 4 (CGA→TGA), causing a premature stop codon at position 239 (R239X). Analysis of family members showed the presence of this heterozygous mutation in the mother, father and one healthy sibling. In summary, we describe a Mexican family with 17α-hydroxylase deficiency due to R239X mutation.

Adenoma adrenal como etiología de síndrome de Cushing: veinte años de experiencia en un centro mexicano de tercer nivel / Adrenal adenoma as a cause of Cushing's syndrome: twenty years’ experience in a referral center in Mexico

Introducción El síndrome de Cushing (SC) incluye una amplia gama de manifestaciones clínicas y de laboratorio resultado final de la exposición crónica a glucocorticoides. Los adenomas adrenales son una causa infrecuente de SC en adultos. Objetivo Describir las características y la evolución de los pacientes con SC causados por adenomas adrenales en un hospital de tercer nivel. Métodos Se trata de un estudio retrospectivo, transversal, observacional. Se estudiaron individuos con el diagnóstico de SC causado por adenomas adrenales, en 20 años. Se describió la experiencia clínica en el diagnóstico y tratamiento. Resultados Se encontró un total de 20 pacientes, 19 mujeres y un hombre. Edad promedio 25,9 años (14 a 52). Los datos clínicos que se documentaron con mayor frecuencia fueron hirsutismo y cara de luna llena. La concentración promedio de cortisol basal fue de 2,9±10,7mcg/dl; del cortisol por la tarde 24,4±8,5mcg/dl y de corticotropina (ACTH) 24±19,4pg/ml. Sólo 4 pacientes (20%) tenían concentraciones de ACTH por debajo de 5pg/ml. Los resultados en las pruebas dinámicas con dexametasona sugirieron adenoma adrenal en el 100% de los casos. El 70% de los adenomas se encontraron en la glándula izquierda. El tamaño promedio de las lesiones fue de 2,8±0,47cm.Conclusiones En las pruebas dinámicas los criterios de no supresión con dosis altas de dexametasona estuvieron presentes en prácticamente todos los pacientes. La medición de ACTH en nuestro centro no resulta confiable para discriminar como causa de hipercortisolismo a los adenomas adrenales (AU)

Introduction Cushing's syndrome (CS) includes a wide range of clinical and laboratory abnormalities and is the final outcome of chronic glucocorticoid exposure. Adrenal adenomas are an uncommon cause of adult CS. Objective To describe the characteristics and outcome of patients with CS caused by adrenal adenomas in a referral center. Methods We performed a retrospective cross-sectional observational study of patients with a diagnosis of CS caused by adrenal adenomas managed in our center over a 20-year period. Our clinical experience in the diagnosis and treatment of this entity was analyzed.Results There were a total of 20 patients, 19 women and one man. The mean age was 25.9 years (14 to 52). The most frequently recorded clinical data were hirsutism and moon face. The mean morning cortisol level was 26.9±10.7mcg/dl, the mean afternoon level was 24.4±8.5mcg/dl and the mean corticotropin (ACTH) concentration was 24±19.4pg/ml. Only four patients (20%) had ACTH levels below 5pg/ml. The results of dynamic testing with dexamethasone suggested adrenal adenoma in 100% of the patients. Seventy percent of adenomas were found in the left gland. The mean size of the lesion was 2.8±0.47cm.Conclusions In dynamic testing, the criteria of non-suppression with high doses of dexamethasone were evident in almost all patients. ACTH measurement in our center was not reliable in identifying adrenal adenoma as a cause of CS (AU)