Ana Megia

Insulin sensitivity and resistin levels in gestational diabetes mellitus and after parturition

CONTEXT Resistin is expressed and secreted by the placenta during pregnancy. Increased serum resistin levels have been found in the second half of normal pregnancy, but its role in the pathogenesis of the insulin resistance of pregnancy is undetermined. OBJECTIVE The objective of the study was to assess the relationship between circulating resistin levels and insulin sensitivity in gestational diabetes mellitus (GDM). DESIGN AND SETTING A case (n=23)-control (n=35) study was performed at the obstetrics and endocrinology clinic of a university hospital. PATIENTS In total, 58 Caucasian women with a singleton pregnancy who had been referred for a 100 g oral glucose tolerance test were enrolled between the weeks 26 and 30, and 22 women with GDM were also evaluated after pregnancy. MAIN OUTCOME MEASURES Serum resistin and insulin sensitivity in GDM during and after pregnancy. The relationship of resistin to metabolic abnormalities was evaluated. RESULTS Resistin levels were lower in GDM women than in pregnant women with normal glucose tolerance (NGT) (4.32+/-1.56 vs 9.30+/-1.32 ng/ml, P<0.001), and experienced a further decrease after parturition (4.24+/-1.56 vs 3.11+/-1.63 ng/ml, P=0.003). The association between low serum resistin levels and the diagnosis of GDM was independent of the degree of insulin sensitivity. CONCLUSION Lower resistin levels were observed in GDM than in NGT women and decreased after parturition, suggesting a role for resistin in the development of this disease. But we have failed to find an independent relationship between resistin levels and insulin sensitivity during pregnancy.

Monocyte chemoattractant protein-1 in obesity and type 2 diabetes. Insulin sensitivity study.

Objective: Our goal was to test any association between human plasma circulating levels of monocyte chemoattractant protein‐1 (cMCP‐1) and insulin resistance and to compare monocyte chemoattractant protein‐1 (MCP‐1) adipose tissue gene expression and cMCP‐1 in relation with inflammatory markers.

Maternal and cord blood adiponectin multimeric forms in gestational diabetes mellitus: a prospective analysis.

OBJECTIVE To analyze the relationship between maternal adiponectin (mAdiponectin) and cord blood adiponectin (cbAdiponectin) multimeric forms (high molecular weight [HMW], medium molecular weight [MMW], and low molecular weight [LMW]) in a cohort of gestational diabetes mellitus (GDM) and normal glucose–tolerant (NGT) pregnant women. RESEARCH DESIGN AND METHODS A total of 212 women with a singleton pregnancy, 132 with NGT and 80 with GDM, and their offspring were studied. Maternal blood was obtained in the early third trimester and cord blood was obtained at delivery. Total adiponectin and the multimeric forms of adiponectin were determined in cord blood and maternal serum. Spearman rank correlation and stepwise linear correlation analysis were used to assess the relationship between cbAdiponectin levels and clinical and analytical parameters. RESULTS No differences in cbAdiponectin concentration or its multimeric forms were observed in the offspring of diabetic mothers compared with NGT mothers. The HMW-to-total adiponectin ratio was higher in cord blood than in maternal serum, whereas the MMW- and LMW-to-total adiponectin ratio was lower. Cord blood total and HMW adiponectin levels were positively correlated with birth weight and the ponderal index (PI), whereas cord blood MMW adiponectin was negatively correlated with the PI. In addition, cbAdiponectin and its multimeric forms were correlated with mAdiponectin concentrations. In the multivariate analysis, maternal multimeric forms of adiponectin emerged as independent predictors of cbAdiponectin, its multimers, and their distribution. CONCLUSIONS cbAdiponectin concentrations are independently related to mAdiponectin levels and unrelated to the diagnosis of GDM. Maternal multimeric forms of adiponectin are independent predictors of the concentrations of cbAdiponectin and its multimeric forms at delivery.

Adipocyte fatty acid-binding protein as a determinant of insulin sensitivity in morbid-obese women.

The aim of the study was to evaluate human plasma circulating levels of adipocyte fatty acid‐binding protein (A‐FABP) and its relationship with proinflammatory adipocytokines and insulin resistance in a severely obese cohort, before and 1 year after a surgical gastric bypass. Plasmatic levels of A‐FABP were measured in 77 morbid‐obese women before and 1 year after bariatric surgery. Anthropometrical parameters and body composition by bioelectrical impedance analysis were determined. Circulating levels of soluble tumor necrosis factor receptor 2 (sTNFR2), Interleukin 18 (IL‐18), adiponectin, and high‐sensitive C‐reactive protein (hsCRP) were also analyzed. Insulin resistance by homeostasis model assessment of insulin resistance (HOMA‐IR) index was calculated. After massive weight loss, A‐FABP plasmatic levels decreased significantly [7.6 (8.9) vs. 4.3 (5.1); P < 0,001] but no association with circulating adipokines or proinflammatory cytokines, both at the beginning and at the end of follow‐up, was observed. A decrease in sTNFR2, IL‐18, hsCRP, and an increase in adiponectin levels (P < 0.001 in all cases) were observed after the gastric bypass. HOMA‐IR index improved 1 year after surgery and after multiple regression analysis remained associated with A‐FABP after controlling for confounding variables (β = 0.322, P = 0.014; R2 for the model 0.281). In morbid‐obese women, plasma A‐FABP concentrations were dramatically reduced after gastric bypass surgery. After weight loss this protein contributed to HOMA‐IR index independently of proinflammatory/antinflammatory cytokine profile. Further studies are warranted to elucidate the role of A‐FABP in the pathogenesis of insulin resistance in morbid obesity.

Parallel downregulation of retinol-binding protein-4 and adiponectin expression in subcutaneous adipose tissue of non-morbidly obese subjects

CONTEXT AND OBJECTIVE Adipokines are involved in the etiopathology of obesity-related disorders. Since the role of adipokine retinol-binding protein-4 (RBP4) in obesity remains uncertain and its relationship with other adipokines and inflammatory markers has not been examined in detail, we investigated the relationships of RBP4 mRNA expression and circulating protein levels with obesity, anthropometric and metabolic variables, as well as with obesity-related inflammatory markers adiponectin and C-reactive protein. SUBJECTS AND METHODS One-hundred and twenty-five subjects participated, 36 lean (body mass index (BMI): <25 kg/m(2)) and 89 obese (overweight/obese; BMI: > or =25<40) whose anthropometric and metabolic variables were assessed. mRNA expression was quantified by real-time PCR in subcutaneous adipose tissue (s.c.-AT) of 46 subjects. RESULTS There was a tendency for circulating RBP4 levels to positively correlate with waist circumference (beta=0.29, P=0.08; R(2)=0.08), but there was no significant association with the obesity-related parameters analysed. RBP4 and adiponectin mRNA expression levels were similarly downregulated in the s.c.-AT of obese subjects (0.5-fold); however, RBP4 downregulation did not affect its circulating protein levels. The expression of RBP4 and adiponectin was positively correlated even after controlling for confounding factors (beta=0.59, P<0.0001; R(2)=0.40). CONCLUSIONS In our population, RBP4 circulating levels were not significantly correlated with obesity-related parameters, although a tendency to correlate with waist circumference suggests a relationship with insulin resistance and other metabolic disorders. In addition, our results suggest that the production of RBP4 by other tissues such as liver, rather than s.c.-AT, may be involved in regulating RBP4 circulating levels.

LMNA mRNA expression is altered in human obesity and type 2 diabetes.

Objective: The aim of this study was to analyze lamin A/C mRNA levels in abdominal subcutaneous adipose tissue in two conditions—obesity and type 2 diabetes—that share common inflammatory and metabolic features, and to assess their relationship with selected inflammatory and adipogenic genes.

Asistencia sanitaria de la mujer gestante con diabetes en España: aproximación usando un cuestionario

OBJECTIVE To ascertain how health care for pregnant women with gestational diabetes (GD) and pregestational diabetes (PGD) is organized, and to estimate the number of Pregnancy and Diabetes Units (PDUs) in Spain in 2013. MATERIAL AND METHODS The Spanish Group of Diabetes and Pregnancy (GEDE) developed and agreed on a questionnaire based on the recommendations of the group. The questionnaire was sent to members of the Spanish Society of Diabetes and the Spanish Society of Endocrinology and Nutrition. RESULTS Eighty-seven questionnaires were received from 81 hospitals, 4 outpatient specialty centers, and 2 primary healthcare centers, which accounted for 51% of the Spanish population and for 39% of births in 2013. GD was mainly diagnosed based on GEDE recommendations (98%), and less than 50% of women were reevaluated after delivery in primary care. Fourteen (26%) of the 53 centers identified as PDUs corresponded to a minimal model. Continuous subcutaneous insulin infusion (CSII) therapy was not available in 30% of centers, and 13% of hospitals had no preconceptional clinics. No nurse support was available in 20% of centers. CONCLUSIONS Care of women with PGD has a fair coverage with PDU, but significant deficits still exist, for instance, in preconception clinic and CSII. However, organization of care for women with GD appears to be adequate. There are aspects in need of improvement such as integration of diabetes educators and coordination with primary care for postpartum reclassification.