Eduardo García-Fuentes

Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life.

CONTEXT The association between thyroid function during pregnancy and the later mental and psychomotor development of the child is supported by numerous experimental, clinical, and epidemiological studies. OBJECTIVE The aim of the study was to evaluate the psychological development of infants aged 3 to 18 months whose mothers had received 300 microg of potassium iodide during the first trimester of their pregnancy and compare with infants whose mothers had received no iodine supplements. DESIGN AND STUDY SUBJECTS The study included 133 women who had received 300 microg of potassium iodine and 61 women who had received no iodine supplements. MAIN OUTCOME MEASURES The neuropsychological status of the children was evaluated with the Bayley Scales of Infant Development, and measurements were made of TSH, free T(3), free T(4), and urinary iodine. RESULTS Those children whose mothers had received an iodine supplement of 300 microg had a more favorable psychometric assessment than those of the other group of mothers. They had higher scores on the Psychomotor Development Index (P = 0.02) and the Behavior Rating Scale. CONCLUSIONS Dietary iodine supplements not only have no harmful effect on the neurodevelopment of the children, they may even be beneficial. Given the possible presence of confounding variables not controlled for in this study, these findings should be considered as preliminary.

Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance

Objective:Lipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations.Design:We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants).Results:Serum NGAL concentration was significantly associated with fasting triglycerides and LPS-binding protein in patients with type 2 diabetes. In obese subjects, the intake of saturated fatty acids was the factor that best explained the variance of NGAL changes after weight loss (contributing independently to 14% of NGAL variance). In fact, weight loss significantly changed the circadian rhythm of NGAL. The acute increase in circulating NGAL after fat overload was significantly associated with fasting insulin (r=0.52, P<0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.36, P=0.02) and post-load triglyceride concentrations (r=0.38, P=0.018). LPS-induced NGAL secretion from adipose tissue explants did not change significantly, but LPS led to a significant increase in NGAL concentration in the whole blood obtained from patients with type 2 diabetes.Conclusion:Metabolic endotoxemia and saturated fat might contribute to circulating NGAL concentration in patients with insulin resistance.

Oxidative Stress in Severely Obese Persons Is Greater in Those With Insulin Resistance

The postprandial state seems to have a direct influence on oxidative status and insulin resistance. We determined the effect of an increase in plasma triglycerides after a high‐fat meal on oxidative stress in severely obese patients with differing degrees of insulin resistance. The study was undertaken in 60 severely obese persons who received a 60‐g fat overload with a commercial preparation. Measurements were made of insulin resistance, the plasma activity of various antioxidant enzymes, the total antioxidant capacity (TAC) and the plasma concentration of thiobarbituric acid reactive substances (TBARS). The patients with greater insulin resistance had a lower plasma superoxide dismutase (SOD) activity (P < 0.05) and a greater glutathione peroxidase (GSH‐Px) activity (P < 0.05). The high‐fat meal caused a significant reduction in SOD activity and an increase in the plasma concentration of TBARS in all the patients. Only the patients with lower insulin resistance experienced a significant increase in plasma catalase activity (2.22 ± 1.02 vs. 2.93 ± 1.22 nmol/min/ml, P < 0.01), remaining stable in the patients with greater insulin resistance. These latter patients had a reduction in plasma TAC (6.92 ± 1.93 vs. 6.29 ± 1.80 mmol/l, P < 0.01). In conclusion, our results show a close association between the degree of insulin resistance and markers of oxidative stress, both before and after a high‐fat meal. The postprandial state causes an important increase in oxidative stress, especially in severely obese persons with greater insulin resistance. However, we are unable to determine from this study whether there is first an increase in oxidative stress or in insulin resistance.

Different effect of laparoscopic Roux-en-Y gastric bypass and open biliopancreatic diversion of Scopinaro on serum PYY and ghrelin levels.

BackgroundThe impact of bariatric surgery on levels of peptide YY (PYY) and ghrelin is still under discussion. We undertook a simultaneous evaluation of the serum changes in PYY and ghrelin depending on the specific type of bariatric surgery.MethodsTotal PYY and ghrelin were analyzed in 29 healthy persons and in morbidly obese persons undergoing open biliopancreatic diversion (BPD) of Scopinaro (n = 38) or laparoscopic Roux-en-Y gastric bypass (RYGB; n = 13).ResultsRYGB resulted in a significantly greater loss of weight and body mass index than BPD. Both RYGB and BPD were associated with a significant increase in PYY, significantly greater for BDP (p = 0.001). Ghrelin rose significantly after RYGB (p = 0.022) but not after BPD. After surgery, PYY correlated positively with weight (r = 0.416, p = 0.009). Ghrelin did not correlate significantly with any of the variables studied. Analysis of variance showed that only the type of surgery contributed significantly to explain the variances in the PYY (p = 0.002) and ghrelin (p = 0.018).ConclusionsBPD results in a greater increase in PYY and a lower weight loss than RYGB. However, only RYGB was associated with a significant increase in ghrelin. The differing weight loss according to the type of bariatric surgery does not seem to be explained by changes arising in PYY and ghrelin.

Study of the Potential Association of Adipose Tissue GLP-1 Receptor with Obesity and Insulin Resistance

The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on β-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.

Incidence of type 2 diabetes in southern Spain (Pizarra Study)

Background  Few European studies have used an oral glucose tolerance test (OGTT) to examine the incidence of type 2 diabetes. We determined the incidence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes in a population from southern Spain.

Obesity and Insulin Resistance-Related Changes in the Expression of Lipogenic and Lipolytic Genes in Morbidly Obese Subjects

BackgroundThe storage capacity of adipose tissue may be an important factor linking obesity, insulin resistance (IR), and associated morbidities. The aim of this study was to analyze the expression of lipogenic and lipolytic genes in adipose tissue and the influence of IR.MethodsWe studied the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) and lipogenic and lipolytic enzymes in the visceral (VAT) and subcutaneous adipose tissue (SAT) from 23 morbidly obese patients (MO; 13 with low IR and ten with high IR) and from 15 healthy, lean controls.ResultsIn the VAT and SAT from the MO, we found an increased expression of PPARγ (p = 0.001 and p = 0.022, respectively), acyl-coenzyme A (CoA)/cholesterol acyltransferase (p < 0.001 and p < 0.001), aquaporin 7 (p < 0.001 and p = 0.003), and adipose triglyceride lipase (p < 0.001 and p < 0.001) and a reduced expression of acetyl-coenzyme A carboxylase (p = 0.004 and p < 0.001), independently of the state of IR. The expression of phosphoenolpyruvate carboxykinase and acyl-CoA synthetase, however, was significantly lower in the MO with high IR (p < 0.05). Glycerol kinase (p = 0.010), hormone-sensitive lipase (p < 0.001), and perilipin (p = 0.006) were only significantly increased in VAT. Acyl-CoA synthetase (p = 0.012) and fatty acid binding protein-4 (p = 0.003) were only significantly decreased in SAT. The expression of the genes studied was only greater in the SAT than the VAT in the controls.ConclusionOur results show an upregulation of genes facilitating triglyceride/fatty acid cycling and a reduction in the genes involved in de novo synthesis of fatty acids in morbid obesity. The expression of some of the genes studied seems to be related with the state of IR. VAT and SAT differ metabolically and also between controls and MO.

Déficit de yodo y función tiroidea en una población de mujeres embarazadas sanas

Fundamento y objetivo: Estudios realizados en Espana demuestran que la ingesta de yodo en mujeres gestantes esta por debajo de los requerimientos nutricionales. Con este estudio se pretende comprobar la ingesta de yodo y su relacion con el volumen tiroideo a lo largo del embarazo en una poblacion de mujeres embarazadas en el sudeste espanol. Pacientes y metodo: Se ha estudiado a 520 mujeres sanas embarazadas a lo largo de los 3 trimestres de embarazo. Como grupo control se ha estudiado a 373 mujeres no gestantes. Se han medido las siguientes variables: hormona tirotropa (TSH) y T3 y T4 libres, tiroglobulina, anticuerpos antiperoxidasa, yoduria y volumen tiroideo. Resultados: Tanto en las controles como en las mujeres embarazadas en el primer trimestre, las medianas de las yodurias estuvieron por debajo de 100 µg/l, para aumentar progresiva y significativamente en el segundo y tercer trimestres. El volumen tiroideo se incremento en el segundo y tercer trimestres respecto al primero. Los valores de TSH fueron menores en el primer trimestre que los de las controles, para aumentar significativamente en el tercer trimestre. La T4 libre disminuyo significativamente en el tercer trimestre. Los valores de TSH se han correlacionado de forma negativa y significativa con el volumen tiroideo (r = ?0,22; p = 0,005). Conclusiones: La ingesta de yodo en las mujeres embarazadas de Malaga es baja. Los resultados indican una situacion de deficit de la funcion tiroidea secundaria al deficit de yodo que se agrava a lo largo del embarazo. Los datos apoyan la conveniencia de administrar sistematicamente un suplemento yodado en la mujer embarazada sana.

Stearoyl-CoA desaturase-1 is associated with insulin resistance in morbidly obese subjects.

Animal studies have revealed the association between stearoyl-CoA desaturase 1 (SCD1) and obesity and insulin resistance. However, only a few studies have been undertaken in humans. We studied SCD1 in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) from morbidly obese patients and their association with insulin resistance, sterol regulatory element binding protein-1 (SREBP-1) and ATPase p97, proteins involved in SCD1 synthesis and degradation. The insulin resistance was calculated in 40 morbidly obese patients and 11 overweight controls. Measurements were made of VAT and SAT SCD1, SREBP-1 and ATPase p97 mRNA expression and protein levels. VAT and SAT SCD1 mRNA expression levels in the morbidly obese patients were significantly lower than in the controls (P = 0.006), whereas SCD1 protein levels were significantly higher (P < 0.001). In the morbidly obese patients, the VAT SCD1 protein levels were decreased in patients with higher insulin resistance (P = 0.007). However, SAT SCD1 protein levels were increased in morbidly obese patients with higher insulin resistance (P < 0.05). Multiple linear regressions in the morbidly obese patients showed that the variable associated with the SCD1 protein levels in VAT was insulin resistance, and the variables associated with SCD1 protein levels in SAT were body mass index (BMI) and ATPase p97. In conclusion, these data suggest that the regulation of SCD1 is altered in individuals with morbid obesity and that the SCD1 protein has a different regulation in the two adipose tissues, as well as being closely linked to the degree of insulin resistance.

Bypass of the duodenum improves insulin resistance much more rapidly than sleeve gastrectomy

BACKGROUND Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitus and cardiovascular complications. Bariatric surgery is the most effective strategy for treating morbidly obese patients. We evaluated the metabolic changes that occur in the early stage after 2 types of bariatric surgery, biliopancreatic diversion of Scopinaro (BPD) and sleeve gastrectomy (SG), in morbidly obese patients. METHODS The study was undertaken in 31 nondiabetic morbidly obese patients (7 men and 24 women). Of the 31 patients, 18 underwent BPD and 13 underwent SG. All patients were examined before bariatric surgery (baseline) and at 15, 30, 45, and 90 days postoperatively. RESULTS Significant improvement occurred in the anthropometric variables after the 2 types of bariatric surgery, without significant differences between the 2 types of interventions. In patients undergoing BPD, the serum glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, and free fatty acids were significantly reduced. The changes that occurred in these biochemical variables after SG were not significant. Insulin resistance decreased significantly during the 90 days after surgery, with the greatest decrease at 15 days. However, in the patients who underwent SG, insulin resistance worsened at 15 days and later diminished. CONCLUSION The results of the present study have shown that the surgical technique that excludes the duodenum (i.e., BPD) has immediate postoperative changes in the degree of insulin resistance in morbidly obese patients compared to those techniques that do not exclude the duodenum (i.e., SG).