José Manuel Gómez

Growth hormone release after glucagon as a reliable test of growth hormone assessment in adults

objective To investigate the GH response to glucagon in adult patients with GH deficiency and in controls compared with the GH response to the insulin tolerance test (ITT) in patients with GH deficiency and to determine whether the use of glucagon results in a diagnostic utility test.

Determinants of thyroid volume as measured by ultrasonography in healthy adults randomly selected.

The relationship between thyroid volume and anthropometric characteristics is a matter of controversy. The aim of this study was to investigate thyroid volume and its determinants in healthy adult subjects from a noniodine‐deficient area.

Is plasma 25(OH) D related to adipokines, inflammatory cytokines and insulin resistance in both a healthy and morbidly obese population?

To analyse in a cohort of healthy subjects and in a group of morbidly obese patients, we studied the association amongst 25(OH) D and plasma concentrations of adipocytokines, inflammatory cytokines and insulin resistance. We also aimed to determine whether vitamin D-deficient patients showed a greater inflammatory profile. In the observational study that the authors conducted, plasma concentrations of 25(OH) D, leptin, resistin, adiponectin and interleukine-18 were determined in 134 healthy men and 127 women. In the population consisting of 44 patients with morbid obesity, plasma concentrations of 25(OH) D, leptin, resistin, adiponectin, interleukine-18, soluble tumor necrosis factor receptors 1 and 2 and C-reactive protein were analysed. In the healthy population, plasma 25(OH) D showed a negative correlation with body mass index, body fat, waist, hip circumference and with leptin. However, no significant associations were found amongst 25(OH) D and plasma concentrations of resistin, adiponectin or interleukine-18. Patients with vitamin D deficiency showed higher body mass index, fat mass percentage and higher leptin concentrations compared with subjects with normal 25(OH) D concentrations. In the morbidly obese subjects, 25(OH) D did not correlate with leptin, resistin, adiponectin, interleukine-18, soluble tumor necrosis factor receptors 1 and 2 or with C-reactive protein. In patients with morbid obesity, no differences were found in adipokines and inflammatory cytokines concentrations regarding 25(OH) D status. No associations were found either between 25(OH) D and plasma glucose and insulin resistance or with lipid profile. Plasma 25(OH) D concentrations are associated with adiposity markers but not with adipocytokines implicated in inflammation. This lack of association does not support a major role of 25(OH) D in the pro-inflammatory environment observed in morbidly obese subjects. In addition, subjects with vitamin D deficiency are not characterized by a greater inflammatory state.

Insulin Resistance, Leptin and TNF-α System in Morbidly Obese Women after Gastric Bypass

Obesity is a complex disease associated with insulin resistance. Leptin and the TNF-α system could be involved in the pathogenesis of obesity and insulin resistance. Gastric bypass (GBP) is a surgical treatment for morbidly obese patients. We conducted a study after GBP to analyze the pattern of variation of anthropometric and body composition variables, leptin and sTNFR1 and 2. Methods: 29 morbidly obese women were studied, at baseline and throughout 6 months after gastric bypass. Results: At baseline, the BMI was 49 ± 6 kg/m2 and patients showed a higher fasting insulin resistance index (FIRI), leptin, leptin/fat mass and sTNFR1 and 2 than did controls. 6 months after GBP, BMI was 35±4, and FIRI, leptin and leptin/fat mass decreased significantly in the first months and throughout the follow-up. sTNFR1 and 2 showed an initial increase, but at 6 months their concentrations were similar to baseline (2.6±0.8 vs 3.1±0.95 ng/ml, P < 0.05; 4.6±1.4 vs 7±2.5 ng/ml, P < 0.05). At baseline, there was no correlation between leptin and BMI and body composition variables but there was a correlation with fat mass (r=0.42, P=0.004) and sTNFR1 (r=0.58, P=0.001). At 6 months, there was a correlation between leptin and BMI (r=0.53, P=0.004) and sTNFR1 (r=0.46, P=0.013). Conclusions: Morbidly obese women after GBP became less insulin resistant with lower leptin concentrations, but showed an initial increase of sTNFR1 and 2. This pattern of variation of the leptin TNF-α axis suggests a disregulation of the system after dramatic weight loss and also that insulin and leptin up-regulate TNF-α production irrespective of insulin resistance status.

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.

Human serum levels of fetal antigen 1 (FA1/Dlk1) increase with obesity, are negatively associated with insulin sensitivity and modulate inflammation in vitro.

Objective:To investigate fetal antigen 1 (FA1) protein within the context of human obesity and its relation with insulin sensitivity.Subjects:Cross-sectional study that analyses circulating levels of FA1 in two selected human cohorts: n=127 men for the study of FA1 circulating levels in the context of obesity and insulin sensitivity (Si); and n=61 severely obese women before and after bariatric surgery. The response in vitro to FA1 protein on human cell lines of monocytes, preadipocytes and mature adipocytes was studied.Measurements:Anthropometrical parameters: body mass index, waist-to-hip ratio, waist circumference, fat-free mass and fat mass. Clinical parameters: lipid profile (high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides), glycemic profile (fasting glucose, insulin, Si, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), cytokines (sIL-6), adipokines (adiponectin) and circulating soluble fractions of tumor necrosis factor-α receptors 1 and 2 (sTNFR1 and sTNFR2).Results:In the obesity study, levels of FA1 in serum were found to increase with obesity. The Si index was negatively dependent on FA1 levels. In severe obesity, serum levels of FA1 decreased 1.4-fold 6 months after bariatric surgery. In vitro assays with FA1 protein on human monocytes and adipocytes cell lines modified the expression of pro-inflammatory cytokines and adipokines (tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), IL-6 (interleukin-6) and adiponectin).Conclusion:FA1 serum levels were increased in obese subjects and might influence Si. The stimulatory effect of FA1 protein on pro-inflammatory cytokines on both immune and adipose cell types could contribute to worsening the inflammatory environment observed in obesity.

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.

Insulin regulation of leptin synthesis and secretion in humans: the model of myotonic dystrophy

Myotonic dystrophy (MyD) is a systemic disorder in which insulin resistance is well recognized. In the present study we have characterized plasma leptin levels in patients with MyD and in age, sex and body mass index (BMI) matched controls and assessed the influence of leptin on the clinical manifestations of MyD.

Relation between human LPIN1, hypoxia and endoplasmic reticulum stress genes in subcutaneous and visceral adipose tissue.

Context:LPIN1 is the phosphatidic acid phosphatase that produces 1,2-diacylglycerol, and thus it is related to the synthesis of triglycerides in the adipocyte. LPIN1 has a role in lipid synthesis and nuclear receptor coactivation, both of which may be involved in lipid homeostasis and metabolism. Among others, hypoxia and endoplasmic reticulum (ER) stress are being shown to be related to the adipose dysfunction found in human obesity.Objective:The aim of this study was to analyze LPIN1 gene expression in human adipose tissue in parallel with several hypoxia, angiogenic, ER stress and peroxisome proliferator-activated receptor (PPAR)-related genes in human obesity.Design and Patients:Gene expression was quantified in abdominal (subcutaneous and visceral) adipose tissue from 62 subjects.Results:We have shown a marked association between LPIN1 and PPARα gene expression both in subcutaneous and visceral adipose tissues. Similarly, a strong interdependence with vascular endothelial growth factor (VEGF) gene expression was also described; in fact, LPIN1 and VEGF expression levels were significantly decreased with obesity to a similar extent.Conclusion:These associations might suggest a possible role of LPIN1 in stress conditions that occur in chronic obesity and underlie insulin resistance.

Height gain at adult-height age in 184 short patients treated with growth hormone from prepubertal age to near adult-height age is not related to GH secretory status at GH therapy onset.

Background: GH release after stimuli classifies short children as severe idiopathic isolated GH deficiency (IIGHD), mild IIGHD, dissociated GH release (DGHR) and normal GH release (NGHR) and anthropometric birth data as adequate for gestational age (AGA) or small for gestational age (SGA). GH release after stimuli classifies AGA patients as IIGHD or as idiopathic short stature (ISS). Aim: To compare height gain induced by GH therapy (31.8 ± 3.5 µg/kg/day, 7.7 ± 1.6 years) started at prepubertal age and stopped at near adult-height age. Methods: A retrospective longitudinal multicenter study including 184 short patients classified as severe IIGHD n = 25, mild IIGHD n = 75, DGHR n = 55 and NGHR n = 29; or as IIGHD n = 78, ISS n = 57 and SGA n = 49. Height gain was evaluated throughout GH therapy and at adult-height age. Results: Height-SDS gain at adult-height age was similar among severe IIGHD (1.8 ± 0.8 SDS), mild IIGHD (1.6 ± 0.6 SDS), DGHR (1.7 ± 0.7 SDS) and NGHR (1.6 ± 0.7 SDS), or among IIGHD (1.7 ± 0.7 SDS), ISS (1.7 ± 0.6 SDS) and SGA (1.6 ± 0.8 SD). Conclusion: GH-release stimuli are of little help for deciding on GH therapy in the clinical management of prepubertal children with IIGHD, ISS or SGA.