The SEEN comprehensive clinical survey of adult obesity: Executive summary. / Abordaje clínico integral SEEN de la obesidad en la edad adulta: resumen ejecutivo.

Obesity is one of the great challenges in healthcare nowadays with important implications for health so requiring comprehensive management. This document aims to establish practical and evidence-based recommendations for the diagnosis and management of in Spain, from the perspective of the clinical endocrinologist. A position statement has been made that can be consulted at www.seen.es, and that has been agreed by the Obesity Group of the Spanish Society of Endocrinology and Nutrition (GOSEEN), together with the Nutrition Area (NutriSEEN) and the Working Group of Endocrinology, Nutrition and Physical Exercise (GENEFSEEN).

Predictive factors of excess body weight loss 1 year after laparoscopic bariatric surgery.

BACKGROUND: Bariatric surgery (BS) is widely accepted for the treatment of patients with morbid obesity (MO). We aimed to determine presurgical predictors of and surgical technique-related differences in excess weight loss (EWL) 1 year after BS. METHODS: This retrospective study included 407 subjects (F/M 3:1, median age = 44 years) who underwent laparoscopic Roux-en-Y gastric bypass (RYGB, n = 307) or sleeve gastrectomy (SG, n = 100) at our University Hospital and were evaluated 1 year after surgery. RESULTS: Baseline median (min-max) body mass index (BMI) was 47 kg/m(2) (range = 36-71). BMI was higher in the SG than in the RYGB group (53 vs. 46 kg/m(2), p < 0.0001). Simple correlation analysis showed negative associations between EWL and age, BMI, waist circumference (WC), fasting glucose, HbA1c, triglycerides (TG), blood pressure, and total cholesterol (all p < 0.01). EWL (mean ± SD) did not differ by gender (p = 0.2), was lower in diabetic than in nondiabetic subjects (71 ± 17% vs. 79 ± 17%, p < 0.0001), and higher in the RYGB vs. SG group (76 ± 18% vs. 68 ± 15%, p < 0.0001). However, SG vs. RYGB differences in EWL disappeared (p = 0.4) after taking into account baseline BMI. Multiple regression and logistic analysis showed that younger individuals with lower BMI but higher WC, and lower HbA1c and TG, had higher EWL and a higher rate of successful (EWL ≥ 60%) weight loss. CONCLUSIONS: Our data indicate that some of the characteristics that would have subjects referred early for BS were associated with higher weight loss. Therefore, the timing of laparoscopic BS might be an important factor for MO individuals in which medical weight loss intervention has failed.

Long-term effects of Roux-en-Y gastric bypass surgery on plasma glucagon-like peptide-1 and islet function in morbidly obese subjects.

CONTEXT: An enlarged incretin response after Roux-en-Y gastric bypass (RYGBP) has been proposed to promote excessive beta-cell function and mass. OBJECTIVE: The objective of the study was to determine whether RYGBP is associated with a steadily increased glucagon-like peptide 1 (GLP-1) response and a disruption of the relationship between insulin sensitivity and insulin secretion required to maintain plasma glucose in the normal range. DESIGN AND PATIENTS: This was a cross-sectional study. Twenty-four women divided into three groups according to time after RYGBP (9-15, 21-30, and more than 36 months). Eight normal-weight and eight morbidly obese women served as controls. MAIN OUTCOME MEASURES: GLP-1 was determined after a standardized test meal. Insulin secretion (AIRg) and insulin sensitivity (S(I)) were derived from an iv glucose tolerance test. Postprandial glucose profile was recorded with a continuous glucose monitoring system. RESULTS: Area under the curve(0-120) of GLP-1 was larger after RYGBP compared with controls (P < 0.01) but was comparable among surgical groups (P =0.314). Time after surgery was not associated with changes in S(I) (P = 0.657), AIRg (P = 0.329), or the disposition index (DI = AIRgS(I), P = 0.915). After surgery, the GLP-1 response and the DI were not significantly correlated (P = 0.304). Glucose less than 50 mg/dl was found in operated subjects, but the proportion did not increase with time after surgery (P = 0.459). Neither the GLP-1 response (P = 0.620) nor the DI (P = 0.457) differed significantly between those with or without hypoglycemic episodes. CONCLUSIONS: Although the GLP-1 response to meal intake is steadily elevated after RYGBP, this does not result over time in the development of an inappropriate insulin secretion relative to the prevailing insulin sensitivity or the occurrence of hypoglycemic episodes.

Circulating peptide YY, weight loss, and glucose homeostasis after gastric bypass surgery in morbidly obese subjects.

OBJECTIVE: To prospectively assess the relationship between circulating peptide YY (PYY), body weight, and glucose tolerance in severely obese subjects undergoing Roux-en-Y gastric bypass (RYGBP). SUMMARY BACKGROUND DATA: The mechanisms accounting for the beneficial effects of RYGBP on body weight and glucose homeostasis are not well understood. METHODS: Prospective study on the response of PYY to a standardized test meal (STM) and its relationship with weight loss and glucose homeostasis (fasting plasma glucose, HbA1c, HOMA-IR, HOMA-B) in nondiabetic (n = 25) and diabetic (n = 10) severely obese subjects evaluated before, and at 6 and 52 weeks after RYGBP. RESULTS: The PYY response to a STM significantly increased (P < 0.001) already at 6 weeks at a time when subjects despite presenting a significant weight loss (-14.6% +/- 1.2%) were still markedly obese. Despite massive weight loss (-43.0% +/- 2.3%), no further increase in the area under the curve of PYY was observed at 52 weeks after surgery (P = 0.44). The PYY response to a STM at 6 weeks after surgery significantly correlated (r = 0.489, P < 0.05) with the percent excess weight loss at 32.5 +/- 1.1 months after surgery. In contrast, no significant correlation was found between PYY and glucose homeostasis parameters in nondiabetic and diabetic patients. CONCLUSION: Our data support the hypothesis that an increased PYY response after meal ingestion is involved in the sustained weight loss observed after RYGBP. In contrast, our data does not support PYY being relevant in the changes in glucose homeostasis occurring after this type of bariatric surgery.

Intra-abdominal fat adiponectin receptors expression and cardiovascular metabolic risk factors in obesity and diabetes.

BACKGROUND: The effects of adiponectin on glucose and lipid metabolism are mediated by the adiponectin receptors, adipoR1 and adipoR2, which are mainly in liver and muscle. We investigated the presence of adiponectin receptors in intra-abdominal adipose tissue (IAAT) in obesity and diabetes and their association with adiponectin expression and components of the metabolic syndrome and/or other metabolic factors associated with atherosclerotic cardiovascular disease (ASCVD). METHODS: AdipoR1 and adipoR2 gene expression was measured by quantitative real time reverse transcription polymerase chain reaction in IAAT from lean and obese patients with or without diabetes type 2. Correlation between metabolic characteristics of obese patients and expression of these receptors was studied. RESULTS: Neither obesity nor diabetes were associated with changes in IAAT-adipoR1 expression. In contrast, IAAT-adipoR2 was decreased by 39.5% in obese non-diabetics and by 52.7% in obese diabetics when compared to lean subjects. AdipoR1 and adiponectin expression was associated in lean (r=0.943, P<0.005) and obese non-diabetic patients (r=0.74, P<0.01), whereas a positive correlation between adipoR2 and adiponectin expression was only found in the presence of diabetes (r=0.883, P<0.002). AdipoR1 expression was associated with plasma free fatty acids (FFA) concentration (r=0.76, P<0.04), and adipoR2 inversely correlated with plasma levels of triglycerides (r=-0.76, P<0.04) and apolipoprotein B (r=-0.74, P<0.05). CONCLUSION: AdipoR1 expression in IAAT was not altered by obesity and/or diabetes and was related to plasma levels of FFA. IAAT-adipoR2 expression was reduced in obesity and diabetes and associated with components of metabolic processes leading to cardiovascular disease in obesity.

Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects.

CONTEXT: The mechanisms underlying weight loss after Roux-en-Y gastric bypass (RYGBP) are not well understood. OBJECTIVE: The objective of the study was to assess the changes in active glucagon-like peptide 1 (GLP-1) and total peptide YY (PYY) after RYGBP and examine their relationship with changes in hunger and satiety. DESIGN: This was a prospective study on the changes in active GLP-1, PYY, hunger, and satiety in response to a standardized test meal in nine normal-glucose-tolerant obese subjects [body mass index (BMI) 47.4 +/- 6.1 kg/m(2)] before and 6 wk after RYGBP. RESULTS: Before surgery, meal ingestion failed to stimulate GLP-1 and PYY secretion. Six weeks after surgery, despite subjects still being markedly obese (BMI 43.6 +/- 7.8 kg/m(2)), the area under the curve(0-120') of GLP-1 and of PYY in response to the standardized test meal were significantly elevated (P < 0.05 and P < 0.01, respectively). These hormonal responses were significantly larger (P < 0.01) than those observed in a group matched for the BMI attained 6 wk after surgery. The 2.9 +/- 1.2- and 1.6 +/- 1.9-fold increase, respectively, in the area under the curve(0-120') of GLP-1 and PYY were accompanied by a significant decrease in fasting (P < 0.05) and postprandial hunger (P = 0.05) and a significant increase in satiety (P < 0.05) after meal intake. Nevertheless, a significant correlation between changes in the hormonal and eating behavior parameters was not found. CONCLUSION: Our data show that RYGBP is associated with an improvement in the active GLP-1 and total PYY response to a liquid-meal intake. Moreover, we provide circumstantial evidence for a potential role of these gastrointestinal hormones on the decreased appetite after RYGBP.

GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects.

BACKGROUND: It has been proposed, that the dramatic amelioration of type 2 diabetes following Roux-en-Y gastric bypass (RYGBP) could by accounted for, at least in part, by changes in glucagon-like peptide-1 (GLP-1) secretion. However, human data supporting this hypothesis is scarce. METHODS: A 12-month prospective study on the changes in glucose homeostasis, and active GLP-1 in response to a standard test meal (STM) was conducted in 34 obese subjects (BMI 49.1+/-1.0 kg/m(2)) who had different degrees of glucose tolerance: normal glucose tolerance (NGT, n=12), impaired glucose tolerance (IGT, n=12), and type 2 diabetes (n=10). RESULTS: At 6 weeks after RYGBP, despite the subjects still being markedly obese (BMI 43.5+/-0.9 kg/m(2)), fasting plasma glucose and HbA1c decreased in the 3 study groups (P<0.05). Insulin sensitivity improved, but was still abnormal in a comparable proportion of subjects among groups (P=0.717). When insulin secretion was accounted for the prevailing insulin sensitivity, an increase was found in subjects with diabetes (P<0.05) although it remained lower compared to NGT- and IGT-subjects (P<0.01). At 12 months follow-up, no differences among groups were found in the evaluated glucose homeostasis parameters. Compared to baseline, at 6 weeks the incremental AUC(0-120') of active GLP-1 in response to the STM increased in NGT and IGT (P<0.05) but not in subjects with diabetes (P=0.285). However, the GLP-1 response to a STM was comparable among groups at 12 months follow-up (P=0.887). CONCLUSIONS: 1) RYGBP was associated with an improvement but not complete restoration of glucose homeostasis at 6 weeks after surgery. 2) GLP-1 is not a critical factor for the early changes in glucose tolerance.

Short-term effects of gastric bypass surgery on circulating ghrelin levels.

OBJECTIVE: To prospectively evaluate the short-term effects of Roux-en-Y gastric bypass (RYGBP) on ghrelin secretion and its relevance on food intake and body weight changes. RESEARCH METHODS AND PROCEDURES: Ghrelin response to a standardized test meal was evaluated in eight obese patients (BMI, 43.5 to 59.1 kg/m2) before and 6 weeks after RYGBP. Ghrelin response was compared with that of an age-matched group of six normal weight individuals (BMI, 19.6 to 24.9 kg/m2). RESULTS: Fasting serum ghrelin levels were lower in obese subjects compared with controls (p < 0.05). Meal ingestion significantly suppressed ghrelin concentration in controls (p < 0.05) and obese subjects (p < 0.05), albeit to a lesser degree in the latter group (p < 0.05). Despite a 10.3 +/- 1.5% weight loss, fasting serum ghrelin levels were paradoxically further decreased in obese subjects 6 weeks after RYGBP (p < 0.05). Moreover, at this time-point, food intake did not elicit a significant ghrelin suppression. The changes in ghrelin secretion after RYGBP correlated with changes in insulin sensitivity (p < 0.05) and caloric intake (p < 0.05). DISCUSSION: This study showed that the adaptive response of ghrelin to body weight loss was already impaired 6 weeks after RYGBP. Our study provides circumstantial evidence for the potential role of ghrelin in the negative energy balance in RYGBP-operated patients.

Insulin lispro is as effective as regular insulin in optimising metabolic control and preserving beta-cell function at onset of type 1 diabetes mellitus.

The aim of the study was to examine the effects of intensive insulin therapy using lispro on metabolic control, immunogenicity and beta-cell function of newly diagnosed type 1 diabetic subjects in comparison with intensive insulin therapy using regular insulin. An open study was conducted in 45 newly diagnosed type 1 diabetic subjects. Patients were randomly assigned to intensive insulin therapy using insulin lispro (lispro) (lispro, n=22; 22.8 years) or intensive insulin therapy using regular insulin (regular) (regular, n=23; 24.4 years): three to five injections of subcutaneous rapid-acting insulin before meals and Neutral Protamine Hagedorn (NPH) before dinner/bed-time. GAD, IA2, insulin antibodies, basal and stimulated plasma C-peptide and HbA(1c) were measured initially and at months 1, 4, 8 and 12. Daily blood glucose profiles tended to be lower in the lispro group, particularly values after breakfast, without reaching statistical significance. There were no differences in terms of HbA(1c) throughout the study. The proportion of subjects achieving an HbA(1c)<6% at the end of the study was similar in both groups (regular 73.9%, lispro 68.0%). The number of mild hypoglycemic episodes tended to be lower with lispro, but not significantly. beta-Cell function was not significantly different in both groups. During follow-up there were no differences in antibodies, including IAAb. In summary, insulin lispro used in intensive insulin therapy is as effective as regular insulin in optimizing metabolic control and preserving beta-cell function at diagnosis of type 1 diabetes.

[Clinical, metabolic, immunologic and genotypic characteristics in non-pediatric patients with type 1A diabetes mellitus. Onset and short-term prognosis]. / Características clínicas, metabólicas, inmunológicas y genotípicas de un grupo de adolescentes y adultos con diabetes mellitus tipo 1A. Inicio y pronóstico a corto plazo.

BACKGROUND AND OBJECTIVE: Around 50% of new cases of type 1 diabetes mellitus (DM1) are seen in subjects aged above 15 years. It is of particular interest the characterization of such a population. THE AIMS OF OUR STUDY WERE: a) to characterize a group of non-pediatric subjects with DM1 at the onset of the disease; b) to evaluate the prognosis of the disease under conventional intensive insulin therapy, and c) to investigate the presence of mutations in the HNF-1* gene in those subjects who did not display pancreatic autoimmune markers. SUBJECTS AND METHOD: All subjects with an age >= 15 and 35 years recently diagnosed DM1 (1998-2001) were included in the study. Pancreatic cell function was assessed by glucagon test (at onset and at 12 months). The presence of pancreatic autoantibodies, GAD, IA2 and IAA was evaluated. HLA class II genes and the 10 exons of HNF-1* gene were analyzed from genomic DNA. RESULTS: We studied 86 subjects (32 women, 23.9 [5.3] year-old). Eighty percent of subjects were positive for any of the studied autoantibodies. Alone or in combination, GAD was positive in 68.6% of subjects, IA2 in 45.3% and IAA in 27.9% of them. Most frequent haplotype was DRB1*0301-DQA1*0501-DQB*0201. There were no differences with regard to clinical, metabolic or genetic characteristics among those subjects with or without presence of pancreatic autoantibodies (at onset and at 12 months). We did not find mutations in the HNF-1* gene in any of the subjects included in our study. After 12 months of follow-up, cell function remained unaltered in comparison with that observed at the onset of the disease. CONCLUSIONS: Clinical, immunological and HLA characteristics of a non-pediatric DM1 population are in agreement with expected results. The absence of pancreatic autoimmune markers neither rules out the existence of type 1A diabetes mellitus nor is associated with mutations in the MODY-3 gene. A therapeutic programme using conventional intensified insulin treatment prevents the impairment of insulin secretory capacity for a short-term follow-up.

Características clínicas, metabólicas, inmunológicas y genotípicas de un grupo de adolescentes y adultos con diabetes mellitus tipo 1A. Inicio y pronóstico a corto plazo / Clinical, metabolic, immunologic and genotypic characteristics in non-pediatric patients with type 1A diabetes mellitus. Onset and short-term prognosis

FUNDAMENTO Y OBJETIVO: Aproximadamente la mitad de los nuevos diagnósticos de diabetes mellitus tipo 1A (DM1A) en nuestro medio se realizan en sujetos mayores de 15 años. En este contexto su caracterización tiene un interés indudable. Los objetivos de nuestro estudio fueron: a) caracterizar un grupo de sujetos, en edad no pediátrica, con DM1A al inicio de la enfermedad; b) valorar su pronóstico tras instaurar tratamiento intensivo con insulina, y c) investigar la presencia de mutaciones en el gen de HNF-1 en los sujetos sin datos de autoinmunidad pancreática. PACIENTES Y MÉTODO: Se estudió a todos los pacientes con edades comprendidas entre los 15 y 35 años, ambas inclusive, con un inicio reciente de DM1A (1998-2001). La función pancreática se evaluó mediante una prueba de estimulación con glucagón (al inicio y a los 12 meses).Se determinó la presencia de autoanticuerpos pancreáticos incluyendo GAD, IA2 y AAI. La tipificación genómica de los genes HLA de clase II y el estudio de los 10 exones del gen HNF-1 se efectuaron a partir de ADN genómico. Todos los pacientes fueron incluidos en un programa de tratamiento convencional intensivo con insulina en múltiples dosis. RESULTADOS: Se incluyó a 86 pacientes (32 mujeres, con una edad media [DE] de 23,9 [5,3] años). Un 80 per cent de los pacientes presentaba positividad para alguno de los autoanticuerpos pancreáticos. Solos o en combinación, GAD fue positivo en el 68,6 per cent de los pacientes; IA2, en el 45,3 per cent, y AAI, en el 27,9 per cent. El haplotipo más frecuente fue DRB1*0301-DQA1*0501-DQB*0201.La presencia o ausencia de anticuerpos antipancreáticos no condicionó diferencias clínicas, metabólicas o genotípicas (inicio y 12 meses). En ninguno de los pacientes estudiados (con o sin la presencia de autoanticuerpos pancreáticos) encontramos mutaciones en el gen HNF-1 . Después de un año de seguimiento la función pancreática permaneció inalterada. CONCLUSIONES: Las características clínicas, inmunológicas y de HLA en una población de edad no pediátrica con DM1A concuerda con lo esperado. La ausencia de marcadores de autoinmunidad pancreática no descarta la presencia de una DM1A ni se asocia a mutaciones del gen MODY-3. La instauración de un tratamiento intensivo con insulina previene el deterioro de la capacidad de secreción de insulina (AU)