Análisis de la evidencia disponible para el consumo de edulcorantes no calóricos. Documento de expertos / Analysis of the available evidence for the intake of non-caloric sweeteners. Expert document

Resumen Los edulcorantes no calóricos representan una buena alternativa para sustituir los sabores dulces sin la respuesta fisiológica que genera el consumo de azúcares. Por sí solos no son herramientas para el control de peso. Su consumo debe ir acompañado de una dieta correcta y un estilo de vida saludable que incluya actividad física. Su utilidad radica en proporcionar el agradable sabor dulce sin el aporte energético. La inocuidad de cada uno de los compuestos aprobados está comprobada y se reevalúa constantemente para tomar en cuenta los resultados de nuevos estudios. Debido a que no existe un edulcorante perfecto, la variedad ayuda a que se desarrollen productos cada vez más agradables para el consumidor. Este trabajo es fruto de una revisión exhaustiva de la bibliografía y de las discusiones de un panel de expertos de diversas especialidades: toxicología, ginecoobstetricia, pediatría, endocrinología, nutrición, medicina interna, salud pública y medicina preventiva, en el que se analizó extensamente la bibliografía se revisó una variedad de trabajos científicos que responden a las interrogantes que habitualmente se hacen los profesionales de la salud acerca de seguridad en diferentes grupos etáreos y con afecciones específicas, ingestión diaria admisible, etc.

Abstract Non-caloric sweeteners are a good alternative to replace the sweet flavors without the physiological response generated by the consumption of sugars. Alone they are not tools for weight control. Its intake must be accompanied by a proper diet and a healthy lifestyle that includes physical activity. Its usefulness lies in providing a pleasant sweet taste without the energy intake. The safety of each of the compounds is tested and approved and constantly reassessed to take into account the results of new studies. Since there is no perfect sweetener, variety helps that more and more pleasing to the consumer products are developed. This work is the result of a comprehensive review of the literature and discussions of a panel of experts from various specialties: toxicology, obstetrics and gynecology, pediatrics, endocrinology, nutrition, internal medicine, public health and preventive medicine, where literature was widely analyzed reviewing a variety of scientific papers that address the questions that usually are made by health professionals on safety in different age groups and with specific diseases, acceptable daily intake, etc.

Control of Tick Infestations in Oryctolagus cuniculus (Lagomorpha: Leporidae) With Spinosad Under Laboratory and Field Conditions.

Because of great economic loss in the world's livestock industry, and the serious risks to human health, the control of ticks and tick-borne diseases is one of the most important health management issues today. Current methodology involves integrated tick control for preventing the development of resistance. Rabbits are hosts for immature stages of the three-host tick Hyalomma lusitanicum Koch; so, we focus on this host as a strategy to interrupt the tick life cycle. Spinosad is an insecticide-acaricide, produced by the fermentation of metabolites of the actinomycete bacterium Saccharopolyspora spinosa. We administered spinosad orally by force-feeding naturally and artificially infested rabbits, and under field conditions by administering treated food via a hopper during the period of peak infestation and reinfestation risk for rabbits. No living larvae were recovered from treated laboratory rabbits. In naturally infested rabbits, the number of live ticks collected from treated rabbits (mean = 0.62 ticks per ear) was significantly lower than those recovered from untreated rabbits (mean = 7.27; P < 0.001), whereas the number of dead ticks collected from untreated rabbits (mean = 6.53) was significantly lower than those recovered from treated rabbits (mean = 18.62; P < 0.001). In addition, free and continually reinfested rabbits freely ingested low doses of spinosad, reducing the tick burden from 48.00 (Day 0) to 26.09 ticks per ear in treated rabbits (Day 16), whereas controls maintained the infection (46.64). This strategy could be useful as an alternative or supplement to traditional acaricides in tick control programs.

Ribavirin stimulates the immune response of Atlantic salmon.

Ribavirin is a synthetic nucleotide analog capable of inhibiting or even preventing some viral infections in mammals and also in fish. It has been seen by others that ribavirin by itself is able to stimulate the immune system of mammals, causing a differentiation of T-cells to T helper 1 cells (Th)-1. In this work, we evaluated the immune effect of ribavirin in vitro on kidney cells from Atlantic salmon and in vivo by oral administration of ribavirin to Atlantic salmon. For this purpose, the transcripts of immune molecules Tbet, GATA3, CD8, CD4, IFNα, IFNγ, IL-4/13, IL-10, IL-12, IL-15 and TGF-B were quantified. The results show that ribavirin administered orally in food to Atlantic salmon increased IFNγ and CD4 transcripts in the in vivo assays and, in addition, increased IL-12, IL-15 and CD8 in the in vitro analyses, indicating that the treatment stimulates a Th1 type response in salmon.

X-PERT: weight reduction with orlistat in obese subjects receiving a mildly or moderately reduced-energy diet: early response to treatment predicts weight maintenance.

AIM: To determine the effect of two different levels of energy deficit on weight loss in obese patients treated with orlistat. METHODS: Patients (n=430) were randomized in a 1-year, multicentre, open-label, parallel group study conducted at 23 hospital centres and university medical departments worldwide. Obese outpatients (body mass index 30--43 kg/m(2)) aged 18--70 years with a body weight of >or=90 kg and a waist circumference of >or=88 cm (women) or >or=102 cm (men) were treated with orlistat 120 mg three times daily plus a diet that provided an energy deficit of either 500 or 1,000 kcal/day for 1 year. Orlistat treatment was discontinued in patients who did not achieve >or=5% weight loss after assessment at 3 and 6 months. The primary outcome measure was change in body weight from baseline at week 52. RESULTS: Reported mean difference in energy intake between the two groups (500-1,000 kcal/day deficit) at weeks 24 and 52 was actually 111 and 95 kcal/day respectively. Of the 430 patients involved in the study, 295 achieved >or=5% weight loss at both 3 and 6 months. In this population, at week 52, weight loss from baseline was similar for patients randomized to either the 500 or the 1,000 kcal/day deficit diet (-11.4 kg vs. -11.8 kg, respectively; p=0.778). After 12 months of treatment with orlistat, 84% (n=118/141) and 85% (n=131/154) of patients in the 500 and 1,000 kcal/day deficit groups, respectively, achieved >or=5% weight loss, and 50% (n=70/141) and 53% (n=82/154) of patients, respectively, achieved >or=10% weight loss. Patients in both the diet treatment groups showed similar significant improvements in blood pressure, lipid levels and waist circumference at week 52. CONCLUSIONS: Treatment with orlistat was associated with a clinically beneficial weight loss, irrespective of the prescribed dietary energy restriction (-500 or -1000 kcal/day). Patients who achieved >or=5% weight loss at 3 months achieved long-term, clinically beneficial weight loss with orlistat plus either diet. Therefore, identifying patients who lose at least 5% weight after 3 months and who maintain this weight loss up to 6 months is a valuable treatment algorithm to select patients who will benefit most from orlistat treatment in combination with diet.

[The immediate results of percutaneous transluminal coronary angioplasty at Hospital San José de Monterrey]. / Resultados inmediatos de la angioplastía coronaria percutánea transluminal en el Hospital San José de Monterrey.

We analyzed 69 consecutive PTCA performed upon 64 patients from January 1990 to May 1992. Age was 55 +/- 12 years and 80% were male. Fifty-nine percent were smokers, 32% had hypertension, 16% a remote myocardial infarction, 14% diabetes, 12% previous PTCA, and 6% previous coronary artery bypass surgery. Total cholesterol was 238 +/- 75 mg/dl. Most of the subjects had an acute coronary syndrome, with unstable angina in 31 and a recent myocardial infarction in 23. Angiographically, 52% had single vessel disease, 39% had double vessel and 9% triple vessel disease. LVEF was 55 +/- 11%, LVEDP 17 +/- 10 mm Hg, and 44% had wall motion abnormalities. We dilated 1.4 lesions/patient (1-4), for a total of 100 lesions. Luminal stenosis was reduced from (mean +/- SEM) 88.5 +/- 1.1% to 22.6 +/- 2.2% (p < 0.0001). The procedure was a total clinical success in 85.6% of the patients and a partial clinical success in 4.3%. Complete revascularization was achieved in 62.3% and incomplete but adequate revascularization in 26%. Multiple lesions dilatation was performed in 30% of the patients and multiple vessel angioplasty in 17%. Forty-seven lesions were on the LAD distribution (91.5% angiographic success), 24 on the circumflex (95.8% angiographic success), 26% on RCA (88.4% angiographic success) and 3 in others. There was a 10% failure and 13% complication rates, but more than half of them were successfully managed medically, although 5.7% required urgent CABG. One patient died.

Factors affecting the urinary excretion of albumin in insulin-dependent diabetes.

To determine the specificity of the urine excretion of albumin as a measure of glomerular permeability in early insulin-dependent diabetic nephropathy, the effect of variable glomerular filtration and urine flow rates on albumin, beta 2-microglobulin excretion, and the fractional renal clearance of neutral dextran (Stokes Einstein Radius 24-46 A) was examined. Five insulin-dependent diabetic subjects with normal glomerular permeability (albumin excretion less than 30 micrograms/min) and one with elevated albumin excretion (195 micrograms/min) were studied pre and post strict glucose control with constant subcutaneous insulin infusion for 7 days. The albumin excretion in the 5 subjects never exceeded 30 micrograms/min during wide variations in glomerular filtration and urine flow rates. A positive correlation between beta 2-microglobulin excretion and urine flow (r = 0.81), and glomerular filtration (r = 0.77) rates was observed. In contrast, albumin excretion showed no correlation, indicating different factors affect the excretion rate of albumin and beta 2-microglobulin. Therefore, elevated albumin excretion (greater than 30 micrograms/min) in insulin-dependent diabetes is due to increased glomerular permeability and not changes in glomerular filtration and urine flow rates, and the albumin/ beta 2-microglobulin ratio may not be a valid indicator of changing glomerular permeability. The fractional neutral dextran clearances remained unchanged with variation in glomerular filtration and urine flow rates. The sieving curve was identical in all subjects for neutral dextran 40 A, the size of albumin, suggesting that reduced glomerular charge selectivity may contribute to increased albuminuria in progressive diabetic glomerulosclerosis.

Effects of weight loss in massive obesity on insulin and C-peptide dynamics: sequential changes in insulin production, clearance, and sensitivity.

In massively obese patients hyperinsulinemia and insulin insensitivity usually improve with weight loss. To clarify the mechanism of these reversible abnormalities eight nondiabetic massively obese patients were studied before and at intervals (3 months and 1 yr) after weight loss following gastroplasty. Insulin dynamics were studied during the hyperglycemic clamp (change in glucose, 7 mmol L-1 for 2 h) by measuring the area under the insulin and C-peptide response curves, representing, respectively, systemic insulin response and insulin production. Compared to lean age-matched normal subjects the massively obese patients had the expected fasting hyperinsulinemia and an exaggerated insulin response (P less than 0.05). Within 3 months and after an approximately 20% weight loss, they had a marked reduction in the systemic insulin response but no change in the C-peptide response. Therefore, the reduction in insulin response was due to enhanced hepatic insulin clearance rather than reduced insulin production. Thus, the liver serves a gate-keeping role in regulating the systemic insulin response to a glucose challenge. With additional weight loss of 14% and then weight maintenance, insulin clearance was further increased, and a reduction in insulin production became evident, since the C-peptide response was reduced. Exogenous insulin clearance was measured using the euglycemic clamp technique before and after weight loss. Insulin clearance was initially lower in the massively obese patients compared to that in the normal subjects (P less than 0.05) and increased toward normal with weight loss (P less than 0.05). Similarly, insulin sensitivity, as measured by the ratio of glucose metabolised per U endogenous insulin, normalized with weight loss and weight maintenance. Thus, after significant weight loss followed by weight maintenance at a reduced, but not ideal, level, insulin clearance, production, and sensitivity all reverted to normal. These findings suggest that adipose mass per se may not be exclusively responsible for altered insulin and glucose dynamics in obesity and that additional factors associated with obesity, such as nutrient load, adipose distribution, fat cell size, or fatty acid flux, play a contributing role.

Changes in insulin sensitivity and clearance in anorexia nervosa.

Anorexia nervosa (AN) is a state of self-induced malnutrition characterized by a marked pursuit of thinness and the fear of obesity. Although low fasting blood glucose and insulin have been demonstrated, there is contradictory data on insulin sensitivity and a lack of information about insulin metabolism and its metabolic effects in AN. Insulin sensitivity, kinetics, and metabolic effects were measured using the euglycemic clamp in nine females with AN (age 25.2 +/- 1.9 years and 70.6 +/- 2.2% ideal body weight), and the results compared with seven female normal controls (NC) (age 23.6 +/- 1.0 years and 92.7 +/- 2.5% ideal body weight). Fasting plasma glucose (FPG), immunoreactive insulin (IRI), and C-peptide were significantly lower in AN as compared to NC (84.3 +/- 1.5 v 91.5 +/- 1.7 mg dL-1, 9.3 +/- 1.0 v 13.5 +/- 1.4 microU mL-1, and 0.26 +/- 0.03 v 0.41 +/- 0.02 pmol mL-1) (P less than 0.05). During the glucose clamp, the glucose metabolized (M), the metabolic clearance rate of glucose (MCRg), and the glucose metabolized per unit of insulin (M/I ratio) were all higher in AN as compared to NC (M, 8.7 +/- 1.2 v 6.9 +/- 0.6 mg min-1 kg-1; MCRg, 9.9 +/- 1.5 v 7.4 +/- 0.6 mL min-1 kg-1; M/I ratio, 8.6 +/- 1.6 v 5.0 +/- 0.3 mg min-1 kg-1/microU mL-1 X 100), but only the M/I ratio attained statistical significance (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparación de tres fórmulas dietéticas en lactantes con diarrea aguda / Comparison of 3 dietetic formulas in infants with acute diarrhea

Se comparan los balances de agua, sales y nitrógeno y la evolución clínica, en 3 grupos de lactantes con Síndrome diarreico agudo, uno de los cuales se realimentó con leche, y los otros dos con quesillo de Eledón reconstituído, con y sin agregado de zanahoria respectivamente. Con las 3 fórmulas se obtuvo absorción y retención nitrogenada satisfactorias. No hubo diferencias significativas en la velocidad del tránsito intestinal al 7§ día, ni en la incidencia de evolución tórpida del cuadro diarreico. El grupo que recibió zanahoria en la dieta presentó pérdidas hidroelectrolíticas por deposiciones algo mayores, aunque no estadísticamente significativas. Destacó la persistencia de pérdidas importantes por deposiciones entre el 4§ y 7§ días, y la ausencia de ganancia ponderal (excepto por cambios de hidratación) en los tres grupos, no obstante lo cual se obtuvo balance nitrogenado positivo en la mayoría de los lactantes. Se concluye que la presencia de fibra en la dieta, o el uso de fórmulas sin lactosa, no modifican ostensiblemente la evolución ni la magnitud de las pérdidas por deposiciones en el Síndrome diarreico agudo del lactante

Effects of massive obesity on insulin sensitivity and insulin clearance and the metabolic response to insulin as assessed by the euglycemic clamp technique.

Insulin sensitivity was studied in nine nondiabetic massively obese patients (one male and eight females ages 39.0 +/- 2.7 years, body mass index 47.1 +/- 1) by the euglycemic clamp technique (40 microU/m2/min) and compared to seven lean control subjects (three males and three females, ages 34.8 +/- 2.5 years, body mass index 23 +/- 1.1). Fasting plasma glucose, immunoreactive insulin, and C-peptide concentrations were higher in the massively obese patients than in the controls (P less than 0.025). Following exogenous insulin infusion, immunoreactive glucagon and C-peptide concentrations decreased similarly in the massively obese patients and controls, indicating normal sensitivity of the alpha and beta cell to insulin. Glucose uptake (M) expressed either as mg X min-1 of fat free mass was significantly reduced in the massively obese patients compared to the controls (P less than 0.001). Similarly, the M/I ratio (glucose uptake per unit of insulin) was significantly reduced in the massively obese patients (P less than 0.001). Free fatty acids and glycerol concentrations measured in the fasting state were significantly elevated in the massively obese patients (free fatty acids 678 +/- 51 v 467 +/- 55 mumol/L, P less than 0.05; glycerol 97 +/- 9 v 59 +/- 11 mumol/L, P less than 0.02). The effects of insulin on antilipolysis was assessed by measuring the reductions in free fatty acids and glycerol concentration during the glucose clamp study. Although the absolute levels remained higher in the massively obese patients, inhibition of lipolysis was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The metabolic response to the euglycemic insulin clamp in type I diabetes and normal humans.

The euglycemic insulin clamp has been utilized extensively to measure in vivo tissue sensitivity to insulin under various circumstances. Insulin sensitivity is determined from the amount of glucose metabolized under steady state conditions. To assess the effect of abnormalities in other insulin responsive metabolic pathways on glucose metabolism and thus insulin sensitivity as measured by the glucose clamp, the concentration of lactate, pyruvate, 3-hydroxybutyrate, glycerol, alanine, and free fatty acids were measured at baseline and during a two-hour euglycemic clamp in 13 nonobese subjects with type I diabetes. The observed responses were compared to 11 normal controls. Insulin sensitivity as measured by M (glucose metabolized), MCRg (metabolic clearance of glucose), and M/I ratio (glucose metabolized per unit insulin) were all significantly decreased in the diabetic subjects (P less than 0.005). Free fatty acids (FFA) and 3-hydroxybutyrate were significantly elevated at baseline in the diabetic subjects (P less than 0.05) and decreased significantly at 60 and 120 minutes in both groups. Baseline blood pyruvate and lactate concentrations were similar in the control and diabetic subjects. Pyruvate increased significantly at 60 minutes in both groups (P less than 0.05) and returned to baseline in the control subjects but remained elevated at 120 minutes in the diabetic subjects (P less than 0.001). Lactate increased similarly in both groups and remained elevated at 60 and 120 minutes. In summary, insulin sensitivity as assessed by the euglycemic insulin clamp is decreased in type I diabetes. However, specific differences in the concentration of several other metabolites both at baseline and in response to hyperinsulinemia were also identified in the diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the acute and long-term effects of exercise on glucose control in type I diabetes.

To determine the long-term effect of exercise training on glucose control, 13 subjects with type I diabetes and 7 control subjects performed 45 min of cycle exercise three times per wk for 12 wk. The acute blood glucose response, the long-term effect on glucose control (glycosylated hemoglobin and fasting plasma glucose), and changes in nutrient intake were assessed. Fitness as measured by VO2 MAX increased in both control (33.8 +/- 1.7 to 43.2 +/- 3.5 ml/min/kg) and diabetic (38.7 +/- 3.3 to 46.5 +/- 3.6 ml/min/kg) (P less than 0.05) subjects although body weight remained unchanged. In the diabetic subjects, an acute glucose-lowering effect occurred with each exercise session throughout the 12-wk training period (225.8 +/- 16.1 to 148.5 +/- 16.8 mg/dl, P less than 0.001). However, fasting plasma glucose and glycosylated hemoglobin remained essentially unchanged (pretraining, 193.7 +/- 27.5 mg/dl and 10.7 +/- 0.3%; 6-wk training, 192.5 +/- 27.1 mg/dl and 10.7 +/- 0.03%; 12-wk training, 202 +/- 30.1 mg/dl and 10.3 +/- 0.8%). Total caloric intake as assessed by diet history increased significantly on exercising days (2569-2849 kcal, P less than 0.05). Although plasma glucose decreases acutely with exercise, increased caloric intake on exercising days obviates a long-term effect of training on glucose control. More precise guidelines and recommendations as to exercise timing and nutrient intake, likely based on self-monitoring of blood glucose, are required to achieve a beneficial effect of exercise training on metabolic control in type I diabetes.