Investigating the effect of sex and ketosis on weight-loss-induced changes in appetite.

BACKGROUND: Diet-induced weight loss (WL) is usually accompanied by increased appetite, a response that seems to be absent when ketogenic diets are used. It remains unknown if sex modulates the appetite suppressant effect of ketosis. OBJECTIVE: The aim of this study was to examine if sex modulates the impact of WL-induced changes in appetite and if ketosis alters these responses. METHODS: Ninety-five individuals (55 females) with obesity (BMI [kg/m 2]: 37  ± 4) underwent 8 wk of a very-low-energy diet, followed by 4 wk of refeeding and weight stabilization. Body composition, plasma concentration of ß-hydroxybutyrate (ß-HB) and appetite-related hormones (active ghrelin, active glucagon-like peptide 1 [GLP-1], total peptide YY [PYY], cholecystokinin and insulin), and subjective feelings of appetite were measured at baseline, week 9 in ketosis, and week 13 out of ketosis. RESULTS: The mean WL at week 9 was 17% for males and 15% for females, which was maintained at week 13. Weight, fat, and fat-free mass loss were greater in males (P < 0.001 for all) and the increase in ß-HB at week 9 higher in females (1.174 ± 0.096 compared with 0.783 ± 0.112 mmol/L, P = 0.029). Basal and postprandial GLP-1 and postprandial PYY (all P < 0.05) were significantly different for males and females. There were no significant sex × time interactions for any other appetite-related hormones or subjective feelings of appetite. At week 9, basal GLP-1 was decreased only in males (P < 0.001), whereas postprandial GLP-1 was increased only in females (P < 0.001). No significant changes in postprandial PYY were observed over time for either sex. CONCLUSIONS: Ketosis appears to have a greater beneficial impact on GLP-1 in females. However, sex does not seem to modulate the changes in the secretion of other appetite-related hormones, or subjective feelings of appetite, seen with WL, regardless of the ketotic state. This trial was registered at clinicaltrials.gov as NCT01834859.

Widespread blunting of hypothalamic and amygdala-septal activity and behavior in rats with long-term hyperglycemia.

Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of ∼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.

Topiramato en monoterapia o en combinación como causa de acidosis metabólica en adultos con epilepsia / Topiramate in monotherapy or in combination as a cause of metabolic acidosis in adults with epilepsy

Objetivo. Determinar la frecuencia de acidosis metabólica y sus factores relacionados en pacientes tratados con topiramato solo o como adyuvante para el tratamiento de epilepsia. Pacientes y métodos. Análisis transversal de la gasometría arterial de pacientes epilépticos que recibieron topiramato durante 2010 en la clínica de epilepsia del Centro Médico Nacional 20 de Noviembre en México. Se registraron datos clínicos concernientes a la epilepsia y su tratamiento, así como de los síntomas comunes de acidosis metabólica. Resultados. Se estudiaron 32 adultos con epilepsia, quienes recibieron topiramato en monoterapia o en combinación por lo menos durante un mes. Se encontró acidosis metabólica en todos los pacientes (HCO3 < 22 Eq/L); nueve tomaron sólo topiramato y 23 tomaron por lo menos dos fármacos antiepilépticos (FAE). Todos los pacientes fueron asintomáticos. No se encontró correlación entre los niveles de bicarbonato y la dosis del medicamento o la duración del tratamiento. La dosis fue significativamente mayor en el grupo de monoterapia y el nivel de bicarbonato fue más bajo en los pacientes que tomaban más de un FAE. Conclusiones. El uso concomitante de FAE incrementa los efectos conocidos del topiramato sobre los niveles séricos de bicarbonato y la presencia de acidosis metabólica; estos efectos parecen ser independientes del número de FAE utilizados (AU)

Aim. To determine the frequency of metabolic acidosis and its related factors in outpatients taking topiramate in monotherapy or as an adjuvant for the treatment of epilepsy. Patients and methods. Cross-sectional analysis of arterial blood gas test of epileptic patients who received topiramate during 2010 in the Epilepsy Clinic at the National Medical Center ‘20 de Noviembre’ in Mexico. Clinical data regarding epilepsy history and management and the common symptoms of metabolic acidosis were recorded. Results. We studied 32 adults with epilepsy at an outpatient epilepsy clinic who were treated with topiramate in monotherapy or in combination for at least one month. Metabolic acidosis was found in all patients (HCO3 < 22 Eq/L); nine were taking topiramate in monotherapy, and 23 were taking at least two antiepileptic drugs (AEDs). All of the patients were asymptomatic. We found no correlation between bicarbonate levels and the dose of the drug or the duration of treatment. The dose was significantly higher in the monotherapy group, and the bicarbonate level was lower in the patients taking more than one AEDs. Conclusions. The use of concomitant AEDs increases the known effects of topiramate on serum bicarbonate levels and the presence of metabolic acidosis, and these effects appear to be independent of the number of AEDs used (AU)

Dificultades en el control glucémico del paciente diabético / Obstacles to achieving glycemic control in diabetics

En la actualidad, el manejo de la diabetes a largo plazo continúa siendo un importante reto para el paciente, su familia y el equipo sanitario. El buen control glucémico es uno de los pilares centrales del tratamiento de la diabetes y sus beneficios son bien conocidos, tanto por los médicos como por los propios pacientes. Pocos años después del descubrimiento de la insulina se puso en evidencia un número importante de dificultades para la consecución de un adecuado control glucémico del paciente diabético. Muchos de estos problemas han venido derivados de las distintas formulaciones de insulina que se usaban inicialmente para obtener insulinas altamente purificadas, posteriormente insulinas humanas y, por último, diversos análogos de insulina de acción rápida y de acción prolongada, que han ido facilitando la consecución de un mejor control metabólico y menos problemas derivados de su tratamiento. El desarrollo de fármacos hipoglucemiantes orales cada vez más específicos, con dianas terapéuticas cada vez más definidas, también ha facilitado el manejo de la diabetes mellitus tipo 2. A las limitaciones que puedan presentar las distintas armas terapéuticas de la diabetes se une la propia historia natural de la enfermedad y la obligatoria implicación del paciente en su manejo, lo cual añade otro amplio grupo de limitaciones. Centrándonos en el paciente con diabetes mellitus tipo 1 o 2 cuando requiere tratamiento insulínico, hemos de reconocer que a pesar del importante avance farmacológico en los preparados insulínicos en la actualidad, todos los profesionales dedicados al manejo de la diabetes tienen experiencia con grupos concretos de pacientes en los que resulta muy difícil conseguir un adecuado control glucémico. Algunos presentan hipoglucemias recurrentes; otros tienen hiperglucemias a pesar de muy altas dosis de insulina, incluso con episodios repetidos de cetoacidosis, y un grupo de ellos combinan cuadros clínicos de hipoglucemia con hiperglucemia. En este espectro de situaciones se encuadra también la entidad conocida como diabetes lábil (AU)

Currently, the long-term management of diabetes continues to pose a major challenge to patients, their families and health teams. Good glycemic control is one of the main pillars of diabetes treatment and its benefits are well known both by physicians and their patients. A few years after the discovery of insulin, a substantial number of obstacles to achieving adequate glycemic control in diabetics became known. Many of these problems were due to the distinct insulin formulations initially used until highly purified formulations became available. Subsequently, human insulin and various rapid-acting and prolonged action insulin analogs have helped to improve metabolic control and reduce treatment-related problems. The development of increasingly specific oral hypoglycemiant agents with well-defined therapeutic targets has also improvement the management of type 2 diabetes mellitus. In addition to the limitations of the various therapeutic options in diabetes, the natural history of the disease and the necessary involvement of the patient in the management of the disease represent further obstacles. All health professionals involved in the management of patients with type 1 or 2 diabetes mellitus requiring insulin therapy have experience of specific groups of patients with difficulties in achieving adequate glycemic control, despite significant improvements in current insulin preparations. Some of these patients show recurrent hypoglycemia, others show hyperglycemia – even with recurrent episodes of ketoacidosis – despite high-dose insulin, and some show a clinical picture of hypoglycemia with hyperglycemia. The entity known as labile diabetes can be included within this spectrum (AU)

The ketogenic diet may have mood-stabilizing properties.

The ketogenic diet, originally introduced in the 1920s, has been undergoing a recent resurgence as an adjunctive treatment for refractory epilepsy, particularly in children. In this difficult-to-treat population, the diet exhibits remarkable efficacy with two-thirds showing significant reduction in seizure frequency and one-third becoming nearly seizure-free. There are several reasons to suspect that the ketogenic diet may also have utility as a mood stabilizer in bipolar illness. These include the observation that several anticonvulsant interventions may improve outcome in mood disorders. Furthermore, beneficial changes in brain-energy profile are noted in subjects on the ketogenic diet. This is important since global cerebral hypometabolism is a characteristic of the brains of depressed or manic individuals. Finally, the extracellular changes that occur in ketosis would be expected to decrease intracellular sodium concentrations, a common property of all effective mood stabilizers. Trials of the ketogenic diet in relapse prevention of bipolar mood episodes are warranted.

Mood and appetite during minimal-carbohydrate and carbohydrate-supplemented hypocaloric diets.

After a baseline period of free-feeding, 20 obese outpatients alternated between four 2-wk periods of minimal-carbohydrate diet (800 kcal; 58% protein and 42% fat by weight) and of a carbohydrate-supplemented diet (1,000 kcal; 42% protein, 30% fat, and 28% carbohydrate). In a comparison of psychological adjustment during the baseline and low-calorie diets, the initial 2 wk of dieting was associated with a decrease in appetite and elevation of psychological well-being, regardless of the composition of the diet. Thereafter, appetite and mood approached basal levels. Further changes in these psychological reactions to dieting did not vary with the type of diet. There was no support for the idea that a minimal-carbohydrate, protein-supplemented fast decreases appetite and elevates mood more in comparison with a similar diet containing enough carbohydrate to minimize ketosis.