Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder.

OBJECTIVE: Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD), but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I. METHODS: The available relatives of the same family were interviewed (DSM-IV-R) and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS), leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs) for the leptin receptor and promoter and PPAR-γ2 genes. The frequency of MS was compared with that recorded in the local general population. RESULTS: Ninety-three relatives of three adults with BD were evaluated (30 aged < 18 years, 63 aged > 18 years). The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c) levels (all p < 0.05), waist circumference (p = 0.057), and leptin and insulin resistance values (in adults only) were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele. CONCLUSIONS: The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees.

Prevalencia del síndrome metabólico, índice de insulino resistencia y niveles de leptina y hormona tiroidea en la población general de Mérida (Venezuela) / Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Mérida (Venezuela)

The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged ³18 years from the Libertador district in Mérida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage ± 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients’ self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

El síndrome metabólico (SM) es un factor de riesgo significativo en la ocurrencia de eventos cardiovasculares. Sin embargo, existe poca información sobre su frecuencia en Venezuela. En la presente investigación transversal, cuantificamos la prevalencia del SM es una muestra probabilística de 274 sujetos con edad mayor o igual a 18 años provenientes del municipio Libertador de la cuidad de Mérida, Venezuela. Como resultados secundarios, se cuantificaron los niveles de leptina, hormonas tiroideas (T4 libre y TSH), y el índice de resistencia a la insulina (HOMA2-RI). La frecuencia de SM (porcentaje ± intervalo de confianza del 95%) de acuerdo a varios criterios diagnósticos fue la siguiente: Panel para el Colesterol (original): 27,4% (22,1-32,7); Panel para el Colesterol (modificado): 31,8% (26,3-37,3); Federación Internacional de Diabetes: 40,9% (35,1-46,7); Asociación Latino-Americana de Diabetes: 27% (21,7- 32,3) y criterios Venezolanos: 31,8% (26,3-37,3). Al utilizar la mayoría de los criterios, el SM fue más frecuente en hombres que en mujeres. La prevalencia estimada de diabetes mellitus tipo 2 fue 2,9% tanto mediante el auto-reporte como mediante la detección de glicemia en ayunas > 126 mg/dL. Se detectaron niveles anormales (por encima del percentil 95) del índice HOMA2-IR, T4 libre y TSH en el 4,5%, 4,4% y 5,1% de la muestra respectivamente. Niveles de T4 y TSH por debajo del percentil 5 se detectaron en el 4,4% y 4,7% de sujetos respectivamente. Los valores del HOMA2-RI y hormonas tiroideas también se presentan con el fin de permitir comparaciones con futuros estudios en poblaciones clínicas específicas. Mientras se realizan estudios adicionales en Venezuela sobre las diversas definiciones del SM, recomendamos analizar y publicar los resultados científicos locales con todos los criterios disponibles con el fin de permitir la comparación con los estudios que ya están disponibles.

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

Objective: Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD), but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I. Methods: The available relatives of the same family were interviewed (DSM-IV-R) and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS), leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs) for the leptin receptor and promoter and PPAR-γ2 genes. The frequency of MS was compared with that recorded in the local general population. Results: Ninety-three relatives of three adults with BD were evaluated (30 aged < 18 years, 63 aged > 18 years). The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c) levels (all p < 0.05), waist circumference (p = 0.057), and leptin and insulin resistance values (in adults only) were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele. Conclusions: The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees. .

Safety of long-term clozapine administration. Frequency of cardiomyopathy and hyponatraemia: two cross-sectional, naturalistic studies.

BACKGROUND: The antipsychotic drug (APD) clozapine (CLZ) is under-prescribed because of concerns about its safety. We evaluated in separate protocols the frequency of cardiomyopathy and hyponatraemia, which are adverse drug effects, where few comparative studies are available. METHODS: Cross-sectional studies in subjects treated for at least 3 consecutive months with the same drug were conducted. Cardiomyopathy: Patients undergoing treatment either with CLZ (n = 125) or with other typical or atypical APDs (n = 59) were examined by a cardiologist who also recorded echocardiograms and electrocardiograms in order to diagnose cardiomyopathy. Hyponatraemia: Fasting sodium levels were assessed in patients receiving any of the following treatments: CLZ (n = 88), other atypical APDs (n = 61), typical APDs (n = 23), typical + atypical APDs (n = 11), and other drugs/drug-free (n = 36). RESULTS: Cardiomyopathy: No case of cardiomyopathy was detected. The frequency of abnormal ventricular ejection fraction (< 55%) was similar in both treatment groups (p = 1). Hyponatraemia: The frequency of hyponatraemia (percentage; 95% CI) was: CLZ (3.4%; -0.7, 7.1); other atypical APDs (4.9%; -0.5, 10.3); typical APDs (26.1%; 8.2, 44.0); typical + atypical APDs (9.1%; -7.8, 26.0); other drugs/drug-free (0%). None of the CLZ hyponatraemia subjects were on monotherapy. CONCLUSIONS: Our results are at odds with previous studies of CLZ-associated cardiomyopathy. However, they must be compared to further cross-sectional or prospective studies because most published data come from either case reports or pharmacovigilance systems. The frequency of hyponatraemia during CLZ administration was similar to that observed with other atypical APDs, and it was significantly lower than that recorded with typical agents. These results, along with numerous case reports on the effects of CLZ in patients with polydipsia and water intoxication, point to a safe or even positive profile of CLZ on electrolytic regulation.

Olanzapine as an add-on treatment in migraine status: A randomized double-blind, placebo-controlled, pilot study

Background and Objectives: The authors assessed the effectiveness of olanzapine as an adjunctive treatment in migraine status. Methods: Randomized, double-blind, placebo-controlled study. Subjects consecutively admitted to a day program of tertiary referral (97 % women; age: 35.8 ± 11.8 yrs.) were assigned to olanzapine (n = 14, 5-10 mg/day) or placebo (n = 17), added to the standard neurological treatment during 4 days. Primary measures were the change in pain and the return to regular daily activities. Secondary and safety measures were the magnitude of sedation, constipation and glucose level changes. Results: No significant differences were observed in the overall analysis of the primary measures. However, change in pain significantly correlated with age in the olanzapine group (p = 0.03). In the > 40 year-old group, olanzapine (n = 5) displayed a significantly higher reduction in pain than placebo (n = 4) at days 1 (p = 0.048) and 3 (p = 0.045). No significant differences were observed in the change of serum glucose levels. Conclusions: Olanzapine was well tolerated and sedation was welcomed by most subjects. The positive effect in subjects aged > 40 years awaits replication (AU)

Migraine life-time prevalence in mental disorders: concurrent comparisons with first-degree relatives and the general population.

The authors quantified the prevalence of migraine in subjects with mental disorders, first-degree relatives and the adult general population (GP) in Mérida, Venezuela. After validation, a modified, short version of the Lipton's diagnostic scale was administered to consecutively admitted in- and out-patients (n = 1059), their first-degree relatives (n = 445) and a probabilistic sample of the GP (n = 516). In the GP, the frequency of migraine (percentage and 95% confidence interval) was 14.9 (11.8-17.9). The migraine frequencies were (percentage and odd ratio probability against the GP: bipolar disorder (15.7%, p = 0.5), schizophrenia (8.3%, p = 0.08), depression and dysthimia (24.4%, p = 0.2), anxiety disorders (10.0%, p = 0.02), personality disorders (11.4%, p = 0.15), all other disorders (15.5%, p = 0.4), relatives of bipolar patients (4.4%, p < 0.001), relatives of schizophrenia patients (3.5%, p = 0.003), and relatives of patients with all other mental disorders (12.8%, p = 0.4). Migraine was more common in women (p < 0.001), and the bipolar patients presented the highest female to male ratio (8:1). A high variability was observed in migraine prevalence among the diagnostic categories, but it was particularly high in subjects with affective disorders, mainly in women, who thus deserve special attention from clinicians.

Migraine life-time prevalence in mental disorders: concurrent comparisons with first-degree relatives and the general population / Prevalencia de migraña en trastornos mentales: comparación concurrente con familiares de primer grado y con la población general

The authors quantified the prevalence of migraine in subjects with mental disorders, first-degree relatives and the adult general population (GP) in Mérida, Venezuela. After validation, a modified, short version of the Lipton’s diagnostic scale was administered to consecutively admitted in- and out-patients (n = 1059), their first-degree relatives (n = 445) and a probabilistic sample of the GP (n = 516). In the GP, the frequency of migraine (percentage and 95% confidence interval) was 14.9 (11.8-17.9). The migraine frequencies were (percentage and odd ratio probability against the GP: bipolar disorder (15.7%, p = 0.5), schizophrenia (8.3%, p = 0.08), depression and dysthimia (24.4%, p = 0.2), anxiety disorders (10.0%, p = 0.02), personality disorders (11.4%, p = 0.15), all other disorders (15.5%, p = 0.4), relatives of bipolar patients (4.4%, p < 0.001), relatives of schizophrenia patients (3.5%, p = 0.003), and relatives of patients with all other mental disorders (12.8%, p = 0.4). Migraine was more common in women (p < 0.001), and the bipolar patients presented the highest female to male ratio (8:1). A high variability was observed in migraine prevalence among the diagnostic categories, but it was particularly high in subjects with affective disorders, mainly in women, who thus deserve special attention from clinicians.

Los autores cuantificaron la prevalencia de migraña en sujetos con trastornos mentales, sus familiares de primer grado y la población general (PG) en Mérida, Venezuela. Se utilizó una versión abreviada de la escala diagnostica de Lipton. Luego de un estudio de validez, tal escala se administró a pacientes ambulatorios u hospitalizados atendidos en forma consecutiva (n = 1.059), a sus familiares de primer grado (n = 445) y a una muestra probabilística de la PG (n = 516). La frecuencia de migraña en la PG (porcentaje e intervalo de confianza de 95%) fue de 14,9 (11,8-17,9). La frecuencia para los diversos trastornos (porcentaje y probabilidad asociada a la razón de momios (odds ratio) con respecto a la PG) fue: trastorno bipolar (15,7%, p = 0,5), esquizofrenia (8,3%, p = 0,08), depresión y distimia (24,4%, p = 0,2), trastornos de ansiedad (10,0%, p = 0,02), trastornos de personalidad (11,4%, p = 0,15), todos los otros trastornos (15,5%, p = 0,4). En los familiares, la frecuencia fue: trastorno bipolar (4,4%, p < 0,001), esquizofrenia (3,5%, p = 0,003), otros trastornos (12,8%, p = 0,4). El diagnóstico de migraña fue más frecuente en mujeres (p < 0,001), y los sujetos con trastorno bipolar presentaron el mayor índice mujer:hombre (8:1). Se observó una alta variabilidad en la prevalencia de migraña en las diversas categorías diagnósticas. Tal frecuencia fue particularmente elevada en sujetos con trastornos afectivos, principalmente en mujeres, las cuales ameritan una atención especial por parte de los médicos tratantes.

The metabolic syndrome and its constituting variables in atypical antipsychotic-treated subjects: comparison with other drug treatments, drug-free psychiatric patients, first-degree relatives and the general population in Venezuela.

BACKGROUND: Few studies on the association between atypical antipsychotic drug (AAP) administration and metabolic dysfunction have concurrently evaluated the general population (GP), other psychotropic drug treatments and drug-free psychiatric patients. METHODS: We assessed the frequency of the metabolic syndrome (MS) according to the National Cholesterol Education Program criteria (NCEP) and its constituting variables in a GP sample (n=271) and in patients receiving, for at least three consecutive months, antiepileptic drugs (n=93), olanzapine (n=162), clozapine (n=105), typical antipsychotics (n=117), other AAP (n=58), other psychotropic drugs (n=185), and drug-free individuals (n=636). Subjects were clinically classified as schizophrenia, bipolar or other axis I disorders (DSM-IV-RT), and as first-degree relatives of each diagnostic group. RESULTS: The MS was detected in 26.6% of the GP (95% confidence interval: 21.5-31.8). No diagnostic or treatment group had a significantly higher age-adjusted frequency than the GP (p>0.05). Treatment duration did not significantly affect the results. However, significant differences were observed in the frequency of abnormal MS constituting variables in comparison to the GP. For example, schizophrenia patients and their relatives, bipolar subjects and olanzapine- and clozapine-treated patients had higher abnormal waist circumference values. In addition, bipolar patients and their relatives and subjects treated with olanzapine and other AAPs had higher frequencies of abnormal glucose levels. Neither schizophrenia nor bipolar patients in the diagnostic categories nor the olanzapine or the clozapine groups displayed higher proportions of abnormal triglycerides, high density cholesterol or blood pressure levels than the GP. CONCLUSIONS: While we did not demonstrate an increased frequency of the MS in AAP-treated subjects, our results confirm that specific metabolic variables must be monitored in psychiatric patients. Besides they stress the importance, in epidemiological studies, of concurrently comparing the figures recorded in AAP-treated patients with those obtained in the local GP, other drug treatment groups and drug-free subjects when referring to the magnitude of the metabolic effects of specific antipsychotic agents.

Pharmacological management of atypical antipsychotic-induced weight gain.

Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.

Metformin plus sibutramine for olanzapine-associated weight gain and metabolic dysfunction in schizophrenia: a 12-week double-blind, placebo-controlled pilot study.

Metformin (850-1700 mg) plus sibutramine (10-20 mg, n=13) or placebo (n=15) was administered for 12 weeks in olanzapine-treated chronic schizophrenia patients. Weight loss was similar in both groups: -2.8+/-3.2 kg vs. -1.4+/-2.6 kg. Except for preventing a triglyceride increase, the drug combination lacked efficacy for metabolic control in this clinical population.

Similar frequency of abnormal correlation between serum leptin levels and BMI before and after olanzapine treatment in schizophrenia.

Melkersson proposed leptin dysregulation as a factor in the olanzapine-induced metabolic dysfunction. Their suggestion was based on the absence of the expected positive correlation between serum leptin levels and the BMI, and the loss of the sex-dependent difference in leptin levels, which are higher in women. Although subsequent studies did not confirm that proposal, few of them assessed basal leptin levels and corrected for body fat percentage. Along with these variables, we added a precise definition of participants out of the expected positive correlation in a large sample of schizophrenia patients. Sixty patients (26 women and 34 men) with severe schizophrenia undergoing chronic hospitalization and conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day). We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of participants with abnormal correlation (out of the 95% confidence interval in the regression line) between leptin levels and the BMI, and the correlation between leptin and insulin, glucose, the insulin resistance index, c-reactive protein (CRP) and treatment response. Leptin levels were higher in women than in men (P<0.01). The positive correlation between leptin levels, BMI and percentage of fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out the 95% confidence interval, and the proportion was similar at baseline. Glucose, insulin, the insulin resistance index and the CRP levels significantly increased after olanzapine. The impact of olanzapine on leptin regulation appears discrete and limited to a small number of participants. Additional studies must clarify the features that render them to metabolic dysregulation.

Metformin as an adjunctive treatment to control body weight and metabolic dysfunction during olanzapine administration: a multicentric, double-blind, placebo-controlled trial.

BACKGROUND: Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables. METHODS: Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment. RESULTS: The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels. CONCLUSIONS: Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.