Efecto, en la práctica clínica, de la fluvastatina de liberación prolongada en los lípidos séricos en pacientes con diabetes tipo 2 y dislipemia / Effect of long-acting fluvastatin on serum lipids in type 2 diabetic patients with dyslipidemia, in clinical practice

Introducción. La reducción del colesterol unido a lipoproteínas de baja densidad (cLDL) con estatinas se asocia a una disminución de las complicaciones macrovasculares en pacientes con diabetes mellitus tipo 2 (DM2). La fluvastatina de liberación prolongada (FLP) presenta una absorción más lenta y una acción más duradera que otras estatinas. Objetivo. Valorar en la práctica clínica el efecto de la FLP en los lípidos séricos (LS), en pacientes con DM2 y dislipemia, en los que dosis máximas de otras estatinas no consigan los objetivos de buen control. Material y método. De 452 pacientes con DM2 y dislipemia tratados con dosis máximas de lovastatina, simvastatina, pravastatina o atorvastatina, se seleccionó a 84 que presentaban un cLDL > 2,97 mmol/l (> 115 mg/dl). Se les midió el colesterol total (CT), el colesterol unido a lipoproteínas de alta densidad (cHDL) y los triglicéridos (TG), se calculó el cLDL y se comparó el porcentaje de ellos que cumplían los objetivos de control para los LS antes y a los 9 meses de sustituir las estatinas que tomaban por una dosis de 80 mg de FLP. Resultados. A los 9 meses del tratamiento con FLP, el 57% de los pacientes alcanzó el objetivo del cLDL (p = 0,000), y se observó una disminución del CT y el cLDL (p = 0,000 para ambos) y un incremento del cHDL (p = 0,000). Conclusiones. En la práctica clínica, la FLP consiguió los objetivos de control para el cLDL en más de la mitad de los pacientes con DM2 y dislipemia de la población estudiada, que no lo habían conseguido con otras estatinas. Esto, unido al incremento del cHDL observado, pone de manifiesto la importancia de la FLP en el tratamiento de pacientes con DM2 y dislipemia (AU)

Introduction. The decrease of low density lipoprotein- cholesterol (LDLc) produced by statins is associated with a reduction in macrovascular complications in patients with type 2 diabetes mellitus (T2DM). Long-acting fluvastatin (LAF) has a slower absorption and longer action time than other statins. Objective. To assess, in clinical practice, the effect of LAF on serum lipids (SL) in T2DM patients in whom maximum doses of other statins failed to achieve the recommended goals. Material and method. Of 452 patients with T2DM and dyslipidemia who were on maximum doses of simvastatin, lovastatin, pravastatin or atorvastatin, 84 with LDLc levels > 2.97 mmol/l (> 115 mg/dl) were selected. Total cholesterol (TC), high density lipoprotein-cholesterol (HDLc), triglycerides (TGs) and LDLc were measured. The percentage of patients achieving recommended goals for SL before and 9 months after switching from the previous statin treatment to LAF 80 mg/day was compared. Results. After 9 months of LAF treatment, 57 % of the patients achieved the LDLc target (P = 0.0000). Mean TC and LDLc significantly decreased (P = 0.000, for both) while HDLc significantly increased (P = 0.000). Conclusions. In clinical practice, LAF treatment achieved the LDLc target in more than 50 % of the patients with T2DM in whom maximum doses of other statins failed to achieve the recommended goals. In addition to this effect, the increase in HDLc observed after LAF treatment shows the importance of this statin in the treatment of T2DM patients with dyslipidemia (AU)

Grado de control de la presión arterial en un grupo de pacientes con diabetes mellitus tipo 2 / Blood pressure control in a group of patients with type 2 diabetes mellitus

Objetivo: Valorar el grado de control de la presión arterial en una población con diabetes mellitus tipo 2 (DM2). Pacientes y métodos: Estudio transversal en 758 pacientes con DM2 tratados con antidiabéticos orales o insulina. De acuerdo con las recomendaciones de la Asociación Americana de Diabetes se aplicaron una presión arterial sistólica (PAS) < 130 mmHg y una diastólica (PAD) < 80 mmHg como objetivos de buen control. Se evaluó también la prescripción de inhibidores de la enzima de conversión de la angiotensina (IECA), antagonistas de los receptores de la angiotensina II (ARA II) y bloqueadores beta. Resultados: La media de edad fue de 65,4 ± 12,2 años; el 44% de los pacientes eran varones. El 49% eran tratados con insulina, el 51% con antidiabéticos orales (ADOS), y el 18% presentaba cardiopatía isquémica. De ellos, el 64% estaba tratado con IECA o ARA II y el 18% con bloqueadores beta. Sólo el 35% de los pacientes presentaba valores de PAS < 130 mmHg, mientras que el 76% alcanzó una PAD < 80 mmHg. Los tratados con insulina presentaron unos valores de PAS superiores a los de aquellos que tomaban ADOS (p = 0,01). Si consideramos sólo a los pacientes en tratamiento con IECA o ARA II el porcentaje que alcanzó la PAD < 80 mmHg fue superior en los tratados con insulina (p = 0,01). Conclusiones: A pesar del elevado consumo de IECA y ARA II, en la población estudiada existe un control pobre de la PAS. Estos datos reflejan la necesidad de tratar más intensivamente la hipertensión arterial en los pacientes con DM2 para alcanzar los objetivos recomendados, y reducir el riesgo de mortalidad y complicaciones relacionadas con la DM2 (AU)

Objective: To assess the degree of blood pressure control in patients with type 2 diabetes mellitus (DM2). Patients and methods: We performed a cross-sectional study of 758 patients with DM2 treated with oral agents and/or insulin. The following parameters were used to define optimal control, based on the recommendations of the American Diabetes Association (ADA): systolic blood pressure (SBP) < 130 mmHg and diastolic blood pressure (DBP) < 80 mmHg. The use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) and beta-blockers was also evaluated. Results: The mean age was 65.4 ± 12.2 years; 44% were male. Forty-nine percent of the patients were receiving insulin therapy and 51% were taking oral hypoglycemic agents. Eighteen percent had a history of ischemic heart disease. Overall, 64% were on ACEIs or ARB therapy, and 18% were on beta-blockers. Only 35% of the patients achieved the SBP target, although 76% reached the DBP target. Insulin users had higher SBP (p = 0.01) than patients taking oral agents. The percentage of patients treated with ACEIs or ARBs who met the recommended ADA target for DBP was higher among subjects receiving insulin therapy than in those taking oral agents (p = 0.01). Conclusions: Despite the large number of patients taking IECAs or ARBs, there was poor control of SBP in the population studied. These data support the need for more aggressive treatment of hypertension in patients with T2DM to achieve the recommended goals and to reduce mortality and complications in these patients (AU)

Glucemia posprandial y riesgo cardiovascular / Posprandial glycemia and cardiovascular risk

La arteriosclerosis es la causa más frecuente de morbilidad y mortalidad cardiovascular en pacientes con diabetes mellitus tipo 2. En los últimos años, estudios epidemiológicos y de intervención han identificado el estado posprandial, caracterizado por un aumento rápido y prolongado de los valores de glucosa en sangre, como un factor de riesgo directo e independiente de arteriosclerosis que contribuye al desarrollo de la enfermedad cardiovascular. La hiperglucemia posprandial podría tener un efecto tóxico directo sobre el endotelio vascular mediado por el estrés oxidativo, lo que favorecería el desarrollo de la disfunción endotelial, una condición protrombótica y proinflamatoria, a través de la producción de radicales libres. Este efecto es independiente de otros factores de riesgo cardiovascular, como la hiperlipidemia. El control y la corrección de los valores de glucemia posprandial es una estrategia muy importante en la prevención de la enfermedad cardiovascular asociada a la diabetes. En esta revisión se han examinado los estudios epidemiológicos y de intervención que asocian la hiperglucemia posprandial con el riesgo de enfermedad cardiovascular, los mecanismos involucrados en estos efectos y las diferentes estrategias terapéuticas para controlar la hiperglucemia posprandial, que incluyen cambios en el estilo de vida y fármacos como los secretagogos de corta duración, los inhibidores de las alfaglucosidasas intestinales, los análogos de insulina de acción rápida y nuevos agentes en desarrollo, como el análogo de amilina, pramlintida; la hormona insulinotrópica GLP-1 y sus homólogos como la exendina, los inhibidores de la dipeptidilpeptidasa IV (DPPIV) o la insulina inhalada (AU)

Atherosclerosis is the most frequent cause of the increased cardiovascular morbidity and mortality observed in type 2 diabetic patients. Over the past few years, epidemiological and preliminary intervention studies have identified that the posprandial state, characterized by a rapid and large increase in blood glucose levels, is a direct and independent risk factor for atherosclerosis and a contributing factor to the development of cardiovascular disease. Posprandial hyperglycemia may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress, which favors the development of endothelial dysfunction, a prothrombotic and proinflammatory condition, through the production of free radicals. This effect is independent of other cardiovascular risk factors such as hyperlipidemia. The control and correction of posprandial glucose levels is an important strategy in the prevention of diabetes-related cardiovascular disease. In this review, epidemiological and intervention studies that associate posprandial hyperglycemia with cardiovascular risk, the mechanisms involved in this effect, and the distinct therapeutic strategies to control posprandial hyperglycemia are reviewed. These therapeutic strategies include life-style changes, drugs such as short-acting secretagogues, alpha-glucosidase inhibitors, fast-acting insulin analogues, and new agents under development, such as the synthetic human amylin analogue pramlintide, the insulinotropic hormone GLP-1, a homologue of GLP-1-exendin, dipeptidylpeptidase IV inhibitors (DPPIV) and inhaled insulin formulations (AU)

Comparison of anthropometric parameters as predictors of serum lipids in premenopausal women.

No single anthropometric parameter has yet been generally accepted as being superior to others in assessing the metabolic risk associated with abdominal obesity. To compare waist circumference (WC) with waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), regarding their association with serum lipids, we studied 166 women aged 20 to 48 yr; 53 were obese [body mass index (BMI) 30-39.9 Kg/m2], 50 were overweight (BMI 25-29.9 Kg/m2) and 63 normal weight (BMI 18.5-24.9 Kg/m2). Height, body weight, waist and hip circumferences, total serum cholesterol (Ch), low (LDL) and high density lipoprotein (HDL)-Ch and triglyceride (TG) concentrations were measured. The correlation coefficients between the concentration of serum lipid fractions and each anthropometric parameter did not differ significantly for any lipid variable when WC, WHR and WHtR were compared in the 166 women. The same applied for the obese and the overweight group, whereas in normal weight women there was significant association only between WC and LDL-Ch and between WHR and Ch/HDL-Ch ratio. Stepwise regression analysis showed that the proportion of variance in serum lipids did not change significantly when WHR or WHR+WHtR were added to WC into the regression model (18%, 18% and 18% for Ch; 13%, 18% and 18% for HDL-Ch; 18%, 18% and 12% for LDL-Ch; 35%, 35% and 37% for TG, respectively). These results indicate that WC is the main parameter associated with serum lipid levels and that the ratios studied do not provide additional substantial information in women who need weight management.

Actualización en el diagnóstico y diagnóstico diferencial del síndrome de Cushing / Update in the diagnosis and differential diagnosis of Cushing´s syndrome

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Evaluation of radial bone mineral content in prepubertal children with constitutional delay of growth.

We have previously reported that children with constitutionally delayed growth (CDG) have significantly lower spinal bone mineralization than children with familial short stature (FSS). The aim of the present study was to evaluate whether the decreased bone mineralization in children with CDG also affects the radius, which has a lower bone turnover than the spine. To avoid the possibility of size-related artifacts in the assessment of bone mineral data, data were corrected for bone and body size. Radial bone mineral content (RBMC) and radial bone mineral density (RBMD) were measured by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 short prepubertal children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of CDG and 27 of them with FSS. The mean (+/- SD) RBMD was significantly lower in the children with CDG than in the FSS group (0.361 +/- 0.035 vs 0.385 +/- 0.033 g/cm2, p<0.05). RBMC was significantly lower in CDG than in FSS, when multiple regression analysis was performed by using radial scanned bone area (RSBA), body weight and height, sex and BA as independent variables (p = 0.03). These data indicate that the decreased bone mineralization in children with CDG also affects peripheral bone, and that this finding is not due to bone or body size artifacts.

Bone mineral status in prepubertal children with constitutional delay of growth and puberty.

OBJECTIVE: We wished to clarify whether the osteopenia reported in adult men with a history of constitutional delay of growth and puberty (CDGP) could be due to the delayed puberty or an independent predisposition to osteoporosis in this condition. DESIGN: Short prepubertal children with CDGP and children with familial short stature (FSS) were matched for height and other auxological variables. The FSS children served as a control group. METHODS: We measured spinal (L1-L4) bone mineral content (BMC) and bone mineral density (BMD) by dual energy X-ray absorptiometry (Hologic QDR 1000/w) in 56 children aged 5-11 years. All children had height below the 10th percentile for chronological age (CA), and bone age (BA) less than 10 years, 29 of them with clinical diagnosis of possible CDGP and 27 of them with FSS. The BMD standard deviation scores (SDS) relative to the values for normal height children were obtained. RESULTS: The mean (+/-S.D.) spinal BMD was significantly lower in the children with CDGP than in the FSS group (0.534+/-0.059 vs 0.623+/-0.060 g/cm2, P< 0.001). Both groups had negative mean lumbar BMD SDS, but in the CDGP group it was significantly lower than in the FSS group as well when the SDS was based on the CA (-1.41+/-0.61 vs -0.38+/-0.51, P< 0.001) and when it was related to BA (-0.78+/-0.64 vs -0.17+/-0.52, P< 0.01). BMC was significantly lower in the CDGP than in the FSS group, when multiple regression analysis was performed by using scanned bone area, body weight and height, sex and BA as independent variables (P = 0.0005). CONCLUSION: The finding of decreased mineralization in prepubertal children with CDGP before the age of puberty suggests that they may have an inherent predisposition to osteopenia.

Serum growth hormone-binding protein is decreased in prepubertal children with idiopathic short stature.

The causes for growth failure in children with idiopathic short stature (ISS) are not definitely established. Peripheral GH resistance due to changes at the level of the GH receptor has been suggested as one of the most probable explanation. In this study, we have selected a group of prepubertal children with ISS to evaluate the GHBP/receptor status by measuring the GH binding protein (GHBP) activity in plasma. Thirty prepubertal children with ISS (18 boys and 12 girls; age range: 4.79 to 11.33 yr) and twenty age-matched children with normal growth (11 boys and 9 girls) were studied. The ISS group presented growth retardation of -2.3 +/- 0.43 SD score (mean +/- SD) and normal GH secretion. Plasma IGF-I levels were below or in the low normal range (mean +/- SD: 136.3 +/- 62.3 micrograms/l, a concentration that was significantly different from IGF-I levels in the normal group (mean +/- SD: 187 +/- 57.5 micrograms/l p < 0.005). Plasma GHBP activity using a GH-binding/gel chromatography assay showed significantly lower values in ISS group (mean +/- SD: 7.17 +/- 1.5%) as compared with those of the control group (mean +/- SD: 12.02 +/- 2.04%; p < 0.001). There were no significant age- or sex-related differences in GHBP values in either group. The decreased GHBP levels observed in this group of children with ISS suggest that they may present a certain degree of GH insensitivity, probably due to a defect at the GH-receptor level.

[Precision and accuracy of the measurement of total cholesterol using the reflectometer Accutrend GC. Usefulness in primary care for diagnosis of hypercholesterolemia]. / Precisión y exactitud de la medida del colesterol total mediante el reflectómetro Accutrend GC. Aplicabilidad en atención primaria para la detección de hipercolesterolemias.

OBJECTIVES: To determine the accuracy and precision of the Accutrend GC (AGC) in measuring cholesterol totals (CT) and its use as a screening test to detect hypercholesterolaemia. DESIGN AND PARTICIPANTS: Venous blood was drawn from 104 patients to measure CT by an enzymatic method (Hitachi 717). At the same time, their capillary blood was also measured with the AGC on two consecutive occasions. Values were divided in three groupings: CT > 149 mg/dl and < or = 199 mg/dl (n = 27); CT > 199 mg/dl and < or = 249 mg/dl (n = 59); and CT > or = 250 mg/dl (n = 18). Accuracy was calculated by obtaining the mean differences (MD) and the confidence intervals of the values obtained with the AGC in the three groupings and comparing them with the values obtained by the laboratory method. Precision was assessed by correlation, the comparison of paired means and the mean coefficient of variation of the values obtained with the AGC in the two successive measurements. MAIN MEASUREMENTS AND FINDINGS: In each grouping the MD of the values obtained with the AGC were lower than those obtained by the laboratory method, respectively. CONCLUSIONS: The AGC is useful as a screening test to detect hypercholesterolaemia, because of its high accuracy and precision. As it also determines glucose it is very useful for diabetics.

Correlations between bone mineral density, insulin-like growth factor I and auxological variables.

Recent studies have shown growth-related changes in spinal bone mineral density (BMD) in children; however, there is less information available on the relationship between BMD and insulin-like growth factor I (IGF-I). The aim of this study was to relate the BMD of the spine and radius with serum IGF-I levels and auxological variables in normally growing children. We used dual X-ray absorptiometry to measure the BMD in the lumbar spine (L1-L4) and distal radius of 121 children (69 boys, 52 girls) aged 3-18 years whose growth velocity was normal. Lumbar and radial BMD increased with age (p < 0.001) and puberty (p < 0.001) and was highly correlated to age, weight, height, body surface and bone age (r = 0.70-0.89 and p < 0.001 for all variables). Partial correlation, with age held constant, was weaker but still significant for most auxological variables. Serum IGF-I concentrations increased slowly during childhood and markedly during early stages of puberty, and correlated with lumbar and radial BMD (r = 0.55 and 0.45, respectively; p < 0.001) and with the auxological variables (p < 0.001). When age was held constant, IGF-I levels still correlated significantly with the auxological variables and with BMD, except in the case of radial BMD in boys. By multiple regression analysis IGF-I, unlike auxological variables, did not reach significance in the ability to predict BMD. Therefore, in healthy children, serum IGF-I levels show a weaker relationship to BMD than do auxological variables.

Comparison between spinal and radial bone mineral density in children measured by X-ray absorptiometry.

Several studies have analyzed the correlation between axial bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) and growth parameters. However, little is known about the growth-related changes in appendicular BMD measured by this technique. We used DXA to measure BMD in the lumbar spine (L1-L4) and distal radius in 121 normal growing children (69 boys, 52 girls), aged 3 to 18 yr. Both lumbar and radius BMD showed a steady increase with age and a steeper increment during puberty. There was a good correlation between spinal and radial BMD (r = 0.83; p < 0.001) and both were highly correlated with growth parameters; their respective correlation coefficients did not differ significantly for chronological age (r = 0.70 vs 0.80), weight (r = 0.77 vs 0.76), height (r = 0.73 vs 0.79), body surface (r = 0.78 vs 0.80), body mass index (r = 0.54 vs 0.49) and bone age (r = 0.77 vs 0.79). By multiple regression analysis the best predictors for spinal BMD were bone age, pubertal stage and weight, while for radial BMD the best predictors were chronological age and weight. We have shown that the measurement of BMD by DXA at distal radius, an easily accessible bone, has a correlation with growth parameters as good as lumbar spine BMD measurements in children.

Is there a place for urinary growth hormone measurement?

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

Long-term evaluation of thyroidal response to partial calorie restriction in obesity.

Twenty obese patients were treated as out-patients with a 3.35 MJ (800 Kcal) per day diet, and, by the double-blind method, ten of the patients were prescribed 40 micrograms of triiodothyronine (T3) daily and the other ten placebo. Body weight and serum thyroxine (T4), T3 and reverse T3 (rT3) concentrations were measured before treatment, then monthly over 6 months. No significant difference in mean weight loss was found between the patients receiving T3 and those on placebo. Serum T3 concentration decreased slightly in patients on placebo and increased in those on T3 but these changes were not statistically significant. However, patients on T3 maintained a significantly higher concentration of T3 in serum than those on placebo. Mean serum T4 and rT3 concentrations remained essentially unchanged in the patients on placebo, whereas both decreased significantly in patients receiving T3. We conclude that changes in serum T3 during dietary treatment of obesity are of minor significance in limiting the expected weight loss in the patients.

The effect of calorie restriction on serum thyroid hormone binding proteins and free hormone in obese patients.

In ten obese euthyroid subjects the concentration of thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) were assayed in serum and of T4 and T3 in urine before and after 2 weeks of 2.1 MJ (500 Kcal) per day diet. Mean serum T4 was unchanged, while T3 decreased and rT3 increased. Urinary excretion of both T4 and T3 decreased after diet. In six subjects the concentrations of serum thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA) and albumin were measured before and after diet. Free T4 and T3 were calculated using a formula based on measured concentration of hormones and their binding proteins. Calorie restriction resulted in a significant decrease in TBG and a greater decrease in TBPA, while albumin was unchanged. Calculation of free hormones showed a fall in absolute free T3 and rise in percentage free T3, but a rise in both absolute and per cent free T4. Our data indicate a selective effect of calorie restriction on the concentrations of TBPA and to a lesser extent TBG and confirm previous reports of altered peripheral monodeiodination of T4. Decreased urinary excretion of T4, despite a calculated increase of free T4 in serum, suggests intrarenal metabolic adjustment, the mechanism of which awaits elucidation.