Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

Estudio crítico del HOMA como método de pesquisa de resistencia insulínica en clínica / A critical study of the HOMA test as a screening for insulin resistance

Background: The hyperinsulinemic euglycemic clamp is the gold standard to measure directly insulin resistance.Unfortunately, the procedure is technically demanding, expensive and, unsuitable for clinical work. Cliniciansare used to request an HOMA test (Homeostasis Model Assessment) to indirectly assess the presence of insulinresistance given that it is an inexpensive and readily performed test but it has several shortcomings. Aim: To studythe diagnostic performance of the HOMA test as it is done in our country. Material and methods: We selected 32 women aged 32 +/- 2 years and 18 men aged 42 +/- 3 years. Half of them were categorized as insulin resistant by the pancreatic suppression test with octreotide, that is highly correlated with the euglycemic clamp but simpler to perform. Insulin was measured in two different laboratories in Santiago (Barnafi-Krause and Laboratorio deNutrición, Universidad Católica) and HOMA results were calculated using serum fasting insulin and glucose levels.Results: The correlation coefficients between HOMA, calculated using insulin values of both laboratories, and the results of the pancreatic suppression test were 0.45 and 0.55 (p< 0.01). Only six of 25 subjects defined as insulin resistant by the pancreatic suppression test were detected with HOMA. Therefore, the sensitivity of the latter for insulin resistance was 24 percent. However all subjects defined as insulin resistant by HOMA (BK) hadan abnormal pancreatic suppression test. Conclusions: Even though HOMA test was positively correlated with insulin resistance, it had a poor diagnostic sensitivity. Clinicians should be aware that the HOMA test is proneto under-diagnose the presence of insulin resistance.

Efecto de un preparado en forma de gel de 17 ß estradiol sobre diferentes parámetros hormonales en mujeres menopáusicas / Effects of a 17 ß estradiol gel preparation on different hormonal parameters in menopausal women

Different delivery forms of supplemental estrogens may differ in their hormonal effects. The aim of this study was to assess the effects of a daily dose of 2.5 g of 17 ß estradiol transdermal gel, given during four weeks, on hormon levels of six postmenopausal women. At the fourth week we observed a significant increase in estradiol and a dicrease in FSH levels. estrone levels alsa increased but the estradiol-estrone ratio was maintained in values over 1. No changes in SHBG or IGF1 levels were observed. Two patients that used the gel in the abdominal skin achieved lower estradiol levels (below 60 pg/ml). We conclude that the gel increased serum estradiol levels over 60 pg/ml in four of six women, that there is a big individual variability and the application zone could influence the serum estradiol levels achieved

Efecto de la fluoxetina sobre la insulino resistencia en pacientes obesos no diabéticos / Effects of fluoxetine on insulin resistance in non diabetic patients

Fluoxetine, a serotonin re-uptake inhibitor with antidepressive and appetite reduction effects, could improve insulin sensitivity. The aim of this work was to assess this effect of fluoxetine in obese subjects. We studied 12 subjects with a body mass index over 30, with normal oral glucose tolerance test and not subjected to dietary restrictions. Insulin sensitivity using Bergman's minimal model, sex hormone binding globulin (SHBG) and insulin like growth factor binding protein 1 (BP 1) were evaluated before and after three weeks of treatment with 60 mg OD of fluoxetine. During treatment, subjects lost a mean of 1.9 kg. When compared with basal values, insulin sensitivity index (S1) improved significantly at the end of threatment (1.71ñ0.44 and 2.72ñ0.63 respectively), SHBG increased (28.9ñ5.1 and 18.2ñ3.4 nM/ml respectively) and BP 1 did not change (2.8ñ0.9 and 1.5ñ0.3 ng/ml respectively). The changes in insulin sensitivity did not correlate with weight changes (r=0.4 NS). Weight or insulin sensitivity changes did not correlate with initial degree of insulin resistance. We conclude that the improvement in insulin sensitivity elicited by fluoxetine is not related to weight changes and may be useful in the treatment of insulin resistant obese subjects

Síndrome de Cushing: una revisión a propósito de una casuística nacional / Cushing's syndrome: a review apropos of a national series

Cushing's syndrome occurs rarely; in analyzing 50 cases studied at our institution we discuss the following aspects: syndromatic diagnosis, etiologic differentiation into the 3 categories of the syndrome, and therapeutic strategies for each variety. We postulate that non-endocrinologists should be responseible for the syndromatic diagnosis, easily done by using 2 simple tools: the measurement of basal free urinary cortisol and the performance of and overnight suppression of the adrenal axis with 1 mg of dexamethasone (Nugent's test). In contrast, the etiologic diagnosis and the therapeutic interventions should be strictly restricted to highly specialized institutions having well seasoned endocrinologists, a reliable endocrine laboratory, easy access to computed tomographies of the brain and abdomen as well as to nuclear resonance imaging of the brain. The usefulness of our in-house devised vasopressin challenge following overnight dexamethasone suppression for the etiologic diagnosis is highlighted. Neurosurgical expertise in the transphenoidal approach to the pituitary gland as well surgeons well experience in adrenal surgery sre a must to offer a reasonable chance of success to patients with the syndrome. Forty one (82 percent) of the series were female patients, 78 percent were pituitary-depent and 22 percent pituitary-independent Cushings. Six out of 8 (75 percent) of the adrenal tumors were carcinomas. Only 3 patients (6 percent) qualified as ectopic ACTH syndormes. The easiest variety to diagnose and treat was the adrenal adenoma (2 cases); adrenal carcinomas were always incurable. The ectopic ACTH syndrome was amenable to successful medical treatment with ketoconazole or surgical resolution with complete resection od the offending tumor (1 of 3 cases) or bilateral adrenalectomy (2 of 3 cases) Pituitary-dependent Cushing are quite tricky to diagnose and difficult to treat. Transphenoidal resection of the offending microadenoma was successful in only 43.5 percent (10/23) of cases and we experienced 3 recurrences of the syndrome even after 8 years of successful removal of the pituitary adenoma. The remainder had to be cured by bilateral adrenalectomy. Seven out 39 patients with Cushing's disease (18 percent) ultimately died for a variety of reasons; six out of 6 patients (100 percent) with adrenal carcinoma died of dissemination; 2 out of 2 adrenal adenomas cured and 1 out of the 3 ectopic ACTH syndromes died of dissemination of a malignant thymic carcinoma. We conclude that Cushing's syndrome is a serious, underdiagnosed disorder, which should be suspected and diagnosed by the non specialized physician and then referred to a specialized center for expert etiologic diagnosis and surgical therapy

Mejoría de la insulinosensibilidad asociada al uso prolongado de acipimox en un obeso mórbido / Improvement of insulin sensitivity associated to the large use of acipimox in a morbidly obese patient

Insulin sensitivity was estimated in a morbidity obese, insulin-resistant, glucose-intolerant patient before and after 4 weeks of treatment with acipimox (250 mg t.i.d), an orally-administred, long-acting antilypolitic drug. The ensuing fall in circulating levels of fasting free fatty acids was associated with a clear amelioration of insulin resistance, as assessed by a minimal model analysis of a frequently sampled intravenous glucose tolerance test as well as by an oral glucose tolerance test. Similarly, this treatment brought about a reappearence of GH response to oral stimulation with clonidine. The evidence showing acipimox-induced amelioration of insulin resistance in this patient without diet, exercise or weight loss should encourage exploring the potential utility of this drug in this type of patient

Sensibilidad a la insulina: ausencia de diferencias sexuales al expresarla en función de la masa magra / Insulin sensitivity: absence of sexual differences when expressed as a function of lean body mass

The hyperinsulinemic, euglycemic clamp techinque was used to test the hypothesis that - when expressed per kiligram of lean body mass - there is a sex-difference in peripheral insulin-mediated glucose disposal (M), as proposed in the literature. Lean body mass wass assessed with tetrapolar bioelectric impedance analysis. We studied 15 normal subjects (volunteers with normal glucose tolerance and body mass indices between 20-25 Kg/m2) of both sexes, 9 women and 6 men, of age-groups, 20-30 year-old and 40-50 year-old. Men and women were similarly aged (33.3 ñ 3.8 and 33.3 ñ 3.8 years, respectively). body mass indices were similar in both sexes (22.5 ñ 0.6 in women and 23.6 ñ 0.7 in men, NS) but percentages of fat mass were not (294 ñ 1.2 in women and 20.6 ñ 1.6 in men, p < 0.001). As no difference in M (mg of glucose metabolized per kilogram of body weight per minute) between age-groups was found (6.4 ñ 0.8 snf 6.8 ñ 1.2 mg/Kg/min, Ns) the data from these 2 age-groups were pooled. When M values obtained in both sexes were compared no differences were found (7.1 ñ 1.5 mg/Kg/min in women and 6.3 ñ 0.6 in men, NS). Similarly, when M was expressed in function of the prevailing insulin levels attained during steady-state, M/l, no differences were disclosed (8.98 ñ 2 mg/Kg/min/µIU insulin in women and 7.8 ñ 1.2 in men, NS). When M was expressed per kilogram of lean body mass, Mmm, the values were similar in both sexes (8.99 ñ 1.86 m/kg lean body mass/min in women and 8.94 ñ 0.8 in men, NS). Finally, another maneuver commonly used to normalize MJ in function of metabolic size, expresing it per square meter of body surface, Ma, failed to disclose a sex-differnce (225.5 ñ 20.6 mg/m2/min in women and 263.5 ñ 52.8 in men, NS). We conclude that no sex-difference exists in M when expressed per kilogram of lean body mass, thus contradicting previous data published elsewhere

Hiperplasia suprarrenal de expresión tardía: optimización de la terapia midiendo la variación circadiana de la 17-OH-progesterona sérica / Late onset adrenal hyperplasia: optimization of treatment by assesment of the circadian variation in serum 17-OH-progesterone

A 19 yr-old female patient with the diagnosis of late onset adrenal hyperplasia was treated since age 15 with different glucocorticoid preparations and dosage schedules plus spsironulactone. In spite of a very tgood response in terms of amelioration of ther hursutism she experienced cushingoid manifestations associated with, adrenal suppression. To overcome these side effects the patient was placed ons hydrocortisone 20 mg at 8 AM plus spironallactone 50 mg q.i.d. Cushingoid features vanished and response to cosyntropin (ACTH 250 ug i.m.) was reestablished. To better ascertain the effects of this administered at 8 AM and compared it with curcadian variations under basal conditions or after late-evening (11 PM) adminsitration of hydrocortisosne, 20 mg. The early morning adminstration of hydro cortisone was unable to prevent the nocturnal elevation of 17-OH-progesterone in spite of normal levels from 9.30 AM to 3 AM. This nocturnal peak was associated with a slightly blunted nocturnal elevation of serum cortisol. In contrast, the late evening adminsitration of hidrocortisone was able to supress 17-OH-progesterone to within normal levels during all day. Serum cortisol during late evening therapy was not different from that observed during early morning adminstration (12.2 ñ 13.1 vs 9.9 ñ 11.3 ug/dl,p = 0.53), yet the corresponding 17-OH-progesterone levels were much lower (0.8 ñ 0.6 vs 5.9 ñ 6.9 ng/ml. We conclude that individualization of therapy is essential in patients with lateosnt adrenal