Determinación y jerarquización de signos clínicos para diagnóstico temprano de xantomatosis cerebrotendinosa / Determination and hierarchy of clinical signs for early detection of cerebrotendinous xanthomatosis

Background: Cerebrotendinous Xanthomatosis (CTX) is an autosomal recessive disease caused by mutations in the CYP27A1 gene resulting in a decreased synthesis of bile acids. An early diagnosis and treatment would reduce the longterm complications observed in this disease. Aim: To identify and hierarchize initial clinical signs of CTX to establish an early diagnostic suspicion index. Material and Methods: Clinical information was collected from 387 patients diagnosed with CTX, published in MEDLINE between 1968 and 2016. Clinical manifestations were identified, determining their prevalence and age of onset. Sensitivity, specificity and the positive Likelihood ratio (LR+) was calculated for each clinical sign evaluated. Results: The average ages for early symptoms' onset and CTX diagnosis were 13.3 ± 10.6 years and 34.6 ± 12.6 years respectively. The early clinical signs and their respective LR+ were: juvenile cataracts (143), epilepsy (81), chronic diarrhea (15.6) and psychomotor development delay (3.4). The presence of consanguinity among parents resulted in a LR+ of 31. The combination of two early signs increased the post-test probability to 30%. If the early diagnostic criteria would have been applied in three Chilean patients with diagnosis of CTX, their disease would have been diagnosed from 12 to 25 years earlier. Conclusions: The use of a hierarchical system of predictive clinical signs allows an early screening of CTX, which may avoid the natural progression of the disease using an appropriate treatment.

Estatinas en enfermedad renal crónica / Statins in chronic kidney disease

La enfermedad renal crónica constituye una patología de prevalencia e impacto creciente en la población mundial por sus múltiples complicaciones, incluyendo un riesgo cardiovascular aumentado, que representa la principal causa de morbimortalidad en pacientes nefrópatas crónicos. Sin embargo, la relevancia de las dislipidemias, especialmente, la hipercolesterolemia LDL, en el deterioro de la función renal y desarrollo de ateroesclerosis en sujetos con daño renal crónico no ha sido claramente establecida. Esta situación ha generado controversia sobre el beneficio real del uso de hipolipemiantes en estos pacientes. En base a la evidencia disponible, incluyendo estudios clínicos recientes, la recomendación más apropiada sugiere que el uso de terapia hipolipemiante basada en estatinas (con o sin ezetimiba) es beneficioso desde un punto de vista cardiovascular en nefrópatas crónicos con insuficiencia renal leve a moderada antes de la diálisis. Por otro lado, no existe evidencia definitiva para apoyar el uso rutinario de este tipo de hipolipemiantes en el manejo del deterioro de la filtración glomerular y/o la proteinuria. Basándose en la evidencia analizada en esta revisión, las futuras guías clínicas para el manejo del daño renal crónico deberán incorporar el uso de estatinas y/o ezetimiba como un elemento más dentro del armamento terapéutico de este tipo de pacientes.(AU)

Chronic kidney disease is a condition of increasing prevalence and impact on the world population by its many complications, including increased cardiovascular risk that represents the leading cause of morbidity and mortality in chronic nephropathy patients. However, the relevance of dyslipidemia, especially high LDL cholesterol, in the impairment of renal function and development of atherosclerosis in subjects with chronic kidney disease has not been clearly established. This situation has generated controversy regarding the real benefit of use of lipid-lowering therapy in these patients. Based on available evidence, including recent clinical studies, the most appropriate recommendation suggests that the use of lipid-lowering therapy based on statins (with or without ezetimibe) is beneficial from a cardiovascular standpoint in chronic nephropathy with mild to moderate renal failure before dialysis. On the other hand, there is no definitive evidence to support the routine use of lipid lowering drugs in the management of impaired glomerular filtration and/or proteinuria. Based on the evidence discussed in this review, future clinical guidelines for management of chronic renal damage should incorporate the use of statins and/or ezetimibe as a key element in the therapeutic armamentarium to be applied in these patients.(AU)

Hipertrigliceridemias de origen genético / Hypertriglyceridemias of genetic origen

Hypertriglyceridemia (HTG) is defined as plasma triglycerides (TG) > 150 mg/dL, and it is a frequent disease in the general population. When plasma TG reach concentrations > 500 mg/dL (severe HTG), there is usually a genetic defect involved. This defect can involve a single gene or be of polygenic inheritance. In polygenic HTG, the phenotypic expression of the disease is usually associated to the presence of certain diseases such as diabetes, obesity or insulin resistance. The most common known genes associated with monogenic hypertriglyceridemia are LPL and APOC2, but in recent years a few cases caused by mutant APOA5, GPIHBP1 and LMF1, have been identified. Furthermore, genome wide association studies (GWA) have brought up new genes that are related to discrete changes in triglyceride plasma levels of the general population. Among them, it is worth mentioning GCKR, TRIB1, MLXIPL, GALNT2, APOB, APOC2, APOA5, APOE, LPL, ANGPTL3 and NCAN. It is remarkable that most severe hypertriglyceridemias are of polygenic origin, and they could involve a major susceptibility gene. Only in a few cases of severe or very severe HTG (TG > 2.000 mg/dL) the genetic cause is known.

Consenso elaborado por la Sociedad Chilena de Endocrinología y Diabetes sobre resistencia a la insulina(RI) y síndrome metabólico (SM): aspectos clínicos y terapéuticos / Chilean society of endocrinology and diabetes consensus on clinical and therapeutic aspects of insulin resistance and metabolic syndrome

Background: The concept insulin resistance as the basis for a series of metabolic alterations and diseases was introduced by Gerald Reaven in 1988, when he described a cluster of alterations that named syndrome X. Aim: To review and discuss the present information about insulin resistance (IR) and metabolic syndrome (MS). Material and methods: The IR concept is defined,the affected metabolic ways, its consequences and relationship with different diseases are presented. The importance of central obesity with its metabolic, inflammatory and prothrombotic consequences playing a key role in cardiovascular risk, is discussed. The cluster of factors focused on cardiovascular disease and eventually diabetes is named MS. Several definitions of MS are analyzed and compared. A proposition is made about the definition to be used in the Chilean population. Differences between IR syndrome and MS are discussed. Diagnostic methods of IR and MS are presented, recommendations are made about their usefulness and reliability. Non pharmacological and pharmacological treatments of IR and MS are analyzed. Other related diseases, such as polycystic ovary syndrome, non alcoholic steatohepatitis and sleep apnea are discussed. Conclusions. Until further studies are made to define a local waist circumference cut-off associated with high risk, the ATPIII MS definition is preferred. A clinical approach is recommended for diagnosis. A search for all components of the MS is important. There is no evidence about the benefits of MS treatment on the prevention of cardiovascular diseases or diabetes. Evidence supports the use of lifestyle changes and some drugs, such as metformin on the prevention of diabetes in prediabetic states.

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.

El rol de la fibra dietética en la nutrición enteral / Role of dietary fiber in enteral nutrition

La fibra dietética está constituida por un grupo heterogéneo de sustancias de origen vegetal que son resistentes a la digestión y absorción en el intestino delgado, pero que sufren una digestión parcial o total en el colon. La fibra insoluble ayuda a mantener un tránsito intestinal normal y la soluble tiene efectos beneficiosos sobre la microflora del colon donde es fermentada generando ácidos grasos de cadena corta (AGCC). Los AGCC son substratos preferenciales para las células intestinales. A pesar del conocimiento sobre los efectos beneficiosos de la fibra, las fórmulas de nutrición enteral (NE) que rutinariamente se indican, no la contienen. Recientemente, se ha incorporado fibra soluble (fructo-oligosacáridos -FOS-) en algunas de estas fórmulas, siendo ellas de utilidad para el manejo de diarreas en pacientes que reciben NE. Además, estas fórmulas parecen ser útiles en el tratamiento de pacientes con enfermedades intestinales inflamatorias y en el síndrome de intestino corto.

Terapia hipolepemiante intensiva en el manejo del riesgo cardiovascular ateroesclerótico / Intensive cholesterol lowering therapy to reduce cardiovascular risk

Primary and secondary prevention trials have clearly demonstrated that lowering serum cholesterol levels with statins reduces the incidence of cardiovascular events. Recent studies plus post hoc analysis of previous clinical trials show that risk reduction is proportional to the magnitude of LDL cholesterol lowering. Therefore, new recommendations of the National Cholesterol Education Program (USA) have defined a category of patients with very high cardiovascular risk, who should achieve serum LDL cholesterol levels below 70 mg/dl. This proposal will require new and more efficient pharmacologic strategies to attain the increasingly strict therapeutic goals for LDL cholesterol. This article reviews the clinical studies that support the use of intensive lipid lowering therapy to reduce cardiovascular risk. An effective reduction of serum cholesterol can be obtained using statins in high doses or a combination of hypolipidemic drugs with different mechanisms of action.

Adiponectina en mujeres premenopausicas obesas y no obesas: su relación con la resistencia insulinica / Adiponectin levels in premenopause obese and non-obese women: its relationship with the insulin resistance

La adiponectina es una hormona producida exclusivamente por el adiposito. Se han reportado concentraciones plasmáticas reducidas en individuos con obesidad, hipertensión o dislipidemia. En este estudio se compararon los niveles de adiponectina en mujeres premenopáusicas no obesas y obesa, divididas en insulinosensibles (IS) e insulinorresistentes (IR). Se midió colesterol total, colesterol de lipoproteína de alta densidad (C-HDL), triglicéridos, glucosa de ayuno, insulina plasmática, adiponectina por RIA y el grado de adiposidad mediante índice de masa corporal (IMC). La resistencia a la insulina determinada por el modelo matemático HOMA IR se asoció negativamente con la adiponectina en mujeres no obesa y obesas independientemente del IMC. Las mujeres no obesa y obesas IS tuvieron los niveles de adiponectina más altos que la no obesas y obesas IR. Asimismo, la concentración de adiponectina se correlacionó positivamente con el C-HDL en ambos grupos de mujeres. En conclusión, encontramos que los niveles disminuidos de adiponectina se asociaron a resistencia a la insulina, hiperinsulinismo, concentración baja de C-HDL y mayores niveles de triglicéridos en mujeres premenopáusicas obesas y no obesas, independientemente de la obesidad.

Polimorfismo del gen de aldosa reductasa y velocidad de aparición de retinopatía en diabéticos no insulinodependientes / Aldose reductase gene polymorphism and rate of appearance of retinopathy in non insulin dependent diabetic patients

Background: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. Aim: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. Patients and methods: A random sample of 27 NIDDM, aged 68.1 ñ 10.6 years, with a mean diabetes duration of 20.7 ñ 4.8 years and a mean glycosilated hemoglobin of 10.6 ñ 1.6 percent, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5Õ end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. Results: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p=0.047). Both groups had similar glycosilated hemoglobin (11.7 ñ 0.2 and 10.5 ñ 1.6 percent respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. Conclusions: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5Õ end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate

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