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Vol. 50. Núm. 10.
Páginas 396-406 (octubre 2003)
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Vol. 50. Núm. 10.
Páginas 396-406 (octubre 2003)
Acceso a texto completo
Resistencia a la acción de la insulina. Evolución histórica del concepto. Técnicas para el estudio in vivo en humanos
Insulin resistance. historical development of the concept. techniques for in vivo studies in humans
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J. Cabezas-Cerratoa,*, D. Araújob
a aDepartamento Universitario de Medicina USC. Hospital Clínico Universitario de Santiago de Compostela. A Coruña
b Servicio de Endocrinología y Nutrición. Hospital Clínico Universitario de Santiago de Compostela. A Coruña. España
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Aunque fue Himsworth quien, en 1936, hizo por primera vez referencia explícita a la sensibilidadinsensibilidad crónica a la insulina de esta forma: “diabetes mellitus its differentiation into insulinsensitive and insulin-insensitive types”, insistiendo sobre ello en publicaciones posteriores, la expresión no hacía otra cosa que catalizar en la terapéutica la existencia de dos tipos mayores de diabetes conocidos desde tiempos remotos y hoy día nominados diabetes mellitus tipos 1 y 2; y cuando, a caballo entre la década de los sesenta y setenta, se descubrió que la resistencia a la insulina en la diabetes y en la obesidad no es sólo para la insulina exógena, sino también para la endógena, y que la misma constituía un pilar fundamental en el desarrollo de diabetes, la cuantificación de su grado se ha hecho imprescindible en la investigación clínica de la diabetes y estados mórbidos relacionados, bien aislados o como concurrentes integrantes del “sindrome metabolico”. La homeostasis de la glucosa se mantiene dentro de los parámetros de la normalidad gracias a la estrecha y permanente intercomunicación entre los tejidos sensibles a la insulina (destacan, por orden de importancia cuantitativa, el músculo, el hígado y el tejido adiposo) y la célula β, de modo que cualquier cambio en la glucemia induce otro adaptativo en la célula β; luego la insulina inhibe la producción hepática de glucosa al tiempo que estimula su captación por los tejidos diana. Pero para que la insulina ejerza estos efectos, una vez secretada ha de pasar, vía vena porta, al hígado, difundirse después a la circulación, pasar al intersticio (“compartimiento remoto del plasma” en la ya antigua terminología), para, finalmente, alcanzar su receptor intacto en una célula diana intacta. Al menos, las principales técnicas de determinación de la resistencia a la insulina in vivo utilizadas en investigación están basadas en esta regulación y hacen referencia explícita a la misma. Otras, las más sencillas, también la contemplan, aunque en su aspecto más simple y último. Se ha de señalar, finalmente, que la sensibilidad a la insulina es muy variable, aun entre los sujetos normales, y depende de la edad, situaciones fisiológicas (pubertad, gestación y puerperio, y envejecimiento), el tipo de dieta, la actividad física, el momento del día y de otros factores desconocidos. De los métodos para cuantificar la sensibilidad a la insulina in vivo, dirigidos a la investigación fisiopatológica, el CEH es el estándar oro; y si se le acopla a las técnicas que se resumen en la figura 5, sus posibilidades en investigación son extraordinarias. Le sigue en fiabilidad, el MMg, del que varios grupos de investigación en España se han servido, con resultados notables. Respecto a los otros métodos basados en la cuantificación basal de la glucosa y de la insulina, el HOMA es el que ha superado mejor los controles de fiabilidad. En cuanto a los métodos que utilizan valores de la glucosa y de la insulina post-TTGO, parecen más robustos que los basados en determinaciones basales, ya que estos últimos valoran fundamentalmente la sensibilidad a la acción hepática de la insulina, pero no la captación muscular.

Palabras clave:
Resistencia a la insulina
RI
Síndrome metabólico
CEH
MMg
HOMA
TTGO

Although it was Himsworth who, in 1936, made the first explicit reference to chronic sensitivity/insensitivity to insulin with the words: “diabetes mellitus its differentiation into insulin-sensitive and insulin-insensitive types”, stressing this distinction in subsequent publications, these terms merely catalyzed in therapeutics the existence of two major types of diabetes known since ancient times and which today are called diabetes mellitus type 1 and 2. When, between the 1960s and 1970s, it was discovered that insulin resistance in diabetes and obesity involves not only exogenous insulin but also the endogenous form and that the latter plays a major role in the development of diabetes, quantification of its degree became essential in clinical investigation into diabetes and related morbid states, whether isolated or as part of “metabolic syndrome”. Glucose homeostasis remains within the normal range due to the close and permanent intercommunication between insulin-sensitive tissues (the most important of which are, in order of quantitative importance, muscle, liver, and adipose tissue) and β cells, so that any change in glycemia induces another adaptive change in β cells; then, insulin inhibits glucose production by the liver at the same time as it stimulates its uptake by the target tissues. However, for insulin to exert these effects once secreted, it must pass through the hepatic portal vein, spread to the circulation and reach the interstitium (the “remote compartment of plasma” in ancient terminology) to finally reach its receptor intact in an intact target cell. At least the main techniques for insulin resistance in vivo used in research are based on this regulation and make specific reference to it. Other, less complex techniques, also consider this process although in a simpler way. Finally, it should be mentioned that insulin sensitivity is highly variable even in normal subjects, depending on age, physiological factors (puberty, pregnancy and puerperium, and aging), type of diet, physical activity, time of day, and other unknown factors. Of the methods used to quantify insulin sensitivity in vivo, aimed at physiopathological investigation, CEH is the gold standard, and if it is adapted to the techniques summarized in fig. 5, it has immense possibilities in research. In terms of reliability, it is followed by MMg, which has been used by various research groups in Spain with notable results. Regarding other methods, of those based on basal quantification of glucose and insulin, HOMA appears to be the most reliable. Of the methods that use post-TTGO glucose and insulin values, the most robust seem to be those based on basal determinations since they mainly evaluate sensitivity to the action of insulin in the liver but not muscular uptake.

Key words:
Insulin resistance
RI
Metabolic syndrome
CEH
MMg
HOMA
TTGO
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