Diabetes screening by telecentric digital holographic microscopy.

Diabetes is currently the world's fastest growing chronic disease and it is caused by deficient production of insulin by the endocrine pancreas or by abnormal insulin action in peripheral tissues. This results in persistent hyperglycaemia that over time may produce chronic diabetic complications. Determination of glycated haemoglobin level is currently the gold standard method to evaluate and control sustained hyperglycaemia in diabetic people. This measurement is currently made by high-performance liquid chromatography, which is a complex chemical process that requires the extraction of blood from the antecubital vein. To reduce the complexity of that measurement, we propose a fully-optical technique that is based in the fact that there are changes in the optical properties of erythrocytes due to the presence of glucose-derived adducts in the haemoglobin molecule. To evaluate these changes, we propose to perform quantitative phase maps of erythrocytes by using telecentric digital holographic microscopy. Our experiments show that telecentric digital holographic microscopy allows detecting, almost in real time and from a single drop of blood, significant differences between erythrocytes of diabetic patients and healthy patients. Besides, our phase measurements are well correlated with the values of glycated haemoglobin and the blood glucose values.

Interchangeability among reference insulin analogues and their biosimilars: regulatory framework, study design and clinical implications.

Biosimilars are regulated differently from small-molecule generic, chemically derived medicines. The complexity of biological products means that small changes in manufacturing or formulation may result in changes in efficacy and safety of the final product. In the face of this complexity, the regulatory landscape for biosimilars continues to evolve, and global harmonization regarding requirements is currently lacking. It is essential that clinicians and patients are reassured that biosimilars are equally safe and effective as their reference product, and this is particularly important when interchangeability, defined as 'changing one medicine for another one which is expected to achieve the same clinical effect in a given clinical setting in any one patient', is considered. Although the automatic substitution (i.e. substitution without input from the prescribing healthcare provider) of biosimilars for reference products is currently not permitted by the majority of countries, this may change in the future. In order to demonstrate interchangeability between reference products and a biosimilar, more stringent and specific studies of the safety and efficacy of biosimilars are likely to be needed; however, guidance on the design of and the need for any such studies is currently limited. The present article provides an overview of the current regulatory framework around the demonstration of interchangeability with biosimilars, with a specific focus on biosimilar insulin analogues, and details experiences with other biosimilar products. In addition, designs for studies to evaluate interchangeability with a biosimilar insulin analogue product are proposed and a discussion about the implications of interchangeability in clinical practice is included.

Old and new basal insulin formulations: understanding pharmacodynamics is still relevant in clinical practice.

Long-acting insulin analogues have been developed to mimic the physiology of basal insulin secretion more closely than human insulin formulations (Neutral Protamine Hagedorn, NPH). However, the clinical evidence in favour of analogues is still controversial. Although their major benefit as compared with NPH is a reduction in the hypoglycaemia risk, some cost/effectiveness analyses have not been favourable to analogues, largely because of their higher price. Nevertheless, these new formulations have conquered the insulin market. Human insulin represents currently no more than 20% of market share. Despite (in fact because of) the widespread use of insulin analogues it remains critical to analyse the pharmacodynamics (PD) of basal insulin formulations appropriately to interpret the results of clinical trials correctly. Importantly, these data may help physicians in tailoring insulin therapy to patients' individual needs and, additionally, when clinical evidence is not available, to optimize insulin treatment. For patients at low risk for/from hypoglycaemia, it might be acceptable and also cost-effective not to use long-acting insulin analogues as basal insulin replacement. Conversely, in patients with a higher degree of insulin deficiency and increased risk for hypoglycaemia, analogues are the best option due to their more physiological profile, as has been shown in PD and clinical studies. From this perspective optimizing basal insulin treatment, especially in type 2 diabetes patients who are less prone to hypoglycaemia, would be suitable making significant resources available for other relevant aspects of diabetes care.

Taspoglutide, a once-weekly glucagon-like peptide 1 analogue, vs. insulin glargine titrated to target in patients with Type 2 diabetes: an open-label randomized trial.

AIMS: To compare the efficacy and safety of once-weekly taspoglutide with insulin glargine in patients with advanced Type 2 diabetes failing metformin and sulphonylurea combination therapy. METHODS: This open-label, parallel-group, multi-centre trial randomized 1049 patients continuing metformin 1:1:1 to taspoglutide 10 mg once weekly, taspoglutide 20 mg once weekly or insulin glargine once daily with forced titration to fasting plasma glucose ≤ 6.1 mmol/l. Sulphonylureas were discontinued before randomization. The primary endpoint was change in HbA(1c) after 24 weeks. RESULTS: After 24 weeks, least-square mean changes from baseline in HbA(1c) in patients receiving taspoglutide 10 mg [-8 mmol/mol (se 1)] [-0.77% (se 0.05)] or taspoglutide 20 mg [-11 mmol/mol (se 1)] [-0.98% (se 0.05)] were non-inferior to insulin glargine [-9 mmol/mol (se 1)] [-0.84% (se 0.05)]; treatment difference of 0.07% (95% CI -0.06 to 0.21) and -0.14% (95% CI -0.28 to -0.01), for taspoglutide 10 and 20 mg, respectively, vs. insulin glargine. Taspoglutide was associated with more adverse events (mainly gastrointestinal) and significantly less hypoglycaemia than insulin glargine. CONCLUSIONS: Compared with insulin glargine, taspoglutide provided non-inferior HbA(1c) reductions associated with less hypoglycaemia, but more gastrointestinal adverse events.

Update on postprandial hyperglycaemia: the pathophysiology, prevalence, consequences and implications of treating diabetes. / Actualización sobre hiperglucemia posprandial: fisiopatología, prevalencia, consecuencias e implicaciones para el tratamiento de la diabetes.

To achieve appropriate glycaemic control, postprandial and baseline hyperglycaemia should be reduced. Various epidemiological studies have suggested an association between fluctuations in postprandial blood glucose and cardiovascular risk. However, studies of interventions performed to date have not shown that selective control of postprandial hyperglycaemia is associated with cardiovascular benefits. Accordingly, an appropriate combination of drugs that control both baseline and postprandial hyperglycaemia (individually based on each patient's characteristics) is the best strategy for achieving good glycaemic control. This review seeks to impart to clinicians the concept of postprandial hyperglycaemia, analysing its causes, how to measure it, its prevalence, its consequences and, ultimately, the available therapeutic strategies for the preferential control of the postprandial hyperglycaemia along with baseline hyperglycaemia.

Adrenocortical scintigraphy with 131I-6-beta-iodomethyl-norcholesterol (NP 59) in bilateral adrenocortical carcinoma.

A case of a 49-year-old man suffering from bilateral adrenocortical carcinoma with local and secondary rapid progression is reported. The results of adrenocortical scintigraphy (NP 59) and histological findings allowed the diagnosis. This case report and a literature review showed the importance of using adrenocortical scintigraphy as a complementary imaging procedure of CT or MR images.

[Psoas abscess secondary to lumbar spondylodiscitis caused by gram negative bacilli]. / Absceso de psoas secundario a espondilodiscitis lumbar por gram negativos.

The association between psoas abscess and lumbar spondylodiscitis by Gram negative bacilli represents a rare clinical entity. Sometimes the absence of demonstrative symptoms complicates the diagnostic schema. We report about a 72 year-old woman, without previous known diabetes mellitus, who was admitted because of fever of one week duration and a non-ketotic hyperosmolar coma. A left psoas abscess was identified by abdominal computed tomography (CT). The abscess was in communication with the L1-L2 intervertebral space. Although Escherichia coli was identified as the causing agent and appropriate antibiotic therapy was administered, the resolution of the abscess occurred only after the implantation of a percutaneous catheter guided by CT without additional surgery. Percutaneous drainage as a diagnostic-therapeutic technique has rendered the surgery as the last resort in the treatment of psoas abscess.

[Factors associated with amputation in diabetic patients with foot ulcer]. / Estudio de factores asociados con amputación, en pacientes diabéticos con ulceración en pie.

OBJECTIVE: To analyse risk factors for amputation in diabetic foot ulcers. METHOD: We have studied 152 diabetic patients (in 14 food ulcers treatment was amputation) who were attendance between January 1996 and June 1998 in the diabetic foot Unit. Subjects with gangrene were excluded. RESULTS: Risk factors for amputation were: previous history of amputation (odds ratio 3.7; 1.0113.7), proliferative retinopathy, osteomielitis, and independently clinical signs of peripheral vasculopathy (7.1; 1.88-27.2) and severe infection (14.4; 2.92-71.2). CONCLUSION: Diabetic subjects with foot ulcers and previous history of amputation, proliferative retinopathy, osteomielitis, clinical signs of peripheral vasculopathy and/or severe infection were a high risk group for amputation and in this group aggressive therapeutical and preventive approaches should be done in order to prevent amputation.

Glucose clamps with the Biostator: a critical reappraisal.

The Biostator makes it possible to perform glucose clamp experiments almost automatically. Thus, blood glucose concentrations can be maintained at (or close to) a target level with substantially less effort than with the manual clamp technique. The automatisation also avoids a potential bias on the part of the investigator. However, as with the non-automated manual clamp technique, blood glucose concentrations do not remain exactly at the target value, as they show a considerable scatter around the target value. This scatter is generated by the time constants of the Biostator, i.e. the whole closed-loop system, and the autoregressive properties of the glucose clamp algorithm used. In order to describe the quality of glucose clamps over time more precisely, "cumulative sums" as an alternative to the usual coefficient of variation can be used. Practical work with the Biostator is burdened with technical difficulties and considerable costs in comparison to the manual clamp technique. Deficits concerning data storage and presentation capability of the Biostator have been overcome by an appropriate programme for an external computer. The use of the Biostator for the glucose clamp technique is not mandatory, but, the use of this machine makes it possible to perform glucose clamp studies under standardised and reproducible conditions.

Comparative dose-related time-action profiles of glibenclamide and a new non-sulphonylurea drug, AG-EE 623 ZW, during euglycaemic clamp in healthy subjects.

Insulin and glucose responses to glibenclamide were studied in comparison to a novel non-sulphonylurea drug (AG) by means of the euglycaemic clamp technique. Nine fasting male subjects were connected to a Biostator and 1.75, 3.5 or 7.0 mg glibenclamide or 1.0, 2.0 or 4.0 mg AG were given and blood glucose concentrations were clamped at 10% below basal values. Glucose infusion rates were registered over 10 h after administration of the tablet. Maximal glucose infusion rates after glibenclamide were 40% higher compared to AG (1.75 vs 1.0 mg, 3.5 vs 2.0 mg, 7.0 vs 4.0 mg, respectively) and were reached after 3-3.5 h for all doses. After glibenclamide, area under the glucose infusion curves and maximal incremental serum insulin responses were higher by 25-40% and by 30% compared to AG when low, medium and high doses of each drug were tested. However, a linear dose relationship was obtained for both drugs when the glucose infusion rate was plotted against the area under the insulin curve. In fact, both drugs were equipotent on a molecular weight basis. The hypoglycaemic index of both drugs (integrated glucose infusion rate divided by integrated insulin release) expressed per mumol of drug revealed a dose-dependent and parallel inverse curvilinear relation to increasing doses. This methodological approach allowed us to quantify and compare the metabolic effects of oral hypoglycaemic agents under standardised experimental conditions.

[Selective therapeutic embolization in malignant insulinoma]. / Embolización terapéutica selectiva en el insulinoma maligno.

A case is reported of a patient with hypoglycemia episodes secondary to a large sized malignant insulinoma with metastases to the liver. For the control of hypoglycemic episodes, both diet and octreotide were initially used but the response obtained was poor. Later, oral diazoxide was used and a good initial response was obtained but treatment was stopped due to severe adverse effects. To obtain a decrease in the tumoral size both adrimaycin and streptozotocin were administered but results were unsuccessful. Finally, embolization of the right hepatic artery was performed and no further hypoglycemic episodes occurred during the following 14 months. We conclude that selective hepatic embolization is a good therapeutic option to control hypoglycemic episodes in malignant insulinoma with metastases to the liver when other therapeutic options have proved unsuccessful.

Hiperglucemia posprandial y variabilidad glucémica: nuevos objetivos de control en la diabetes / Postprandial hyperglycemia and glycemic variability: new targets in diabetes management

La diabetes mellitus tipo 2 se caracteriza por la presencia de hiperglucemia deayuno y posprandial. Actualmente, la hemoglobina glucosilada (HbA1c) se considerael patrón de referencia en la evaluación del control glucémico en pacientescon diabetes. Los estudios de intervención en la diabetes mellitus tipo 1 y tipo 2demostraron de forma concluyente que reducir la HbA1c a menos del 7% previenela aparición/progresión de las complicaciones crónicas. Adicionalmente,otros estudios epidemiológicos y de intervención preliminares han demostradoque la hiperglucemia posprandial es un factor de riesgo independiente de enfermedadcardiovascular. La hiperglucemia crónica sostenida produce una glicaciónproteica excesiva, pero también los pacientes diabéticos presentan a diario fl uctuacionesagudas de la glucemia (variabilidad glucémica). Estas situaciones puedenactivar el estrés oxidativo y contribuir a la disfunción endotelial, que puededesempeñar también un papel en el desarrollo de las complicaciones diabéticas.De hecho, en los pacientes diabéticos, muchos factores de riesgo cardiovascularson modifi cados en el periodo posprandial, y están afectados directamente porlas oscilaciones agudas de la glucemia. Por tanto, reducir la hiperglucemia posprandialy la variabilidad glucémica se considera actualmente una prioridad terapéutica,y debe incluirse en la estrategia de prevención y tratamiento de la enfermedadcardiovascular en la diabetes(AU)

Type 2 diabetes is characterized by the presence of both fasting and postprandialhyperglycemia. Currently, glycated hemoglobin (HbA1c) is considered the«gold standard» for assessing glycemic control in patients with diabetes. Interventionalstudies in type 1 and type 2 diabetes have conclusively demonstratedthat reducing HbA1c to <7% prevent appearance and progression of chroniccomplications. Additionally, other epidemiological studies and preliminaryintervention studies have shown that postprandial hyperglycemia is an independentrisk factor for cardiovascular disease. Sustained chronic hyperglycemiaproduces excessive protein glycation, but people with diabetes suffersalso from daily acute glucose fluctuations, i.e. glucose variability. Acute changesof blood glucose may activate oxidative stress and contribute to endothelialdysfunction, which may also play a role in the development of diabeticcomplications. In fact, in diabetic subjects, most of the cardiovascular risk factorsare modified in the postprandial period, being affected directly by acuteoscillations of blood glucose. Therefore, reducing postprandial hyperglycemiaand glucose variability are now recognized as a treatment priority and shouldform part of the strategy for prevention and management of cardiovasculardisease in diabetes(AU)

Obstrucción intestinal aguda por bezoar en un paciente diabético tipo 2 con neuropatía / Acute intestinal obstruction caused by bezoar in a patient with type 2 diabetes and neuropathy

Un bezoar es una masa o concreción de material ingerido que se acumula en el estómago, desde donde puede pasar al resto del tracto intestinal. Son poco frecuentes, siendo el más común el fitobezoar. Éste se ha relacionado con la cirugía gástrica y con procesos que alteran la motilidad intestinal, como la gastroparesia diabética o la neuropatía alcohólica. En la mayoría de los casos se descubren de forma casual, y más raramente por la presencia de complicaciones asociadas. Presentamos el caso de un paciente con antecedentes de diabetes tipo 2 e ingesta crónica de alcohol, que presentó un cuadro obstructivo intestinal agudo causado por dos bezoares(AU)

A bezoar is a mass or concretion of ingested material which accumulates in the stomach, from it can progress into the rest of gastrointestinal tract. Bezoars are unusual, being the phytobezoar the most common. Phytobezoar shave been associated with gastric surgery and other pathologies that can alter intestinal motility, as diabetes gastroparesis or alcoholic neuropathy. In most cases they are found incidentally or, more rarely, they are discovered by associated complications. We report the case of a patient with type 2 diabetes and chronic alcoholism that presented an acute intestinal obstruction caused by two bezoars(AU)

Implementación de la estrategia basal plus en la práctica clínica / Basal plus strategy implementation in clinical practice

El tratamiento con insulina puede ser necesario en la diabetes tipo 2, dado que muchos pacientes, con el tiempo, no consiguen alcanzar o mantener los objetivos glucémicos para prevenir las complicaciones crónicas asociadas a la hiperglucemia sostenida. Inicialmente, la adición de insulina basal al tratamiento previo con agentes orales suele ser la pauta más habitual. Esta estrategia se basa en el control óptimo de la glucemia en ayunas. Sin embargo, un porcentaje significativo de pacientes no consiguen alcanzar o mantener el objetivo de HbA1c <=7%, debido a que presentan elevaciones excesivas de la glucemia posprandial. En consecuencia, el paso siguiente en la intensificación deltratamiento podría ser la adición de una dosis única de insulina prandial antes de la comida que provoca la mayor excursión posprandial (estrategia basal plus), manteniendo el tratamiento previo con insulina basal y agentes orales. Este régimen ha demostrado ser sencillo, eficaz y adecuado para un gran número de pacientes. Además, en caso necesario, facilita la introducción progresiva de inyecciones adicionales de insulina prandial hasta una estrategia bolo basal. En este artículo se resumen las recomendaciones de un grupo de trabajo multidisciplinar para una adecuada implementación de la estrategia basal plus en la práctica clínica habitual (AU)

Insulin treatment may be necessary in type 2 diabetes, because many patients are not able overthe time to achieve or maintain glycemic targets to prevent chronic complications associated to sustained hyperglycemia. Initially, addition of basal insulin to previous treatment with oral agentsis the most commonly used regimen. This strategy is based on optimal control of fasting plasma glucose. However, a significant proportion of patients does not achieve or maintain HbA1c target <=7%, because they show excessive postprandial glucose values. Therefore, the next step for intensification of treatment might be the addition of a single dose of prandial insulin before the main meal, which is associated with the greatest postprandial glucose excursion (basal plus strategy), maintaining previous treatment with basal insulin and oral agents. This regimen has demonstrated to be easy to use, effective and appropriate for many patients. Furthermore, if necessary, it makes easier progressive introduction of additional injections of prandial insulin until the basal bolus strategy. In this manuscript, recommendations from a multidisciplinary working group are summarized for an adequate implementation of the basal plus strategy in the routine clinical practice (AU)

Síndrome de falta de reconocimiento de la hipoglucemia. Factores de riesgo y tratamiento / Hypoglycemia unawareness syndrome. Risk factors and treatment

La falta de reconocimiento de la hipoglucemia es un importante factorlimitante del tratamiento en la diabetes mellitus tipo 1 y tipo 2avanzada. Este problema, que ocurre hasta en un 25% de los pacientestratados con insulina, se caracteriza por una pérdida de lossíntomas autónomos de alarma antes de la aparición de la neuroglucopenia.La hipoglucemia inadvertida se asocia a un incremento deaproximadamente 7 veces el riesgo de sufrir hipoglucemias graves.Se han identifi cado diversos factores de riesgo para la hipoglucemiainadvertida, incluida la diabetes de larga duración, el control metabólicoestricto (valores bajos de HbA1c) y los episodios repetidos de hipoglucemia.La disminución de la respuesta contrarreguladora frentea la hipoglucemia es la causa principal de la hipoglucemia inadvertida.Evitar estrictamente las hipoglucemias restablece casi completamentesu percepción. En consecuencia, se han desarrollado diferentesestrategias terapéuticas para prevenir las hipoglucemias. Entreellas, el desdoblamiento de la insulina NPH nocturna, la infusión subcutáneacontinua de insulina, el uso preferente de los análogos deinsulina y, más recientemente, la monitorización continua de glucosa,han demostrado ser efectivas en la mayoría de casos(AU)

Hypoglycemia unawareness is a major limiting factor in the managementof type 1 and advanced type 2 diabetes. This common problem,which occurs in about 25% of patients treated with insulin, ischaracterized by loss of autonomic warning symptoms before developmentof neuroglycopenia. Hypoglycemia unawareness is also associatedwith ~7-fold increase in the risk to suffer severe hypoglycemia.Several risk factors for hypoglycemia unawareness have beenidentified, including long duration of diabetes, tight glycemic control(low HbA1c values), and repeated episodes of hypoglycemia. Reductionof counterregulatory hormone responses to hypoglycemia areprimarily responsible for hypoglycemia unawareness. Strict avoidingof hypoglycemia restores almost completely awareness of hypoglycemia.Therefore, several therapeutic strategies have been designedto prevent hypoglycemia. Among them, evening NPH insulin splitting,continuous subcutaneous insulin infusion, preferential use of insulinanalogues and, more recently, continuous glucose monitoring havebeen proved to be effective in most cases(AU)

Criterios profesionales sobre el papel de ezetimiba en el manejo clínico del paciente dislipémico en el ámbito de atención primaria / Professional criteria about the role of ezetimibe in clinical management of dyslipidemia in primary care

Introducción: A pesar de que ezetimiba fue introducida en España hace más de 5 años, existen todavía diferencias de criterio sobre el papel actual de este fármaco en el manejo de la dislipemia en atención primaria. Objetivos: Promover un consenso sobre el uso clínico de ezetimiba entre profesionales de atención primaria. Material y métodos: El estudio fue dividido en cuatro fases: 1) creación de un comité científico multidisciplinar (atención primaria, endocrinología y medicina interna) para revisión bibliográfica y formulación de un uestionario de 46 ítems sobre dislipemia y ezetimiba; 2) selección del panel de 91 médicos de atención primaria expertos en este campo; 3) encuesta Delphi en dos rondas, enviada por correo electrónico, y 4) sesión presencial final de discusión de resultados. Resultados: Participaron 87 profesionales que, en la primera ronda, lograron consensuar 34 de las 46 cuestiones analizadas. Tras la interacción del panel, el consenso aumentó hasta 42 ítems. En las 4 cuestiones restantes el consenso fue insuficiente, debido a las opiniones dispares o a la ausencia de criterio en la mayoría de los encuestados. Conclusiones: En este consenso, se presenta una amplia lista de criterios profesionales y/o recomendaciones para el uso de ezetimiba en atención primaria, que resumen la opinión profesional vigente entre los expertos de esta especialidad (AU)

Background: Since ezetimibe was first marketed in Spain more than 5 years ago, differences in criteria continue to exist about the current role played by ezetimibe in treating dyslipaemia in the primary care in Spain. Objectives: To develop consensus regarding the clinical use of ezetimibe in treating dyslipaemia in primary care. Methods: The study was divided into four stages: 1) constitution of a multidisciplinary scientific committee (primary care, endocrinology, internal medicine) for bibliographic review and formulation of a 46-items survey about dyslipaemia and ezetimibe; 2) constitution of a panel of 84 primary care professionals with expertise in this field; 3) Delphi survey in two rounds, sent by mail; and 4) a final discussion of the results in a face-to-face meeting. Results: Eighty-seven experts participated and, during the first round, reached a consensus in 34 out of 46 analysed questions. Following interaction by the panel, the consensus increased until 42 items. In the remaining 4 questions, insufficient consensus was obtained, due to opinion disparities existing among the professionals or to the absence of an established criterion for most of the experts. Conclusions: In this consensus, a long list of professional criteria and/or recommendations is included for the use of ezetimibe in primary care, summarising prevailing professional opinion of primary care experts (AU)

Diagnóstico diferencial entre osteomielitis de pie y artropatía de Charcot aguda / Differential diagnosis between foot osteomyelitis and acute Charcot arthropathy

No disponible

No disponible

Estudio de factores asociados con amputación en pacientes diabéticos con ulceración en pie / Study of factors associated with amputation in diabetic patients with foot ulceration

Objetivo: Analizar factores asociados con amputación en pacientes diabéticos que presentan úlceras en sus pies, con el fin de identificar sujetos con alto riesgo para amputación.Método: Hemos estudiado 152 diabéticos que acudieron a la Unidad del pie diabético desde enero de 1996 hasta junio de 1998 con úlceraciones en sus pies. En 14 de ellos fue necesaria la amputación. Se excluyeron sujetos con gangrena.Resultados: Los factores asociados con amputación fueron: antecedentes personales de amputación previa (odds ratio 3,7; 1,01-13,7), retinopatía proliferativa, osteomielitis y, de forma independiente, la presencia de vasculopatía (7,1; 1,88-27,2) e infección grave (14,4; 2,92-71,2).Conclusión: Los pacientes diabéticos con úlceras en pie que presenten antecedentes de amputación, signos clínicos de vasculopatía periférica, infección grave, osteomielitis o retinopatía avanzada son de alto riesgo para la amputación y en ellos se deben instaurar precozmente medidas terapéuticas y preventivas intensas. (AU)

Terapias basadas en el efecto incretina para el tratamiento de la diabetes tipo 2: revisión sistemática / Incretin-based therapies for the treatment of type 2 diabetes: a systematic review

Muchos pacientes con diabetes tipo 2 no logran alcanzar los objetivos glucémicos establecidos con los tratamientos disponibles, incluso cuando se usan en combinación, y desarrollan eventualmente complicaciones micro y macro vasculares. En consecuencia, se necesitan nuevos fármacos que traten con más eficacia la enfermedad, su progresión y sus complicaciones asociadas. Un área de emergente interés está centrada en las acciones de las hormonas con efecto incretinaGLP-1 (glucagon-like peptide-1; péptido 1 semejante al glucagón) y GIP (glucose-dependent insulinotropic polypeptide; polipéptidoinsulinotrópico dependiente de la glucosa). Estas hormonas aumentan la secreción de insulina estimulada por la ingesta e inhibenla secreción de glucagón. Además, tienen también efectos tróficos sobre la célula beta, incrementan la saciedad y disminuyen el apetito(GLP-1). Sobre la base de las acciones favorables de las incretinas, recientemente se han aprobado dos nuevas clases de fármacos para el tratamiento de la diabetes tipo 2: los análogos del GLP-1, estables y de larga duración (incretinmiméticos), y los inhibidores de la DPP-4 (dipeptidil peptidasa-4), la enzima responsable de la degradación rápida de las incretinas (potenciadores del efecto incretina). Estos fármacos consiguen reducciones sustanciales de la hemoglobina glucosilada, disminuyendo tanto la glucemia en ayunas como la glucemia pos prandial, y mejorando varios índices de la secreción de insulina. Los análogos de GLP-1, que deben administrarse por vía subcutánea, inducen pérdida de peso, pero tienen efectos adversos gastrointestinales relevantes. Los inhibidores de la DPP-4 son fármacos orales bien tolerados, sin efectos adversos asociados importantes, y neutros respecto al peso. Aunque se presentarán ambas clases de fármacos, esta revisión se centrará especialmente en los inhibidores de la DPP-4, los únicos fármacos disponibles hoy en España

Many patients with type 2 diabetes fail to achieve adequate glycaemic control with the available treatments, even when used in combination, and eventually develop micro- and macrovascular diabetic complications. Therefore, there is a need for new agents that more effectively treat the disease, its progression and its associated complications. One emerging area of interest is centered upon the actions of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). These hormones enhancemeal-induced insulin secretion and inhibit glucagon secretion. Additionally, they have also trophic effects on the beta-cell, increase satiety and diminish appetite (GLP-1). Based on the favorable actions of the incretin hormones, two new classes of agents have recently approved for therapy of type 2 diabetes: long-acting stable GLP-1-analogues (incretin mimetics) and inhibitors of dipeptidyl peptidase 4(DPP-4), the enzyme responsible for the rapid degradation of the incretin hormones (incretin enhancers). These agents achieve meaningful reduction of HbA1c, diminishing both fasting plasma glucose and postprandial hyperglycemia, and improving several indices of insulin secretion. GPL-1 analogues should be administered subcutaneously, induce weight reduction but have relevant gastrointestinal adverse effects.DPP-4 inhibitors are well tolerated oral drugs, without any significant associated adverse events, and weight neutral. Although both classes of agents will be discussed, this review will focus mainly onDPP-4 inhibitors, the only currently available drugs in Spain