Clinical use of the co-formulation of insulin degludec and insulin aspart.

AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. METHODS: Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. RESULTS: In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. CONCLUSIONS: IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins.

Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type 2 diabetes mellitus.

Men with type 2 diabetes mellitus (DM2) have lower testosterone levels and a higher prevalence of hypogonadism. It still remains unclear the mechanism by which there is a relationship between hypogonadism and DM2. The objective was to evaluate the hypothalamic-pituitary-gonadal axis at different levels in eugonadal patients with DM2. Fourteen patients with DM2 (DM2 group) and 15 subjects without DM2 (normal glucose tolerance test) as control group (CG) were included. We assessed: (i) fasting glucose, insulin, Homeostasis Model Assessment (HOMA); (ii) luteinizing hormone (LH) pulsatility through blood collections every 10 min for 4 h; (iii) gonadotropin-releasing hormone (GnRH) test: basal LH and 30, 60 and 90 min after 100 µg of i.v. GnRH; (iv) human chorionic gonadotropin (hCG) test: basal total testosterone (TT), bioavailable testosterone (BT), free testosterone (FT), estradiol (E2), bioavailable E2 (BE2) and sex hormone-binding globulin (SHBG) and 72 h post 5000 IU of i.m. hCG. There were no differences in age, body mass index and waist circumference between groups. Glucose was higher in the DM2 group vs. CG: 131.1 ± 25.5 vs. 99.1 ± 13.6 mg/dL, p = 0.0005. There were no difference in basal insulin, HOMA, TT, BT, FT, E2, BE2, SHBG and LH levels between groups. The DM2 group had lower LH pulse frequency vs. CG: 0.8 ± 0.8 vs. 1.5 ± 0.5 pulses, p = 0.009. Differences in LH pulse amplitude were not found. A negative correlation was found between the number of LH pulses and glucose, r: -0.39, p = 0.03. There were no differences in the response of LH to GnRH between groups nor in the response of sexual steroids and SHBG to hCG. Patients with DM2 showed lower hypothalamic pulse frequency without changes in the pituitary response to GnRH nor testicular response to hCG. Glucose levels negatively correlated with the number of LH pulses which suggests a negative effect of hyperglycaemia in the hypothalamic secretion of GnRH.

El estudio A1chieve: un estudio observacional, de no intervención en pacientes con diabetes tipo 2 que inician o cambian a un tratamiento con análogos de insulina: datos de la población argentina / The A1chieve study: An observational non-interventional study of patients with type 2 diabetes initiating or changing to insulin analogue therapy: data from the Argentinean population

Objetivos: el objetivo de este artículo es informar acerca de la seguridad y la efectividad de iniciar o cambiar a un tratamiento con insulinas análogas en la subpoblación argentina del estudio A1chieve. Materiales y métodos: estudio observacional, de no intervención. En la cohorte argentina participaron 607 pacientes con diabetes tipo 2 (DM2), con o sin tratamiento previo con insulina, quienes inciaron un tratamiento con insulina aspártica bifásica 30, insulina detemir o insulina aspártica con o sin antidiabéticos orales (ADOs). Resultados: el grado de control metabólico al inicio del estudio, medido por HbA1c basal (± DE) fue pobre: 9,4 ± 2,1 %. A los 6 meses, se observó una reducción de HbA1c de -1,8 ± 2,1 % en la cohorte completa, y -2,3 ± 2,1% y -1,1 ± 1,8 % para los pacientes sin tratamiento previo con insulina y con tratamiento previo con insulina, respectivamente. En general, la tasa de hipoglucemia se incrementó en aquellos pacientes que recibieron insulina por primera vez, mientras que se observó una disminución en los pacientes que, previamente, recibían otras insulinas. Se observó un incremento del peso corporal (± DE) en los pacientes sin tratamiento previo con insulina (0,8 ± 4,3 kg). Conclusiones: en la población argentina del estudio A1chieve, se observó un control metabólico deficiente. Se logró una mejoría de la HbA1c al iniciar un tratamiento con análogos de insulina, ya sea en pacientes na´ve usuarios previos de insulina,siendo una gran oportunidad para lograr amplias mejorías en el autocuidado y en el control metabólico, independientemente del tipo de regimen insulínico utilizado, con buena tolerabilidad y seguridad. Estos hallazgos coinciden con los resultados obtenidos en la cohorte completa del estudio.(AU)

Objectives: The aim of this paper is to report the safety and effectiveness of initiating or switching to insulin analogue therapy in the Argentinean subpopulation of the A1chieve study. Materials and methods: Observational, non-interventional study. The Argentinean cohort included 607 patients with type 2 diabetes (T2D), both insulin-na´ve and prior insulin users, who initiated treatment with biphasic insulin aspart 30, insulin detemir or insulin aspart ± oral antidiabetic agents. Results: Baseline HbA1c (±SD) was poor: 9.4 ± 2.1 %. At 6 months, a reduction in the HbA1c of -1.8 ± 2.1 % was observed in the entire cohort, and of -2.3 ± 2.1 % and -1.1 ± 1.8 % in insulin-na´ve patients and prior insulin users, respectively. Overall, the rate of hypoglycaemia increased in insulin-na´ve patients, whereas a reduction was observed in those switching from other insulins. An increase in the body weight (±SD) was noted in insulin-na´ve patients (0.8 ± 4.3 kg). Conclusions: Poor glycemic control was observed in the Argentinean population of the A1chieve study. The initiation of insulin analogue therapy showed an improvement in HbA1c, in both insulin-na´ve patients and previous insulin users, which was a good opportunity for improvements in self-care and metabolic control, regardless of the type of insulin regimen used, with a good tolerability and safety profile. These findings are consistent with those obtained from the entire A1chieve study cohort.(AU)

El estudio A1chieve: un estudio observacional, de no intervención en pacientes con diabetes tipo 2 que inician o cambian a un tratamiento con análogos de insulina: datos de la población argentina / The A1chieve study: An observational non-interventional study of patients with type 2 diabetes initiating or changing to insulin analogue therapy: data from the Argentinean population

Objetivos: el objetivo de este artículo es informar acerca de la seguridad y la efectividad de iniciar o cambiar a un tratamiento con insulinas análogas en la subpoblación argentina del estudio A1chieve. Materiales y métodos: estudio observacional, de no intervención. En la cohorte argentina participaron 607 pacientes con diabetes tipo 2 (DM2), con o sin tratamiento previo con insulina, quienes inciaron un tratamiento con insulina aspártica bifásica 30, insulina detemir o insulina aspártica con o sin antidiabéticos orales (ADOs). Resultados: el grado de control metabólico al inicio del estudio, medido por HbA1c basal (± DE) fue pobre: 9,4 ± 2,1 %. A los 6 meses, se observó una reducción de HbA1c de -1,8 ± 2,1 % en la cohorte completa, y -2,3 ± 2,1% y -1,1 ± 1,8 % para los pacientes sin tratamiento previo con insulina y con tratamiento previo con insulina, respectivamente. En general, la tasa de hipoglucemia se incrementó en aquellos pacientes que recibieron insulina por primera vez, mientras que se observó una disminución en los pacientes que, previamente, recibían otras insulinas. Se observó un incremento del peso corporal (± DE) en los pacientes sin tratamiento previo con insulina (0,8 ± 4,3 kg). Conclusiones: en la población argentina del estudio A1chieve, se observó un control metabólico deficiente. Se logró una mejoría de la HbA1c al iniciar un tratamiento con análogos de insulina, ya sea en pacientes naïve usuarios previos de insulina,siendo una gran oportunidad para lograr amplias mejorías en el autocuidado y en el control metabólico, independientemente del tipo de regimen insulínico utilizado, con buena tolerabilidad y seguridad. Estos hallazgos coinciden con los resultados obtenidos en la cohorte completa del estudio.

Objectives: The aim of this paper is to report the safety and effectiveness of initiating or switching to insulin analogue therapy in the Argentinean subpopulation of the A1chieve study. Materials and methods: Observational, non-interventional study. The Argentinean cohort included 607 patients with type 2 diabetes (T2D), both insulin-naïve and prior insulin users, who initiated treatment with biphasic insulin aspart 30, insulin detemir or insulin aspart ± oral antidiabetic agents. Results: Baseline HbA1c (±SD) was poor: 9.4 ± 2.1 %. At 6 months, a reduction in the HbA1c of -1.8 ± 2.1 % was observed in the entire cohort, and of -2.3 ± 2.1 % and -1.1 ± 1.8 % in insulin-naïve patients and prior insulin users, respectively. Overall, the rate of hypoglycaemia increased in insulin-naïve patients, whereas a reduction was observed in those switching from other insulins. An increase in the body weight (±SD) was noted in insulin-naïve patients (0.8 ± 4.3 kg). Conclusions: Poor glycemic control was observed in the Argentinean population of the A1chieve study. The initiation of insulin analogue therapy showed an improvement in HbA1c, in both insulin-naïve patients and previous insulin users, which was a good opportunity for improvements in self-care and metabolic control, regardless of the type of insulin regimen used, with a good tolerability and safety profile. These findings are consistent with those obtained from the entire A1chieve study cohort.

Insulinorresistencia y disfunción eréctil: Efecto del tratamiento con metformina / Insulin resistance and erectile dysfunction: Effect of treatment with metformin

La erección depende de la liberación de óxido nítrico (ON) endotelial. La insulinorresistencia (IR) produce disfunción endotelial por menor síntesis y liberación de ON. El tratamiento con metformina mejora la función eréctil en ratones con IR y disfunción eréctil (DE). Objetivos: Evaluar en pacientes con DE: 1) la presencia de IR; 2) el grado de severidad de la DE según la presencia de IR y 3) el efecto del tratamiento con metformina sobre la función eréctil en pacientes con DE e IR. Material y métodos: Estudio prospectivo, randomizado, doble ciego con placebo. Se incluyeron 81 pacientes con DE y 20 hombres sin DE (grupo control). Se evaluó función eréctil con el cuestionario IIEF-5. Se evaluó IR con el índice HOMA. Se consideró IR si HOMA ≥3. Treinta pacientes con DE, IR y pobre respuesta al sildenafil fueron randomizados para recibir tratamiento con metformina o placebo. Resultados: Se encontró una diferencia significativa entre pacientes con DE y el grupo control en HOMA: 4.9±2.8 versus 3.6±2.6 (p=0.03). La prevalencia de IR fue mayor en los pacientes con DE que en el grupo control: 77.7% versus 45.0% (p=0.008). Se halló una correlación negativa entre HOMA e IIEF-5: r:-0.21 (p=0.04). Los pacientes con DE e IR tuvieron menor score IIEF-5 que los pacientes con DE sin IR. Luego del tratamiento con metformina, los pacientes con DE tuvieron un incremento significativo en el score IIEF-5 y una disminución significativa del HOMA a los 2 y 4 meses de tratamiento, no se observaron cambios en IIEF-5 ni HOMA en los pacientes que recibieron placebo. Conclusión: nuestros hallazgos hacen suponer que la disfunción endotelial causada por IR podría ser uno de los mecanismos fisiopatológicos de la DE. El tratamiento con metformina en pacientes con DE reduce la IR y podría mejorar la respuesta al tratamiento con sildenafil. Rev Argent Endocrinol Metab 47: 13-20, 2010. Los autores declaran no tener conflictos de interés.

Erection depends largely on the release of nitric oxide (NO) by vascular endothelium. Insulin resistance (IR), present in most subjects who have obesity, metabolic syndrome (MS) or type 2 diabetes mellitus (DM2) is a metabolic abnormality that produces endothelial dysfunction determined by minor synthesis and release of NO. Treatment with metformin improves erectile function in mice with erectile dysfunction (ED) and IR. Aims: To evaluate in ED patients: 1) the presence of IR; 2) the degree of severity of ED according to the presence of IR; 3) the effect of treatment with metformin on erectile function in patients with ED and IR. Methods: Prospective, randomized, controlled, double-blind placebo study. We included 81 patients with ED and 20 men without ED (control group). Exclusion criteria: pharmacologic, anatomic or endocrine ED (hypogonadism or hyperprolactinemia), DM2, prior prostatic surgery or chronic illnesses. The erectile function was rated according the International Index of Erectile Function 5. IR was measerud by HOMA index. Thirty patients with ED, IR and poor response to sildenafil were randomized to receive metformin or placebo. Results: Patients with ED had higher HOMA index versus control group: 4.9 ± 2.8 versus 3.6 ± 2.6, p=0.03. The prevalence of IR was higher in ED group versus control group: 77.7% versus 45.0%, p=0.008. We found a negative correlation between HOMA and IIEF-5: r:-0.21, p=0.04. Patients with ED and IR (n=62) had lower IIEF-5 score when compared with those without IR (n=19): 13.6 ± 4.3 versus 16.0 ± 3.1, p=0.04. After treatment with metformin patients with ED showed a significant increase in IIEF-5 score and a significant decrease in HOMA index both at 2 and 4 months of treatment. Changes in the IIEF-5 score and HOMA index were not observed in patients with ED receiving placebo. Conclusion: Our findings suggest that endothelial dysfunction caused by IR could be one of the pathophysiologial mechanisms of ED. Treatment with metformin in patients with ED reduces IR and could improve response to treatment with sildenafil. Rev Argent Endocrinol Metab 47: 13-20, 2010 No competing finantial interests exist.

La disfunción eréctil se asocia a elevada prevalencia de obesidad y síndrome metabólico / Erectile dysfunction is associated with a high prevalence of obesity and metabolic syndrome

La disfunción eréctil (DE) afecta a un porcentaje importante de la población masculina y suele estar relacionada con enfermedades endocrino-metabólicas de las cuales la Diabetes Mellitus tipo 2 (DM2) es la que se asocia con mayor frecuencia, aún en pacientes con buen control glucémico. Estas observaciones unidas al hecho que la DE aparece asociada a otros componentes del síndrome metabólico (SM) tales como hipertensión arterial (HTA), obesidad abdominal, dislipidemia (DLP), aún sin considerar la hiperglucemia manifiesta, nos han orientado a considerar la hipótesis que la DE podría instalarse tempranamente, en pacientes con SM y previamente al diagnóstico de DM2. Objetivos: Evaluar en un grupo de pacientes con DE: 1) la prevalencia de factores de riesgo metabólicos y cardiovasculares y de SM y 2) la prevalencia de tolerancia alterada a la glucosa. Se incluyeron 77 pacientes con DE (grupo P) y 17 varones sin DE como grupo control (grupo C). La prevalencia de SM fue determinada según criterios: International Diabetes Federation (IDF) y National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII). La prevalencia de HTA y DLP fue superior en el grupo P vs. grupo C: 82.2 % vs. 23.5 % (p=0.03) y 68.5 % vs. 23.5 % (p=0.04), respectivamente. Se detectaron 20 nuevos casos de HTA y 24 nuevos casos de DLP. Los pacientes del grupo P presentaron mayor perímetro de cintura y mayor índice de masa corporal vs grupo C: 105.3 ± 9.7 vs. 98.1 ± 7.5 cm (p=0.004) y 29.8 ± 4.3 vs. 26.2 ± 2.9 kg/m² (p=0.0003), respectivamente. La prevalencia de SM-IDF y SM-NCEP-ATPIII fue superior en el grupo P vs. grupo C: 68.5 % vs. 23.5 % (p=0.04) y 52.1 % vs 11.8 % (p=0.02), respectivamente. No se observaron diferencias en la prevalencia de tolerancia alterada a la glucosa. Los pacientes con DE presentan una elevada prevalencia de HTA, DLP, obesidad y SM. La detección temprana de éstos factores en pacientes con DE provee una oportunidad única para prevenir la progresión a DM2 y enfermedad cardiovascular.

Introduction: The erectile dysfunction (ED) is associated with metabolic and endocrine diseases and with high frequency to Type 2 Diabetes Mellitus (DM2), even with good glycemic control. Besides ED is associated with others metabolic syndrome (MS) components like hypertension (HT), obesity and dyslipidemia (DLP), without hyperglycemia. These observations has guided us to consider the hypothesis that ED could be installed early in patients with the MS and previously to DM2 diagnosis. Aims: To evaluate in a ED patients group: 1) metabolic and cardiovascular risk factors and MS prevalence; 2) impaired glucose tolerance prevalence. Methods: We included 77 patients with ED (group P). Control group: 17 men without ED (group C). Exclusion criteria: pharmacologic, anatomic or endocrine ED (hypogonadism or hyperprolactinemia), DM2, prior prostatic surgery or chronic illnesses. The erectile function was rated according the International Index of Erectile Function 5. Multiple metabolic and cardiovascular risk factors were evaluated: HT, DLP, obesity, smoking and sedentarism lifestyle. The MS was evaluated according the International Diabetes Federation (IDF) and National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Results: The prevalence of HT and DLP was higher in group P vs group C: 82.2 % vs 23.5 % (p=0.03) and 68.5 % vs 23.5 % (p=0.04), respectively. Twenty new cases of HT and 24 new cases of DLP were detected. Group P patients had a higher waist circumference and body mass index than group C ones: 105.3 ± 9.7 vs 98.1 ± 7.5 cm (p=0.004) and 29.8 ± 4.3 vs 26.2 ± 2.9 kg/m² (p=0.0003), respectively. The prevalence of MSIDF and MS-NCEP-ATPIII was higher in group P vs group C: 68.5 % vs 23.5 % (p=0.04) and 52.1 % vs 11.8 % (p=0.02), respectively. No differences were found in impaired glucose tolerance prevalence. Conclusion: Men with ED have a high prevalence of HT, DLP, obesity and MS. Early detection of these factors in patients with ED provides an unique opportunity for DM2 and cardiovascular disease prevention.

An algorithm for the treatment of type 2 diabetes in Latin America.

Diabetes is a principal and growing health concern in Latin America, accounting for significant mortality and morbidities. Large, randomized, prospective trials of various interventional therapies in patients with both type 1 and type 2 diabetes have demonstrated that reductions in hyperglycaemia and management of diabetes-related risk factors can significantly reduce the micro- and macrovascular complications of diabetes. Therefore, patients with type 2 diabetes will benefit from more aggressive treatment regimens to help decrease the occurrence and rate of progression of diabetic complications. Given the many complexities of diabetes management, it is often difficult for general practice physicians to stay abreast of emerging treatment strategies and therapies. Owing to the high prevalence of type 2 diabetes in Latin America, the majority of patients with diabetes are treated by generalists rather than specialists. This article was intended to assist physicians and other healthcare professionals in developing and using effective treatment strategies to stem the growing epidemic of diabetes and its complications in Latin America.

[Self monitoring of capillary blood glucose. Evaluation of long-term results (3 to 7 years)]. / Autocontrol de la glucemia capilar. Evaluación del resultado a largo plazo (3 a 7 años).

We analyzed data provided by 60 diabetic patients (DP) included in a Program (P) of Self Blood Glucose Monitoring (SBGM) which showed an initial adherence of at least 6 months. Total follow-up was 67,293 DP-days (110,504 capillary glycemias). Only 50% of DP's remained for > 3 years. Rates of drop-out (DO) peaked early (3th semester (S) and late (10th. S) mean +/- SE of daily SBGM reported in the preprogram period and during the 1st S on P-SBGM by the future DO was significantly higher (4.25 +/- 0.22) than those reported by their P-SBGM-mates who stayed in the program (3.11 +/- 0.29; p < 0.01). DO showed a higher % of capillary glycemias < 60 mg/dl (hypoglycemia) (5.34 +/- 1.49 vs 2.85 +/- 1.14; p < 0.01). During the 3rd S early DO showed significantly higher Glycosilated Hemoglobin (HbA1) levels (10.4 +/- 0.49%) than late DO (8.19 +/- 0.45%; p < 0.01). HbA1's recorded by the late DO's just before leaving P-SBGM were significantly higher (10.14 +/- 0.61%) than those seen at 2nd/5th S (8.2 +/- 0.2; p < 0.01). However, HbA1's of 1-DO at time of abandoning P-SBGM were comparable to those shown by those DP's who remained (10.14 +/- 0.61 vs 9.46 +/- 0.27%). DP's performed daily SBGM's in 70% of possible days during 4 years and in only 50% afterwards. Daily SBGM's was 3.3 +/- 1 during the first 3 years and 2.1 +/- 0.8 thereafter. Compared to preprogram period, all DP's improved HbA1's (12.5 +/- 0.31 vs 9.46 +/- 0.27; p < 0.001) and mean blood glucose (166 +/- 5.2 vs 146 +/- 3.6; p < 0.01). DP's who reached a faster and more satisfactory degree of glycemic control in earlier stages of P-SBGM showed the highest rates of drop-out. Early identification of such patients, as well as setting of feasable and individualy adjusted goals of glycemic control may improve current compliance of DP's on long term tight control.

[Kidney and pancreas transplantation: initial experience at a single transplant center in Argentina]. / Trasplante renopancrático. Experiencia inicial en un centro de trasplante en Argentina.

After more than 10,000 cases reported all over the world until 1998, simultaneous kidney and pancreas transplantation has become a safe clinical practice, and it may probably represent the best treatment available for diabetic patients in end-stage renal disease. Here we present our results after 12 cadaveric pancreas transplants (8 whole organ, and 4 islet transplants), performed on insulin-dependent diabetic patients. Eleven of these patients received a kidney simultaneously, and one of them required a kidney retransplantation. All vascularised pancreatic grafts were positioned intraperitoneally, anastomosed to the iliac vessels, and bladder drained. One year patient, whole pancreas, and kidney survival rates were 86%, 86% and 71%, respectively. All of these patients remain insulin and dialysis-free, the longest for 37 months. Islets for transplantation were obtained from single cadaveric donors. Fresh, unpurified cells were transplanted intraperitoneally by laparoscopy (equivalent islet yields: 3 x 10(5), 4 x 10(5), 1 x 10(6) and 5 x 10(5)). None of the islet recipients resulted insulin-independent but they all reduced daily requirements in about 40%, with better metabolic control (mean HbA1c pretransplant 9.4 +/- 1.8, vs 7.9 +/- 1.6 posttransplant). One kidney graft was lost due to venous thrombosis. Simultaneous kidney and pancreas transplantation offers the diabetic patient in end-stage renal disease a chance of independence both from dialysis and exogenous insulin. Whole pancreas transplantation has better functional outcome than islet transplantation. Nevertheless, for those diabetic patients who do not meet the criteria to receive a vascularised graft, pancreatic cells may still improve carbohydrate metabolism with minor surgical risk.

Trasplante renopancrático. Experiencia inicial en un centro de trasplante en Argentina. / [Kidney and pancreas transplantation: initial experience at a single transplant center in Argentina]

After more than 10,000 cases reported all over the world until 1998, simultaneous kidney and pancreas transplantation has become a safe clinical practice, and it may probably represent the best treatment available for diabetic patients in end-stage renal disease. Here we present our results after 12 cadaveric pancreas transplants (8 whole organ, and 4 islet transplants), performed on insulin-dependent diabetic patients. Eleven of these patients received a kidney simultaneously, and one of them required a kidney retransplantation. All vascularised pancreatic grafts were positioned intraperitoneally, anastomosed to the iliac vessels, and bladder drained. One year patient, whole pancreas, and kidney survival rates were 86

, 86

and 71

, respectively. All of these patients remain insulin and dialysis-free, the longest for 37 months. Islets for transplantation were obtained from single cadaveric donors. Fresh, unpurified cells were transplanted intraperitoneally by laparoscopy (equivalent islet yields: 3 x 10(5), 4 x 10(5), 1 x 10(6) and 5 x 10(5)). None of the islet recipients resulted insulin-independent but they all reduced daily requirements in about 40

, with better metabolic control (mean HbA1c pretransplant 9.4 +/- 1.8, vs 7.9 +/- 1.6 posttransplant). One kidney graft was lost due to venous thrombosis. Simultaneous kidney and pancreas transplantation offers the diabetic patient in end-stage renal disease a chance of independence both from dialysis and exogenous insulin. Whole pancreas transplantation has better functional outcome than islet transplantation. Nevertheless, for those diabetic patients who do not meet the criteria to receive a vascularised graft, pancreatic cells may still improve carbohydrate metabolism with minor surgical risk.

Autocontrol de la glucemia capilar. Evaluación del resultado a largo plazo (3 a 7 años). / [Self monitoring of capillary blood glucose. Evaluation of long-term results (3 to 7 years)]

We analyzed data provided by 60 diabetic patients (DP) included in a Program (P) of Self Blood Glucose Monitoring (SBGM) which showed an initial adherence of at least 6 months. Total follow-up was 67,293 DP-days (110,504 capillary glycemias). Only 50

of DPs remained for > 3 years. Rates of drop-out (DO) peaked early (3th semester (S) and late (10th. S) mean +/- SE of daily SBGM reported in the preprogram period and during the 1st S on P-SBGM by the future DO was significantly higher (4.25 +/- 0.22) than those reported by their P-SBGM-mates who stayed in the program (3.11 +/- 0.29; p < 0.01). DO showed a higher

of capillary glycemias < 60 mg/dl (hypoglycemia) (5.34 +/- 1.49 vs 2.85 +/- 1.14; p < 0.01). During the 3rd S early DO showed significantly higher Glycosilated Hemoglobin (HbA1) levels (10.4 +/- 0.49

) than late DO (8.19 +/- 0.45

; p < 0.01). HbA1s recorded by the late DOs just before leaving P-SBGM were significantly higher (10.14 +/- 0.61

) than those seen at 2nd/5th S (8.2 +/- 0.2; p < 0.01). However, HbA1s of 1-DO at time of abandoning P-SBGM were comparable to those shown by those DPs who remained (10.14 +/- 0.61 vs 9.46 +/- 0.27

). DPs performed daily SBGMs in 70

of possible days during 4 years and in only 50

afterwards. Daily SBGMs was 3.3 +/- 1 during the first 3 years and 2.1 +/- 0.8 thereafter. Compared to preprogram period, all DPs improved HbA1s (12.5 +/- 0.31 vs 9.46 +/- 0.27; p < 0.001) and mean blood glucose (166 +/- 5.2 vs 146 +/- 3.6; p < 0.01). DPs who reached a faster and more satisfactory degree of glycemic control in earlier stages of P-SBGM showed the highest rates of drop-out. Early identification of such patients, as well as setting of feasable and individualy adjusted goals of glycemic control may improve current compliance of DPs on long term tight control.

Growth hormone-insulin-like growth factor-I axis in adult insulin-dependent diabetic patients: evidence for central hypersensitivity to growth hormone-releasing hormone and peripheral resistance to growth hormone.

The aim of this study was to assess the GH-IGFI axis, GH receptor availability, as reflected by the levels of GH-BP, and the amount of GH-dependent IGFBP-3 in adult IDDM patients with different degrees of metabolic control. Thus, 10 adult well-controlled IDDMs (HbA1 7.8 +/- 0.4%), 10 adult non-ketotic poorly controlled IDDMs (HbA1 13.3 +/- 7%) and 14 sex- and age-matched healthy controls were subjected to two intravenous GH-RH stimulation tests with 0.1 and 1.0 microg/kg body weight respectively, and a plasma IGF-1 generation test induced by the administration of hGH. Poorly controlled IDDM patients exhibited an exaggerated GH response to 1.0 microg/kg of GH-RH when compared to healthy control subjects. Low fasting plasma IGF-1 levels and a blunted IGF-1 response to exogenously administered hGH were also found in poorly controlled IDDMs when compared to the healthy control group. GH-BP levels were significantly lower in IDDMs than in normal controls, and correlated positively with the IGF-1 generation capacity after hGH. Serum IGFBP-3 levels measured by RIA were similar in IDDM and control groups. Good glycemic control for 5.7 +/- 0.9 months did not correct the above mentioned abnormalities of the GH-IGF-1 axis. Our findings suggest that IDDM is associated with a diminished availability of GH receptors and synthesis of IGF-1. GH might then increase as a compensatory mechanism, further down-regulating liver GH receptors, and thus perpetuating the initial abnormality.

[A new methodology for the preoperative localization of occult insulinomas]. / Nueva metodología para la localizacion preoperatoria de insulinomas ocultos.

UNLABELLED: In patients with hypoglycemic syndrome, preoperative localization of the insulinoma highly contributes to surgical removal. When the ultrasonography, computed tomography, magnetic resonance and pancreatic angiography fail to visualize the tumor, they are called occult insulinomas (OI). In this paper we describe the results of a new diagnostic method to localize OI, performed in 5 patients with hypoglycemic syndrome secondary to endogenous hyperinsulinism. In four out of five patients, computed tomography, magnetic resonance and angiography failed to show any tumor. In just one single case, these imaging methods showed the pancreatic tumor. All patients were studied by selective intraarterial pancreatic stimulation (SIPS): a) infusion of calcium gluconate (0.025 mEq/kg) in each artery that supplies the pancreas: gastroduodenal, superior mesenteric and splenic arteries as well as the hepatic artery; b) insulin venous sampling in the right supra-hepatic vein at 30 and 60 seconds after arterial stimulation (in one patient an additional sample at 90 seconds was obtained). The study was considered pathologic when the gradient (basal vs post-stimulus) increased at least 100%. RESULTS: In all five patients a pathological gradient was found. The suspected preoperative localization of the tumor was confirmed at surgery in four cases. The anatomopathologic examination revealed insulinoma in four cases and malignant insulinoma in the remaining. It is concluded that the results of this preliminary experience show the usefulness of SIPS in the preoperative localization of occult insulinomas.