Familial bilateral macronodular adrenal hyperplasia due to a novel ARMC 5 germline mutation: Clinical status and possible association with other neoplasms.

INTRODUCTION/OBJECTIVES: Mutations in the ARMC5 (armadillo repeat containing 5, OMIM 615549) gene, a putative tumor suppressor gene, have recently been identified as a common cause of sporadic and familial bilateral macronodular adrenal hyperplasia (BMAH). Familial BMAH is thought to be caused by two mutations, one germline and the other somatic, as suggested by the 2-hit theory. The objective is to describe a new mutation and develop its clinical characteristics and implications. METHODS, RESULTS AND CONCLUSIONS: We present an affected family with 11 members carrying a novel mutation of the ARMC5 gene (NM_001288767.1): c.2162T>C p. (Leu721Pro). Two of the carriers developed clinical Cushing's syndrome (CS), two mild autonomous cortisol secretion (MACS) and one presented with autonomous cortisol secretion (ACS). Four patients developed other tumors, three of whom died from this cause. It is not known whether these tumors could be related to the described mutation.

Outcomes of a multidisciplinary Diabetic Foot Day Unit.

OBJECTIVE: To analyse the main characteristics of patients and the health outcomes obtained and to evaluate the impact of peripheral artery disease (PAD) in patients treated in our multidisciplinary Diabetic Foot Unit. RESEARCH DESIGN AND METHODS: Observational prospective study. 273 patients from two different populations (with and without PAD - classified according to the presence of distal pulses) treated over a 14-month period in the multidisciplinary Diabetic Foot Unit were included. The data on patient characteristics and outcomes were analysed for the purpose of comparison. For the inference study, a comparison of medians with the non-parametric test for independent samples for the quantitative variables and a χ2 test for the comparison of proportions in qualitative variables were performed. RESULTS: Patients with PAD ulcers were older (60 (54-67) vs. 64 (75-81), p=0.000) and had a higher macrovascular burden (8.1% vs. 29% for ischaemic heart disease history, p=0.000; 6.7% vs. 18.1% for cerebrovascular disease history, p=0.004). Their Texas Score was higher (p=0.000) and their major amputation rate was higher (1.4% vs. 12.3%, p=0.001). They had less background of previous ulcers (52.6% vs. 26.8%, p=0.000), their episode duration was shorter (4 (0-10) vs. 0 (0-3) weeks, p=0.000), and their proportional need for antibiotic therapy was lower (64.4% vs. 51.4%, p=0.03). CONCLUSIONS: The differences found between ulcers with and without vascular involvement support the need for a different approach and for the inclusion of vascular surgeons on the team. The multidisciplinary care model for diabetic foot patients could be effective and improve health outcomes.

Description of a Cohort of Type 1 Diabetes Patients: Analysis of Comorbidities, Prevalence of Complications and Risk of Hypoglycemia.

BACKGROUND: Despite major medical advances, Type 1 Diabetes (T1D) patients still have greater morbimortality than the general population. Our aim was to describe our cohort of T1D patients and identify potential risk factors susceptible to prevention strategies. METHODS: Cross-sectional, observational study, including T1D patients treated at our center, from 1 March 2017 to 31 March 2020. INCLUSION CRITERIA: T1D, age > 14 years and signed informed consent. EXCLUSION CRITERIA: diabetes other than T1D, age < 14 years and/or refusal to participate. RESULTS: Study population n = 2181 (49.8% females, median age at enrollment 41 years, median HbA1c 7.7%; 38.24% had at least one comorbidity). Roughly 7.45% had severe hypoglycemia (SH) within the prior year. Macro/microvascular complications were present in 42.09% (5.83% and 41.14%, respectively). The most frequent microvascular complication was diabetic retinopathy (38.02%), and coronary disease (3.21%) was the most frequent macrovascular complication. The risk of complications was higher in males than in females, mainly macrovascular. Patients with SH had a higher risk of complications (OR 1.42; 1.43 in males versus 1.42 in females). CONCLUSIONS: Our T1D population is similar to other T1D populations. We should minimize the risk of SH, and male patients should perhaps be treated more aggressively regarding cardiovascular risk factors.

Relación entre el control metabólico y la automonitorización de la glucemia capilar en pacientes con diabetes mellitus tratados con insulina / Relationship between metabolic control and self-monitoring of blood glucose in insulin-treated patients with diabetes mellitus

OBJETIVO: Evaluar la relación entre el grado de control metabólico (CM) y la frecuencia de la automonitorización de la glucemia capilar (AGC) en pacientes con diabetes mellitus (DM) tipo 1 (DM1) y 2 (DM2) tratados con insulina, y analizar factores asociados al CM. MATERIAL Y MÉTODOS: Estudio observacional multicéntrico transversal en el que endocrinólogos incluyeron a pacientes con DM tratados con insulina que utilizaban un glucómetro. El punto de corte para definir un CM fue una HbA1c ≤ 7% y no control > 7%. Se valoró en una escala analógica visual (EAV) el grado de aceptación del glucómetro. RESULTADOS: Fueron evaluables 341 pacientes (53,5% varones), con una edad media ± DE de 52,8 ± 16,3 años, HbA1c media de 7,69 ± 1,25%, 128 (37,5%) con DM1 y 211 (61,9%) con DM2. El 86,1% de los pacientes utilizaron el glucómetro al menos una vez en la semana. No se observó ninguna relación entre el CM y la AGC ni en la muestra total (p = 0,678), ni en DM1 (p = 0,940) ni DM2 (p = 0,343). En el modelo de regresión logística, se asociaron a un mal CM en la muestra total y en DM2 los episodios de hiperglucemias (Exp-b [riesgo] 1,794, p = 0,022, y Exp-b 2,538, p = 0,004, respectivamente), las concentraciones de HbA1c falsamente elevadas (Exp-b 3,182 p = 0,005, y Exp-b 3,125, p = 0,012), y la EAV (Exp-b 1,269, p = 0,008, y Exp-b 1,316, p = 0,026), y en la DM1 el índice de masa corporal (Exp-b 1,143, p = 0,046). CONCLUSIONES: En este estudio observacional no controlado en pacientes con DM tratados con insulina que utilizan un glucómetro no se observa ninguna relación entre el grado de CM y la frecuencia de su uso en el último mes

OBJECTIVE: To assess the relationship between metabolic control (MC) and frequency of self-monitoring of blood glucose (SMBG) in insulin-treated patients with type 1 (T1DM) and type 2 (T2DM) diabetes mellitus, and to analyze the factors associated to MC. MATERIAL AND METHODS: A multicenter, cross-sectional, observational study was conducted in which endocrinologists enrolled diabetic patients treated with insulin who used a glucometer. The cut-off value for MC was HbA1c ≤ 7%. Grade of acceptance of the glucometer was assessed using a visual analogue scale (VAS). RESULTS: A total of 341 patients (53.5% males) with a mean age (SD) 52.8 (16.3) years, mean HbA1c of 7.69% (1.25) and 128 (37.5%) with T1DM and 211 (61.9%) with T2DM were evaluable. SMBG was done by 86.1% at least once weekly. No relationship was seen between MC and SMBG (P=.678) in the overall sample or in the T1DM (P=.940) or T2DM (P=.343) subgroups. In the logistic regression model, hyperglycemic episodes (Exp-b [risk] 1.794, P=0.022), falsely elevated HbA1c values (Exp-b 3.182,P=.005), and VAS (Exp-b 1.269, P=.008) were associated to poor MC in the total sample. Hyperglycemic episodes (Exp-b 2.538, P=.004), falsely elevated HbA1c values (Exp-b 3.125, P=.012), and VAS (Exp-b 1.316, P=.026) were associated to poor MC in the T2DM subgroup, while body mass index (Exp-b 1.143, P=.046) was associated to poor MC in the T1DM subgroup. CONCLUSIONS: In this retrospective, non-controlled study on patients with DM treated with insulin who used a glucometer, no relationship was seen between the degree of metabolic control and frequency of use of the glucometer

Relationship between metabolic control and self-monitoring of blood glucose in insulin-treated patients with diabetes mellitus.

OBJECTIVE: To assess the relationship between metabolic control (MC) and frequency of self-monitoring of blood glucose (SMBG) in insulin-treated patients with type 1 (T1DM) and type 2 (T2DM) diabetes mellitus, and to analyze the factors associated to MC. MATERIAL AND METHODS: A multicenter, cross-sectional, observational study was conducted in which endocrinologists enrolled diabetic patients treated with insulin who used a glucometer. The cut-off value for MC was HbA1c ≤ 7%. Grade of acceptance of the glucometer was assessed using a visual analogue scale (VAS). RESULTS: A total of 341 patients (53.5% males) with a mean age (SD) 52.8 (16.3) years, mean HbA1c of 7.69% (1.25) and 128 (37.5%) with T1DM and 211 (61.9%) with T2DM were evaluable. SMBG was done by 86.1% at least once weekly. No relationship was seen between MC and SMBG (P=.678) in the overall sample or in the T1DM (P=.940) or T2DM (P=.343) subgroups. In the logistic regression model, hyperglycemic episodes (Exp-b [risk] 1.794, P=0.022), falsely elevated HbA1c values (Exp-b 3.182, P=.005), and VAS (Exp-b 1.269, P=.008) were associated to poor MC in the total sample. Hyperglycemic episodes (Exp-b 2.538, P=.004), falsely elevated HbA1c values (Exp-b 3.125, P=.012), and VAS (Exp-b 1.316, P=.026) were associated to poor MC in the T2DM subgroup, while body mass index (Exp-b 1.143, P=.046) was associated to poor MC in the T1DM subgroup. CONCLUSIONS: In this retrospective, non-controlled study on patients with DM treated with insulin who used a glucometer, no relationship was seen between the degree of metabolic control and frequency of use of the glucometer.

Eficacia y seguridad de la insulina aspartato bifásica 30/70 en el tratamiento de pacientes con diabetes mellitus tipo 2 / Efficacy and safety of biphasic insulin aspart 30/70 in the treatment of patients with type 2 diabetes mellitus

Objetivo: Evaluar la seguridad y la eficacia de la insulina aspartato bifásica 30/70 en pacientes con diabetes mellitus tipo 2 (DM2). Material y métodos: Estudio observacional, multicéntrico y prospectivo. Participaron en el estudio 3.054 pacientes con DM2 procedentes de atención primaria y especializada en tratamiento con insulina aspartato bifásica 30/70 (iniciado en los 15 días previos a la inclusión). De todos ellos se disponía de la siguiente información previa al inicio del tratamiento con dicha insulina: glucohemoglobina (HbA1c), glucemia en ayunas (GA), perfil de glucosa 4 puntos (antes y 90 min después de desayuno y cena) y número de hipoglucemias/semana; 2.887 completaron el estudio (26 ± 1 semana). Las variables analizadas fueron: frecuencia de acontecimientos adversos, hipoglucemias/semana, HbA1c, GA y perfil glucémico de 4 puntos. Resultados: El 10,7% de los pacientes presentaron algún acontecimiento adverso (el 2,3% relacionados con el tratamiento y el 1,4%, graves). Hubo un descenso significativo (final del estudio frente a basal, p < 0,0001 en todas las comparaciones) de las cifras de HbA1c (el 7,3 y el 8,9%, respectivamente), media de hipoglucemias/semana menores (0,3 y 0,5) y mayores (0,02 y 0,07), GA (145 y 207 mg/dl) y glucemia posprandial (162 y 225 mg/dl). La mejoría en el control metabólico se consiguió tanto en pacientes tratados previamente con antidiabéticos orales como con insulina. El número de hipoglucemias disminuyó en los tratados previamente con insulina. Conclusiones: El tratamiento con insulina aspartato bifásica 30/70 en pacientes con DM2 mejora el control glucémico con independencia del tratamiento previo, con una tasa baja de acontecimientos adversos y un número menor de hipoglucemias que en los tratados previamente con insulina (AU)

Objective: To assess the safety and efficacy of biphasic insulin aspart 30/70 in patients with type 2 diabetes mellitus (DM2). Material and methods: We performed an observational, multicenter, prospective study in 3,054 DM2 patients from primary care and specialized settings, treated with biphasic insulin aspart 30/70 (started within 15 days prior to inclusion). In all patients, the following information was available before starting insulin treatment: HbA1c levels, fasting plasma glucose (FPG), 4-point glucose profile (before and 90 minutes after breakfast and dinner) and number of hypoglycemic episodes/week. A total of 2,887 patients completed the study (26 ± 1 week). The variables evaluated were rate of adverse events (AE), number of hypoglycemic episodes/week, HbA1c, FPG and 4-point glucose profile. Results: At least one AE occurred in 10.7% of the patients (2.3% related to the study drug and 1.4% severe). There was a significant decrease (end of study vs baseline; p < 0.0001 for all the comparisons) in HbA1c (7.3% and 8.9%, respectively), the mean number of minor (0.3/0.5) and major (0.02/0.07) hypoglycemic episodes/week, FPG (145/207 mg/dl) and postprandial glycemia (162/225 mg/dl). The improvement in metabolic control was achieved both in patients previously treated with oral antidiabetic drugs and in those treated with insulin. The number of hypoglycemic episodes decreased in patients previously treated with insulin. Conclusions: Treatment with biphasic insulin aspart 30/70 in patients with DM2 improves glycemic control, irrespective of previous treatment, with a low rate of AE and fewer hypoglycemic episodes in patients previously treated with insulin (AU)

Mantenimiento a largo plazo con dosis bajas de fármacos antitiroideos de síntesis frente a retirada, en pacientes con hipertiroidismo de la enfermedad de Graves / Long-term maintenance of low-dose antithyroid drugs versus drug withdrawal in patients with Graves’ hyperthyroidism

Objetivo: La recurrencia del hipertiroidismo de la enfermedad de Graves tras dar por finalizado un ciclo de antitiroideos, es frecuente. El objetivo de este trabajo es investigar de forma prospectiva la recaída del hipertiroidismo durante el mantenimiento de 5 años con dosis bajas de fármacos antitiroideos de síntesis. Material y método: Desde marzo de 1997 se reclutó para la intervención a todos los pacientes con hipertiroidismo de la enfermedad de Graves que acudían consecutivamente a una misma consulta, y habían alcanzado el eutiroidismo con dosis bajas de antitiroideos (2,5-5 mg/día de carbimazol o metimazol) en 2 revisiones sucesivas (10-12 meses). Se intentó mantener desde entonces, en lugar de suspenderlo, un tratamiento con estas dosis durante 5 años, y se estudió en ese intervalo la tasa de recaída del hipertiroidismo (grupo M, 53 pacientes). Desde la misma fecha (marzo de 1997), se recogieron también datos de los pacientes con hipertirodismo de la enfermedad de Graves que se revisaban consecutivamente en dicha consulta, pero a los que, con anterioridad a esa fecha, se les había suspendido la medicación antitiroidea al conseguir las mismas condiciones señaladas anteriormente; de igual modo se estudió la tasa de recurrencia del hipertiroidismo durante los 5 años que seguían a la suspensión (grupo R, histórico, control, 31 pacientes). Resultado principal: El hipertiroidismo recayó en 12/53 (22,64%) pacientes del grupo M, por 24/31 (77,42%) pacientes del grupo R (p < 0,000). Conclusiones: La tasa de recaída del hipertiroidismo de la enfermedad de Graves mientras se mantenían dosis bajas de fármacos antitiroideos de síntesis fue menor, de forma significativa, que la recogida tras suspenderlos (AU)

Objective: The relapse rate of Graves' hyperthyroidism after finishing an antithyroid cicle is high. The objective of this work was to prospectively investigate the relapse rate of Graves' hyperthyroidism (GH) in patients with maintenance of a low dose of antithyroid drug (ATD) therapy. Patients and method: From March 1997, all patients with GH consecutively attending the same center who remained euthyroid with low doses of synthetic ATD (carbimazole or methimazole: 2.5-5 mg/day) on 2 consecutive follow-up visits (at 10-12 months) were included in this study. Instead of withdrawing ATD, the aim was to continue with this low dose for a 5-year period (group M: 53 patients). From March 1997, data were also collected from patients with GH who were consecutively followed-up and who, meeting the criteria for inclusion in group M, had stopped receiving ATD before the start of the study (March 1997) (group R: 31 patients). Main outcome: GH relapse was observed in 12/53 patients in group M (22.64%) and in 24/31 patients in group R (77.42%) (p < 0.000). Conclusions: The GH relapse rate was significantly lower with long-term maintenance of a low dose of ATD than with therapy withdrawal (AU)

Long-term maintenance of low-dose antithyroid drugs versus drug withdrawal in patients with Graves' hyperthyroidism.

OBJECTIVE: The relapse rate of Graves' hyperthyroidism after finishing an antithyroid cicle is high. The objective of this work was to prospectively investigate the relapse rate of Graves' hyperthyroidism (GH) in patients with maintenance of a low dose of antithyroid drug (ATD) therapy. PATIENTS AND METHOD: From March 1997, all patients with GH consecutively attending the same center who remained euthyroid with low doses of synthetic ATD (carbimazole or methimazole: 2.5-5mg/day) on 2 consecutive follow-up visits (at 10-12 months) were included in this study. Instead of withdrawing ATD, the aim was to continue with this low dose for a 5-year period (group M: 53 patients). From March 1997, data were also collected from patients with GH who were consecutively followed-up and who, meeting the criteria for inclusion in group M, had stopped receiving ATD before the start of the study (March 1997) (group R: 31 patients). MAIN OUTCOME: GH relapse was observed in 12/53 patients in group M (22.64%) and in 24/31 patients in group R (77.42%) (p<0.000). CONCLUSIONS: The GH relapse rate was significantly lower with long-term maintenance of a low dose of ATD than with therapy withdrawal.

Efficacy and safety of biphasic insulin aspart 30/70 in the treatment of patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the safety and efficacy of biphasic insulin aspart 30/70 in patients with type 2 diabetes mellitus (DM2). MATERIAL AND METHODS: We performed an observational, multicenter, prospective study in 3,054 DM2 patients from primary care and specialized settings, treated with biphasic insulin aspart 30/70 (started within 15 days prior to inclusion). In all patients,the following information was available before starting insulin treatment: HbA(1c) levels, fasting plasma glucose (FPG), 4-point glucose profile (before and 90 minutes after breakfast and dinner) and number of hypoglycemic episodes/week. A total of 2,887 patients completed the study (26 ± 1 week). The variables evaluated were rate of adverse events (AE), number of hypoglycemic episodes/week, HbA(1c), FPG and 4-point glucose profile. RESULTS: At least one AE occurred in 10.7% of the patients (2.3% related to the study drug and 1.4% severe). There was a significant decrease (end of study vs baseline; p < 0.0001 for all the comparisons) in HbA(1c) (7.3% and 8.9%, respectively), the mean number of minor (0.3/0.5) and major (0.02/0.07) hypoglycemic episodes/week, FPG (145/207 mg/dl) and postprandial glycemia (162/225 mg/dl). The improvement in metabolic control was achieved both in patients previously treated with oral antidiabetic drugs and in those treated with insulin. The number of hypoglycemic episodes decreased in patients previously treated with insulin. CONCLUSIONS: Treatment with biphasic insulin aspart 30/70 in patients with DM2 improves glycemic control, irrespective of previous treatment, with a low rate of AE and fewer hypoglycemic episodes in patients previously treated with insulin.