Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Double-blind, randomized clinical trial comparing the efficacy and safety of continuing or discontinuing the dipeptidyl peptidase-4 inhibitor sitagliptin when initiating insulin glargine therapy in patients with type 2 diabetes: The CompoSIT-I Study.

AIMS: To compare the effects of continuing versus discontinuing sitagliptin when initiating and intensively titrating insulin glargine. MATERIALS AND METHODS: Eligible patients had inadequately controlled type 2 diabetes on metformin (≥1500 mg/d) in combination with a dipeptidyl peptidase-4 (DPP-4) inhibitor and/or a sulphonylurea. Those on metformin + sitagliptin were directly randomized; all others were switched to metformin + sitagliptin (discontinuing other DPP-4 inhibitors and sulphonylureas) and stabilized during a run-in period. At randomization, patients were allocated to continuing sitagliptin or discontinuing sitagliptin, with both groups initiating insulin glargine and titrating to a target fasting glucose of 4.0 to 5.6 mmol/L. RESULTS: A total of 743 participants (mean glycated haemoglobin [HbA1c] 72.6 mmol/mol [8.8%], disease duration 10.8 years), were treated. After 30 weeks, the mean HbA1c and least squares (LS) mean change from baseline in HbA1c were 51.4 mmol/mol (6.85%) and -20.5 mmol/mol (-1.88%) in the sitagliptin group and 56.4 mmol/mol (7.31%) and -15.5 mmol/mol (-1.42%) in the placebo group; the difference in LS mean changes from baseline HbA1c was -5.0 mmol/mol (-0.46%; P < 0.001). The percentage of participants with HbA1c <53 mmol/mol (<7.0%) was higher (54% vs. 35%) and the mean daily insulin dose was lower (53 vs. 61 units) in the sitagliptin group. Despite lower HbA1c, event rates and incidences of hypoglycaemia were not higher in the sitagliptin group. Adverse events overall and changes from baseline in body weight were similar between the two treatment groups. CONCLUSION: When initiating insulin glargine therapy, continuation of sitagliptin, compared with discontinuation, resulted in a clinically meaningful greater reduction in HbA1c without an increase in hypoglycaemia. ClinicalTrials.gov Identifier: NCT02738879.

A randomized trial comparing perinatal outcomes using insulin detemir or neutral protamine Hagedorn in type 1 diabetes.

OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented. METHODS: Subjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8-12 gestational weeks. RESULTS: For IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments. CONCLUSION: IDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.

Sodium-glucose co-transporter-2 inhibitors: the challenge of a new insulinindependent mechanism of action in the treatment of type 2 diabetes mellitus. Introducción / No disponible

No disponible

Diabetes mellitus tipo 2 y obesidad: ¿tratar la obesidad o la diabetes? / Type 2 diabetes mellitus and obesity: should we treat the obesity or the diabetes?

En este artículo revisamos los resultados que pueden esperarse tras una significativa corrección del exceso de peso en pacientes con diabetes mellitus tipo 2. Aportamos documentación basada en consensos avalados por la American Diabetes Association, la European Association for the Study of Diabetes y la International Diabetes Federation en relación con la importancia del ejercicio físico, la cirugía bariátrica-metabólica y el tratamiento farmacológico. Por último, aportamos nuestra experiencia personal en los estudios publicados en los últimos años referidos a los análogos del péptido similar al glucagón tipo 1 y en relación con la nueva familia de fármacos orales conocida como gliflozinas, concretamente los estudios publicados con dapagliflozina (AU)

In this article, we review the results that can be expected after significant weight loss in patients with type 2 diabetes mellitus. We provide consensus-based documentation supported by the American Diabetes Association, the European Association for the Study of Diabetes, and the International Diabetes Federation on the importance of physical exercise, metabolic-bariatric surgery, and drug therapy. Lastly, we report the results of studies published in the last few years on glucagon-like peptide-1 analogs and the new family of oral drugs known as gliflozins, specifically studies published on dapagliflozin (AU)

Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: a ≥52-week randomized, double-blind study.

OBJECTIVE: To evaluate the efficacy and long-term safety of linagliptin added to basal insulins in type 2 diabetes inadequately controlled on basal insulin with or without oral agents. RESEARCH DESIGN AND METHODS: A total of 1,261 patients (HbA1c ≥7.0% [53 mmol/mol] to ≤10.0% [86 mmol/mol]) on basal insulin alone or combined with metformin and/or pioglitazone were randomized (1:1) to double-blind treatment with linagliptin 5 mg once daily or placebo for ≥52 weeks. The basal insulin dose was kept unchanged for 24 weeks but could thereafter be titrated according to fasting plasma glucose levels at the investigators' discretion. The primary end point was the mean change in HbA1c from baseline to week 24. The safety analysis incorporated data up to a maximum of 110 weeks. RESULTS: At week 24, HbA1c changed from a baseline of 8.3% (67 mmol/mol) by -0.6% (-6.6 mmol/mol) and by 0.1% (1.1 mmol/mol) with linagliptin and placebo, respectively (treatment difference -0.65% [95% CI -0.74 to -0.55] [-7.1 mmol/mol]; P < 0.0001). Despite the option to uptitrate basal insulin, it was adjusted only slightly upward (week 52, linagliptin 2.6 IU/day, placebo 4.2 IU/day; P < 0.003), resulting in no further HbA1c improvements. Frequencies of hypoglycemia (week 24, linagliptin 22.0%, placebo 23.2%; treatment end, linagliptin 31.4%, placebo 32.9%) and adverse events (linagliptin 78.4%, placebo 81.4%) were similar between groups. Mean body weight remained unchanged (week 52, linagliptin -0.30 kg, placebo -0.04 kg). CONCLUSIONS: Linagliptin added to basal insulin therapy significantly improved glycemic control relative to placebo without increasing hypoglycemia or body weight.

Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes.

OBJECTIVE: This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account. RESULTS: A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups. CONCLUSIONS: Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

Análogos de insulina humana en el tratamiento de las pacientes diabéticas gestantes / Insulin analogues for the treatment of diabetes during pregnancy

En la diabetes gestacional, los análogos de insulina de absorción rápida permiten un mejor control de la glucemia posprandial: el tratamiento con insulina lispro (ILisp) permite alcanzar valores casi normales a los 60 min de la ingesta; la ILisp no atraviesa la placenta. El estudio realizado con insulina aspart (IAsp) indica que la IAsp es igualmente segura y efectiva que la insulina regular (IReg), si bien los controles posprandiales son mejores con IAsp. No hay estudios publicados con insulina glulisina ni con análogos de acción lenta. En la diabetes pregestacional, los estudios publicados se centran en pacientes con diabetes tipo 1: las pacientes tratadas con ILisp frente a IReg presentaron valores de hemoglobina glucosilada (HbA1c) significativamente menores en el segundo y tercer trimestres, y en el momento del parto. En las pacientes tratadas con IAsp, los valores de HbA1c fueron significativamente mejores al confirmarse la gestación (el 7,0 frente al 8,6%; p < 0,05) durante ésta y en el momento del parto (el 5,8 frente al 6,7%; p <0,05). Los incrementos posprandiales de glucemia (valores medios de las 2 h posdesayuno + almuerzo+ cena) fueron significativamente menores con IAsp que con IReg en el primer trimestre(0,73 frente a 1,49 mM; p < 0,003) y en el tercer trimestre (1,10 frente a 1,50 mM; p < 0,044).Las pacientes que resultaron gestantes después del período de estricto control preconcepcional tratadas con IAsp tuvieron una menor incidencia y gravedad de episodios hipoglucémicos antes, durante la gestación y en el posparto inmediato, comparadas con la pacientes tratadas con IReg. La correlación observada entre los valores de anticuerpos anti insulina maternos y los detectados en el cordón umbilical en pacientes tratadas con ambas insulinas indican la existencia de una trasferencia de dichos anticuerpos a través de la barrera placentaria. No tenemos evidencias que apoyen la trasferencia de IAsp a través de la placenta. En relación con los acontecimientos perinatales, la IAsp es segura y efectiva al igual que la IReg, con una fuerte tendencia a menos partos prematuros en las pacientes tratadas con IAsp.En relación con los análogos de acción lenta comentamos el primer estudio realizado. Se trata de un estudio aleatorizado para demostrar la no inferioridad en términos de eficacia y la seguridad de la insulina detemir (IDet) comparada con la NPH (neutral protamine Hagedorn) (utilizando en ambos brazos del estudio IAsp como insulina prandial). El valor estimado de HbA1c en la 36 semana fue del 6,27% con IDet y del 6,33% con NPH. La IDet no fue inferior ni tampoco superior a la NPH. La incidencia de hipoglucemias fue similar en ambos grupos durante todo el embarazo. La glucemia en ayunas fue significativamente mejor con IDet frente a NPH, tanto a las 24 (96,8 frente a 113,8 mg/dl; p = 0,012) como a las 36 semanas de gestación (85,7 frente a 97,4 mg/dl; p = 0,017). No se detectan diferencias entre los 2 grupos en lo relativo a deterioro de la retinopatía

In gestational diabetes, rapid-acting insulin analogues improve postprandial glycemic control: treatment with insulin lispro (ILisp) achieves near-normal values 60 min after intake; ILisp does not cross the placenta. A study conducted with insulin aspart (IAsp) suggests that IAsp is as safe and effective as regular insulin (IReg), although postprandial control is better with IAsp. There are no published studies with insulin glulisine or slow-acting analogues. Published studies on pre-gestational diabetes are focused on patients with type 1 diabetes: patients treated with ILisp vs IReg had significantly lower HbA1c values in the second and third quarters and at the time of delivery. In patients treated with IAsp, HbA1c values were significantly better when pregnancy was confirmed (7.0% vs. 8.6%, p < 0.05), during pregnancy and at the time of delivery (5.8% vs. 6.7%, p < 0.05). Postprandial glucose increases (mean values 2h after breakfast + lunch + dinner) were significantly lower with IAsp than with IReg in the first quarter(0.73 vs 1.49 mM, p < 0.003) and in the third quarter (1.10 vs 1.50 mM, p < 0.044).Patients treated with IAsp who become pregnant after a strict pre-conception control period had a lower incidence and severity of hypoglycemic episodes before and during pregnancy and in the immediate postpartum than did patients treated with IReg. The correlation observed between levels of maternal anti-insulin antibodies and those detected in the umbilical cord in patients treated with both types of insulin suggests that these antibodies can transfer through the placental barrier. We have no evidence supporting the transfer of IAsp through the placenta. In terms of perinatal events, IAsp is as safe and effective as IReg, with a strong tendency to fewer preterm births in patients treated with IAsp. The first study conducted in slow-acting analogues was a randomized trial to prove the non inferiority of insulin determir (IDet) in terms of efficacy and safety compared with NPH insulin(used in both arms of the study, with IAsp as prandial insulin). The estimated value of HbA1c at week 36 was 6.27% with IDet and 6.33% with NPH. IDet was neither inferior nor superior to NPH. The incidence of hypoglycemia was similar in both arms throughout pregnancy. Fasting blood glucose was significantly better with IDet vs NPH both at 24 weeks (96.8 mg/dl vs. 113.8 mg/dl, p = 0.012) and 36 weeks of gestation (85.7 mg/dl vs. 97.4 mg/dl, p = 0.017)

Utilidad del estudio genético en la hipercalcemia hipocalciúrica familiar en familias con presentaciones clínicas atípicas / Usefulness of genetic tests in familial hypocalciuric hypercalcemia with atypical clinical presentation

Tradicionalmente se ha pensado que las pruebas bioquímicas del metabolismo fosfocálcico permiten diferenciar el hiperparatiroidismo primario (HPT1) y la hipercalcemia hipocalciúrica familiar (HHF) pero hay casos de difícil diagnóstico incluso para clínicos experimentados. Nos planteamos como objetivo evaluar la validez de las pruebas diagnósticas de la HHF así como la correcta indicación del estudio genético. Pacientes y métodos Hemos realizado un estudio descriptivo de 2 familias con hipercalcemia y sospecha de HHF de características atípicas. En orina de 24h hemos valorado los índices de excreción urinaria de calcio (eliminación de calcio [CE], cociente calcio/creatinina [CR] y cociente aclaramiento de calcio/aclaramiento de creatinina [CCCR]), junto con las concentraciones séricas de PTH y 25 hidroxivitamina D. A los casos índices se les realizó el estudio genético. Resultados Una paciente presentó hipercalciuria franca y persistente con valores más concordantes con HPT1 que de HHF si consideramos, como proponen las guías, un CCCR inferior a 0,01 como indicativo de HHF y superior a 0,02 como HPT1. Al caso índice de la segunda familia se le extirpó un adenoma de paratiroides. En ambos casos índice, encontramos la misma mutación c. 164C>T (p.Pro55Leu) en el exón 2 en heterocigosis descrita como responsable de HHF. Conclusiones El diagnóstico definitivo de HHF en las guías clínicas actuales requiere confirmación genética, lo cual ha permitido en nuestro caso la detección de 2 familias con HHF y características clínicas atípicas. En nuestra opinión el uso racional de estas pruebas ante la sospecha de HFF puede evitar intervenciones quirúrgicas innecesarias y gastos excesivos en su monitorización (AU)

Objectives: Biochemical tests related to calcium and phosphorus metabolism have traditionally been considered as a reliable tool to differentiate familial hypocalciuric hypercalcemia (FHH) from primary hyperparathyroidism (PHPT). However, diagnosis may sometimes be difficult even for experienced clinicians. Our objective was to assess the accuracy of diagnostic tests in FHH and the circumstances in which genetic studies are required. Patients and methods: A descriptive study was conducted of two families with hypercalcemia and suspected atypical FHH. Urinary calcium excretion was measured in 24-hour urine using different tests (calcium excretion (CE), urinary calcium/creatinine clearance ratio (UCCR)),and serum PTH and 25-hydroxyvitamin D levels were tested. Index cases underwent genetic study. Results: One patient from the first family showed overt, persistent hypercalciuria with values more consistent with PHPT than with FHH if we consider, as proposed by guidelines, a UCCR lower than 0.01 as diagnostic of FHH and a value higher than 0.02 as diagnostic of PHPT. The index case of the second family underwent surgery for a parathyroid adenoma. Both cases had a mutation c. 164C>T (Pro55Leu) in exon 2 in heterozygosis. Conclusions: According to current clinical guidelines, definitive diagnosis of FHH requires genetic confirmation, which allowed in our case for detection of two families with FHH and atypicalclinical presentations. We think that rational use of genetic tests may avoid unnecessary surgery and excess monitoring costs (AU)

Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial.

OBJECTIVE: Although initially effective, sulfonylureas are associated with poor glycemic durability, weight gain, and hypoglycemia. Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects. We compared the efficacy, safety, and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy. RESEARCH DESIGN AND METHODS: This 52-week, double-blind, multicenter, active-controlled, noninferiority trial randomized patients with type 2 diabetes (baseline mean HbA(1c), 7.7%), who were receiving metformin monotherapy, to add-on dapagliflozin (n = 406) or glipizide (n = 408) up-titrated over 18 weeks, based on glycemic response and tolerability, to ≤10 or ≤20 mg/day, respectively. RESULTS: The primary end point, adjusted mean HbA(1c) reduction with dapagliflozin (-0.52%) compared with glipizide (-0.52%), was statistically noninferior at 52 weeks. Key secondary end points: dapagliflozin produced significant adjusted mean weight loss (-3.2 kg) versus weight gain (1.2 kg; P < 0.0001) with glipizide, significantly increased the proportion of patients achieving ≥5% body weight reduction (33.3%) versus glipizide (2.5%; P < 0.0001), and significantly decreased the proportion experiencing hypoglycemia (3.5%) versus glipizide (40.8%; P < 0.0001). Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to standard treatment and rarely led to study discontinuation. CONCLUSIONS: Despite similar 52-week glycemic efficacy, dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin. Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors.

[Usefulness of genetic tests in familial hypocalciuric hypercalcemia with atypical clinical presentation]. / Utilidad del estudio genético en la hipercalcemia hipocalciúrica familiar en familias con presentaciones clínicas atípicas.

OBJECTIVES: Biochemical tests related to calcium and phosphorus metabolism have traditionally been considered as a reliable tool to differentiate familial hypocalciuric hypercalcemia (FHH) from primary hyperparathyroidism (PHPT). However, diagnosis may sometimes be difficult even for experienced clinicians. Our objective was to assess the accuracy of diagnostic tests in FHH and the circumstances in which genetic studies are required. PATIENTS AND METHODS: A descriptive study was conducted of two families with hypercalcemia and suspected atypical FHH. Urinary calcium excretion was measured in 24-hour urine using different tests (calcium excretion (CE), urinary calcium/creatinine clearance ratio (UCCR)), and serum PTH and 25-hydroxyvitamin D levels were tested. Index cases underwent genetic study. RESULTS: One patient from the first family showed overt, persistent hypercalciuria with values more consistent with PHPT than with FHH if we consider, as proposed by guidelines, a UCCR lower than 0.01 as diagnostic of FHH and a value higher than 0.02 as diagnostic of PHPT. The index case of the second family underwent surgery for a parathyroid adenoma. Both cases had a mutation c. 164C>T (Pro55Leu) in exon 2 in heterozygosis. CONCLUSIONS: According to current clinical guidelines, definitive diagnosis of FHH requires genetic confirmation, which allowed in our case for detection of two families with FHH and atypical clinical presentations. We think that rational use of genetic tests may avoid unnecessary surgery and excess monitoring costs.

Analizan la calidad de vida de los padres de enfermos con síndrome de Wolfram / The quality of life of parents of Wolfram syndrome patients analyzed

Objetivo: Conocer factores relevantes que inciden en la calidad de vida de los padres de personas afectadas por esta enfermedad. Diseño: Estudio analítico de casos y controles. Emplazamiento: Domicilio familiar de los afectados. Población y muestra: Familiares de aquejados por el síndrome de Wolfram en España. Se tomó contacto con pacientes diagnosticados en hospitales y sus familiares a través de esos mismos centros. Con la creación de la Asociación Española del Síndrome de Wolfram, en 1999, se conocieron nuevos pacientes y sus familias. La muestra procede de estas fuentes y está integrada por 17 familias (23 personas afectadas). Intervenciones: Se aplicó el Cuestionario de Calidad de Vida a los pacientes y sus familiares; una entrevista estructurada a los padres para conocer las reacciones manifestadas al saber que su hijo padecía una enfermedad crónica degenerativa. Se analizó el impacto económico, social y de pareja en la vida diaria; igualmente se atendieron las conductas de afrontamiento y los logros alcanzados en esta línea. Resultados: Las variables generales tomadas en conjunto no muestran diferencias significativas entre el grupo de pacientes y el de control. Tras un análisis más detallado de los ítem que componen el cuestionario CCV se desprende que las actividades sociales de los familiares se ven mermadas, los padres requieren mayor apoyo psicológico y necesitan un mínimo de dos años de adaptación a estas nuevas circunstancias. Conclusiones: La calidad de vida de los familiares cuidadores de enfermos DIDMOAD se ve afectada en algunos aspectos, se encontraron diferencias con relación al grupo control. Estas diferencias no alcanzan significación estadística pero resultan relevantes de cara a la intervención clínica con estos pacientes y sus familiares.

Analizan la calidad de vida de los padres de enfermos con síndrome de Wolfram / The quality of life of parents of Wolfram syndrome patients analyzed

Objetivo: Conocer factores relevantes que inciden en la calidad de vida de los padres de personas afectadas por esta enfermedad. Diseño: Estudio analítico de casos y controles. Emplazamiento: Domicilio familiar de los afectados. Población y muestra: Familiares de aquejados por el síndrome de Wolfram en España. Se tomó contacto con pacientes diagnosticados en hospitales y sus familiares a través de esos mismos centros. Con la creación de la Asociación Española del Síndrome de Wolfram, en 1999, se conocieron nuevos pacientes y sus familias. La muestra procede de estas fuentes y está integrada por 17 familias (23 personas afectadas). Intervenciones: Se aplicó el Cuestionario de Calidad de Vida a los pacientes y sus familiares; una entrevista estructurada a los padres para conocer las reacciones manifestadas al saber que su hijo padecía una enfermedad crónica degenerativa. Se analizó el impacto económico, social y de pareja en la vida diaria; igualmente se atendieron las conductas de afrontamiento y los logros alcanzados en esta línea. Resultados: Las variables generales tomadas en conjunto no muestran diferencias significativas entre el grupo de pacientes y el de control. Tras un análisis más detallado de los ítem que componen el cuestionario CCV se desprende que las actividades sociales de los familiares se ven mermadas, los padres requieren mayor apoyo psicológico y necesitan un mínimo de dos años de adaptación a estas nuevas circunstancias. Conclusiones: La calidad de vida de los familiares cuidadores de enfermos DIDMOAD se ve afectada en algunos aspectos, se encontraron diferencias con relación al grupo control. Estas diferencias no alcanzan significación estadística pero resultan relevantes de cara a la intervención clínica con estos pacientes y sus familiares.(AU)

Hypoglycemia in type 1 diabetic pregnancy: role of preconception insulin aspart treatment in a randomized study.

OBJECTIVE A recent randomized trial compared prandial insulin aspart (IAsp) with human insulin in type 1 diabetic pregnancy. The aim of this exploratory analysis was to investigate the incidence of severe hypoglycemia during pregnancy and compare women enrolled preconception with women enrolled during early pregnancy. RESEARCH DESIGN AND METHODS IAsp administered immediately before each meal was compared with human insulin administered 30 min before each meal in 99 subjects (44 to IAsp and 55 to human insulin) randomly assigned preconception and in 223 subjects (113 for IAsp and 110 for human insulin) randomly assigned in early pregnancy (<10 weeks). NPH insulin was the basal insulin. Severe hypoglycemia (requiring third-party assistance) was recorded prospectively preconception (where possible), during pregnancy, and postpartum. Relative risk (RR) of severe hypoglycemia was evaluated with a gamma frailty model. RESULTS Of the patients, 23% experienced severe hypoglycemia during pregnancy with the peak incidence in early pregnancy. In the first half of pregnancy, the RR of severe hypoglycemia in women randomly assigned in early pregnancy/preconception was 1.70 (95% CI 0.91-3.18, P = 0.097); the RR in the second half of pregnancy was 1.35 (0.38-4.77, P = 0.640). In women randomly assigned preconception, severe hypoglycemia rates occurring before and during the first and second halves of pregnancy and postpartum for IAsp versus human insulin were 0.9 versus 2.4, 0.9 versus 2.4, 0.3 versus 1.2, and 0.2 versus 2.2 episodes per patient per year, respectively (NS). CONCLUSIONS These data suggest that initiation of insulin analog treatment preconception rather than during early pregnancy may result in a lower risk of severe hypoglycemia in women with type 1 diabetes.

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)

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.

Insulina inhalada en la práctica clínica: nuestra experiencia con pacientes diabéticos tipo 2 / Inhaled insulin in clinical practice: our experience in patients with type 2 diabetes

A partir de los datos recogidos en los cuestionarios de satisfacción utilizados en nuestro trabajo se puede concluir que es fácil el aprendizaje y manejo del inhalador de insulina, incluso para pacientes de edad avanzada. Es fácil incorporarlo a la vida diaria. Los pacientes consideran que la insulina en polvo, el inhalador y la vía de absorción son eficaces para conseguir un buen control de la glucemia. Definitivamente, reduce el rechazo a utilizar insulina y les gustaría seguir utilizándolo como dispositivo de administración de la misma. Recomendarían el tratamiento con el inhalador de insulina y con la insulina Exubera® a otros pacientes con diabetes similar a la suya (AU)

Data from the patient satisfaction questionnaires used in our center indicate that the use of inhaled insulin is easy to learn and manage, even in elderly patients. This form of insulin can easily be incorporated into daily life. The patients reported that powder insulin, the inhaler and the route of absorption are effective in achieving good blood glucose control. Inhaled insulin reduces patients’ reluctance to use insulin. The patients would like to continue with this form of insulin administration and would recommend treatment with the Exubera® insulin inhaler to other patients with diabetes similar to their own (AU)

The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial.

BACKGROUND: Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported. OBJECTIVE: To compare the effects of exenatide versus placebo on glycemic control. DESIGN: Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005. SETTING: 49 sites in Canada, Spain, and the United States. PATIENTS: 233 (exenatide group, n = 121; placebo group, n = 112) patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin). Mean (+/-SE) baseline glycated hemoglobin A1c level was 7.9% +/- 0.1%. INTERVENTIONS: Subcutaneous abdominal injections of 10 microg of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks. MEASUREMENTS: The primary outcome was change from baseline in hemoglobin A1c level. Other outcomes were fasting serum glucose level, body weight, self-monitored blood glucose level, and any adverse events. RESULTS: Exenatide treatment reduced hemoglobin A(1c) level (mean difference, -0.98% [95% CI, -1.21% to -0.74%]), serum fasting glucose level (mean difference, -1.69 mmol/L [-30.5 mg/dL] [CI, -2.22 to -1.17 mmol/L {-40.0 to -21.1 mg/dL}]), and body weight (mean difference, -1.51 kg [CI, -2.15 to -0.88 kg]). Sixteen percent of patients in the exenatide group and 2% of patients in the placebo group discontinued treatment because of adverse events. In the exenatide group, 40% (n = 48) of patients experienced nausea (mostly mild [n = 21] or moderate [n = 19]), 13% experienced vomiting, and 11% experienced hypoglycemia. In the placebo group, 15% of patients experienced nausea, 1% experienced vomiting, and 7% experienced hypoglycemia. LIMITATIONS: Combinations with TZDs and sulfonylureas were not tested. Trial duration was relatively short. Only 71% and 86% of patients in the exenatide and placebo groups, respectively, completed the study. CONCLUSIONS: Exenatide therapy improved glycemic control, reduced body weight, and caused gastrointestinal symptoms more than placebo in patients with type 2 diabetes that was suboptimally controlled with TZD therapy. ClinicalTrials.gov registration number: NCT00099320. For more information on exenatide click here.