Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

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.

OBJECTIVEThis 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 METHODSPatients 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.RESULTSA 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.CONCLUSIONSTreatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

OBJECTIVE To compare the risk of severe adverse pregnancy complications in women with preexisting diabetes. RESEARCH DESIGN AND METHODS Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations or perinatal or neonatal death (primary end point) following treatment with insulin detemir (detemir) versus other basal insulins. RESULTS Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations or perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01, 0.04]; adjusted risk difference −0.003 [95% CI −0.03, 0.03]). The crude prevalence of one or more congenital malformations (major plus minor) was 9.4% vs. 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064, 0.000]) and after (−0.036 [95% CI –0.081, 0.009]) adjustment for confounders. Crude data showed lower maternal HbA1c during the first trimester (6.5% vs. 6.7% [48 vs. 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300, −0.062]) and the second trimester (6.1% vs. 6.3% [43 vs. 45 mmol/mol]; −0.139 [95% CI −0.232, −0.046]) and a lower prevalence of major hypoglycemia (6.0% vs. 9.0%; risk difference −0.030 [95% CI −0.058, −0.002]), preeclampsia (6.4% vs. 10.0%; −0.036 [95% CI −0.064, −0.007]), and stillbirth (0.4% vs. 1.8%; −0.013 [95% CI −0.024, −0.002]) with detemir compared with other basal insulins. However, differences were not significant postadjustment. CONCLUSIONS Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, preeclampsia, and stillbirth.

En el valle de los ríos Trujala, Hornos y Guadalimar en la Sierra de Segura, al noreste de la provincia de Jaén, se conserva un articulado sistema de estructuras medievales que configuran un paisaje. Para orientarse en él, hace falta un mapa que represente con precisión los elementos que intervienen en su conformación. El objetivo de este trabajo es revelar esos puntos y trazar una cartografía que sirva para comprender e interpretar el palimpsesto del paisaje. Con ese fin se realiza una prospección intensiva del territorio que documente los vestigios existentes, elaborando posteriormente un modelo de evaluación basado en Sistemas de Información Geográfica. Este proceso permite cuantificar variables, obtener datos estadísticamente relevantes y clasificar la información obtenida en los lugares donde se conserva alguna preexistencia medieval. Los resultados suministran parámetros útiles en la lectura analítica del paisaje, aportan conocimiento cuantitativo sobre factores que intervienen en los emplazamientos y permiten la determinación de sus patrones de asentamiento. También revelan el modo de ocupación en un territorio perteneciente alʿamal Šaqūra como reflejo de la organización campesina en el mundo rural y el rol antropizador que han tenido en la configuración del paisaje los poblamientos asociados a unas estructuras construidas en tapia durante el siglo XII.

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The beneficial effects of solar radiation on human health are well documented. One necessary mechanism triggers the production of vitamin D, whose insufficiency has been linked to a variety of disorders such as diabetes; hypertension; and, more recently, amyloidosis and Alzheimer’s disease. However, there are few architectural designs capable of ensuring the adequate provision of solar radiation inside buildings. Conventional fenestration is not sufficient to provide for significant doses of sunlight, even to prevent seasonal affective disorder (SAD). In this paper, we discuss the effect of new design alternatives for skylights, especially in the refurbishment of obsolete facilities. Based on the authors’ previous studies, we defined a theoretical model that was subsequently adapted to a real building that was to be retrofitted in an area near Sevilla. After such complex refurbishment was executed, we analyzed the performance of buildings in warm and sunny climates, as is the case of southern Spain, where cloudiness is very scarce and available simulation models are not useful. The study of the factors that relate to sunlight; UV reception and energy; and, to a certain extent, other aspects such as ventilation and insulation has been considered a priority. Many architectural designs are presented as correct if the thermal requirements alone are met, even at the risk of later energy waste in lighting devices and visual or physical discomfort. On the other hand, large glazed areas allow for more daylight and UV radiation into a space if properly treated, but they may also produce excessive heat gains or losses, which increase the air-conditioning cooling or heating load, respectively. The uncontrolled increase in temperature can have negative effects on the well-being of a person with Alzheimer’s dementia. To avoid these problems, we have considered the combined effect of daylight and energy from the beginning of the skylight design-process. Daylighting software, based on configuration factors that we have applied in studies of the complex problem of there being direct sunlight over architectural structures, has been used. This question cannot be treated adequately with conventional programs for overcast skies. The skylights have already been constructed, with special UV increasing glazing and on-site measurements in the offices to complement the computer simulation data. The results show that it is possible to achieve energy saving and high radiation levels in winter without increasing heat loads during the summer. Ventilation is also improved through the aerodynamic design of the clerestories. All this is considered beneficial to improve the condition of users with cognitive diseases as Alzheimer’s disease, by virtue of adapted spaces.