Relaciones entre las profesiones de los padres y de los hijos

Fil: Gourdy, Martha. Universidad de Buenos Aires. Facultad de Derecho. Buenos Aires, Argentin

Roles of Estrogens in the Healthy and Diseased Oviparous Vertebrate Liver.

The liver is a vital organ that sustains multiple functions beneficial for the whole organism. It is sexually dimorphic, presenting sex-biased gene expression with implications for the phenotypic differences between males and females. Estrogens are involved in this sex dimorphism and their actions in the liver of several reptiles, fishes, amphibians, and birds are discussed. The liver participates in reproduction by producing vitellogenins (yolk proteins) and eggshell proteins under the control of estrogens that act via two types of receptors active either mainly in the cell nucleus (ESR) or the cell membrane (GPER1). Estrogens also control hepatic lipid and lipoprotein metabolisms, with a triglyceride carrier role for VLDL from the liver to the ovaries during oogenesis. Moreover, the activation of the vitellogenin genes is used as a robust biomarker for exposure to xenoestrogens. In the context of liver diseases, high plasma estrogen levels are observed in fatty liver hemorrhagic syndrome (FLHS) in chicken implicating estrogens in the disease progression. Fishes are also used to investigate liver diseases, including models generated by mutation and transgenesis. In conclusion, studies on the roles of estrogens in the non-mammalian oviparous vertebrate liver have contributed enormously to unveil hormone-dependent physiological and physiopathological processes

IMPACT OF TYPE 2 DIABETES ON THE DEVELOPMENT OF PERIODONTAL DISEASE IN THE MOUSE

Oral Communication presented at the ";;Forum des Jeunes Chercheurs";;, Brest (France) 2011

Impact of Age on the Effectiveness and Safety of Insulin Glargine 300 U/mL: Results from the REALI European Pooled Data Analysis

Introduction: Patients aged ≥ 65 years continue to be underrepresented in clinical studies related to type 2 diabetes mellitus (T2DM). Accordingly, the REALI pooled analysis was performed to evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) across different age subgroups, using data from 14 interventional and non-interventional studies. Methods: Pooled efficacy and safety data were collected from 8106 European patients with uncontrolled T2DM who were initiated on or switched to Gla-300 injected once daily for 24 weeks. Patients were categorised into five age subgroups: < 50 (N = 727), 50–59 (N = 2030), 60–69 (N = 3054), 70–79 (N = 1847) and ≥ 80 years (N = 448). Results: Mean baseline haemoglobin A1c (HbA1c) decreased linearly from the youngest (9.10%) to the oldest (8.46%) age subgroup. Following Gla-300 initiation, there were similar HbA1c reductions across age groups, with a least squares mean (95% confidence interval) change in HbA1c from baseline to week 24 of − 1.09% (− 1.18 to − 1.00), − 1.08% (− 1.14 to − 1.03), − 1.12% (− 1.17 to − 1.07), − 1.18% (− 1.24 to − 1.12) and − 1.11% (− 1.23 to − 0.99) in the < 50, 50–59, 60–69, 70–79 and ≥ 80 years subgroups, respectively. The incidences and event rates of reported hypoglycaemia were overall low. Compared to younger age subgroups, lower incidences of symptomatic hypoglycaemia occurring at any time of the day (5.9 vs. 7.6–9.4% for the younger subgroups) or during the night (0.5 vs. 1.6–2.5%) were recorded in patients aged ≥ 80 years. By contrast, the highest incidence of severe hypoglycaemia occurring any time of the day was reported in the subgroup aged ≥ 80 years (1.1 vs. 0.1–0.6% for the younger age subgroups). Conclusion: Gla-300 initiated in patients with uncontrolled T2DM provides glycaemic improvement with a favourable safety profile across a wide range of ages

Glycaemic Control with Insulin Glargine 300 U/mL in Individuals with Type 2 Diabetes and Chronic Kidney Disease: A REALI European Pooled Data Analysis

INTRODUCTION: Management of type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease is complex. Using the REALI European pooled database, we determined the impact of baseline renal function on the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiated in adults with inadequately controlled T2DM. METHODS: Data from 1712 patients with available estimated glomerular filtration rate (eGFR) at baseline were pooled from six 24-week prospective studies. Patients who received once-daily subcutaneous injections of Gla-300 were classified into four renal function subgroups, according to baseline eGFR: ≥ 90 (N = 599), 60–89 (N = 786), 45–59 (N = 219), and 15–44 mL/min/1.73 m2 (N = 108). RESULTS: Compared to those with baseline eGFR ≥ 60 mL/min/1.73 m2, patients with lower eGFR values tended to be older, had a longer T2DM duration, and were more likely to present diabetic complications. After 24 weeks of Gla-300 therapy, the least-squares mean (95% confidence interval) decrease in haemoglobin A1c (HbA1c) from baseline (− 1.14% [− 1.28 to − 1.00], − 1.21% [− 1.34 to − 1.08], − 1.19% [− 1.36 to − 1.01], and − 0.99% [− 1.22 to − 0.76]) and the proportion of patients achieving HbA1c < 7.5% (53.3%, 51.3%, 49.5%, and 51.5%) were comparable in the ≥ 90, 60–89, 45–59, and 15–44 mL/min/1.73 m2 subgroups, respectively. Although the incidence of hypoglycaemia was overall low, more patients in the eGFR 15–44 mL/min/1.73 m2 subgroup experienced hypoglycaemia at night or at any time of the day compared with higher eGFR subgroups. There were no notable differences between the renal function subgroups in the changes in Gla-300 daily dose and body weight from baseline to week 24. CONCLUSION: Although an eGFR of 15–44 mL/min/1.73 m2 was associated with a slightly increased risk of hypoglycaemia among patients with inadequately controlled T2DM, Gla-300 provided glycaemic improvement with an overall favourable safety profile regardless of baseline eGFR

Does Gender Influence the Effectiveness and Safety of Insulin Glargine 300 U/ml in Patients with Uncontrolled Type 2 Diabetes? Results from the REALI European Pooled Analysis

Introduction: Gender differences in risk factors and treatment outcomes for type 2 diabetes mellitus (T2DM) may exist. We used the REALI European database to investigate whether there were gender-specific differences in baseline characteristics and clinical outcomes among patients with inadequately controlled T2DM initiated on insulin glargine 300 U/ml (Gla-300). // Methods: Data were pooled from 14 multicentre, prospective, interventional and non-interventional studies. Impact of gender on glycaemic control, insulin dose, body weight and hypoglycaemia was evaluated after 12 and 24 weeks of Gla-300 treatment. // Results: Women (N = 3857) were older than men (N = 4376) (median age, 65.0 versus 63.0 years), with greater mean body mass index (32.5 versus 31.6 kg/m2) and lower median estimated glomerular filtration rate (77.5 versus 84.0 ml/min/1.73 m2). Peripheral arterial disease and a history of myocardial infarction were more frequent in men (20.1% versus 11.7% and 12.0% versus 5.8%, respectively). At baseline, mean haemoglobin A1c (HbA1c) was 8.74% in men and 8.79% in women. Least square (LS) mean (95% CI) reduction in HbA1c from baseline to week 24 was − 1.17% (− 1.21 to − 1.13) in men and − 1.07% (− 1.11 to − 1.02) in women, resulting in a LS mean difference of − 0.10% (− 0.15 to − 0.05; p < 0.0001). At 24 weeks, 21.6% of women and 27.2% of men achieved target HbA1c of < 7.0% (p < 0.001; chi-square). Reported incidence for symptomatic (8.5% versus 8.7%) and severe (0.3% versus 0.5%) any-time-of-the-day or symptomatic (2.4% versus 1.8%) and severe (0.1% versus 0.2%) nocturnal hypoglycaemia was overall low and comparable between men and women. Changes in daily Gla-300 dose and body weight were also similar. // Conclusion: Despite some gender differences in baseline characteristics, Gla-300 treatment improved glycaemic control, with overall low hypoglycaemia incidences in both men and women. However, women had statistically significantly lower HbA1c reductions than men, although these differences were clinically modest

Glycaemic Control in People with Type 2 Diabetes Mellitus Switching from Basal Insulin to Insulin Glargine 300 U/ml (Gla-300): Results from the REALI Pooled Database

INTRODUCTION: Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes. METHODS: Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI. Of the 4463 participants, 1282 (28.7%) were pre-treated with neutral protamine Hagedorn (NPH) insulin and 2899 (65.0%) with BI analogues (BIAs), and 282 (6.3%) had undetermined prior BI. RESULTS: There were no meaningful differences in baseline characteristics between subgroups, except for a higher prevalence of diabetic neuropathy in the NPH subgroup (21.6% versus 7.8% with BIAs). Mean ± standard deviation haemoglobin A1c (HbA1c) decreased from 8.73 ± 1.15% and 8.35 ± 0.95% at baseline to 7.71 ± 1.09% and 7.82 ± 1.06% at week 24 in the NPH and BIA subgroups, respectively. Least squares (LS) mean change in HbA1c was - 0.85% (95% confidence interval - 0.94 to - 0.77) in NPH subgroup and - 0.70% (- 0.77 to - 0.64) in BIA subgroup, with a LS mean absolute difference between subgroups of 0.16 (0.06-0.26; p = 0.002). Gla-300 mean daily dose was slightly increased at week 24 by 0.07 U/kg/day (approximately 6 U/day) in both subgroups. Incidences of symptomatic and severe hypoglycaemia were low, without body weight change. CONCLUSIONS: Irrespective of previous BI therapy (NPH insulin or BIAs), switching to Gla-300 improved glycaemic control without weight gain and with low symptomatic and severe hypoglycaemia incidences. However, a slightly greater glucose-lowering effectiveness was observed in people pre-treated with NPH insulin