Continuous subcutaneous insulin infusion (CSII) in diabetic pregnancy: a review RECENT PATENTS ON ENDOCRINE, METABOLIC & IMMUNE DRUG DISCOVERY

RECENT PATENTS ON ENDOCRINE, METABOLIC & IMMUNE DRUG DISCOVE Codice rivista: E194263 Titolo rivista: RECENT PATENTS ON ENDOCRINE, METABOLIC & IMMUNE DRUG DISCOVERY Issn: 1872-2148 Cordiali saluti CINECA - Servizio Gestione Rivist

Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes

Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c), hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P < 0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin) were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement

Mortality in SARS-CoV-2 Hospitalized Patients Treated with Remdesivir: A Nationwide, Registry-Based Study in Italy

Remdesivir is the first drug approved for treatment of COVID-19 but current evidence for recommending its use for the treatment of moderate-to-severe disease is still controversial among clinical guidelines. We performed a nationwide, registry-based study including all Italian hospitalized patients with COVID-19 treated with remdesivir to assess the impact of major confounders on crude 15-day and 29-day mortality. Mortality was calculated using the Kaplan-Meier estimator and the Cox proportional-hazards model was applied to analyze the risks by patient's baseline features. In total, 16,462 patients treated with remdesivir from 29 October 2020 to 17 December 2020 were entered in the study. Crude 15-day and 29-day mortality were 7.1% (95% CI, 6.7-7.5%) and 11.7% (95% CI, 11.2-12.2%), respectively. Being treated within two days of admission reduced the risk of death by about 40% (HR 1.4, 95% CI, 1.2-1.6). Results from the largest cohort of remdesivir-treated patients suggests that mortality in SARS-CoV-2 hospitalized patients is substantially influenced by the days between SARS-CoV-2 diagnosis and drug prescription. Current recommendations and future clinical trials for remdesivir alone or in combination should carefully consider the target population and timing for best efficacy of treatment

Mortality in SARS-CoV-2 Hospitalized Patients Treated with Remdesivir: A Nationwide, Registry-Based Study in Italy

Remdesivir is the first drug approved for treatment of COVID-19 but current evidence for recommending its use for the treatment of moderate-to-severe disease is still controversial among clinical guidelines. We performed a nationwide, registry-based study including all Italian hospitalized patients with COVID-19 treated with remdesivir to assess the impact of major confounders on crude 15-day and 29-day mortality. Mortality was calculated using the Kaplan–Meier estimator and the Cox proportional-hazards model was applied to analyze the risks by patient’s baseline features. In total, 16,462 patients treated with remdesivir from 29 October 2020 to 17 December 2020 were entered in the study. Crude 15-day and 29-day mortality were 7.1% (95% CI, 6.7–7.5%) and 11.7% (95% CI, 11.2–12.2%), respectively. Being treated within two days of admission reduced the risk of death by about 40% (HR 1.4, 95% CI, 1.2–1.6). Results from the largest cohort of remdesivir-treated patients suggests that mortality in SARS-CoV-2 hospitalized patients is substantially influenced by the days between SARS-CoV-2 diagnosis and drug prescription. Current recommendations and future clinical trials for remdesivir alone or in combination should carefully consider the target population and timing for best efficacy of treatment

Long Lasting Effects of Breastfeeding on Metabolism in Women with Prior Gestational Diabetes

Background &amp; Aims: Breastfeeding improves glucose tolerance in the early postpartum period of women with prior gestational diabetes GDM, but it is unclear whether future risk of metabolic alterations, like type 2 diabetes, is reduced. The aim of this study was to investigate the effect of lactation, three years after pregnancy, on glucose and lipid metabolism in women with prior gestational diabetes. Materials &amp; Methods: A population of women with prior gestational diabetes (Carpenter and Coustan Criteria) was evaluated with comparison of results for “lactating” [BF] versus “nonlactating women” [non BF]. Breast feeding was defined [BF] if lasting? 4 weeks. In each woman a 75-g oral glucose tolerance test (OGTT) was performed to analyze the glucose tolerance, insulin sensitivity/resistance and b-cell function. Fasting serum was used to study their lipid profile (total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglycerides), apolipoprotein B, apolipoprotein A1, homocysteine, fibrinogen, hs- CRP, uric acid, microalbuminuria. Statistics: Paired and Un-paired t-test, Mann-Whitney and χ2 tests were used, as appropriate. Results: A total of 81 women were evaluated (62 [BF] and 19 [non BF]). Maternal age (37.1 ± 4.6 vs 37.4 ± 4.9 years), body mass index (26.3 ± 5.6 vs 26.4 ± 5.3 kg/m2), parity (1.9 ± 0.8 vs 1.7 ± 0.8) and length of follow-up (32.2 ± 20.2 vs 32.1 ± 20,0) were not different between the two groups. No effect was visible on glucose tolerance, HOMA-IR and other b-cell function indexes as well as hs-CRP (not significantly lower in non BF), uric acid, total cholesterol, HDL and LDL cholesterol. Levels of significance were only reached for “HOMA-IS” [BF] 1.0 ± 0.7 vs [non BF] 0.6 ± 0.4, p = 0.04) and triglycerides [BF] 83.8 ± 46.7 vs [non BF] 123.2 ± 94.0 mg/dl, p = 0.02). Conclusions: Breastfeeding does not improve the glucose tolerance of our women with prior GDM three years after delivery, even though lower levels of triglycerides and improved insulin sensitivity are still visible

Continuous Glucose Monitoring During Breastfeeding in Women with Recent Gestational Diabetes Mellitus

This study monitored blood glucose profiles in normotolerant breastfeeding women, with and without previous gestational diabetes, in real life in order to identify normal blood glucose fluctuations during breastfeeding. Two groups were studied: (1) 18 women with recent gestational diabetes mellitus but normotolerant postpartum (pGDM-N group) and (2) 15 women normotolerant both during pregnancy and postpartum (pN-N group). All participants underwent continuous glucose monitoring during which they recorded their main daily activities and three standardized events: "suckling," "meal," and "meal and suckling." Other than these three events, these women were essentially on an "ad lib" diet. Data were expressed as median and SD values. Student's t test and Fisher's test were used to compare mean, variances, and percentages. Differences were significant with P<0.05. Clustering analysis was used to determine the normal range of glucose values. The two groups were matched for age, follow-up duration, and monitoring measurements but not for body mass index. Blood glucose levels and variances were higher in the pGDM-N group, particularly during daytime and the three standardized events, and were not related to body mass index. Suckling had no direct effect on glucose profile during both the non-fed and the fed state. Blood glucose levels that best represent the normal breastfeeding population were between 50 and 126 mg/dL (from 2.8 to 7.0 mmol/L). Three months after delivery, normotolerant women with recent gestational diabetes had higher daily blood glucose levels than women who were always normotolerant, with no direct effect of suckling. The blood glucose profiles of healthy subjects could be representative of the normal range of the population during breastfeeding

Real-World Effectiveness of PCSK9 Inhibitors in Reducing LDL-C in Patients With Familial Hypercholesterolemia in Italy: A Retrospective Cohort Study Based on the AIFA Monitoring Registries

: Background Information on the real-world use of proprotein convertase subtilisin kexin 9 inhibitors (PCKS9is) in familial hypercholesterolemia are limited. We evaluated the pattern of prescription and the long-term efficacy of alirocumab and evolocumab in Italian patients with familial hypercholesterolemia in clinical practice. Methods and Results The data set for analysis was extracted from the PCKS9i Italian Medicines Agency (AIFA) registry and included 2484 patients with heterozygous familial hypercholesterolemia (HeFH) and 62 patients with homozygous familial hypercholesterolemia (HoFH) who were prescribed PCKS9is from February 2017 to December 2021. As the follow-up schedules were not prespecified and could vary, persistence and adherence as well as low-density lipoprotein cholesterol (LDL-C) changes during 2 years of treatment were analyzed in a final cohort of 1299 patients with familial hypercholesterolemia. At baseline, 53.8% of patients with HeFH and 69.4% of patients with HoFH were receiving maximally tolerated lipid-lowering therapies, while 45.9% of patients with HeFH and 30.7% of patients with HoFH reported statin intolerance; mean LDL-C was 197.7±52.3 mg/dL in HeFH and 252.0±106.2 mg/dL in HoFH. The 6-month persistence and adherence to therapy were >85%, and LDL-C reduction reached 58.6% (to 79.7 mg/dL) in HeFH and 57.6% (to 95.1 mg/dL) in HoFH after 24 months of treatment. The European Atherosclerosis Society/European Society of Cardiology LDL-C goals were achieved in 43.3% of patients with HeFH and 37.5% of patients with HoFH. Conclusions PCKS9i prescribed to patients with familial hypercholesterolemia in clinical practice showed LDL-C-lowering efficacy similar to that observed in controlled trials. However, 2 of 5 HeFH cases and 2 of 6 HoFH cases achieved the recommended LDL-C goals. The full achievement of European Atherosclerosis Society/European Society of Cardiology LDL-C goals should require a lower threshold for PCKS9i initiation and a combination of multiple therapies

The loss of entropy circadian rhythm in sinusal R-R intervals of type 1 diabetic pregnant women suggests an indeterministic chaos in cardiac pacing (minimum delirium cordis syndrome). A newly identifiable type of silent cardiac dysautonomia?

OBJECTIVE: The scope of this study is to detect whether or not the entropy (E) circadian rhythm (CR) is maintained preserved in sinusal R-R intervals (SRRI), its loss being the expression of a transition to an indeterministic chaos in heart rate variability (HRV). METHODS: The E of SRRI was estimated in 14 type I diabetic pregnant women (DPW) in the first trimester of an apparently uncomplicated gestation (7 patients - mean age = 30.3 +/- 4.1 y - without clinical and laboratory evidence of cardiac autonomic neuropathy, and 7 patients - mean age = 30.7 +/- 3.6 y - with positive tests for a cardiac dysautonomia). The E CR was studied via the single cosinor method, and summarized via the population-mean cosinor method. RESULTS: The E CR was found not to be preserved in both the investigated type I DPW, despite the occurrence of the SRRI CR. CONCLUSIONS: The loss of the E CR confirms that in type I DPW there is a transition to an indeterministic disorder in HRV due to the lack of an autocorrelated periodic chaos in cardiac pacing. Such an unphysiological neurovegetative regulation suggests a new silent cardiac dysautonomic syndrome, that we intend to call "minimum delirium cordis syndrome" (MDCS). Can the MDCS be regarded as a condition of cardiovascular risk? To answer this question, it seems justified to suggest that the study of the E CR should be added to the routine tests that are presently applied to clinical analysis of the Holter ECG, being the classic tests of linear analysis not methodologically suitable for detecting the indeterministic chaos of the MDCS