Daily Endocrinology Research Analysis

BACKGROUND: The optimal dietary macronutrient composition during pregnancy to mitigate obesity risk in mothers and offspring remains unclear. OBJECTIVES: This study aims to assess associations between maternal dietary macronutrient composition and obesity outcomes in mothers and offspring. METHODS: We analyzed 66,360 singleton pregnancies from the Danish National Birth Cohort, with dietary intake assessed at gestational week 25. Outcomes included maternal postpartum weight retention (PPWR) at 6 and 18 mo and offspring's birth weight, risks of small for gestational age (SGA) and large for gestational age (LGA), body mass index (BMI) z-scores, and overweight/obesity (OWOB) risk at ages 7, 11, and 14 y. Mixture models with response surface visualization examined interactive macronutrient associations, and mixed restricted cubic splines assessed potential nonlinear relationships between maternal protein intake and obesity outcomes. RESULTS: Mean maternal macronutrient compositions were 15.2% protein, 30.2% fat, and 54.1% carbohydrate. Response surfaces revealed that maternal lower protein intake (%), diluted by higher fat and/or carbohydrate, was associated with higher maternal PPWR at 6 and 18 mo but lower birth weight and BMI z-scores in offspring at ages 7, 11, and 14 y. Mixed restricted cubic splines indicated nonlinear associations between maternal protein intake (%) and SGA risk (nonlinear P = 0.003) and LGA (nonlinear P = 0.04), with a threshold around 15% protein; below this, SGA risk increased whereas LGA risk decreased. Linear associations were observed for risks of substantial PPWR (PPWR >5 kg) and childhood OWOB risk (nonlinear P > 0.05). Each 5% higher protein intake during pregnancy was related to a lower risk of substantial PPWR at 6 mo (odds ratio: 0.90; 95% confidence interval: 0.85, 0.95) and 18 mo (0.88; 0.82, 0.94) but higher risks of OWOB at ages 7 y (1.07; 1.01, 1.15) and 11 y (1.11; 1.03, 1.18), with no association at 14 y (1.02; 0.95, 1.10). CONCLUSIONS: Higher maternal protein intake during pregnancy was associated with lower PPWR and SGA risk but higher LGA and childhood OWOB risks, highlighting potential trade-offs in maternal and offspring obesity outcomes.

Cognitive impairment is common in people with multiple sclerosis (PwMS). There is an urgent need to identify/develop novel therapies that can help cognitive function in MS. Insulin is critical for helping with regulation of multiple CNS functions, including learning and memory. Insulin administrated intranasally has shown to improve memory and learning in healthy people and in those with some neurodegenerative disorders. Hence, there was rationale for investigating intranasal insulin in PwMS who experience cognitive impairment. We completed a phase Ib/II, randomized, double-blind, placebo-controlled trial; participants were randomized in a 1:1:1 fashion, stratified by relapsing versus progressive MS, to intranasal insulin 10 ​international units (IU) twice a day, 20 IU twice a day, or placebo for 24 weeks. One-hundred and five PwMS were enrolled, 69 of whom had at least one follow up visit during the active treatment phase of the trial (baseline to week 24). The cohort's mean age was 52.4 ​± ​9.7years, 62 ​% were female, and ∼60 ​% had relapsing-remitting MS. The most common side effects amongst treatment groups included headache, rhinorrhea, and dizziness. There were 13 SAEs which were not deemed study drug related; there were no deaths. The main clinical outcome measure, SDMT, did not demonstrate any difference between intranasal insulin and placebo. Similar findings were noted for all secondary outcome measures. Intranasal insulin appeared safe and well-tolerated in PwMS. However, it was not superior to placebo in any of the clinical outcome measures assessed, which could have been impacted by the duration of the trial, small sample size for a three-arm trial design, data missingness (particularly during COVID-19), outcome measure insensitivity to change, baseline cognitive reserve, or other factors. Nonetheless, intranasally-administered therapeutics may be of interest to develop further as a way to get across the blood brain barrier.

AIMS: This study examined new onset diabetes following COVID-19 infection in large datasets. METHODS: A retrospective cohort study design was used in three distinct databases: data from a large academic medical center (University of Kentucky Healthcare, UKHC), claims data from privately insured patients in the Merative MarketScan (MarketScan) database, and a subset of the MarketScan database with lab tests. Control groups included patients from the prepandemic timeframe (prepandemic cohort), as well as COVID-era patients without documented COVID infection (COVID - cohort). RESULTS: Incident diabetes in COVID infected patients was higher in all datasets. In the UKHC and MarketScan datasets, the adjusted Hazard ratios (HR) were 3.46 and 2.13 in UKHC and MarketScan. Incident diabetes was elevated even in patients who were treated in the outpatient setting and much higher in patients who were treated in the inpatient setting, especially those who required inpatient interventions. In MarketScan, the HR for developing type 1 diabetes was 1.61. CONCLUSIONS: Persons infected with COVID-19 during the initial 18 months of the pandemic demonstrated a higher incidence of new onset diabetes, which was evident in all populations. Diabetes incidence was especially high in an academic center population with higher health disparities, and in patients with a more severe infection with the virus.