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4 vs -25.2Kcal/day; LS mean difference 31.6 [95% confidence interval -90.6, 153.8]). In patients with T1D, there was no significant difference in insulin sensitivity between the eptinezumab and placebo groups. AZD8055 Eptinezumab was well tolerated in both studies with a similar rate of adverse events between treatment groups, and no new safety signals were identified.
Eptinezumab was well tolerated and not associated with adverse metabolic effects in patients who were overweight/obese or had T1D, providing ongoing support for the use of eptinezumab in these subgroups of patients with migraine.
Eptinezumab was well tolerated and not associated with adverse metabolic effects in patients who were overweight/obese or had T1D, providing ongoing support for the use of eptinezumab in these subgroups of patients with migraine.
The neurosteroid allopregnanolone modulates oxytocin expression in the brain, and its effects arise from its action on the GABA
receptor. Whether neurosteroid levels and the function of the GABA
receptor are involved in the risk of preterm labour in pregnant women is unknown.
Pregnant women with (
=16) or without (
=20) threatened preterm labour (TPL) in gestational week 33+6days to 37+0days were studied prospectively with procedures including foetal heart rate monitoring, vaginal examination, ultrasound examination and blood tests to determine allopregnanolone, progesterone and oxytocin levels. The GABA
receptor function in both groups was measured with a saccadic eye velocity test (SEVT).
Plasma oxytocin levels were higher in the TPL group than in the control group (41.5 vs. 37.0pmol/L, respectively,
=.021). Although the allopregnanolone and progesterone levels in both groups did not differ, there was a negative association between blood oxytocin and allopregnanolone (as predictor) levels inigated during a challenge test with a GABAA receptor agonist.
Several studies have examined the incidence of childhood T1DM in Japan from the 1970s onwards, but none have been long-term studies using registration data. We estimate the incidence of childhood type 1 diabetes mellitus (T1DM) from 1986 to 2018 in Yamanashi Prefecture, Japan.
We began a population-based, long-term study of childhood T1DM in 1986 involving every hospital paediatrics department in Yamanashi Prefecture. In the Prefecture, every child newly diagnosed with T1DM is referred to a hospital, and therefore, almost 100% of new patients aged <15 years are registered. We calculated the incidence of T1DM among children aged <15 years from 1986 to 2018. All cases met the Japan Diabetes Society diagnostic criteria and were tested for T1DM-related autoantibodies whenever possible.
Ninety-nine patients (44 boys and 55 girls) were newly diagnosed with T1DM. The annual incidence among 5- to 9-year-olds increased by 5.35% over the study period (95% confidence interval 2.34%-8.35%,
= .0005), and the and that the age of onset is decreasing.
Lipid metabolism might be compromised in type 1 diabetes, and the understanding of lipid physiology is critically important. This study aimed to compare the change in plasma lipid concentrations during carbohydrate dietary changes in individuals with type 1 diabetes and identify links to early-stage dyslipidaemia. We hypothesized that (1) the lipidomic profiles after ingesting low or high carbohydrate diet for 12weeks would be different; and (2) specific annotated lipid species could have significant associations with metabolic outcomes.
Ten adults with type 1 diabetes (mean±SD age 43.6±13.8years, diabetes duration 24.5±13.4years, BMI 24.9±2.1kg/m
, HbA
57.6±2.6mmol/mol) using insulin pumps participated in a randomized 2-period crossover study with a 12-week intervention period of low carbohydrate diet (< 100g carbohydrates/day) or high carbohydrate diet (> 250g carbohydrates/day), respectively, separated by a 12-week washout period. A large-scale non-targeted lipidomics was performed with mass siated with BMI and positively associated with HDL cholesterol (p<.001). Results from this study warrant for more investigation on the long-term effect of single lipid species in type 1 diabetes.
Lipidome-wide outcome analysis of a randomized crossover trial of individuals with type 1 diabetes following a low carbohydrate diet showed an increase in sphingomyelins and phosphatidylcholines which are thought to reduce dyslipidaemia. The polyunsaturated phosphatidylcholine 354 was inversely associated with BMI and positively associated with HDL cholesterol (p less then .001). Results from this study warrant for more investigation on the long-term effect of single lipid species in type 1 diabetes.
The aim of this study was to explore the effect of insulin treatment initiation on weight by taking weight change prior to initiation into account.
We performed an observational retrospective inception cohort study, concerning Dutch primary care. We identified all patients that initiated insulin treatment (
=7967) and individually matched patients with a reference patient (
=5213 pairs). We obtained estimated mean weight changes in the five years prior to five years post insulin therapy. We applied linear regression analysis on weight change in the first year after insulin therapy (T0 to T+1), with matched group as primary determinant adjusted for pre-insulin weight change and additional covariates.
Estimated mean weight increased in the five consecutive years prior to insulin therapy (-0.23kg in year T-5 to T-4, 0.01kg in year T-4 to T-3, 0.07kg in year T-3 to T-2, 0.24kg in year T-2 to T-1, and 0.46kg in year T-1 to T0) and continued to increase in the first year after, that is T0 to T+1, at a slighffect on weight was small and subject to substantial variation. Pre-insulin weight change is identified as a relatively strong inverse determinant of weight change after insulin initiation.
To understand the mechanism by which imeglimin (a new oral hypoglycemic agent whose phase 3 development program in Japan has now been completed) decreases hepatic glucose production.
We compared the effect of imeglimin and metformin on glucose production, ATP/ADP ratio, oxygen consumption rate, mitochondrial redox potential and membrane potential in primary rat hepatocytes.
We found that both imeglimin and metformin dose-dependently decreased glucose production and the ATP/ADP ratio. Moreover, they both increased mitochondrial redox potential (assessed by mitochondrial NAD(P)H fluorescence) and decreased membrane potential (assessed by TMRM fluorescence). However, contrary to metformin, which inhibits mitochondrial Complex I, imeglimin did not decrease the oxygen consumption rate in intact cells. By measuring the oxygen consumption of in situ respiratory chain as a function of the concentration of NADH, we observed that imeglimin decreased the affinity of NADH for the respiratory chain but did not affect its Vmax (ie competitive inhibition) whereas metformin decreased both the Vmax and the affinity (ie uncompetitive inhibition).