A 3.5-year-old child with hypertrophic obstructive cardiomyopathy and recurrent syncope underwent surgical left-ventricular outflow tract myectomy and implantation of a single-chamber automatic ...cardioverter defibrillator. A single-coil active fixation lead was introduced via a purse-string suture in the right atrial appendage and the lead tip positioned and fixed in the right-ventricular apex under direct visualization via a small right atriotomy incision. Described configuration may be considered in small children undergoing intracardiac surgery at the time of defibrillator implantation.
To determine if temporal glucose profiles differed between
) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG),
) women who used ...insulin pumps or multiple daily insulin injections (MDIs), and
) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT).
Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM,
= 100; SMBG,
= 100) taken at baseline and at 24- and 34-weeks' gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups.
FDA revealed that women using RT-CGM had significantly lower glucose (0.4-0.8 mmol/L 7-14 mg/dL) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4-0.9 mmol/L 7-16 mg/dL) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4-0.7 mmol/L (7-13 mg/dL) for 4.5 h/day at baseline, by 0.4-0.9 mmol/L (7-16 mg/dL) for 16 h/day at 24 weeks, and by 0.4-0.7 mmol/L (7-13 mg/dL) for 14 h/day at 34 weeks.
FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.
To compare glycemic control, quality of life, and pregnancy outcomes of women using insulin pumps and multiple daily injection therapy (MDI) during the Continuous Glucose Monitoring in Women With ...Type 1 Diabetes in Pregnancy Trial (CONCEPTT).
This was a prespecified analysis of CONCEPTT involving 248 pregnant women from 31 centers. Randomization was stratified for pump versus MDI and HbA
. The primary outcome was change in HbA
from randomization to 34 weeks' gestation. Key secondary outcomes were continuous glucose monitoring (CGM) measures, maternal-infant health, and patient-reported outcomes.
At baseline, pump users were more often in stable relationships (
= 0.003), more likely to take preconception vitamins (
= 0.03), and less likely to smoke (
= 0.02). Pump and MDI users had comparable first-trimester glycemia: HbA
6.84 ± 0.71 vs. 6.95 ± 0.58% (51 ± 7.8 vs. 52 ± 6.3 mmol/mol) (
= 0.31) and CGM time in target (51 ± 14 vs. 50 ± 13%) (
= 0.40). At 34 weeks, MDI users had a greater decrease in HbA
(-0.55 ± 0.59 vs. -0.32 ± 0.65%,
= 0.001). At 24 and 34 weeks, MDI users were more likely to achieve target HbA
(
= 0.009 and
= 0.001, respectively). Pump users had more hypertensive disorders (
= 0.011), mainly driven by increased gestational hypertension (14.4 vs. 5.2%;
= 0.025), and more neonatal hypoglycemia (31.8 vs. 19.1%,
= 0.05) and neonatal intensive care unit (NICU) admissions >24 h (44.5 vs. 29.6%;
= 0.02). Pump users had a larger reduction in hypoglycemia-related anxiety (
= 0.05) but greater decline in health/well-being (
= 0.02).
In CONCEPTT, MDI users were more likely to have better glycemic outcomes and less likely to have gestational hypertension, neonatal hypoglycemia, and NICU admissions than pump users. These data suggest that implementation of insulin pump therapy is potentially suboptimal during pregnancy.
Metformin is increasingly being used during pregnancy, with potentially adverse long-term effects on children. We aimed to examine adiposity in children of women with type 2 diabetes from the ...Metformin in Women with Type 2 Diabetes in Pregnancy (MiTy) trial, with and without in-utero exposure to metformin, up to 24 months of age.
MiTy Kids is a follow-up study that included infants of women who participated in the MiTy randomised controlled trial, receiving either oral 1000 mg metformin twice daily or placebo. Caregivers and researchers remained masked to the type of medication (metformin or placebo) mothers received during their pregnancy. Anthropometric measurements, including weight, height, and skinfold thicknesses, were taken at 3, 6, 12, 18, and 24 months. At 24 months, linear regression was used to compare the BMI Z score and sum of skinfolds in the metformin versus placebo groups, adjusted for confounders. Fractional polynomials were used to assess growth trajectories. This study is registered with ClinicalTrials.gov, NCT01832181.
Of the 465 eligible children, 283 (61%) were included from 19 centres in Canada and Australia. At 24 months, there was no difference between groups in mean BMI Z score (0·84 SD 1·52 with metformin vs 0·91 1·38 with placebo; mean difference 0·07 95% CI -0·31 to 0·45, p=0·72) or mean sum of skinfolds (23·0 mm 5·2 vs 23·8 mm 5·4; mean difference 0·8 mm -0·7 to 2·3, p=0·31). Metformin was not a predictor of BMI Z score at 24 months of age (mean difference -0·01 95% CI -0·42 to 0·37, p=0·92). There was no overall difference in BMI trajectory but, in males, trajectories were significantly different by treatment (p=0·048); BMI in the metformin group was higher between 6 and 24 months. Children of women with type 2 diabetes were approximately 1 SD heavier than the WHO reference population.
Anthropometrics were similar in children exposed and those not exposed to metformin in utero; hence, overall, data are reassuring with regard to the use of metformin during pregnancy in women with type 2 diabetes and the long-term health of their children.
Canadian Institute for Health Research.
The CONCEPTT trial compared real-time Continuous Glucose Monitoring (RT-CGM) to capillary glucose monitoring in pregnant women with type 1 diabetes. We analyzed CGM and glycated hemoglobin (HbA
) ...measures in first (
= 221), second (
= 197), and third (
= 172) trimesters, aiming to examine target glucose attainment and associations with pregnancy outcomes. CGM targets were Time-in-range (TIR) > 70%, Time-above-range (TAR) <25%, and Time-below-range (TBR) < 4%, and HbA
targets < 6.5% (National Institute for Health and Care Excellence NICE) and HbA
< 6.0% in second and third trimesters (American Diabetes Association ADA). TIR/TAR/TBR targets were achieved by 7.7/14.5/30.3% participants in first, 10.2/14.2/52.8% in second, and 35.5/37.2/52.9% in third trimesters. CGM target attainment was low but increased during pregnancy and with RT-CGM use. In the adjusted analyses, achieving TBR target was associated with a higher risk of pre-eclampsia and neonatal hypoglycemia. ADA HbA
target attainment was low and unchanged during pregnancy (23.5/27.9/23.8%) but increased with RT-CGM use. In the adjusted analyses, HbA
target attainment was associated with a lower risk of preterm birth, large-for-gestational age and neonatal hypoglycemia. We conclude that CONCEPTT trial participants had a low rate of CGM and of HbA
target attainment. Attainment of CGM and NICE HbA
targets increased throughout gestation and all targets (both NICE/ADA HbA
and CGM) were more likely to be achieved by RT-CGM users, at 34 weeks' gestation. ADA HbA
target achievement was independently associated with better perinatal outcomes, while the independent association of TBR target achievement with increased risk warrants further study. ClinicalTrials.gov Registration Identifier NCT01788527.
To characterize the phenotype in individuals with
-related autosomal dominant optic atrophy and cataract (ADOAC) and peripheral neuropathy (PN).
Two probands with multiple affected relatives and one ...sporadic case were referred for evaluation of a PN. Their phenotype was determined by clinical ± neurophysiological assessment. Neuropathologic examination of sural nerve and skeletal muscle, and ultrastructural analysis of mitochondria in fibroblasts were performed in one case. Exome sequencing was performed in the probands.
The main clinical features in one family (n = 7 affected individuals) and one sporadic case were early-onset cataracts (n = 7), symptoms of gastrointestinal dysmotility (n = 8), and possible/confirmed PN (n = 7). Impaired vision was an early-onset feature in another family (n = 4 affected individuals), in which 3 members had symptoms of gastrointestinal dysmotility and 2 developed PN and cataracts. The less common features among all individuals included symptoms/signs of autonomic dysfunction (n = 3), hearing loss (n = 3), and recurrent pancreatitis (n = 1). In 5 individuals, the neuropathy was axonal and clinically asymptomatic (n = 1), sensory-predominant (n = 2), or motor and sensory (n = 2). In one patient, nerve biopsy revealed a loss of large and small myelinated fibers. In fibroblasts, mitochondria were frequently enlarged with slightly fragmented cristae. The exome sequencing identified
variants in all probands: a novel variant (c.23T>C) and the known mutation (c.313C>G) in
.
A syndromic form of ADOAC (ADOAC+), in which axonal neuropathy may be a major feature, is described.
mutations should be included in the differential diagnosis of complex inherited PN, even in the absence of clinically apparent optic atrophy.
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