In the last decade Sanger method of DNA sequencing has been replaced by next generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal ...diabetes mellitus (NDM).
To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) versus 2013-2022 (NGS).
We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM+c.SIR) of the Italian dataset.
Fiftyfive patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103,340 (NDM) and 1:1,240,082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, p= 0.034 vs 2003-2012). Notably, five among rare genes were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA), were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes and the individual with lipodystrophy caused by BSCL2 was started on metreleptin.
NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and congenital SIR in Italy.
Albuminuria and reduced eGFR are hallmarks of Diabetic Kidney Disease in adults. Our aim was to analyze factors associated with albuminuric and non-albuminuric mildly reduced eGFR phenotypes in ...youths with type 1 diabetes.
This multicenter cross-sectional study included 1549 youths (age 5–17 years) with type 1 diabetes enrolled at 14 Italian Pediatric Diabetes Centers. Albuminuria, creatinine, glycosylated hemoglobin (HbA1c), lipids, blood pressure (BP), neutrophils (N) and lymphocytes (L) count were analyzed. Uric acid (UA) was available in 848 individuals. Estimated GFR (eGFR) was calculated using bedside Schwartz's equation. The sample was divided in three phenotypes: 1) normoalbuminuria and eGFR ≥90 mL/min/1.73 m2 (reference category, n = 1204), 2) albuminuric and normal GFR phenotype (n = 106), 3) non-albuminuric mildly reduced GFR (MRGFR) phenotype (eGFR 60–89 mL/min/1.73 m2, n = 239). Albuminuric and non-albuminuric reduced eGFR phenotypes were significantly associated with autoimmune thyroiditis (P =0.028 and P=0.044, respectively). Albuminuric phenotype showed high risk of high HbA1c (P=0.029), high BP (P < 0.001), and low HDL-C (P =0.045) vs reference category. Non-albuminuric MRGFR phenotype showed high risk of high BP (P < 0.0001), low HDL-C (P =0.042), high Triglycerides/HDL-C ratio (P =0.019), and high UA (P < 0.0001) vs reference category.
Non albuminuric MRGFR phenotype is more prevalent than albuminuric phenotype and shows a worst cardiometabolic risk (CMR) profile). Both phenotypes are associated with autoimmune thyroiditis. Our data suggest to evaluate both albuminuria and eGFR earlier in type 1 diabetes to timely identify young people with altered CMR profile.
•Diabetic kidney disease (DKD) is characterized by albuminuric and non-albuminuric phenotypes.•The characteristics of these phenotypes in youths with type 1 diabetes are unknown.•Both phenotypes are associated with an altered cardiometabolic risk (CMR) profile•Non-albuminuric mildly reduced eGFR is the phenotype more prevalent.•Early detection of these phenotypes is important in order to monitoring DKD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Presenter:
M. Rinaldi (e-mail: matrinaldi@gmail.com)
Introduction:
Chorioamnionitis or intra-amniotic infection is an acute inflammation of the membranes and chorion of the placenta, typically due to ...ascending polymicrobial bacterial infection in the setting of membrane rupture. It complicates as many as 40 to 70% of preterm births with premature membrane rupture or spontaneous labor and 1 to 13% of term births. The most common microorganisms that cause this pathology are:
U. Urealyticum
;
M. Hominis
;
G. Vaginalis
;
E. Coli
. Clinical, microbiological, or histological criteria can be used to diagnose chorioamnionitis. Histopathological examination of the placenta is the gold standard for evaluating antenatal inflammatory processes that might influence fetal development. Chorioamnionitis is often associated with significant maternal, perinatal and long term adverse outcomes. Adverse maternal outcomes include an increased risk of cesarean delivery, postpartum infection and sepsis, while adverse infant outcomes include stillbirth, premature birth, neonatal sepsis, brain injury and chronic lung disease. The purpose of this study was to determine whether or not histological chorioamnionitis is associated with adverse outcome in very low birth weight neonates (VLBW).
Materials and Methods:
This was a retrospective study. The placental histopathologic findings and the charts of the VLBW patients who were admitted to neonatal intensive care unit of Azienda Ospedaliera Ospedali Riuniti di Foggia from January 2012 to December 2014 were reviewed. Histologic examination of placenta and extraplacental membranes were performed, and neonates’ clinical data were extracted from Vermont-Oxford Network. Analyses included χ
2
test, Student
t
-test, Fisher exact test, standard deviation and mean. Parametric and nonparametric statistics were used for data analysis.
Results:
Among the 92 placentas examined, the frequency of acute histologic chorioamnionitis was 23% (21/92). Histological chorioamnionitis was associated with a greater frequency of nulliparity (80%), vaginal delivery (76%), lower gestational age (25 ± 1.95), lower birth weight (800 ± 201.47), Apgar score <7 at first (95%) and fifth minute (71%), retinopathy of prematurity (38%; OR: 3.2; 95% CI: 1.02; 8.78) and necrotizing enterocolitis (5%; OR: 1.72; 95% CI: 0.14;19.93). The mortality rate of newborns with maternal chorioamnionitis was of 33%. However, no significant difference was observed in the incidence of neonatal distress respiratory syndrome (100%), bronchopulmonary dysplasia (5%; OR: 1.13; 95% CI: 0.11; 11.38), patent ductus arteriosus (9%; OR: 0.42; 95% CI: 0.08; 1.9), periventricular leukomalacia and intraventricular hemorrhage (28%; OR: 2.5; 95% CI: 0.7; 5.84) (see
Table 1
).
Conclusion:
This study proves that premature neonates born from pregnancies complicated by histological chorioamnionitis have a lower birth weight, gestational age and Apgar score at first and fifth minutes than that without chorioamnionitis. Moreover, histologic chorioamnionitis is a risk factor for ROP and NEC, but not for other causes of major morbidity.
Keywords:
chorioamnionitis, preterm, retinopathy of prematurity, necrotizing enterocolitis
Characteristics
HCA (−)
HCA (+)
OR 95% CI
p
-value
Gestational age
29.42 ± 3.3
25.28 ± 1.95
<0.05
Birth weight
1101.5 ± 302
800 ± 201.47
<0.05
Maternal age
32 ± 5,8
32 ± 6,8
1-minute Apgar score < 7
42 (59)
20 (95)
13.8 108.2; 1.76
<0.001
A5-minute Apgar score < 7
22 (31)
15 (71)
5.56 16.2; 1.9
<0.01
Cesarean delivery
63 (89)
5 (24)
0.089 0.27; 0.028
<0.0001
IVH
14 (20)
6 (28)
2.5 5.84; 0.7
>0.05
PVL
0
0
ROP
12 (17)
8 (38)
3.2 8.78; 1.02
<0.05
NEC
2 (3)
1 (5)
1.72 19.93; 0.14
<0.05
PDA
14 (20)
2 (9)
0.42 1.9; 0.08
>0.05
LOS
2 (3)
0
EOS
3 (4)
2 (9)
2.38 39; 0.14
>0.05
RDS
64 (90)
21 (100)
>0.05
BPD
3 (4)
1 (5)
1.13 11.38; 0.11
>0.05
Omega-3 polyunsaturated fatty acids (PUFAs) represent valuable dietary adjuncts for subjects with hypertriglyceridemia and at increased risk of cardiovascular disease, including subjects with type 1 ...diabetes (T1D). However, the exact role of omega-3 PUFAs in the regulation of glucose homeostasis and chronic complications in patients with diabetes remains uncertain. Herein, we report a 3-year follow-up of an athlete adolescent with T1D who started to use continuous glucose monitoring (CGM) two years after the diagnosis, and initiated omega-3 PUFA supplementation four years after the clinical onset of T1D. CGM metrics related to a 18-month period of omega-3 PUFA supplementation (50 mg/Kg/day of EPA and DHA) was compared to CGM metrics referring to a 18-month period prior to the nutrition intervention. Omega-3 PUFA supplementation resulted in a significant reduction of mean glucose and glucose variability, along with a significant increase in Time in range (TIR) 70-180 mg/dL. No significant changes were observed in daily insulin requirements between the two study periods. Future studies will be of assistance to better understand the exact impact of omega-3 PUFAs on the regulation of glucose homeostasis in patients with type 1 and its complications.
This cohort study analyzes changes to the time with glucose level in target range among children and adolescents with type 1 diabetes after a software update to a closed-loop glucose control system.
Context: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in ...energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference.
Objective: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding.
Methods: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals.
Results: Ghrelin levels in cord blood (median 25th–75th centile) 184; 122–275 pg/ml were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89–190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348–649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302–775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = −0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen.
Conclusions: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.
To assess burden and clinical features of type 1 diabetes in migrant with respect to Italian children. Prevalent children with type 1 diabetes were identified through a multicenter study, including ...46 pediatric outpatients diabetic clinics. A nested case–control study was also performed, comparing features at diabetes onset and after 1 year of insulin treatment in 84 migrants and 75 Italian children with onset in 2011, matched for age and sex. Out of 7,812 children cared for by pediatric diabetologists, 761 (10 %) were migrant and 548 of them were born in Italy. Age at diagnosis was lower in migrants born in Italy (5.1 years, interquartile range (IQR) 2.2–7.7) than in those born in their original countries (7.8 years, IQR 5.3–10.3) and in Italians (9.8 years, IQR 5.9–13.0,
p
< 0.001). At diabetes onset, migrants had lower frequencies of positivities of markers of β-cell autoimmunity (96 vs. 99.5 %,
p
< 0.01), higher values of weight loss (11 vs. 7 %,
p
< 0.01), HbA1c (70 vs. 58 mmol/mol,
p
< 0.001), and insulin requirement (0.70 ± 0.03 vs. 0.63 ± 0.10 UI/kg/die,
p
= 0.05) and lower levels of 25-OH vitamin D3 (15.0 ± 2.8 vs. 20.8 ± 1.3,
p
= 0.03). Moreover, they experienced higher frequencies of hospitalizations during the first year of disease (19.2 vs. 2.7 %,
p
< 0.001). Burden of type 1 diabetes in migrant children is increasing in Italy, with younger age at onset and different clinical features than in Italian children. Higher hospitalization rates and poorer glycemic control over the first year underline that approach to diabetes care in migrants needs to be improved.
Full text
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide ...analysis of respiratory care in very low birth weight infants.
We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices.
We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement.
In Type 1 Diabetes (T1D) in children, close to the onset the requirements of insulin are often reduced. This represents a transient recovery of endogenous insulin secretion named "honeymoon" because ...transient and followed by a progressive decline in C-peptide secretion. This case report describes the effect of administration of high dose vitamin D and Ω-3 fatty acids on T1D progression in a 8-year-old child. At today after one year and a half from the onset of T1D, the subject shows a near-normal blood glucose with the administration of 1.5-2 UI of insulin once a day. Thus this report may be of assistance to design additional studies to determine and validate the effect of administration of vitamin D and Ω-3 fatty acids on the progression of T1D.
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