Publications by authors named "Silvia Savastio"

19 Publications

  • Page 1 of 1

Albuminuric and non-albuminuric reduced eGFR phenotypes in youth with type 1 diabetes: Factors associated with cardiometabolic risk.

Nutr Metab Cardiovasc Dis 2021 Jun 31;31(7):2033-2041. Epub 2021 Mar 31.

Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy.

Background And Aim: 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.

Methods And Results: 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 m (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 m, 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.

Conclusion: 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.
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http://dx.doi.org/10.1016/j.numecd.2021.03.019DOI Listing
June 2021

Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy.

Eur J Endocrinol 2021 Apr;184(4):575-585

Department of Pediatrics, University of Rome Sapienza, Rome, Italy.

Objective: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP/TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features.

Design: Retrospective analysis of the Italian data set of patients with TNDM.

Methods: Clinical features and treatment of 22 KATP/TNDM patients and 12 6q24/TNDM patients were compared.

Results: Fourteen KATP/TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; -2.27 SD) than those with KATP mutations (4.0 weeks; -1.04 SD) (P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP/TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) (P = 0.002). Two KATP/TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8/L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy.

Conclusions: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP/TNDM mutations respond favourably to sulfonylurea monotherapy.
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http://dx.doi.org/10.1530/EJE-20-1030DOI Listing
April 2021

Risk factors for type 1 diabetes, including environmental, behavioural and gut microbial factors: a case-control study.

Sci Rep 2020 10 16;10(1):17566. Epub 2020 Oct 16.

Department of Public Health and Pediatrics, University of Turin, Piazza Polonia 94, 10126, Torino, Italy.

Type 1 diabetes (T1D) is a common autoimmune disease that is characterized by insufficient insulin production. The onset of T1D is the result of gene-environment interactions. Sociodemographic and behavioural factors may contribute to T1D, and the gut microbiota is proposed to be a driving factor of T1D. An integrated preventive strategy for T1D is not available at present. This case-control study attempted to estimate the exposure linked to T1D to identify significant risk factors for healthy children. Forty children with T1D and 56 healthy controls were included in this study. Anthropometric, socio-economic, nutritional, behavioural, and clinical data were collected. Faecal bacteria were investigated by molecular methods. The findings showed, in multivariable model, that the risk factors for T1D include higher Firmicutes levels (OR 7.30; IC 2.26-23.54) and higher carbohydrate intake (OR 1.03; IC 1.01-1.05), whereas having a greater amount of Bifidobacterium in the gut (OR 0.13; IC 0.05 - 0.34) was a protective factor for T1D. These findings may facilitate the development of preventive strategies for T1D, such as performing genetic screening, characterizing the gut microbiota, and managing nutritional and social factors.
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http://dx.doi.org/10.1038/s41598-020-74678-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568546PMC
October 2020

Vitamin D Supplementation Modulates ICOS+ and ICOS- Regulatory T Cell in Siblings of Children With Type 1 Diabetes.

J Clin Endocrinol Metab 2020 12;105(12)

SCDU of Pediatrics, University Hospital Maggiore della Carità, Novara, Italy.

Objectives: Vitamin D plays an immunoregulatory activity. The aim of this study was to assess the correlation between blood serum 25(OH)D levels and Th17 and Treg circulating subsets, mainly Treg/inducible costimulatory-positive (ICOS+), which seems to have a protective role in autoimmunity, in children with type 1 diabetes mellitus (T1D) and their healthy siblings (S). The secondary aim was to evaluate the impact of vitamin D supplementation on these subsets.

Patients And Methods: 22 T1D and 33 S were enrolled. Glucose, hemoglobin A1c, 25 OH vitamin D (25[OH]D), T helper type 17 (Th17; CD4+CCR6+), regulatory T cells (Treg; CD4+CD25+Foxp3+), and Treg/ICOS+ cells were evaluated. According to human leukocyte antigen (HLA) haplotypes, subjects were classified as "at risk" (HLA+), "protective haplotypes" (HLA-; "nested controls"), and "undetermined" (HLAUND). T1D and S subjects were supplemented with cholecalciferol 1000 IU/die and evaluated after 6 months.

Results: Vitamin D insufficiency (74.4%) and deficiency (43%) were frequent. S subjects with 25(OH)D levels <25 nmol/L had Th17, Treg (p < 0.01), and Treg/ICOS+ (P < 0.05) percentages higher than subjects with 25(OH)D >75 nmol/L. Treg/ICOS+ percentages (P < 0.05) were higher in HLA- S subjects compared to percentages observed in S with T1D. At baseline, in S subjects, a decreasing trend in Th17 and Treg/ICOS+ values (P < 0.05) from vitamin D deficiency to sufficiency was observed; 25(OH)D levels were negative predictors of Treg/ICOS+ (R2 = 0.301) and Th17 percentages (R2 = 0.138). After 6 months, supplemented S subjects showed higher 25(OH)D levels (P < 0.0001), and lower Th17 (P < 0.0001) and Treg/ICOS+ (P < 0.05) percentages than at baseline; supplemented T1D patients only had a decrease in Th17 levels (P < 0.05).

Conclusion: Serum 25(OH)D levels seem to affect Th17 and Treg cell subsets in S subjects, consistent with its immunomodulating role. HLA role should be investigated in a larger population.
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http://dx.doi.org/10.1210/clinem/dgaa588DOI Listing
December 2020

Microbiota, epidemiological and nutritional factors related to ketoacidosis at the onset of type 1 diabetes.

Acta Diabetol 2020 Nov 27;57(11):1337-1349. Epub 2020 Jun 27.

Department of Public Health and Pediatrics, University of Study of Torino, Piazza Polonia 94, 10126, Turin, Italy.

Aims: The incidence of type 1 diabetes has increased over the last decades. The pathological pathway is not yet clear, even if genetic and environmental risk factors are known. An early diagnosis can avoid ketoacidosis and its complications. This work aims to discuss the determinants of both ketoacidosis at the onset and access by hospital emergency departments without a suspected diagnosis.

Methods: An observational bi-centric prospective study was conducted in Northern Italy, on a paediatric population including Italian and migrant patients at the diabetes onset. Seventy-four type 1 diabetes patients, both Italian and migrant, were included in the study. Anthropometric, socio-economic, behavioural, clinical data were collected, and microbiota analyses were performed using stool samples.

Results: Regular physical activity is associated with lower ketoacidosis incidence at onset (OR 0.33 95% CI 0.12-0.95 p < 0.05), as is higher blood vitamin D level (OR 0.92 95% CI 0.85-0.99 p < 0.05). Moreover, a higher weaning age (OR 0.49 95% CI 0.27-0.89 p < 0.05), higher vitamin D level (OR 0.90 95% CI 0.83-0.98 p < 0.05) and a higher level of Akkermansia muciniphila (OR 0.46 95% CI 0.25-0.87 p < 0.05) are associated factors to lower frequency of type 1 diabetes onset without a suspected diagnosis. Diabetes migrant status is not a risk factor for severe type 1 diabetes onset; on the other hand, some protective factors are significantly more diffused among Italians, such as regular sport activity and non-critical vitamin D levels.

Conclusion: Behavioural and nutritional data, such as microbiota bio-indicators, seem to be useful to identify an at-risk population to prevent ketoacidosis and its severe complications.
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http://dx.doi.org/10.1007/s00592-020-01555-zDOI Listing
November 2020

Vitamin D effects and endocrine diseases.

Minerva Pediatr 2020 Aug 4;72(4):326-339. Epub 2020 Jun 4.

Unit of Pediatrics, Maggiore della Carità University Hospital, University of Eastern Piedmont, Novara, Italy.

A lack of vitamin D has been linked to autoimmune diseases including type 1 diabetes, autoimmune thyroiditis and to obesity. The prevalence of vitamin D deficiency is higher in diabetic or obese children and patients with thyroiditis compared to healthy controls. Moreover, low vitamin D values seem to be associated with major complications and poor glycemic control, in particular in obese children. Supplementation with vitamin D, which has immune-regulatory properties, may support our therapies and improve the outcomes in different diseases. Although some studies suggest a possible role of vitamin D in the etiology of autoimmune diseases and obesity, data on supplementation benefits are inconclusive and further studies are needed. In this paper, we focus on the current evidence regarding vitamin D function in endocrine diseases and possible benefits of its supplementation in pediatric age.
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http://dx.doi.org/10.23736/S0026-4946.20.05915-0DOI Listing
August 2020

Vitamin D and Cardiovascular Risk: which Implications in Children?

Int J Mol Sci 2020 May 16;21(10). Epub 2020 May 16.

SCDU of Pediatrics, Azienda Ospedaliero-Universitaria Maggiore della Carità, University of Piemonte Orientale, 28100 Novara, Italy.

Vitamin D (25OHD) pleiotropic effects are widely recognized and studied. Recently, vitamin D cardiovascular effects are gaining interest, especially in children, although the studies present conflicting data. Some randomized controlled trials (RCTs) have demonstrated that cardiovascular risk markers, such as lipid parameters, inflammation markers, blood pressure, and arterial stiffness, are unaffected by vitamin D supplementation. By contrast, other studies show that low vitamin D levels are associated with higher risk of cardiovascular disease (CVD) and mortality, and support that increased risk of these diseases occurs primarily in people with vitamin D deficiency. An update on these points in pediatric patients is certainly of interest to focus on possible benefits of its supplementation.
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http://dx.doi.org/10.3390/ijms21103536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279000PMC
May 2020

Nutritional behavior in Italian and immigrant children.

Minerva Pediatr 2019 Dec;71(6):481-487

Department of Medical Sciences, University of Turin, Turin, Italy -

Background: There are 1.2 million of immigrant children living in Italy. However, data on their nutritional habits are limited. The aim of this study was to assess the nutritional profile in a cohort of both Italian and immigrant children.

Methods: The study included 86 children aged 5-15 consecutively enrolled from January 2016 to May 2017 within a larger epidemiological study on determinants of diabetes. Immigrant state was defined on the basis of the parent origin. Data on nutritional profile, frequency of food group consumption, and eating habits were collected using the 24-hour dietary recall method and a questionnaire. Anthropometric parameters were measured.

Results: In the cohort of immigrant children there was a higher prevalence of both overweight (27.3 vs. 14.1%) and obesity (18.2 vs. 3.1%) subjects and a greater total calorie intake compared to Italian children, mainly due to excess simple carbohydrate intake. Immigrant children had a higher consumption of sweets, snacks, and drinks with added sugar. Moreover, unhealthy habits, such as eating alone and eating while watching TV, were more frequent among immigrant children.

Conclusions: In this cohort, immigrant children had a higher prevalence of overweight/obesity possibly due to less healthy nutritional habits. Culturally-tailored nutritional interventions may help preventing the development of obesity-related diseases in this population.
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http://dx.doi.org/10.23736/S0026-4946.19.05654-8DOI Listing
December 2019

[Teething: from symptomatology to practical approach].

Minerva Pediatr 2018 Feb;70(1 Suppl 1):1-10

Clinica Pediatrica, A.O.U. Maggiore Carità, Novara, Italia -

Scopo della presente trattazione è promuovere la consapevolezza del pediatra nei confronti della sintomatologia legata alla dentizione nei bambini con il supporto delle evidenze più significative reperibili nella letteratura scientifica. Dopo la caratterizzazione dei disturbi più comuni, con la relativa incidenza e durata nella popolazione pediatrica, e del ruolo dell'infiammazione saranno definiti i limiti delle terapie attualmente disponibili. Saranno quindi illustrate le prerogative di un medicinale omeopatico, Camilia® (Boiron, Francia), che interviene sull'infiammazione locale e sistemica e sulla composita fenomenologia correlata al processo di dentizione, con il vantaggio di un'azione multifunzionale ed efficace e l'assenza di effetti indesiderati o rischi di interazione con altri farmaci.
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http://dx.doi.org/10.23736/S0026-4946.17.05159-3DOI Listing
February 2018

Vitamin B12, folate and homocysteine status in obese and atopic children: a preliminary study.

Minerva Pediatr 2018 04 31;70(2):201-202. Epub 2017 May 31.

Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.

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http://dx.doi.org/10.23736/S0026-4946.17.04955-6DOI Listing
April 2018

Vitamin D Deficiency and Glycemic Status in Children and Adolescents with Type 1 Diabetes Mellitus.

PLoS One 2016 8;11(9):e0162554. Epub 2016 Sep 8.

Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.

Background: Vitamin D (25OHD) effects on glycemic control are unclear in children and adolescents with type 1 diabetes. Aims of this study were to investigate 25OHD status among children with T1DM and its relationship with insulin sensitivity and glycemic status.

Subjects And Methods: A cross sectional study was carried out between 2008-2014. A total of 141 patients had a T1DM >12 months diagnosis and were enrolled in the present study. Of these 35 (24.8%) were migrants and 106 (75.2%) Italians (T2). We retrospectively analyzed data at the onset of the disease (T0)(64 subjects) and 12-24 months before the last visit (T1,124 subjects). Fasting glucose, glycated hemoglobin (HbA1c), 25OHD levels and daily insulin requirement were evaluated and Cholecalciferol 1000 IU/day supplementation for the management of vitamin D insufficiency (<75 nmol/L) was systematically added.

Results: A generalized 25OHD insufficiency was found at each study time, particularly in migrants. At T0, the 25OHD levels were inversely related to diabetic keto-acidosis (DKA) severity (p<0.05). At T1 and T2, subjects with 25OHD ≤25nmol/L (10 ng/mL) showed higher daily insulin requirement (p<0.05) and HbA1c values (p<0.01) than others vitamin D status. The 25OHD levels were negatively related with HbA1c (p<0.001) and daily insulin dose (p<0.05) during follow up. There was a significant difference in 25OHD (p<0.01) between subjects with different metabolic control (HbA1c <7.5%,7.5-8%,>8%), both at T1 and T2. In supplemented subjects, we found a significant increase in 25OHD levels (p<0.0001) and decrease of HbA1c (p<0.001) between T1 and T2, but this was not significant in the migrants subgroup. Multivariate regression analysis showed a link between HbA1c and 25OHD levels (p<0.001).

Conclusions: Children with T1DM show a generalized 25OHD deficiency that impact on metabolic status and glycemic homeostasis. Vitamin D supplementation improves glycemic control and should be considered as an additional therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162554PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015862PMC
August 2017

High Prevalence of Vitamin D Deficiency in Native versus Migrant Mothers and Newborns in the North of Italy: A Call to Act with a Stronger Prevention Program.

PLoS One 2015 11;10(6):e0129586. Epub 2015 Jun 11.

Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy; IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.

Background: Vitamin D status during pregnancy is related to neonatal vitamin D status. Vitamin D deficiency has been associated with an increased risk of rickets in children and osteomalacia in adults. Aim of this study was to investigate 25OHD levels in maternal serum and in neonatal blood spots in native and migrant populations living in Novara (North Italy, 45°N latitude).

Methods And Findings: We carried out a cross sectional study from April 1st 2012 to March 30th 2013, in a tertiary Care Center. Maternal blood samples after delivery and newborns' blood spots were analyzed for 25OHD levels in 533 pairs. Maternal country of origin, skin phototype, vitamin D dietary intake and supplementation during pregnancy were recorded. Multivariate regression analysis, showed a link between neonatal and maternal 25OHD levels (R-square:0.664). Severely deficient 25OHD values (<25 nmol/L) were found in 38% of Italian and in 76.2% of migrant's newborns (p <0.0001), and in 18% of Italian and 48,4% of migrant mothers (p <0.0001) while 25OHD deficiency (≥25 and <50 nmol/L) was shown in 40.1% of Italian and 21.7% of migrant's newborns (p <0.0001), and in 43.6% of Italian and 41.3% of migrant mothers (p <0.0001). Italian newborns and mothers had higher 25OHD levels (34.4±19.2 and 44.9±21.2 nmol/L) than migrants (17.7±13.7 and 29.7±16.5 nmol/L; p<0.0001). A linear decrease of 25OHD levels was found with increasing skin pigmentation (phototype I 42.1 ±18.2 vs phototype VI 17.9±10.1 nmol/l; p<0.0001). Vitamin D supplementation resulted in higher 25OHD values both in mothers and in their newborns (p<0.0001).

Conclusions: Vitamin D insufficiency in pregnancy and in newborns is frequent especially among migrants. A prevention program in Piedmont should urgently be considered and people identified as being at risk should be closely monitored. Vitamin D supplementation should be taken into account when considering a preventative health care policy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129586PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466139PMC
May 2016

Vitamin D levels at birth and risk of type 1 diabetes in childhood: a case-control study.

Acta Diabetol 2015 Dec 28;52(6):1077-81. Epub 2015 May 28.

Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy.

Aims: To assess whether vitamin D levels at birth were associated with risk of having type 1 diabetes up to 10 years of age and the potential modifier effect of ethnic group.

Methods: The Piedmont Diabetes Registry and the Newborn Screening Regional data were linked to identify cases (n = 67 incident children aged ≤10 years at diabetes onset, 2002-2012) and up to five controls (n = 236) matched for birthday and ethnic group. Cards with neonatal blood spot were used and 25-hydroxyvitamin D(3) assessed with tandem mass spectroscopy.

Results: In conditional logistic regression, OR for unit increment of log vitamin D was 0.78 (95 % CI 0.56-1.10). Vitamin D was significantly lower in migrant than in Italian control newborn babies (p < 0.0001), and interaction between vitamin D and migrant status was statistically significant (p = 0.04). Compared to migrant newborns babies with vitamin D ≥ 2.14 ng/ml, migrants with lower levels had an OR of 14.02 (1.76-111.70), whereas no association was evident in Italians.

Conclusions: Our case-control study within the Piedmont Diabetes Registry showed no association between vitamin D levels at birth and risk of having type 1 diabetes up to 10 years of age, apart from the subgroup of migrant babies, which might have clinical implications if confirmed.
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http://dx.doi.org/10.1007/s00592-015-0772-6DOI Listing
December 2015

Effects of growth hormone (GH) therapy withdrawal on glucose metabolism in not confirmed GH deficient adolescents at final height.

PLoS One 2014 30;9(1):e87157. Epub 2014 Jan 30.

Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy ; Endocrinology, Department of Clinical and Experimental Medicine, University of Piemonte Orientale, Novara, Italy ; I.C.O.S. (Interdisciplinary Center for Obesity Study), Novara, Italy.

Context Objective: Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR).

Design Setting: We performed a longitudinal study (1 year) in a tertiary care center.

Methods: 23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%β, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR.

Results: In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMAβ and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMAβ, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01).

Conclusions: In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-β and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0087157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3907518PMC
September 2014

Obestatin levels are associated with C-peptide and antiinsulin antibodies at the onset, whereas unacylated and acylated ghrelin levels are not predictive of long-term metabolic control in children with type 1 diabetes.

J Clin Endocrinol Metab 2014 Apr 17;99(4):E599-607. Epub 2014 Jan 17.

Division of Pediatrics (F.P., F.C., S.B., S.M., E.P., S.S., G.B.), Department of Health Sciences, Division of Endocrinology (F.P.), Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy; and Interdisciplinary Center for Obesity Study (F.P., S.B., G.B.), Interdisciplinary Research Center of Autoimmune Diseases (F.C., G.B.), and Division of Endocrinology, Diabetology, and Metabolism (L.T.), Department of Medical Sciences, University of Torino, 10126 Torino, Italy.

Context And Objective: Ghrelin secretion is altered at the onset and after the start of insulin therapy in children with type 1 diabetes. Contemporary regulation of acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (OBST) remains undefined in this disease. It is unknown as to whether they could be good predictors of changes in glucose and metabolic control.

Design, Setting, And Subjects: This was a longitudinal study conducted in a tertiary care center. AG, UAG, and OBST were measured at baseline and after 2 years of follow-up in 51 children and adolescents with a history of type 1 diabetes extending beyond 1 year. A total of 33 healthy matched subjects were used as controls.

Results: Age-, puberty-, and body mass index-adjusted UAG levels were lower (P < .005) and OBST levels were higher (P < .009) in children with type 1 diabetes, with respect to controls. AG levels were similar to controls, but all ratios of the three peptides are altered in diabetic patients. OBST (P < .05) was negatively correlated with C-peptide (P < .05) and insulin antibodies (P < .008) at the onset of diabetes. In diabetic patients, baseline AG and UAG levels were negatively correlated with insulin dosage in the short and long term (P < .001). AG, but not OBST, was positively correlated with C-peptide levels 2 years after diagnosis (P < .05). Overall, the peptides were not predictive of glucose and metabolic control.

Conclusions: UAG, AG, OBST, and their ratios are differently regulated in children with type 1 diabetes, suggesting a role in the metabolic balance of the disease, with insulin a likely regulator of AG and UAG. The peptides do not appear to be good long-term predictors of glucose control, with further investigations needed to explain whether OBST could be a precocious predictor of islet dysfunction.
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http://dx.doi.org/10.1210/jc.2013-3294DOI Listing
April 2014

Increasing burden, younger age at onset and worst metabolic control in migrant than in Italian children with type 1 diabetes: an emerging problem in pediatric clinics.

Acta Diabetol 2014 Apr 25;51(2):263-7. Epub 2013 Sep 25.

Division of Pediatrics, Department of Health Sciences, Università del "Piemonte Orientale Amedeo Avogadro", Novara, Italy.

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.
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http://dx.doi.org/10.1007/s00592-013-0514-6DOI Listing
April 2014

Vitamin D status in cord blood and newborns: ethnic differences.

Ital J Pediatr 2013 Jun 4;39:35. Epub 2013 Jun 4.

Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy.

Background: A deficiency in vitamin D (25OHD) is common throughout the world in both adults and children, being related to skin pigmentation, sun exposure, dietary intake and obesity. Limited data are available for the neonatal age. The aim of the study is to understand the differences in 25OHD levels with respect to skin colour and ethnicity in newborns.

Methods: We randomly enrolled 62 neonates, born at term and appropriate for gestational age. Thirty two were born from Italian mothers with fair skin (FS) and 30 from non-Caucasian mothers (North African, African, Asian and Latin American): 10 with light olive/light brown (LOB) and 20 with medium brown/black skin (MBB). Vitamin D was measured in the cord blood at birth and in neonatal serum during metabolic screening.

Results: 25OHD levels were (mean ± SD) 21.4 ± 11 ng/ml in cord blood and 14.9 ± 7 ng/ml in serum after birth. 25OHD values were higher in cord blood (p < 0.01) and neonatal serum (p < 0.001) in subjects supplemented with Vitamin D. Newborn FS showed higher vitamin D levels in cord blood when compared to LOB and MBB (p < 0.01), and higher levels in neonatal serum when compared to LOB (p < 0.01). In cord blood, 25OHD levels were higher in Italian newborns than in North African (p < 0.004) and African (p < 0.01). In neonatal serum, 25OHD levels were higher in Italian infants only when compared with North African infants (p < 0.03).

Conclusions: The present study shows a high prevalence of vitamin D insufficiency and deficiency in newborns with significant differences observed to be due to ethnicity, skin colour and maternal supplementation during the pregnancy.
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http://dx.doi.org/10.1186/1824-7288-39-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685533PMC
June 2013

Traumatic brain injury-induced hypopituitarism in adolescence.

Pituitary 2005 ;8(3-4):255-7

Unit of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale Amedeo Avogadro, Novara, Italy.

Childhood hypopituitarism may be present at birth or may be acquired. Young children and teenagers are particularly susceptible to TBI; in fact TBI is one of the first causes of death and disability in children older than one month of age since the most common cause of TBI is car crashes, including pedestrian-car and bicycle-car encounters, falls, child abuse, violence and sports injuries. Furthermore younger kids are more likely to have TBI due to falls while teenagers have more TBI than any other population from motor vehicle crashes. As reported for the adult patients hypopituitarism in adolescence should be suspected within an appropriate clinical context. In adolescents affected by TBI no experience about this condition has been reported but it is well known that treatment of hypopituitarism, in particular of GH deficiency, has multiple beneficial effects in addition to its promotion of linear growth and in particular in the transition phase. These include maintenance of normal body composition, structure function and metabolism through adult life. Therefore, the onset of TBI-induced GH deficiency in this particular phase of life should be strictly evaluated and corrected for the possible adult health consequences.
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http://dx.doi.org/10.1007/s11102-006-6050-4DOI Listing
October 2007
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