Patrizia Ippolita Patera

A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

BACKGROUND AND AIMS A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. PATIENTS AND METHODS We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. RESULTS In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. CONCLUSION Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

Obese children with low birth weight demonstrate impaired β-cell function during oral glucose tolerance test.

OBJECTIVE Epidemiological studies have shown an association between birth weight and future risk of type 2 diabetes, with individuals born either small or large for gestational age at increased risk. We sought to investigate the influence of birth weight on the relation between insulin sensitivity and beta-cell function in obese children. SUBJECTS AND METHODS A total of 257 obese/overweight children (mean body mass index-sd score, 2.2 +/- 0.3), aged 11.6 +/- 2.3 yr were divided into three groups according to birth weight percentile: 44 were small for gestational age (SGA), 161 were appropriate for gestational age (AGA), and 52 were large for gestational age (LGA). Participants underwent a 3-h oral glucose tolerance test with glucose, insulin, and C-peptide measurements. Homeostasis model of assessment for insulin resistance, insulinogenic index, and disposition index were calculated to evaluate insulin sensitivity and beta-cell function. Glucose and insulin area under the curve (AUC) were also considered. One-way ANOVA was used to compare the three groups. RESULTS SGA and LGA subjects had higher homeostasis model of assessment for insulin resistance than AGA subjects, but they diverged when oral glucose tolerance test response was considered. Indeed, SGA subjects showed higher glucose AUC and lower insulinogenic and disposition indexes. Insulin AUC was not different between groups, but when singular time points were considered, SGA subjects had lower insulin levels at 30 min and higher insulin levels at 180 min. CONCLUSIONS SGA obese children fail to adequately compensate for their reduced insulin sensitivity, manifesting deficit in early insulin response and reduced disposition index that results in higher glucose AUC. Thus, SGA obese children show adverse metabolic outcomes compared to AGAs and LGAs.

Use of metformin in pediatric age

Brufani C, Fintini D, Nobili V, Patera PI, Cappa M, Brufani M. Use of metformin in pediatric age.

Basal insulin supplementation in Type 1 diabetic children: A long-term comparative observational study between continuous subcutaneous insulin infusion and glargine insulin

No long-term data are available on the efficacy of glargine insulin in comparison with continuous sc insulin infusion (CSII) in children and adolescents affected by Type 1 diabetes (T1D). Our aim was to compare the 2-yr efficacy of the 2 insulin approaches, in order to know how to best supply basal insulin in these patients. Thirty-six 9 to 18-yr-old consecutive children with at least 3 yr previous T1D diagnosis were enrolled. As part of routine clinical care, the patients consecutively changed their previous insulin scheme (isophane insulin at bedtime and human regular insulin at meals) and were randomly selected in order to receive either multiple daily injections (MDI) treatment with once-daily glargine and human regular insulin at meals, or CSII with aspart or lispro insulin. Both groups showed a significant decrease in glycosylated hemoglobin (HbA1c) values during the 1st year of therapy, though only in the CSII treated children was the decrease also observed during the 2nd year. The overall insulin requirement significantly decreased only in the CSII group and exclusively during the 1st year, while no significant differences were observed concerning body mass index SD score, severe hypoglycémic episodes and basal insulin supplementation. The work illustrates the first long-term study comparing the efficacy of CSII to MDI using glargine as basal insulin in children. Only with CSII were better HbA1c values obtained for prolonged periods of time, so that CSII might be considered the gold standard of intensive insulin therapy also for long-term follow-ups.

Monogenic Diabetes Accounts for 6.3% of Cases Referred to 15 Italian Pediatric Diabetes Centers During 2007 to 2012

Context An etiologic diagnosis of diabetes can affect the therapeutic strategy and prognosis of chronic complications. Objective The aim of the present study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers and the influence of an etiologic diagnosis on therapy. Design, Setting, and Patients This was a retrospective study. The clinical records of 3781 consecutive patients (age, 0 to 18 years) referred to 15 pediatric diabetes clinics with a diagnosis of diabetes or impaired fasting glucose from January 1, 2007 to December 31, 2012 were examined. The clinical characteristics of the patients at their first referral to the centers, type 1 diabetes-related autoantibodies, molecular genetics records, and C-peptide measurements, if requested for the etiologic diagnosis, were acquired. Main Outcome Measures The primary outcome was to assess the percentage of each diabetes subtype in our sample. Results Type 1 diabetes represented the main cause (92.4%) of diabetes in this group of patients, followed by monogenic diabetes, which accounted for 6.3% of cases [maturity onset diabetes of the young (MODY), 5.5%; neonatal diabetes mellitus, 0.6%, genetic syndromes, 0.2%]. A genetic diagnosis prompted the transfer from insulin to sulphonylureas in 12 patients bearing mutations in the HNF1A or KCNJ11 genes. Type 2 diabetes was diagnosed in 1% of the patients. Conclusions Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. A genetic diagnosis guided the therapeutic decisions, allowed the formulation of a prognosis regarding chronic diabetic complications for a relevant number of patients (i.e.,GCK/MODY), and helped to provide genetic counseling.

Incidence of Type 1 Diabetes Has Doubled in Rome and the Lazio Region in the 0- to 14-Year Age-Group: A 6-Year Prospective Study (2004–2009)

Incidence of type 1 diabetes is rising, especially among younger children (1,2). We evaluated type 1 diabetes incidence in the years 2004–2009 among subjects <15 years of age residing in Rome and in its region (Lazio). Primary ascertainment was based in diabetes clinics and specialized hospitals, whereas secondary independent ascertainment was from the archives where all patients register to receive free medications within the National Health System. We identified 666 subjects (369 males and 297 females) with type 1 diabetes (American Diabetes Association criteria diagnosed by a pediatrician/diabetologist). All but 10 patients (1.5%) were Caucasians; 95% of patients tested positive for at least one autoantibody (insulin autoantibody, GAD antibody, or insulinoma-associated protein 2 [IA2]), 175 children …

Can HbA1c combined with fasting plasma glucose help to assess priority for GCK-MODY vs HNF1A-MODY genetic testing?

Maurizio Delvecchio1 · Giuseppina Salzano2 · Clara Bonura3 · Vittoria Cauvin4 · Valentino Cherubini5 · Giuseppe d’Annunzio6 · Adriana Franzese7 · Sabrina Giglio8 · Valeria Grasso9 · Vanna Graziani10 · Dario Iafusco11 · Lorenzo Iughetti12 · Riccardo Lera13 · Claudio Maffeis14 · Giulio Maltoni15 · Vilma Mantovani16 · Claudia Menzaghi17 · Patrizia I. Patera18 · Ivana Rabbone19 · Petra Reindstadler20 · Sabrina Scelfo21 · Nadia Tinto22 · Sonia Toni23 · Stefano Tumini24 · Fortunato Lombardo2 · Antonio Nicolucci25 · Fabrizio Barbetti9,26 · The Diabetes Study Group of the Italian Society of Pediatric Endocrinology and Diabetes (ISPED)

Pre-diabetes in Italian obese children and youngsters

Background and Aim: Metabolic characteristics and rate of progression to overt Type 2 diabetes (T2D) in low-risk European obese children are not well documented. Aim of the study was to investigate differences in insulin sensitivity and secretion in Italian obese children and youngsters with pre-diabetes. Methods: Ninety-six obese children and youngsters with pre-diabetes, pair-matched with individuals with normal glucose tolerance (NGT) were included in the present study. Participants were screened by oral glucose tolerance. Pre-diabetes was classified as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and combined IFG-IGT. Homeostasis model assessment of insulin resistance (HOMA-IR), 2-h insulin, insulin sensitivity index (ISI) and disposition index (DI) were calculated to estimate fasting, peripheral and whole body insulin sensitivity and capacity of pancreatic islets to compensate for lower insulin sensitivity, respectively. One-way analysis of variance was used to compare groups. Results: Eleven subjects had IFG (11.5%), 79 IGT (82.3%), 6 combined IFG-IGT (6.3%). Individuals with IFG showed the highest HOMA-IR (p=0.0007), those with IGT the highest 2-h insulin (p<0.0001), those with IFG-IGT the lowest ISI (p<0.0001), with severely reduced DI (p=0.0003). Compared with NGT, DI was 60% lower in those with IFG-IGT. Conclusion: IFG is linked primarily to fasting insulin resistance, IGT to peripheral insulin resistance. IFG-IGT is hallmarked by reduced whole body insulin sensitivity and an additional severe defect in DI. Further longitudinal studies are needed to understand wheteher the different categories of pre-diabetes in European obese adolescents represent real pre-diabetic alterations.