Nutritional behavior in Italian and immigrant children.

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.

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus.

BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes. METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels. RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences. CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period. (Funded by Diamyd Medical and the Swedish Child Diabetes Foundation; ClinicalTrials.gov number, NCT00723411.).

Early life socioeconomic indicators and risk of type 1 diabetes in children and young adults.

OBJECTIVE: To examine the potential role of 2 early-life socioeconomic indicators, parental education, and crowding index, on risk of type 1 diabetes (T1DM) in patients up to age 29 years to test heterogeneity by age at onset according to the hygiene hypothesis. STUDY DESIGN: The study base was 330 950 individuals born from 1967 to 2006 who resided in the city of Turin at any time between 1984 and 2007. Data on their early life socioeconomic position were derived from the Turin Longitudinal Study; 414 incident cases of T1DM up to age 29 years were derived from the Turin T1DM registry. RESULTS: Socioeconomic indicators had opposing effects on risk of T1DM in different age at onset subgroups. In a Poisson regression model that included both socioeconomic indicators, there was a 3-fold greater risk of T1DM (relative risk 2.91, 95% CI 0.99-8.56) in children age 0-3 years at diagnosis living in crowded houses. In the 4- to 14-year subgroup, a low parental educational level had a protective effect (relative risk 0.50, 95% CI 0.29-0.84), and the effect of crowding nearly disappeared. In the 15- to 29-year subgroup, neither crowding nor parental educational level was clearly associated with the incidence of T1DM. CONCLUSIONS: We provide evidence of heterogeneity by age at onset of the association between early-life socioeconomic indicators and the risk of T1DM. This finding is consistent with the hypothesis that infectious agents in the perinatal period may increase the risk, whereas in the following years they may become protective factors (hygiene hypothesis).

Gut microbiota, behavior, and nutrition after type 1 diabetes diagnosis: A longitudinal study for supporting data in the metabolic control.

Introduction: Type 1 diabetes (T1D) risk involves genetic susceptibility but also epigenetics, environment, and behaviors. Appropriate metabolic control, especially quickly after the diagnosis, is crucial for the patient quality of life. Methods: This study aimed to produce a quantitative comparison of the behavior, nutrition habits, and gut microbiota composition between the onset and the 1-year follow-up in 35 children with T1D. Results and discussion: At follow-up, with the metabolic control, many parameters improved significantly, with respect to the onset, such as glycated hemoglobin (-19%), body mass index (BMI), and also nutritional behaviors, such as normal calorie intake (+6%), carbohydrate intake (-12%), extra portion request (-4%), and meals distribution during the day. Moreover, glycated hemoglobin decrement correlated with both total and rapid absorption carbohydrate intake (Spearman's rho = 0.288, 95% CI 0.066-0.510, p = 0.013), showing as the nutritional behavior supported the insulin therapy efficiency. The next-generation sequencing (NGS) analysis of microbiota revealed abundance differences for Ruminococcus bromii and Prevotella copri (higher at onset, p < 0.001) and the genera Succinivibrio and Faecalibacterium (lower at onset, p < 0.001), as a consequence of nutritional behavior, but it was not the only changing driver. The qRT-PCR analysis showed significant variations, in particular for Bacteroidetes and Bifidobacterium spp. (+1.56 log gene copies/g stool at follow-up, p < 0.001). During the year, in 11% of the patients, severe clinical episodes occurred (hypoglycemic or ketoacidosis). The likelihood of a severe hypoglycemic episode was modulated when the Methanobrevibacter smithii amount increased (odds ratio 3.7, 95% CI 1.2-11.4, p = 0.026). Integrated evaluation, including nutritional behavior and microbiota composition, could be considered predictive of the metabolic control management for children cohort with a recent diagnosis of T1D.

Pandemic influenza vaccination coverage in children with type 1 diabetes: analysis from seven Italian centers.

The pandemic influenza vaccination coverage in children with type 1 diabetes has been analysed. 1461 charts have been reviewed (788 M and 673 F, ages 13.0±4.1 yrs, disease duration 6.0±4.8 yrs, HbA1c 7.9±1.2%). Among them, 428 patients (29.3%) underwent A/H1N1 vaccination. A special effort is required to implement an increased immunization rate.

Continuous subcutaneous hydrocortisone infusion (CSHI) in a young adolescent with congenital adrenal hyperplasia (CAH).

Congenital adrenal hyperplasia (CAH) is an autosomal recessive enzymatic defect caused by mutations or deletions of the cytochrome P450 21-hydroxylase CYP21 gene. Oral therapy with glucocorticoids and mineralcorticoids is administered to prevent adrenal crisis and to control hyperandrogenism. During puberty this type of therapy is difficult to manage owing to physiological and hormonal changes and poor compliance. We describe a case of a pubertal boy affected by CAH, in whom continuous subcutaneous infusion of hydrocortisone led to improved metabolic control and compliance.

Enhanced expression of human endogenous retroviruses in new-onset type 1 diabetes: Potential pathogenetic and therapeutic implications.

Human endogenous retroviruses (HERVs) have been studied and proposed as relevant cofactors in several autoimmune diseases, including type 1 diabetes (T1D), though with controversial results and no study at disease onset. In order to gather further information on the potential role of HERVs in the development of T1D we assessed the transcription levels of pol genes of HERV-H, HERV-K, and HERV-W in peripheral leucocytes from 37 children and adolescents with new-onset T1D and 50 age-matched control subjects. A PCR real time Taqman amplification assay was used to evaluate HERV transcripts with normalisation of the results to glyceraldehyde-3-phosphate dehydrogenase. The expression levels of HERV-H-pol gene and HERV-W-pol gene were significantly higher in diabetic patients than in control subjects. Conversely, no significant difference emerged in the expression levels of HERV-K-pol gene between diabetic patients and controls. The activation of HERV-H and HERV-W in new-onset T1D suggests their importance in the pathogenesis of the disease and supports targeted therapeutic attempts to hinder their activation.

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

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.

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

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.

Early cardiovascular autonomic dysfunction, beta cell function and insulin resistance in obese adolescents.

AIMS: The aim of this study was to assess the metabolic and cardiovascular autonomic phenotype in adolescent obesity. METHODS: Eighteen non diabetic obese individuals and ten lean age-matched control adolescents were included in the study. All subjects underwent Oral Glucose Tolerance Test (OGTT) with insulin and glucose determination for the calculation of AUC, OGIS, QUICKI, and disposition index. Cardiovascular assessments included 24-hour Holter ECG for HRV measurements, ABP monitoring and echocardiography. RESULTS: Obese adolescents had higher serum lipids, reduced insulin sensitivity and higher insulin resistance. Obese individuals showed indeed a normal beta-cell function, with insulin AUC and disposition index similar to controls. However, obese adolescents presented a progressive reduction ofvagal indexes (RMSSD, HF) and an increase in sympathetic indexes (LF, LF/HF), which correlated with OGIS and beta-cell function parameters. CONCLUSION: Adolescent obesity is characterized by insulin resistance with normal beta-cell function. Metabolic modifications may lead to an early impairment of the autonomic pattern.

Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects.

Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the pore-forming subunit of the ATP-sensitive K(+) channel (K(ATP) channel), are a common cause of neonatal diabetes. We identified a novel KCNJ11 mutation, R50Q, that causes permanent neonatal diabetes (PNDM) without neurological problems. We investigated the functional effects this mutation and another at the same residue (R50P) that led to PNDM in association with developmental delay. Wild-type or mutant Kir6.2/SUR1 channels were examined by heterologous expression in Xenopus oocytes. Both mutations increased resting whole-cell currents through homomeric and heterozygous K(ATP) channels by reducing channel inhibition by ATP, an effect that was larger in the presence of Mg(2+). However the magnitude of the reduction in ATP sensitivity (and the increase in the whole-cell current) was substantially larger for the R50P mutation. This is consistent with the more severe phenotype. Single-R50P channel kinetics (in the absence of ATP) did not differ from wild type, indicating that the mutation primarily affects ATP binding and/or transduction. This supports the idea that R50 lies in the ATP-binding site of Kir6.2. The sulfonylurea tolbutamide blocked heterozygous R50Q (89%) and R50P (84%) channels only slightly less than wild-type channels (98%), suggesting that sulfonylurea therapy may be of benefit for patients with either mutation.

Incidence of type 1 and type 2 diabetes in adults aged 30-49 years: the population-based registry in the province of Turin, Italy.

OBJECTIVE: Incidence of type 1 diabetes is considered to be low in adults, but no study has been performed in Mediterranean countries. RESEARCH DESIGN AND METHODS: We extended the study base of the registry of the province of Turin, Italy, to subjects aged 30-49 years in the period 1999-2001 to estimate the incidences of type 1 and type 2 diabetes. Diagnosis of type 1 diabetes was based on permanent insulin treatment or a fasting C-peptide level < or =0.20 nmol/l or islet cell (ICA) or GAD (GADA) antibody positivities. RESULTS: We identified 1,135 case subjects with high completeness of ascertainment (99%), giving an incidence rate of 58.0 per 100,000 person-years (95% CI 54.7-61.5). The incidence of type 1 diabetes was 7.3 per 100,000 person-years (6.2-8.6), comparable with the rates in subjects aged 0-14 and 15-29 years (10.3 [9.5-11.2] and 6.8 [6.3-7.4]). Male subjects had a higher risk than female subjects for both type 1 (rate ratio [RR] 1.70 [95% CI 1.21-2.38]) and type 2 (2.10 [1.84-2.40]) diabetes. ICA and/or GADA positivities were found in 16% of the cohort. In logistic regression, variables independently associated with autoimmune diabetes were age 30-39 years (odds ratio [OR] 2.39 [95% CI 1.40-4.07]), fasting C-peptide <0.60 nmol/l (3.09 [1.74-5.5]), and BMI <26 kg/m2 (2.17 [1.22-3.85]). CONCLUSIONS: Risk of type 1 diabetes between age 30 and 49 years is similar to that found in the same area between age 15 and 29 years. Further studies are required to allow geographical comparisons of risks of both childhood and adulthood autoimmune diabetes, the latter being probably higher than previously believed.

Residual beta-cell function and male/female ratio are higher in incident young adults than in children: the registry of type 1 diabetes of the province of Turin, Italy, 1984-2000.

OBJECTIVE: The hypothesis of age-dependent variations in epidemiologic and clinical features at onset of type 1 diabetes has been assessed in the registry of the province of Turin, Italy. RESEARCH DESIGN AND METHODS: The study base is the population 0-29 years of age of the province of Turin, in the period from 1984 to 2000. Islet cell antibody (ICA), GAD antibody (GADA), antibodies to protein tyrosine phosphatase (IA2), and C-peptide were measured in subgroups of the cohort. RESULTS: One thousand fifty-six incident cases have been identified (completeness of ascertainment 98.1%). Rates per 100,000 person-years were similar in males and females in the age-group 0-14 years (10.7, 95% CI 9.5-12.0 vs. 9.8, 8.6-11.1). In the age-group 15-29 years, males had higher risk than females (7.7, 6.9-8.6 vs. 5.3, 4.6-6.1; rate ratio, 1.46, 95% CI 1.23-1.74; P = 0.00002). Fasting plasma C-peptide values (n = 575) were twofold lower in the age-group 0-14 years than in the age-group 15-29 years (0.10 vs. 0.23 nmol/l; P < 0.0001). Frequencies of ICA and IA2 positivities (n = 183) decreased with increasing age, whereas frequency of GADA positivity increased. Idiopathic cases were 12.6% and had higher mean values of fasting (0.28 vs. 0.14 nmol/l; P = 0.043) and stimulated C-peptide (0.59 vs. 0.34 nmol/l; P = 0.05). In logistic regression analyses, subjects with fasting C-peptide values in the upper quartile had higher likelihood of being older (odds ratio 1.20 for year, 95% CI 1.11-1.28), ICA negative (0.26, 0.10-0.70), and female (1.29, 0.48-3.42). CONCLUSIONS: This study shows 1) sex differences in incidence rates in young adults; 2) better preserved beta-cell function in young adults, in idiopathic cases (12%), and in ICA-negative cases; and 3) lower frequencies of ICA and IA2 positivities and higher frequency of GADA positivity in young adults than in children.

Successful treatment of young infants presenting neonatal diabetes mellitus with continuous subcutaneous insulin infusion before genetic diagnosis.

AIMS: Neonatal diabetes mellitus (NDM) is defined as hyperglycemia and impaired insulin secretion with onset within 6 months of birth. While rare, NDM presents complex challenges regarding the management of glycemic control. The availability of continuous subcutaneous insulin infusion pumps (CSII) in combination with continuous glucose monitoring systems (CGM) provides an opportunity to monitor glucose levels more closely and deliver insulin more safely. METHODS: We report four cases of young infants with NDM successfully treated with CSII and CGM. Moreover, in two cases with Kir 6.2 mutation, we describe the use of CSII in switching therapy from insulin to sulfonylurea treatment. RESULTS: Insulin pump requirement for the 4 neonatal diabetes cases was the same regardless of disease pathogenesis and c-peptide levels. No dilution of insulin was needed. The use of an integrated CGM system helped in a more precise control of BG levels with the possibility of several modifications of insulin basal rates. Moreover, as showed in the first two case-reports, when the treatment was switched from insulin to glibenclamide, according to identification of Kir 6.2 mutation and diagnosis of NPDM, the CSII therapy demonstrated to be helpful in allowing gradual insulin suspension and progressive introduction of sulfonylurea. CONCLUSIONS: During the neonatal period, the use of CSII therapy is safe, more physiological, accurate and easier for the insulin administration management. Furthermore, CSII therapy is safe during the switch of therapy from insulin to glibenclamide for infants with permanent neonatal diabetes mellitus.

Ketoacidosis at diagnosis in childhood-onset diabetes and the risk of retinopathy 20years later.

AIMS: To investigate on the relationship between severity of ketoacidosis, an important risk factor for C-peptide preservation, and long-term microvascular complications in childhood-onset type 1 diabetes mellitus (T1DM). METHODS: 230 childhood-onset diabetic patients (177 pre-pubertal), aged 7.0±3.8years followed for at least 15years after their diagnosis, were enrolled. Clinical and laboratory data at diagnosis, and C-peptide levels in a subset of patients, were compared with the severity of retinopathy and nephropathy, after a mean of 19.6±3.8years of disease. Digital retinal photographs were taken in all patients, and centrally graded. Repeated measurements of HbA1c and microalbuminuria for the whole duration of diabetes were collected in over half of the cases. RESULTS: Out of 230 patients, those with the lowest age at diagnosis had the most severe DKA and clinical conditions (p<0.05), and lower C-peptide levels (p<0.0001) at diagnosis. There was a significant relationship between pH and clinical severity (r=-0.783, p<0.0001), and between pH and C-peptide levels (r=0.278, p<0.05). The severity of ketoacidosis had no relationship with subsequent lifetime HbA1c values and long-term microvascular complications. In logistic regression analysis, the only variables that independently influenced severity of retinopathy were lifetime HbA1c (B=0.838, p<0.001), duration of disease (B=0.208, p<0.005) and age at diagnosis (B=0.116, p<0.05). CONCLUSIONS: The degree of metabolic derangement at diagnosis is not associated with retinopathy and nephropathy in childhood-onset T1DM. Age at diagnosis seems to be an important variable to be considered when evaluating the long-term effects of residual beta-cell function.

KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.

Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (K(ATP)) channel of the pancreatic beta-cell, were found in patients with PNDM. Closure of the K(ATP) channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes.

Role of health care providers in educational training of patients with diabetes.

Diabetes mellitus is a high prevalence chronic disease, in which several health care providers are involved in the treatment of patients. Multifaceted professional and organizational interventions that facilitate structured and regular review of patients are effective in improving the process of care. Moreover, patient education and enhancement of role of nurses improve clinical outcomes and process of care. As diabetic management requires strict commitment of the patients, their educational therapy is mandatory. Therapeutic Patient Education (TPE) is a continous process, integrated in health care; it is a permanent care process, patient-centred, that must be adapted to the evolution of illness and to the patient's lifestyle; TPE must be structured and organized and it should receive benefits from the appropriate pedagogic means. Since the publication of DCCT data it was clear that intensive insulin therapy had been successfully applied only in centers where a diabetologist, a specialized nurse, a dietician, a psycologist and a motivated patient worked all together, i.e. where there was a "team". The team has to follow a pedagogic, multidisciplinary and patient-centred methodology of care. Well structured integration between health care providers may help to avoid the burn-out syndrome.

Younger age at onset and sex predict celiac disease in children and adolescents with type 1 diabetes: an Italian multicenter study.

OBJECTIVE: To estimate the prevalence of biopsy-confirmed celiac disease in Italian children and adolescents with type 1 diabetes and to assess whether age at onset of type 1 diabetes is independently associated with diagnosis of celiac disease. RESEARCH DESIGN AND METHODS: The study group was a clinic-based cohort of children and adolescents with type 1 diabetes cared for in 25 Italian centers for childhood diabetes. Yearly screening for celiac disease was performed using IgA/IgG anti-gliadin and IgA anti-endomysium antibodies. RESULTS: Of the 4,322 children and adolescents (age 11.8 +/- 4.2 years) identified with type 1 diabetes, biopsy-confirmed celiac disease was diagnosed in 292 (prevalence 6.8%, 95% confidence interval [CI] 6.0-7.6), with a higher risk seen in girls than in boys (odds ratio [OR] 1.93, 1.51-2.47). In 89% of these, diabetes was diagnosed before celiac disease. In logistic regression analyses, being younger at onset of diabetes, being female, and having a diagnosis of a thyroid disorder were independently associated with the risk of having diabetes and celiac disease. In comparison with subjects who were older than 9 years at onset of diabetes, subjects who were younger than 4 years at onset had an OR of 3.27 (2.20-4.85). CONCLUSIONS: We have provided evidence that 1) the prevalence of biopsy-confirmed celiac disease in children and adolescents with type 1 diabetes is high (6.8%); 2) the risk of having both diseases is threefold higher in children diagnosed with type 1 diabetes at age <4 years than in those age >9 years; and 3) girls have a higher risk of having both diseases than boys.

Case Report: When an Induced Illness Looks Like a Rare Disease.

The recognition of fabricated illness (FI) in a child represents a diagnostic challenge. The suspicion of FI often arises from the discrepancy between laboratory tests and clinical history. For instance, (unnecessary) insulin injections by caregivers has been widely described as a common cause of factitious hypoglycemia that may be inferred from discrepancies between plasma insulin and c-peptide. However, contemporary administration of insulin with an insulin secretagogue (glyburide), and of additional drugs, can make the diagnostic pathway problematic. We report the case of a child 4 years and 11 months old, admitted for alternance of hypo- and hyperglycemia associated with hirsutism, hypokalemia, nephrocalcinosis, and neurodevelopmental delay. All these features were compatible with Rabson-Mendenhall syndrome, a rare disorder of severe insulin resistance linked to mutations of insulin receptor. At admission, plasma insulin levels were high during hypoglycemic episodes, but c-peptide was repeatedly in the normal range. The genetic analysis of insulin receptor was negative. The story of previous hospital admissions, inconsistency between insulin and c-peptide values, and association between hypoglycemic episodes in the child with the presence of the mother, raised the suspicion of FI. This hypothesis was confirmed by a video recording that revealed the administration by the mother of multiple drugs (insulin, glyburide, progesterone, and furosemide) that mimicked most of the features of Rabson-Mendenhall syndrome, including hirsutism and hypoglycemia with coincident, inappropriately normal c-peptide values due to the administration of the insulin secretagogue. Our case indicates that inconsistency among consecutive diagnostic tests should be regarded as a clue of FI.

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

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.