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.

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.

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.

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.

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.

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.

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.

Carbohydrate counting with an automated bolus calculator helps to improve glycaemic control in children with type 1 diabetes using multiple daily injection therapy: an 18-month observational study.

AIMS: This study aimed to investigate the effect of carbohydrate counting (carbC), with or without an automated bolus calculator (ABC), in children with type 1 diabetes treated with multiple daily insulin injections. METHODS: We evaluated 85 children, aged 9-16 years, with type 1 diabetes, divided into four groups: controls (n=23), experienced carbC (n=19), experienced carbC+ABC (n=18) and non-experienced carbC+ABC (n=25). Glycated haemoglobin (HbA1c), insulin use, and glycaemic variability - evaluated as high blood glucose index (HBGI) and low blood glucose index (LBGI) - were assessed at baseline and after 6 and 18 months. RESULTS: At baseline, age, disease duration, BMI, HbA1c, insulin use, and HBGI (but not LBGI; p=0.020) were similar for all groups. After 6 months, HbA1c improved from baseline, although not significantly - patients using ABC (according to manufacturer's recommendations) HbA1c 7.14 ± 0.41% at 6 months vs. 7.35 ± 0.53% at baseline, (p=0.136) or without carbC experience HbA1c 7.61±0.62% vs. 7.95 ± 0.99% (p=0.063). Patients using ABC had a better HBGI (p=0.001) and a slightly worse LBGI (p=0.010) than those not using ABC. ABC settings were then personalised. At 18 months, further improvements in HbA1c were seen in children using the ABC, especially in the non-experienced carbC group (-0.42% from baseline; p=0.018). CONCLUSIONS: CarbC helped to improve glycaemic control in children with type 1 diabetes using multiple daily injections. ABC use led to greater improvements in HbA1c, HBGI and LBGI compared with patients using only carbC, regardless of experience with carbC.

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.

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 ß-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.

Six cases with severe insulin resistance (SIR) associated with mutations of insulin receptor: Is a Bartter-like syndrome a feature of congenital SIR?

Biallelic insulin receptor (INSR) gene mutations cause congenital syndromes of severe insulin resistance (SIR) known as Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). At presentation, DS and RMS are difficult to differentiate since they share many clinical features; however, while patients with DS usually die within 1 year of birth, individuals classified as RMS can reach adult age. INSR mutations can be also found in pubertal females with hyperinsulinism, hyperandrogenism, and acanthosis nigricans (type A SIR). We studied the INSR gene in five subjects with congenital SIR and in a patient with type A SIR. Nine biallelic INSR gene mutations (eight novels, including an in-frame deletion of INSR signal peptide) were identified in patients with congenital SIR; a heterozygous, spontaneous INSR mutation was detected in the patient with type A SIR. Two probands, presenting severe hirsutism at birth, died at the age of 3 months and were classified as DS, while other 2, currently 2 and 3 years old, were diagnosed with RMS (patients 3 and 4). The fifth patient with congenital SIR died when 14 months old. Nephrocalcinosis, hyperaldosteronism, hyperreninemia, and hypokalemia, in the absence of hypertension, were discovered in patients 3 and 5 when 24 and 4 months old, respectively. Patient 3, now 3 years/3 months old, still shows hyperreninemic hyperaldosteronism requiring potassium supplementation. We conclude that renal abnormalities resembling antenatal Bartter's syndrome type II, recently reported also by others, is a common observation in patients with congenital SIR.

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).

Sensor-augmented pump therapy in very young children with type 1 diabetes: an efficacy and feasibility observational study.

BACKGROUND: Efficacy and feasibility of sensor-augmented pump (SAP) therapy were evaluated in very young children with type 1 diabetes (T1D). SUBJECTS AND METHODS: SAP (Dexcom [San Diego, CA] Seven Plus™ usage combined with insulin pump) therapy was retrospectively evaluated in 28 children (15 boys) younger than 7 years (mean age, 5.8 ± 1.2 years; range, 3-7 years), with T1D. Glycosylated hemoglobin (HbA1c) was evaluated at baseline and at the end of the study, as were efficacy and feasibility of the system, using a rating scale (with 3 being the most positive). RESULTS: SAP has been used for at least 6 months by 85% of patients, with an overall good satisfaction (92%). The greatest perceived benefit was the reduced fear of hypoglycemia (score of 3, 81%). HbA1c significantly improved only in patients with baseline HbA1c >7.5% (P = 0.026). CONCLUSIONS: SAP therapy is effective and feasible in preschool children with T1D. In patients with high HbA1c at baseline it provide a 0.9% decrease, sustained for at least 6 months.

Infant and toddler type 1 diabetes: complications after 20 years' duration.

OBJECTIVE: To compare the effect of the prepubertal duration of diabetes on the occurrence of complications in two groups of patients after the same number of years of the disease. RESEARCH DESIGN AND METHODS: This multicenter study enrolled 105 patients aged 16-40.3 years; 53 were prepubertal at diagnosis (aged 0-3) and 52 were pubertal (Tanner stage) and aged 9-14.9. The mean duration of disease was 19.8 and 19.5 years for prepubertal and pubertal patients, respectively. In all patients, retinal photographs were taken and centrally graded. Urinary albumin excretion (UAE; 86 case subjects), blood pressure (BP; 89 case subjects), and lifetime HbA(1c) (72 case subjects) were also evaluated. RESULTS: The prevalence of diabetic retinopathy (DR) was higher in pubertal than in prepubertal patients, both for any grade DR (71 vs. 40%, P = 0.002) and for mild or more severe DR (P = 0.005). The prevalence of abnormal UAE was not different in the two groups. Hypertension was found only in three patients, all pubertal at diagnosis. In the small group with moderate-to-severe DR, lifetime HbA(1c) levels, as percentages above the upper normal reference value, were higher (P < 0.01) in prepubertal than in pubertal patients. CONCLUSIONS: If diabetes is diagnosed in infants or toddlers and the prepubertal duration of diabetes is very long, the patients seem to be protected against DR. This protection disappears if lifetime metabolic control is bad. Instead, when onset is at puberty, the DR risk is higher and less dependent on metabolic control and may be influenced by age-related factors, such as BP.

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.).

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.

Insulin pump therapy management in very young children with type 1 diabetes using continuous subcutaneous insulin infusion.

BACKGROUND: Compared to older children and adolescents very young patients with type 1 diabetes represent a unique population. We analyzed the age-dependent characteristics and parameters of continuous subcutaneous insulin infusion (CSII) in children under 6 years of age with type 1 diabetes. METHODS: We evaluated metabolic control and pump-dependent characteristics in 46 children with type 1 diabetes after 0.89 +/- 0.62 years of CSII. RESULTS: Metabolic control significantly improved after CSII initiation (glycosylated hemoglobin, 8.12 +/- 1.24% vs. 7.30 +/- 0.67%; P < 0.05), without increased risk for diabetic ketoacidosis or hypoglycemia. Interestingly, very young patients required bigger boluses than expected, especially in the morning and at the afternoon snack. CONCLUSIONS: These data support the need to personalize pump-dependent characteristics, especially in very young children with type 1 diabetes, in order to optimize CSII therapy in this unique age group of patients.

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.