Diet, physical, and biochemical characteristics of children and adolescents with type 1 diabetes: relationship between dietary fat and glucose control.

BACKGROUND: Nutritional habits may significantly influence glycemic control and cardiovascular risk factors in youth with type 1 diabetes (T1D). AIMS: To assess dietary intake, cardiovascular risk factors, and the association between diet composition and glycemic control in Italian youth with T1D. METHODS: Subjects included 114 youth aged 6-16 yr with T1D receiving a routine treatment program with nutrition counseling and 448 controls. Cross-sectional measures included dietary intake, anthropometry, blood pressure, lipid profile, and, in children with diabetes, HbA1c. RESULTS: In prepubertal children, BMI, subcutaneous skinfolds, the prevalence of overweight/obesity, and LDL cholesterol (LDL-CH) were significantly lower in patients than in controls, whereas HDL cholesterol (HDL-CH) was higher. Pubertal boys with T1D did not differ significantly from controls in either anthropometry or lipid profile. Pubertal girls with T1D had a higher BMI and higher triceps skinfolds than controls but not significantly different prevalence of overweight/obesity or lipid profile. Compared to controls, participants with T1D had a lower intake of lipids and simple carbohydrates, a higher ratio of unsaturated/saturated fats and fibre, and a dietary intake closer to the National Reference Dietary Intakes (RDIs). The odds of having an HbA1c higher than 7.5, adjusted for BMI, lipid, and fibre intake, increases by 53% for every 1% increase of energy intake from saturated fat in the diet and by 30% for every year of duration of diabetes. CONCLUSIONS: Youth with T1D having regular nutritional counseling had a diet closer to RDIs than controls and not different cardiovascular risk factors. High saturated fatty acid intake was associated with poor blood glucose control.

Technical solution for data collection, data safety and data privacy legislation: experiences from the SWEET study.

BACKGROUND: One of the most important tasks of the SWEET study is benchmarking the data collected. Information on the occurrence of the disease of diabetes, the treatment, and their outcomes in children from the different member states of European Union (EU) is crucial. How the collection of data is realized is essential, concerning both the technical issues and the results. The creation of SWEET Centers of Reference (CoR), all over Europe will be facilitated by the access to safe data collection, where legal aspects and privacy are ascertained. OBJECTIVE: To describe the rationale for- and the technical procedure in the data collection implementation, in the SWEET study. SUBJECTS: Selected data on all patients treated at SWEET CoR are collected. METHODS: The SWEET project data collection and management system, consists of modular components for data collection, online data interchange, and a database for statistical analysis. CONCLUSION: The SWEET study and the organization of CoR aims for the goal of offering an updated, secure, and continuous evaluation of diabetes treatment regimens for all children with diabetes in Europe. To support this goal, an appropriate and secure data management system as described in this paper has been created.

The ALBA project: an evaluation of needs, management, fears of Italian young patients with type 1 diabetes in a school setting and an evaluation of parents' and teachers' perceptions.

OBJECTIVE: To determine how Italian parents and school personnel of 6-13-year-old children with type 1 diabetes (T1D) manage during school hours, including insulin administration, management of hypoglycemia, and glucagon use. A further aim was an investigation into the responsibilities and training of school personnel regarding diabetes. RESEARCH DESIGN AND METHODS: After an initial qualitative phase, semi-structured questionnaires were completed by a sample of parents and teachers. RESULTS: 220 parent and 52 teacher questionnaires were completed. 43.6% of parents said diabetes had negatively influenced school activities. Children either self-administer insulin, or have help from a parent, since there is very rarely a nurse present (3.6%) or a teacher who will take responsibility for the treatment (2.9%). Most parents (55.9%) stated either that the school had no refrigerator to store glucagon or that they did not know if the school was so equipped. A small percentage of teachers considered their schools to be equipped to manage an emergency (23%) and said they would use glucagon directly in an emergency (14.9%). Only 40.4% of teachers said that they had received any specific training. CONCLUSIONS: The study shows that people who are not directly involved have superficial knowledge of the different aspects of diabetes, even though no parents reported episodes of neglect/incorrect management. There is no legislation which clearly defines the role of the school in the care of children with T1D, and teachers are not trained to help them. Training sessions for school personnel and greater legislative clarity about the 'insulin and glucagon question' are key factors that may improve the full integration of the child with diabetes.

Insulin pump therapy in children and adolescents with type 1 diabetes: the Italian viewpoint.

BACKGROUND AND AIM: A panel of experts of the Italian Society of Paediatric Endocrinology and Diabetology translated into Italian the international insulin pump therapy recommendations in children and adolescents with type 1 diabetes. METHODS: After an extensive review of the literature using evidence-based recommendations, several issues were taken into account, such as patient selection, advantages and disadvantages, instrument choice, insulin type, therapy planning and follow-up, emergencies, nutrition, particular occasions (like parties, holidays, sick days, travels), exercise, continuous glucose monitoring and integrated system, neonatal diabetes. The panel evaluated the cost-effectiveness of insulin pump therapy compared to multiple daily injection therapy, analysing the cost-benefit ratio. RESULTS: Some tweak was needed due to the Italian dietetic singularity, meal schedule, climate and lifestyle. Insulin pump therapy in neonatal diabetes is a new issue and no guidelines have been published yet for this age-group. Moreover, legal issues according to the Italian law have been added and are peculiarity of our recommendations. An "informed therapeutic agreement" between the patient and his/her family and the diabetic team has to be signed before starting insulin pump therapy. CONCLUSIONS: We think that nowadays the need for clinical guidelines is important and worth the effort that all countries develop faithful adaptation into their local languages taking into account specific contexts and local peculiarities, without making substantial modifications to the original text.

Adiponectin/resistin levels and insulin resistance in children: a four country comparison study.

BACKGROUND: There are few reports on the effects of ethnicity or gender in the association between adipocytokines and insulin resistance in children of different ages. This study assessed associations between serum concentrations of adiponectin/resistin and parameters of insulin resistance in children from 4 different countries. METHODS: A total of 2,290 children were analyzed in this study; each was from one of 4 different countries (Japan, Thailand, Italy and USA), and grouped according to age (8-11 years old in Group 1 and 12-15 years old in Group 2). RESULTS: Adioponectin was higher in female than in male children, and in Group 1 than in Group 2. Generally, adiponectin was lower in Asian as compared to Italian and American children. These tendencies remained even after adjustment for body mass index (BMI) or waist circumstance (WC). Among older children (Group 2), resistin was higher in female than in male children. Significant correlations by non-parametric univariate correlation coefficients and Spearman's rank correlation coefficients were found between adiponectin and homeostasis model assessment of insulin resistance (HOMA-IR), and fasting serum insulin levels in young Japanese, Italian, and American female children(p < 0.01, p < 0.05, p < 0.05, respectively). Correlations between serum adiponectin and HOMA-IR were also found among older male Italian, American, and Thai children (p < 0.05, p < 0.001, p < 0.001, respectively). In multiple regression analysis by forced entry method, adiponectin correlated with HOMA-IR in Italian and American male children, and in all older female children regardless of country of origin. There was no correlation between resistin and markers of insulin resistance in children from any of the countries. CONCLUSIONS: We conclude that serum adiponectin concentrations are lower in Asian as compared to Italian and American children, and that adiponectin but not resistin contributes to differences in markers for insulin resistance in children from different populations.

Incomplete gastric metaplasia in children with insulin-dependent diabetes mellitus and celiac disease. An ultrastructural study.

BACKGROUND: The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. METHODS: We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. RESULTS: All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. CONCLUSIONS: The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia.

A novel synonymous substitution in the GCK gene causes aberrant splicing in an Italian patient with GCK-MODY phenotype.

GCK gene analysis in an Italian MODY patient revealed a novel synonymous substitution in exon 4 (c.459T>G; p.Pro153Pro) resulting in an aberrant transcript lacking the last eight codons of the same exon. Our findings emphazise the importance of not underestimating synonymous variations when screening for disease-causing mutations.

A high-fat vs. a moderate-fat meal in obese boys: nutrient balance, appetite, and gastrointestinal hormone changes.

Meal composition is a contributing factor to fat gain. In this study, we investigated the relationship between postprandial nutrient balance, satiety, and hormone changes induced by a high-fat meal vs. a moderate-fat meal. Ten prepubertal obese boys (BMI z-score range: 1.3-3.0) were recruited. Two meals (energy: 590 kcal) were compared: (i) high-fat (HF) meal: 12% protein, 52% fat, 36% carbohydrates; (ii) moderate-fat (MF) meal: 12% protein, 27% fat, 61% carbohydrates. Pre- and postprandial (5 h) substrate oxidation (indirect calorimetry), appetite (visual analogue scale), biochemical parameters and gastrointestinal hormone concentrations were measured. Carbohydrate balance was significantly (P < 0.001) lower (31.3 (5.7) g/5 h vs. 66.9 (5.9) g/5 h) and fat balance was significantly (P < 0.001) higher (11.5 (3.3) g/5 h vs. -0.7 (2.9) g/5 h) after HF than MF meal. Appetite (area under the curve (AUC)) was significantly reduced after an MF than an HF meal (494 (55) cm.300 min vs. 595 (57) cm.300 min, P < 0.05). Postprandial triglyceride concentration (AUC) was significantly (P < 0.05) higher after an HF than an MF meal: 141.1 (30.3) mmol.300 min/l vs. 79.3 (23.8) mmol.300 min/l, respectively. Peptide YY (PYY), cholecystokinin (CCK), and ghrelin concentrations (AUC) were not significantly different after an HF and MF meal. Glucagon-like peptide-1 (GLP-1) was significantly (P < 0.05) higher after an HF than after an MF meal (72.3 (9.8) ng/ml vs. 22.7 (7.6) ng/ml, respectively), but it did not affect subjective appetite. In conclusion, an MF meal induced a better postprandial metabolic nutrient balance, triglyceride levels, and appetite suppression than an HF meal. Gastrointestinal hormones were not related to clinically assessed hunger suppression after both meals.

Fasting plasma glucose (FPG) and the risk of impaired glucose tolerance in obese children and adolescents.

A timely diagnosis of impaired glucose tolerance (IGT) is desirable in obesity. The oral glucose tolerance test (OGTT), the gold standard to diagnose this condition, may not be realistically performed in all patients due to discomfort, labor, and cost. The aim of this study was to assess whether one or more biochemical indexes measured in fasting conditions could be used to identify obese children at risk of IGT. A cohort of 563 white obese children and adolescents (M/F: 315/248; aged 4-17 years) was recruited and underwent anthropometric evaluation and OGTT. Anthropometric parameters, fasting plasma glucose (FPG), fasting serum insulin (FSI), and homeostasis model assessment of insulin resistance (HOMA(IR)) were tested in pursuit of a possible threshold to be used as a predictor of IGT. Thirty-seven children (6.9%) had IGT and one child (0.1%) had type 2 diabetes (T2D). FPG, FSI, and HOMA(IR) were all significantly higher in children with IGT than in children without IGT. Receiver-operating characteristic (ROC) curve analyses run for gender and puberty-adjusted FPG, FSI, and HOMA(IR) were all significant: area under the curve (95% confidence interval) equaled 0.68 (0.59-0.76), 0.66 (0.56-0.76), and 0.68 (0.59-0.78), respectively. The three parameters did not show significantly different sensitivity/specificity in the pooled population or in the gender/puberty subgroups. Thresholds varied among gender/puberty subgroups for FSI and HOMA(IR), but not for FPG, which showed a fixed threshold of 86 mg/dl. A gender/puberty independent cutoff of FPG may be considered a screening tool to narrow clinical indication to OGTT in obese white children and adolescents.

Early detrimental metabolic outcomes of rs17300539-A allele of ADIPOQ gene despite higher adiponectinemia.

Minor allele A of single-nucleotide polymorphism (SNP) 11391 G/A of ADIPOQ gene (rs17300539) has been consistently associated with higher adiponectin levels in adults and children. The aim of this study was to investigate the metabolic role of this variant in a large cohort of children of European origin. A total of 1,852 children from two general populations in Verona and in Fleurbaix-Laventie and from the Lille childhood obesity cohort, were genotyped and pooled together after checking for the absence of genetic heterogeneity for rs17300539 between Italian and French children. The genotype of rs17300539 was studied in relation to circulating adiponectin levels, BMI, fasting plasma glucose, fasting serum insulin (FSI), insulin resistance index (homeostasis model assessment of insulin resistance (HOMA(IR))), high-density lipoprotein cholesterol, and triglycerides. After adjustment for known confounders, rs17300539 GA+AA carriers had 1.6 microg/ml higher adiponectin levels (P = 6 x 10(-8)) than GG carriers. They also showed higher BMI (B = 0.97, P = 0.015) and higher prevalence of obesity (OR = 1.35 (1.06-1.85), P = 0.015) than GG carriers. Before adjusting for obesity status, GA+AA carriers had higher FSI (B = 1.10, P = 0.040) and higher HOMA(IR) (B = 0.31, P = 0.020) than GG carriers. After adjustment for obesity status, they did not differ from GG carriers for any metabolic parameter, either among obese or nonobese children. The rs17300539-A variant, though consistently associated with higher adiponectin levels, does not exert any appreciable protective metabolic effect in children, either in the presence or absence of obesity. In contrast, this SNP may increase the risk for childhood obesity and related insulin resistance.

The Q121 variant of ENPP1 may protect from childhood overweight/obesity in the Italian population.

Ectonucleotide Pyrophosphatase Phosphodiesterase 1 (ENPP1) downregulates insulin signaling by inhibiting the insulin receptor's tyrosine-kinase. K121Q and other ENPP1 single-nucleotide polymorphisms (SNPs), IVS20delT-11 and A/G+1044TGA, have been previously associated with obesity in French children, and the risk haplotype QdelTG has also been associated with this condition in both French and German children. Our aim was to perform a case-control replication study in order to assess the possible association of childhood obesity and overweight with the above-mentioned ENPP1 SNPs, and with the QdelTG haplotype, in the Italian population. A total of 865 healthy Italian children were studied: 453 normal-weight, 243 overweight and 169 obese subjects. Genotyping was performed by Taq-Man or Light-Cycler Technology. The Q variant of K121Q showed a negative association with overweight-obesity under both additive (odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.57-0.97, P = 0.030) and recessive (OR = 0.32, 95% CI = 0.10-0.97, P = 0.035) modes of inheritance. The Z-score of BMI showed a significant decreasing trend from children K/K homozygous to K/Q heterozygous, and to Q/Q homozygous (0.45 vs. 0.28 vs. -0.19; P = 0.009), according to the additive model. The two other SNPs and the QdelTG haplotype did not exhibit any association with overweight/obesity. This is the first child-based study showing a protective role of the 121Q variant of ENPP1 against overweight/obesity.

Teaching children with diabetes about adequate dietary choices.

Recent recommendations by the American Diabetes Association suggest that children with type 1 diabetes should follow the recommendations for age, sex and body size of the general population. In the case of being overweight or obese, weight-control strategies should be applied. Adherence to recommendations should be pursued by continuous nutritional education that should start at the onset of diabetes and maintained by means of nutritional counselling to the family. The second main target of nutritional intervention is to encourage a reproducible daily meal plan that can be maintained by acquiring good habits when making nutritional choices. Finally, children and parents should be taught how to count carbohydrates, which would help them manage exceptions in their daily meal plan. Specifically, nutritional recommendations for children with diabetes focus on limiting the intake of foods of animal origin (red meat, cheese, cold cuts), moderating fat intake and promoting the intake of foods that naturally contain fibre (mainly vegetables, legumes, fruit). There are two at-risk periods in the lives of children when nutritional education procedures as well as diabetes care in general are less likely to be effective: early years of life and adolescence. In the case of very young children, new behavioural-based intervention strategies to help parents improve mealtimes could be useful in teaching diabetic children to learn to follow a structured eating schedule, which is desirable for long-lasting efficacy in diabetes care. In adolescents, eating disorders and insulin misuse for weight control purposes are concrete and difficult problems to deal with. A good balance between eating for pleasure and maintaining one's health is a challenge for anyone. Appropriate nutritional education helps children with diabetes to find this balance and enjoy a better quality of life.

Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene.

The melanocortin-4 receptor (MC4R) gene pathogenic mutations are the most prevalent forms of monogenic obesity, responsible for approximately 2% of obesity cases, but its role in common obesity is still elusive. We analyzed the contribution of non-synonymous mutations V103I (rs2229616, c.307G > A) and I251L (no rs, c.751A > C) to obesity in 16 797 individuals of European origin from nine independent case-control, population-based and familial cohorts. We observed a consistent negative association of I251L variant (prevalence ranging 0.41-1.21%) with both childhood and adult class III obesity [odds ratio (OR) ranging from 0.25 to 0.76, 0.001 < P-value < 0.05] and with modulation of body mass index (BMI) in general populations, in eight out of nine studies, whereas only one study showed an association between V103I and BMI. Meta-analyses of previous published data with the current ones provided strong evidence of the protective effect of I251L toward obesity (OR = 0.52, P = 3.58 10-5), together with a modest negative association between V103I and obesity (OR = 0.80, P = 0.002). Taken together, gain-of-function mutations I251L and V103I may be responsible for a preventive fraction of obesity of 2%, which mirrors the prevalence of monogenic obesity due to MC4R haploinsufficiency. These results also emphasize the importance of the MC4R signalling tonus to prevent obesity, even in the context of our current obesogenic environment.