Worldwide differences in childhood type 1 diabetes: The SWEET experience.

OBJECTIVE: To study worldwide differences in childhood diabetes, comparing relevant indicators among five regions within the SWEET initiative. SUBJECTS: We investigated 26 726 individuals with type 1 diabetes (T1D) from 54 centers in the European region; 7768 individuals from 30 centers in the Asia/Middle East/Africa region; 2642 people from five centers in Australia/New Zealand; 10 839 individuals from seven centers in North America, and 1114 patients from five centers in South America. METHODS: The SWEET database was analyzed based on the following inclusion criteria: T1D, time period 2015-2019, and age < 21 years, with analysis of the most recent documented year of therapy. For the statistical analysis, we used multivariable linear and logistic regression models to adjust for age (<6 years, 6- < 12 years, 12- < 18 years, 18- < 21 years), gender, and duration of diabetes (<2 years, 2- < 5 years, 5- < 10 years, ≥10 years). RESULTS: Adjusted HbA1c means ranged from 7.8% (95%-confidence interval: 7.6-8.1) in Europe to 9.5% (9.2-9.8) in Asia/Middle East/Africa. Mean daily insulin dose ranged from 0.8 units/kg in Europe (0.7-0.8) and Australia/New Zealand (0.6-0.9) to 1.0 unit/kg 0.9-1.1) in Asia/Middle East/Africa. Percentage of pump use was highest in North America (80.7% [79.8-81.6]) and lowest in South America (4.2% [3.2-5.6]). Significant differences between the five regions were also observed with regards to body mass index SD scores, frequency of blood glucose monitoring and presence of severe hypoglycaemia. CONCLUSIONS: We found significant heterogeneity in diabetes care and outcomes across the five regions. The aim of optimal care for each child remains a challenge.

Contribution of SWEET to improve paediatric diabetes care in developing countries.

Diabetes affects many children living in developing countries. Through an informal survey, five SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers from developing countries (Mali, Costa Rica, Argentina and two from India) share their perspective on caring for children with diabetes. Each center provides a description of the population of children with diabetes they serve, the organization of care, and the challenges encountered on a daily basis in the provision of this care. In the second part, we summarize the anticipated benefits and challenges associated with participation in SWEET. This resulting article is a testimony of the reality of managing diabetes by dynamic teams striving to achieve recommended standards of care for pediatric diabetes in an environment with limited resources.

[Obesity and risk factors for metabolic syndrome in young people with type 1 diabetes]. / Obesidad y factores de riesgo del síndrome metabólico en jóvenes con diabetes tipo 1.

Changes in the clinical presentation of diabetes mellitus in childhood and adolescence associated with obesity have resulted in an overlap of the two most common types of diabetes with a greater clinical heterogeneity. In order to characterize the type of diabetes at onset and assess the effect of obesity, 50 children with diabetes were studied. The patients were divided into two groups according to their nutritional status at diagnosis (over-weight/obese vs. normal weight). Insulin reserve was evaluated by measuring basal C-peptide and stimulated C-peptide in response to a mixed meal (MMTT) as well as HLA-DQB1 genotype, antibodies, and family history of risk factors for metabolic disease. Of all 50 patients, 38% was overweight/obese, 84% had a positive family history of metabolic syndrome, 82% had positive antibodies, and 100% were positive for the high-risk HLA-DQB1 genotype. No significant differences were found in fasting C-peptide or glycemic index/C-peptide levels between the two groups. In the overweight/obese group C-peptide response to MMTT showed higher levels at 60 and 120 minutes (p = 0.02 and 0.03) and the area under the curve for C-peptide was also higher (1.77 ng / ml vs. 5.5 ng/ ml, p = 0.0007) than in the normal-weight group. In conclusion, overweight/obese patients with type 1A diabetes had a greater pancreatic reserve, suggesting that nutritional status may accelerate disease onset.

Evaluation of two dietary treatments in obese hyperinsulinemic adolescents.

UNLABELLED: Hyperinsulinemia increases the risk of cardiovascular disease in obese children. Only a few treatments are available to decrease insulin resistance. The reduction of hyperinsulinemia by dietary means would be a simple, physiologic and economic way to reduce the risk of metabolic disease. OBJECTIVE: To compare the effects of two low-energy diets on serum insulin concentrations and weight loss in obese hyperinsulinemic adolescents. MATERIALS AND METHODS: Eighty-six randomly assigned insulin-resistant obese adolescents completed a 16 week calorie-restricted diet. The experimental diet had a reduced glycemic index designed to evoke a low insulin response (LIR), with carbohydrates and proteins ingested in separate meals. The control diet was a conventional (CD) with similar proportions (60%, 20% and 20%). Variables studied were blood glucose and insulin concentrations after an oral glucose load, body mass index, waist circumference, and insulin resistance (homeostasis model assessment, HOMA). RESULTS: Mean weight [+/- Standard Deviation (SD)] was significantly reduced after the LIR (-0.53 +/- 0.5) and the CD (-0.54 +/- 0.4), but a greater decrease of waist circumference (cm) was observed after the LIR (-9.1 +/- 4.8 vs. -6.6 +/- 4.6, p = 0.02). Fasting insulin concentrations (-17.9 +/- 27.9 vs. -9.4 +/- 14.8, p = 0.01) and HOMA dropped significantly more after the LIR than after the CD (-3.5 +/- 4.9SD vs. -2.4 +/- 1SD, p < 0.0001). CONCLUSIONS: The LIR diet reduces serum insulin concentrations and waist circumference more than conventional treatment and appears to be a promising alternative to a conventional diet in insulin-resistant obese adolescents. Long-term follow-up is needed to evaluate the maintenance of weight loss and metabolic parameters.

Metformin, estrogen replacement therapy and gonadotropin inhibition fail to improve insulin sensitivity in a girl with aromatase deficiency.

BACKGROUND: Insulin resistance (IR), abnormal lipid profile, and other features of the metabolic syndrome have been described in CYP19 gene knockout mice and in aromatase-deficient adult men but not in prepubertal affected girls. AIMS: To study insulin sensitivity, as well as the effects of estrogen, metformin and GnRHa treatment on glucose homeostasis, in an aromatase-deficient girl. METHODS: Clinical, metabolic and hormonal follow-up data, from 8 to 12 years of age, is presented. RESULTS: At 9 years of age, IR (HOMA 5.6) and glucose intolerance was detected, along with high serum testosterone (2.28 nmol/l), androstenedione (4.92 nmol/l) and FSH (13.4 mIU/ml) levels. Estrogen replacement was ineffective to suppress gonadotropin and androgen levels, as well as IR. Under metformin therapy, she developed type 2 diabetes and acanthosis nigricans. GnRHa administration for 1 year resulted in marked decreases in gonadotropin and serum androgens, but severe IR persisted. CONCLUSION: Postnatal estrogen replacement and a marked decrease of endogenous androgens failed to improve IR and glucose tolerance. We propose that, in females, the increment of androgens and/or lack of estrogens during fetal life might alter the mechanism of fetal programming of insulin sensitivity.

Assessment of risk factors of poor metabolic control in type 1 diabetic children assisted in a public hospital in Argentina.

OBJECTIVE: To evaluate predictive risk variables of poor diabetes control that are present at the onset of the disease. SUBJECTS AND METHODS: A prospective cohort study was carried out in a population of children with type 1 diabetes mellitus by means of a survey with information related to the clinical control of the patients, the sociodemographic and economic situations of their families, and the importance that the families attached to health care. The sample population had had the disease for over 2 yr, had no associated pathology, and was followed in an Argentinean hospital. RESULTS: Data from 148 patients, 71 male (48%), were collected, with a mean hemoglobin A1c (HbA1c) of 9.3 +/- 1.62%. Patients with HbA1c <8.4% (25th percentile) were considered as having better metabolic control (BC), and those with HbA1c >10% (75th percentile) were considered with poorer control (PC). PC was significantly associated with the fact that the patients' biological parents did not live together (p = 0.01) and had not done the diabetic education together at debut of diabetes (p = 0.007). A linear regression model was used to analyze predictors of BC: presence of both parents during diabetes instruction (OR: 3.82), both parents lived together with the patient (OR: 2.39), and lower age of patients (OR: 0.89). Predictors of PC were unsatisfied basic food needs (OR: 4.33) and mothers' low level of education (OR: 2.13). CONCLUSIONS: This study showed that socioeconomic and familial factors were strongly associated with metabolic control, and they will allow us to make an early detection of those patients who are more susceptible of having poor progression of diabetes.

Opiniones y recomendaciones de la Sociedad Argentina de Diabetes. Glucemia en ayunas alterada: ¿es oportuno utilizar el punto de corte en 100 mg/dl en Argentina? / Opinions and recommendations of the Argentine Diabetes Society. Impaired fasting blood glucose: is it appropriate to use a cut-off point of 100 mg/dl in Argentina?

Establecer el punto de corte entre la glucemia en ayunas normal y la alterada resulta de suma importancia a los efectos de considerar a un paciente en riesgo, tanto de progresar a estdos más avanzados de la enfermedad como de sufrir complicaciones micro y macroangiopáticas. Desde 2006 la Sociedad Argentina de Diabetes (SAD), sobre la base de la evidencia considerada en ese momento, estableció el límite inferior de la glucemia alterada en ayunas (GAA) en 110 mg/dl; posteriormente, durante 2022, la Comisión Directiva de la SAD convocó a un grupo de expertos con el objeto de evaluar si esta recomendación debía mantenerse o, al igual que otras sociedades científicas de prestigio, adoptar a tal efecto 100 mg/dl. En este documento de Opiniones y Recomendaciones se encuentran los fundamentos por los cuales la SAD adoptará, de ahora en más, 100 mg/dl como límite inferior de la GAA, en base a las nuevas evidencias científicas que muestran que desde este punto de corte se produce un aumento en la progresión a la diabetes mellitus y de las complicaciones tanto macro como microangiopáticas.

To establish the cut-off point between normal and impaired fasting glycemia (IFG) is extremely important for the purposes of considering a patient at risk both of progressing to more advanced stages of the disease and of suffering micro- and macroangiopathic complications. Since 2006, the Argentine Diabetes Society (ADS), based on the evidence considered at that time, established the lower limit of IFG at 110 mg/d, laterduring the year 2022, The Board of Directors of the ADS vened a group of experts in order to assess whether this recommendation should be maintained or, like other prestigious scientific societies, adopt 100 mg/dl for this purpose. This Opinions and Recommendations document contains therationale for which the SAD will adopt, from now on, 100 mg/dlas the lower limit of the IFG, based on the new scientific edence that shows that from this cut-off point it produces increase in progression to diabetes and both macro and microangiopathic complications.

Diabetes y obesidad. Dos enfermedades enlazadas / Diabetes and obesity. Two diseases linked

La obesidad es una enfermedad crónica, progresiva y recurrente. Es esta la descripción sencilla, firme y basada en la evidencia que organizaciones y sociedades científicas de renombre y relevancia global usan en la actualidad. La obesidad migró en su consideración desde un factor de riesgo a una enfermedad primaria. No solo es una condición subyacente a enfermedades crónicas no transmisibles -como la enfermedad cardiovascular (ECV), la diabetes mellitus tipo 2 (DM2) o el cáncer, entre otras- sino que es una enfermedad perse que afecta a la población en forma epidémica, universal y a cualquier edad.

Excessive weight gain in exclusively breast-fed infants.

BACKGROUND: Breastfeeding is recommended as the best source of nutrition in the first months of life and observational studies have associated exclusive breastfeeding with decreased weight gain and a protective effect against obesity in childhood. The objective of this study was to describe the characteristics of a cohort of exclusively breastfed obese infants to determine factors that may lead to this unusual weight gain. METHODS: Infants seen between 2003 and 2015 who were exclusively breastfed and showed excessive weight gain in the first year of life were followed with a focus on features of the mother, the child, feeding patterns and the presence of concomitant factors that influence nutritional status. Additionally, in a subset of the sample, macronutrients of the maternal breast milk were analyzed. A descriptive, prospective cross-sectional study was conducted. RESULTS: Of 73 patients, 63% were girls. At 3 months of life, 64% had a weight-for-height standard deviation score (SDS) >2. At 6 and at 12 months, 100% of the patients had a weight-for-height >2 SDS. The mean age at semisolid-food introduction was 7 months. The mean age at weaning was 15.8 months. The babies were fed on demand and no hunger-satiety pattern was observed. In the breast milk samples analyzed, a significantly lower fat content was found. CONCLUSIONS: The results of our study lead to the assumption that inter-individual variations in mother's milk composition may affect the growth patterns of children.

Factors Associated With Diabetes-Specific Health-Related Quality of Life in Youth With Type 1 Diabetes: The Global TEENs Study.

OBJECTIVE: Our objective was to characterize diabetes-specific health-related quality of life (D-HRQOL) in a global sample of youth and young adults with type 1 diabetes (T1D) and to identify the main factors associated with quality of life. RESEARCH DESIGN AND METHODS: The TEENs study was an international, cross-sectional study of youth, 8-25 years of age, with T1D. Participants (N = 5,887) were seen in clinical sites in 20 countries across 5 continents enrolled for 3 predetermined age groups: 8-12, 13-18, and 19-25 years of age. To assess D-HRQOL, participants completed the PedsQL Diabetes Module 3.0 and were interviewed about family-related factors. Specifics about treatment regimen and self-management behaviors were collected from medical records. RESULTS: Across all age groups, females reported significantly lower D-HRQOL than did males. The 19-25-year age group reported the lowest D-HRQOL. Multivariate linear regression analyses revealed that D-HRQOL was significantly related to HbA1c; the lower the HbA1c, the better the D-HRQOL. Three diabetes-management behaviors were significantly related to better D-HRQOL: advanced methods used to measure food intake; more frequent daily blood glucose monitoring; and more days per week that youth had ≥30 min of physical activity. CONCLUSIONS: In all three age groups, the lower the HbA1c, the better the D-HRQOL, underscoring the strong association between better D-HRQOL and optimal glycemic control in a global sample of youth and young adults. Three diabetes-management behaviors were also related to optimal glycemic control, which represent potentially modifiable factors for clinical interventions to improve D-HRQOL as well as glycemic control.

Characterization of alterations in carbohydrate metabolism in children with Prader-Willi syndrome.

OBJECTIVE: To study carbohydrate metabolism and insulin sensitivity and secretion in children and adolescents with Prader-Willi syndrome (PWS) compared with multifactorial obesity (MO) controls. PATIENTS AND METHODS: Seventy-five patients with PWS and 395 controls with MO were studied by oral glucose tolerance test. Insulin resistance (IR) and beta-cell function were assessed by homeostasis model assessment (HOMA), insulin glucose index, fasting insulin and insulin sensitivity index. RESULTS: The incidence of diabetes mellitus was 0% in PWS and 1.5% in MO, while carbohydrate intolerance was 9.3% in the former group and 7.6% in the latter (NS); basal insulin level (12 +/- 8.2 vs 22.3 +/- 25 mU/ml) and HOMA-IR (2.47 +/- 1.6 vs 4.18 +/- 5.05) were lower in PWS (p = 0.004 and 0.04, respectively), whereas HOMA beta-cell index was lower in PWS than in MO (59 +/- 42 vs 102 +/- 119, p = 0.03). ISI Composite was higher in PWS compared to MO (6 +/- 5.7 vs 4.18 +/- 5.05, p = 0.04). CONCLUSION: Patients with PWS presented lower insulin resistance and a dissociation between beta-cell secretion and the degree of obesity.

Waist-to-height ratio as a marker of low-grade inflammation in obese children and adolescents.

BACKGROUND: The epidemic of childhood obesity is associated with early atherosclerosis. Several reports have related this event to low-grade inflammation described in obesity. CRP and IL6 are markers that correlate with adiposity. The waist-to-height ratio (WtHR) is an anthropometric marker associated with insulin resistance and inflammation. The objective of this study was to assess the correlation between WtHR, metabolic complications and pro-inflammatory factors in obese children and adolescents. METHODS: Weight, height, waist circumference, glycemia, insulin, CRP, TNF-α and IL-6 were measured in the baseline sample in 280 patients 6-19 years of age with overweight or obesity (OW/OB) and 112 normal-weight controls. Logistic regression was performed using WtHR as an independent variable. p>0.05 STATA11. RESULTS: Mean WtHR was 0.6±0.06 in OW/OB and 0.43±0.02 in controls (p<0.01). WtHR was increased in 93% of the OW/OB vs. 2% of the controls. In the OW/OB inflammatory markers were significantly increased (p<0.01) compared to the controls (CRP 2.2 vs. 0.8; Il-6 2.9 vs. 2.1; and TNF-α 6.2 vs. 5.5). In the WtHR>0.5, insulin resistence and inflammatory markers were significantly increased (p<0.01) compared to the WtHR<0.5 (HOMA 3.4 vs. 1.4; CRP 2.3 vs. 0.6; Il-6 2.9 vs. 2.1; and TNF-α 6.4 vs. 5.55). In logistic regression, a significant independent association was found between WtHR with CRP (OR1.47), IL6 (OR1.60) and TNF-α (OR1.79). CONCLUSIONS: Obese children and adolescents have high inflammatory markers that may increase cardiovascular risk. WtHR is associated with low-grade inflammation and may be considered a relevant anthropometric marker in the clinical practice.

Cardio-metabolic risk factors in Argentine children. A comparative study.

UNLABELLED: Obesity and its complications are emerging in an epidemic manner in Latin American countries. AIMS: To estimate the prevalence of Cardio-Metabolic Risk Factors (CMRFs) and Metabolic Syndrome (MS) in overweight/obese (OW/OB) and normal weight (NW) adolescents and to examine the associated variables. MATERIAL AND METHODS: A cross-sectional comparative study was conducted in two groups of children, between 10 and 19 years of age, in seven Argentine provinces. A survey on dietary habits, physical activity, anthropometric and biochemical data was collected to identify CMRF and MS. The WHO definition adapted to children was used. RESULTS: 1009 children were assessed; 398 were male (39.4%), 601 (59.6%) were NW and 408 (40.4%) were OW/OB. The OW/OB had a significantly higher proportion of values defined as CMRF: 3.7% impaired fasting glucose >110mg/dl; 27.9% insulin >15 or 20µU/l as they were pubertal/prepubertal; 53.2% Homeostatic Model Assessment (HOMA)>2.5; 45.6% High Density Lipoprotein (HDL)<40mg/dl; 37.7% TG>110mg/dl and 13.5% hypertension (SBP and/or diastolic Blood Pressure percentile >90). Prevalence of the MS in OW/OB patients was 40.3%. The MS was not observed in NW children. Significant differences were found for: family history of OW/OB, birth weight (BW), age at menarche, presence of acanthosis nigricans, waist circumference (WC) >90th percentile. The WC was positively correlated with BP, TG, insulin, HOMA and Body mass index Z score and negatively with HDL in the study population. CONCLUSIONS: We confirm obesity as a major determinant of CMRF and MS (40%), especially fat centralization. We stress the need to address obesity prevention plans in children and adolescents.

Impact of maternal nutritional status before and during pregnancy on neonatal body composition: A cross-sectional study.

BACKGROUND: The existence of early factors which, acting during critical periods of intrauterine or immediate postnatal development, determine long-term health has become increasingly recognized. Both high and low birth weight have been associated with cardiovascular risk factors in adulthood. Therefore, body composition at birth rather than birth weight may be a marker to predict future diseases. Maternal weight previous to and gained during pregnancy is associated with intrauterine fetal growth. OBJECTIVE: To evaluate the correlation between maternal nutritional status before and during pregnancy and neonatal body composition. MATERIAL AND METHODS: We studied consecutive mother-child pairs at delivery at an Argentinean public hospital during 5 months period, evaluating maternal and neonatal anthropometry before 24h of life as well as the history of the mother before and during pregnancy. Neonatal body composition was calculated according to a mathematical formula based on skinfold thickness measurement validated in newborns. RESULTS: Mothers of newborns with high body fat mass were more frequently obese (72.7% versus 35.1%, p 0.005), and more frequently showed weight gain above 18kg during pregnancy (76.4% versus 31%, p 0.03). CONCLUSIONS: Our findings confirm the hypothesis that maternal obesity before pregnancy is highly correlated with neonatal fat mass in the first hours of life.

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in obese Argentinean children and adolescents.

The aim of this study was to evaluate the prevalence of type 2 diabetes mellitus (DM2) and impaired glucose tolerance (IGT) in obese children and adolescents and to examine insulin resistance and insulin secretion. We studied 427 asymptomatic obese patients. DM2 and IGT were diagnosed by an oral glucose tolerance test. Insulin resistance and P-cell function were assessed by using homeostasis model assessment (HOMA), insulin/glucose index (I/GI), fasting insulin and insulin sensitivity index (ISI-composite). Thirty patients showed IGT (7%) and seven had DM2 (1.6%). The mean age was 10.7 +/- 3.5 years, the diabetic group being significantly older than the normal group (p < 0.01). The mean body mass index was 30 +/- 5.3 kg/m2 without significant differences between groups. beta-Cell function declined significantly in the patients with IGT and DM2, and insulin resistance increased significantly. Given the rather high prevalence of glucose metabolism impairment, children with obesity should undergo glucose tolerance testing for appropriate therapeutic intervention.

[HLA DQB1 genotyping in latent autoimmune diabetes of adults (LADA)]. / Genotipificacion del gen HLA DQB1 en diabetes autoinmune del adulto (LADA)

Autoimmune diabetes is a complex, multifactorial disease caused by the interaction of genetic and environmental factors. This autoimmune diabetes is commonly manifested in childhood and adolescence with a fast onset (type 1 diabetes, IDDM) and it can occur in adult patients with a slow onset with delayed insulin requirement, (latent autoimmune diabetes in adults, LADA ). Autoimmune diabetes has strong class II HLA association mainly with DQB gene which constitutes the first susceptibility locus. However, association with the 5'INS- VNTR and CTLA-4 genes has been established. In this study, we analysed the polimorphic allele frequencies of DQB HLA gene in 63 LADA patients, 70 IDDM and 79 control subjects. The HLA DQB1 alleles typing was detected through Olerup SSP DQ kit using sequence specific primers. We observed a positive association of *0201-*0302 and *0201-*0201 genotypes in both types of diabetic patients compared to the control group (p < 0.05). Moreover, *0201-*0302 genotype was higher in IDDM than in LADA (p < 0.05). On the other hand, the *0602 protective allele analysis showed a high prevalence in the normal group compared to the diabetic population. In Argentina, the most frequent allele of susceptibility in LADA and IDDM patients was the *0201. Summing up, the finding of an increase in the *0201 allele, both in allelic and genotypic frequencies, allows the characterisation of our population of patients, LADA and IDDM, unlike other populations, in which the most frequent allele is *0302.

Association between insulin resistance and risk of complications in children and adolescents with type 1 diabetes.

BACKGROUND: It has been hypothesized that insulin resistance may be involved in the development of type 1 diabetes complications and early diagnosis would be important for their prevention. Our aim was to study insulin resistance in our population of children with type 1 diabetes and to identify associated early risk factors for micro- and macrovascular complications. METHODS: A descriptive, cross-sectional study was conducted including 150 children with type 1 diabetes. Anthropometric, bioelectric impedance, carotid Doppler ultrasonography, electromyography, and conduction velocity studies were performed. Baseline plasma glucose, lipid profile, uric acid, plasma thyrotropin, glycosylated hemoglobin A1C, and microalbuminuria were assessed. More insulin-resistant patients were defined as those having an estimated glucose disposal rate (eGDR) value below the first quartile. RESULTS: Clinically manifest microvascular complications were not found in any of the patients. More insulin-resistant patients had a greater sub scapular fold thickness, a higher incidence of obesity (12% vs. 1.7% p 0.007), higher fructosamine levels (496 vs. 403 p<0.00019, and a higher incidence of altered lipid metabolism (70% vs. 39% p 0.0007). CONCLUSION: In the subgroup of patients with lower eGDR there were more children with lipid disorders, obesity, and worse diabetic control, which, if not corrected, may lead to development of micro- and macrovascular complications.

[Evaluation of an intensive treatment education program for type 1 diabetes in a group of adolescents. A two year follow up]. / Evaluación de un programa de educación de tratamiento intensivo en adolescentes con diabetes tipo 1. Seguimiento por dos años.

During the past decade several reports were published showing that intensive treatment of type 1 diabetes can prevent and delay disease-related microvascular complications. However, several problems were reported in children and adolescents such as frequent hypoglycemic episodes and weight gain. The aim of this study was to describe the results of intensified treatment for type 1 diabetes in a group of Argentinean adolescents after a follow-up of two years. Twenty five adolescents with type 1 diabetes older than 10 years with at least one year from diagnosis were selected. All patients received a one-week teaching program during admission to our center. All patients were followed-up monthly during two years. Treatment schedule included 4-5 controls in fasting conditions, two doses of NPH insulin and four doses of regular insulin according to glycemia and the amount of calculated carbohydrate intake. Median age was 13.5 years (range 10 to 19 years). Mean time from diagnosis to inclusion in the study was 3.8 years (range 1.25 to 9 years). Mean total dose of NPH insulin decreased significantly when measured at the inclusion in the study (0.9 IU/kg) and after a year of follow-up 0.8 IU/kg (p 0.04). However, there were no changes in NPH insulin dose after two years follow-up (0.85 IU/kg). On the contrary, the dose of regular insulin administered on fasting conditions with normal glycemia increased from 0 to 0.21/kg after a year (p 0.0001) and to 0.69 after two years (non significant). Median HbA1C showed a significant reduction from 10 +/- 1.62% to 8.53 +/- 1.04% after a year (p 0.03) and to 8.72 +/- 0.81% after two years. BMI Z score increased from significantly from 0.7 +/- 0.9 to 1.06 +/- 1.15 after a year (p 0.03) with a further reduction without a significant difference from the basal value after two years. We found no significant differences in the frequency of hypoglycemia or other metabolic features. Our results show that intensive treatment of type 1 diabetes in children and adolescents can achieve significant and sustained reductions of HbA1C without increasing the risk of hypoglycemia or other adverse effects.