Nonalcoholic fatty liver disease (NAFLD), a common cause of chronic liver disease in adults, is incompletely characterized in children. We conducted a prospective study to better characterize the ...clinical presentation of NAFLD in children and to determine the effect of lifestyle advice in the management of pediatric NAFLD. From June 2001 to April 2003, 84 children (age 3‐18.8 yr) who had elevated aminotransferases and the diagnosis of NAFLD confirmed via liver biopsy underwent a 2‐hour oral glucose tolerance test and a 12‐month program of lifestyle advice consisting of diet and physical exercise. Thirty‐four (40.5%) patients were obese (body mass index BMI >97th percentile), and 43 (51.2%) were overweight (BMI 85th‐97th percentile). Ten (12%) had abnormal glucose tolerance; 10 (12%) had elevated triglycerides, cholesterol, or both; and all had normal blood pressure. Most children (67/84, 80%) were insulin‐resistant, including the 7 children with normal BMI (<85th percentile). Increased liver fibrosis was present in 49 (58.1%) patients and was independently associated with obesity (OR 2.7, 95% CI 1.2‐6.2) and age (1‐year increase; OR 1.2, 95% CI 1.04‐1.5). A 12‐month program with diet and physical exercise resulted in a significant decrease in BMI, and levels of fasting glucose, insulin, lipids, and liver enzymes, as well as liver echogenicity on ultrasonography. In conclusion, children with NAFLD are almost always insulin‐resistant regardless of BMI. Obesity and older age are independently associated with increased liver fibrosis. A simple lifestyle advice program significantly improves insulin resistance, and the liver disease in pediatric NAFLD. (HEPATOLOGY 2006;44:458–465.)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background Tight glycemic control is essential for the normal growth and development of preschool children. The aim of our study was to evaluate the impact of advanced hybrid closed loop (AHCL) ...systems in a real-life setting in children younger than 6 years. Methods We conducted a two-center prospective study. We enrolled 19 patients with a median age at disease onset of 2.6 years interquartile range (IQR) 1.6; 4.4 and a median disease duration of 1.4 years (IQR 0.9; 2.8) who were switched to AHCL from multiple daily injections or open-loop insulin therapy and with a 6-month follow-up. Clinical data, sensor glycemic metrics, and pump settings were collected and analyzed. Results After 6 months of follow-up, there was a significant reduction in median HbA1c ( p = 0.0007) and glucose management indicator ( p = 0.03). A reduction in both mild (>180 mg/dL) ( p = 0.04) and severe (>250 mg/dL) ( p = 0.01) hyperglycemia was observed after 1 month of auto mode, and in mild hyperglycemia, it persisted up to 6 months ( p = 0.02). A small increase in time below range (<70 mg/dL) was observed ( p = 0.04) without a significant difference in time <54 mg/dL ( p = 0.73). Time in range increased significantly, reaching a 10% increment ( p = 0.03) compared with baseline. A significant reduction in the average sensor glucose was observed ( p = 0.01) while coefficient of glucose variability (CV%) remained stable ( p = 0.12). No episodes of ketoacidosis or severe hypoglycemia have been recorded. Conclusion AHCL systems are effective and safe for children younger than 6 years and should be considered as a valid therapeutic option from diabetes onset.
Aim
In the pediatric diabetes clinic, patients with type 1 diabetes mellitus (T1D) account for more than 90% of cases, while monogenic forms represent about 6%. Many monogenic diabetes subtypes may ...respond to therapies other than insulin and have chronic diabetes complication prognosis that is different from T1D. With the aim of providing a better diagnostic pipeline and a tailored care for patients with monogenic diabetes, we set up a monogenic diabetes clinic (MDC).
Methods
In the first 3 years of activity 97 patients with non-autoimmune forms of hyperglycemia were referred to MDC. Genetic testing was requested for 80 patients and 68 genetic reports were available for review.
Results
In 58 subjects hyperglycemia was discovered beyond 1 year of age (Group 1) and in 10 before 1 year of age (Group 2). Genetic variants considered causative of hyperglycemia were identified in 25 and 6 patients of Group 1 and 2, respectively, with a pick up rate of 43.1% (25/58) for Group 1 and 60% (6/10) for Group 2 (global pick-up rate: 45.5%; 31/68). When we considered probands of Group 1 with a parental history of hyperglycemia, 58.3% (21/36) had a positive genetic test for
GCK
or
HNF1A
genes, while pick-up rate was 18.1% (4/22) in patients with mute family history for diabetes. Specific treatments for each condition were administered in most cases.
Conclusion
We conclude that MDC
may
contribute
to provide a better diabetes care in the pediatric setting.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background: There is no consensus on the treatment of pediatric nonalcoholic fatty liver disease (NAFLD). However, in a small pilot study conducted in 10 children, metformin has been ...proposed to be effective. Objective: We aimed to determine the effect of metformin in addition to lifestyle intervention/modification in children with NAFLD. Methods: Overweight or obese children aged 9 to 18 years with biopsy-proven NAFLD or nonalcoholic steatohepatitis were enrolled in an observational pilot study, initially planned for 12 months, which aimed to estimate the effect of metformin on liver enzymes. The study was extended to 24 months to estimate outcomes on liver histology. All subjects received lifestyle intervention (nutritional counseling and a physical exercise regimen) and metformin 1.5 g/d (MET group). To serve as the control in this study, we selected a control group from a separate but parallel study (N = 30) that had identical inclusion criteria on the use of antioxidants in NAFLD. End points were changes in liver enzymes and histology. Insulin resistance (IR) was estimated by the Homeostasis Model Assessment of IR (HOMA-IR) and liver biopsy was determined by the NAFLD activity score (NAS). Results: Sixty patients were assessed for inclusion in this study. However, 2 patients in the MET group dropped out of the study during the first year because they relocated abroad, and 1 patient in the control group refused follow-up after 12 months. Thus, study data is based on the findings in the 57 remaining patients. Alanine aminotransferase significantly improved from baseline with decreasing body weight in both groups (MET: 35 range, 21–43 to 32 20–46 U/L; control: 66 28–121 to 33 14–45 U/L; P ≤ 0.01). HOMA-IR significantly improved in both groups from baseline with decreasing body weight as well (MET: 1.4 range, 0.5–5.11 to 1.3 0.13–4.21; control: 2.29 0.86–5.76 to 1.5 0.70–4.23; P ≤ 0.01). Steatosis was reduced in both the MET ( P = 0.02) and control ( P = 0.02) groups as well as ballooning (both, P = 0.008). Lobular inflammation improved from baseline in the MET group ( P = 0.003). The NAS score decreased from baseline (both, P = 0.001), but no significant changes in fibrosis were detected. Conclusion: In this small, 24-month observational study, metformin did not appear more effective than lifestyle intervention in ameliorating levels of aminotransferases, steatosis, and liver histology in these children with NAFLD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective To clarify the effects of insulin therapy on ovarian androgen production, hyperandrogenism and polycystic ovary syndrome (PCOS) in adolescents and young women with type 1 diabetes (T1D). ...Design Case-control study. Setting Children’s research hospital. Patient(s) Fifty-four consecutive T1D subjects (age, 15–25 years), without residual endogenous insulin secretion, treated by intensive insulin therapy (multiple injection therapy MI or continuous SC insulin infusion CSII); and one-hundred fifty age-matched healthy women. Intervention(s) Analysis of the prevalence and risk factors of ovarian hyperandrogenism and PCOS in T1D adolescents and young women. Main Outcome Measure(s) Biometric, glycemic, and metabolic parameters. Evaluation of androgen levels and ovary ultrasound during the early follicular phase of the menstrual cycle. Result(s) Androgen levels were significantly higher in T1D subjects than in the control group (T, 68.8 ± 23.4 vs. 46.1 ± 20.8 ng/dL). Four subjects (7.4%) were affected by PCOS according to the Rotterdam criteria. No correlation was evident between HbA1c% and androgen levels. No significant differences were evident between subjects on MI or CSII therapy. Multivariable linear regression analysis showed a direct and independent effect of age and body mass index on T levels. T levels were also negatively affected by birth weight. Conclusion(s) Androgen levels are significantly increased in T1D adolescents and young women treated by intensive insulin therapy. The presence and severity of ovarian hyperandrogenism seem to be primarily related to common risk factors such as age, low birth weight, overweight, and obesity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BackgroundPuberty is a period of rapid growth associated with metabolic, hormonal, and body composition changes that can influence risk factors for chronic diseases such as type 2 ...diabetes.ObjectiveTo evaluate body composition and insulin sensitivity (IS) modifications throughout puberty in a large group of obese Caucasian subjects.MethodsFive hundred and nineteen obese subjects (4–19 years), grouped according to gender and Tanner stage (T), underwent oral glucose tolerance test. Quantitative insulin check index (QUICKI) and ISI were calculated as indexes of IS. In 309 subjects, body composition by dual-energy X-ray absorptiometry, IGF1, adiponectin, and leptin were also evaluated.ResultsBody composition modifications were sexually dimorphic, with girls not modifying fat and lean percentage and fat distribution (P>0.15), and boys decreasing fat percentage and increasing lean percentage and central fat depot (P<0.001) across Ts. IS decreased during mid-puberty and returned to prepubertal levels by the end of puberty. Girls showed lower IS than boys (P<0.01 and =0.03 for QUICKI and ISI respectively). In multivariate analysis factors that negatively influenced IS, independently from T or age, were total fat mass and central fat depot in girls (P<0.05 and <0.01, respectively), total fat and lean mass in boys (P<0.01). IGF1, adiponectin, and leptin were not related to pubertal IS.ConclusionsIn obese Caucasian subjects, further decrease of IS observed during puberty is a transient phenomenon. Factors that independently from T or age influence IS are central fat depot in girls, lean amount in boys, and total fat mass in both sexes.
Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy.
Childhood ...obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM).
Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy.
Methods: The study group included 510 overweight/obese subjects (3–18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA‐IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta‐cell function was estimated by insulinogenic index. Fat mass was measured by dual‐energy x‐ray absorptiometry.
Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA‐IR and glucose‐stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA‐IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT.
Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Management of Type 1 Diabetes (T1D) poses numerous challenges, especially for young children and their families. Parental care positively influencesthe outcomesofchildren with T1D, while there are ...often criticisms in school environment. The COVID-19 pandemic has forced children and parents to spend many hours at home and diabetes care has returned mainly in the hands of parents.
To evaluate the effectiveness of exclusive return to parental care in pre-school and school children with T1D treated with Tandem Basal IQ system during the COVID-19 pandemic.
22 children (M:F = 14:8) with T1D have been evaluated. We compared insulin and CGM data (TIR, TBR and TAR) of two periods: PRE-COV and IN-COV, in which children have transitioned from normal school attendance to the exclusive care of their parents.
During the IN-COV period a significantly (p < 0.001) higher median value of TIR (66,41%) was observed as compared to PRE-COV period (61,45%). Patients also showed a statistically significant difference (p < 0.002) between the IN-COV period and the PRE-COV period as concerning the TAR metric: respectively 29,86 ± 10,6% vs 34,73 ± 12,8%. The difference between the bolus insulin doses was statistically significant (PRE-COV 5,3 IU/day, IN-COV 7,9 IU/day – p < 0.05).
Our observational real-life study confirms the positive effect of parental care in T1D very young children and demonstrates that during the COVID-19 pandemic it was possible to obtain a good glycometabolic compensation despite the significant change in lifestyle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim of our study was to identify factors that are related to a more aggressive -cell destruction in children at presentation of type 1 diabetes mellitus (T1D). We analyzed age, HbA1c, pH, ...bicarbonate, IAA, IA2, GADA, C peptide of 290 consecutive patients with T1D at onset. Seventy-three (25.2%) were younger than 4 years; 217 (74.8%) were aged 4-18 years. Younger patients had lower C peptide, pH and bicarbonate than older ones. Age at T1D onset was negatively related to IAA titers (r: -0.3404, p < 0.001), positively related to IA2 titers (r: 0.1249, p: 0.03) and to C peptide (r: 0.42, p: < 0.001). Multivariable linear regression showed that C peptide was negatively related to HbA1c and positively related to age, pH at admission and IAA titers. T1D in very young children is characterized by a more extensive -cell destruction, and younger age at onset is related to a more severe decompensation.
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