Danila Benevento

Sexual dimorphism in growth and insulin-like growth factor-I in children with type 1 diabetes mellitus

OBJECTIVE Impaired linear growth and reduced IGF-I levels in children with type 1 diabetes (T1DM) have been related to poor metabolic control. The aim of this study was to identify additional factors which may negatively affect growth and IGF system in patients with T1DM. DESIGN Ninety-one T1DM children (54 males, age=: 11.73±3years, disease duration=5.6±2.1years) were studied. All children were on intensive insulin therapy: 62 children were on multiple injection therapy (MI) and 29 children on continuous subcutaneous insulin infusion (CSII). RESULTS Height velocity (HV) SDS and IGF-I levels were higher in females and in pubertal children [HV SDS: females=0.6±2.4 vs males=-0.45±2.3 (p=0.04); IGF-I SDS: females=-1.09±0.58 vs males=-1.4±0.6 (p=0.02); IGF-I/IGFBP-3 molar ratio: females=0.25±0.1 vs males=0.21±0.08 (p=0.04); IGF-I SDS: pre-pubertal=-1.58±0.46 vs pubertal=-1.15±0.65 (p<0.001); IGF-I/IGFBP-3 molar ratio: pre-pubertal=0.16±0.08 vs pubertal=0.26±0.09 (p<0.001)]. No differences between children on CSII or MI therapy were found. IGF-I SDS was positively related to C peptide level (p<0.001), puberty (p<0.001) and female gender (p=0.02) and negatively related to HbA1c (p=0.04). IGF-I/IGFBP-3 molar ratio was positively affected by C peptide level (p<0.001), puberty (p<0.001) and daily insulin dose (p<0.001). CONCLUSIONS Our results indicate that despite intensive insulin therapy, T1DM still negatively affects IGF-I secretion and linear growth. Growth impairment is more severe in males and primarily related to poor glycemic control and loss of the residual beta cell mass.

Residual β-Cell Mass Influences Growth of Prepubertal Children With Type 1 Diabetes

Background: The growth deceleration observed in children with type 1 diabetes (T1D) has been related to poor glycemic control. It is unclear whether growth impairment persists despite the optimization of therapy. We analyzed the effects of intensive insulin treatment on prepubertal growth. Methods: One hundred and four T1D children were evaluated from T1D diagnosis up to puberty onset. Height, weight, insulin requirement and glycated hemoglobin (HbA1c) were recorded at 3- to 6-month intervals. Residual β-cell mass was estimated by fasting C-peptide at T1D onset. Results: Age at T1D onset was 5.91 ± 1.9 years. Follow-up duration was 4.84 ± 1.58 years. Height velocity standard deviation score (SDS) was -0.14 ± 1.84. Height SDS changed from 0.52 ± 1.04 at T1D onset, to 0.36 ± 1.10 at the end of follow-up (p = 0.04). BMI SDS increased from -0.04 ± 1.48 to 0.32 ± 1.03 (p = 0.01). Multivariate analysis showed that height velocity was directly affected by C-peptide (p = 0.03) and insulin requirement (p = 0.004) and inversely related to HbA1c (p = 0.006). BMI gain was negatively influenced by HbA1c (p = 0.01) and positively related to T1D duration (p = 0.01). Conclusion: Despite insulin intensive therapy, T1D still negatively affects growth. Residual β-cell mass has a direct positive impact on growth, independently from the quality of glycemic control.

Ovarian hyperandrogenism in adolescents and young women with type I diabetes is primarily related to birth weight and body mass index

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 Childrens 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.

Early Glucose Derangement Detected by Continuous Glucose Monitoring and Progression of Liver Fibrosis in Nonalcoholic Fatty Liver Disease: An Independent Predictive Factor?

Background: Glucose derangement has been reported to increase oxidative stress, one of the most important factors underlying the progression of hepatic fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). To date, careful evaluation of the glucose profile in pediatric NAFLD has not been performed. Methods: A total of 30 severely obese children (15 males; mean age 12.87 ± 2.19 years) with biopsy-proven NAFLD were enrolled in this study from September to December 2013. All patients underwent anthropometric and laboratory evaluation, including the oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM). Results: Our study reveals some differences between OGTT and CGM in detecting NAFLD children with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). OGTT showed 2 (6.67%) patients with IFG and 1 (3.34%) with IGT, while CGM showed 5 (16.67%) patients with IFG and 6 (20%) with IGT. The daily blood glucose profile positively correlated with the baseline blood glucose (r = 0.39, p = 0.04) and the homeostatic model assessment (r = 0.56, p = 0.05). A positive correlation between hyperglycemia and liver fibrosis was found (r = 0.65, p < 0.05). Mean glucose values (F3-F4 group: 163.2 ± 35.92 mg/dl vs. F1 group: 136.58 ± 46.83 mg/dl and F2 group: 154.12 ± 22.51 mg/dl) and the difference between the minimum and maximum blood glucose levels (F3-F4 group: 110.21 ± 25.26 mg/dl vs. F1 group: 91.67 ± 15.97 mg/dl and F2 group: 92 ± 15.48 mg/dl) were significantly (p < 0.05) higher in the F3-F4 group compared to the F1 and F2 groups. Conclusion: Glucose profile derangement as detected by CGM is associated with the severity of hepatic fibrosis in children with NAFLD.

Clinical features suggestive of non-classical 21-hydroxylase deficiency in children presenting with precocious pubarche

Abstract Precocious pubarche (PP) is defined as the onset of pubic hair at 8 years of age in girls and at 9 years of age in boys. PP is idiopathic (IPP) in most children, but it is the earliest manifestation of non-classical congenital adrenal hyperplasia owing to steroid 21-hydroxylase deficiency (NC21OHD) in 5%–20% of cases. 17-Hydroxyprogesterone (17OHP) levels after ACTH stimulation test are used to distinguish the two forms. We studied clinical indicators of NC21OHD in 289 PP children: 14 (4.8%) showed post-ACTH 17OHP levels >30 nmol/L and NC21OHD due to CYP21A2 gene mutations was confirmed. NC21OHD children were younger (p: 0.006) and thinner (p: 0.003) than IPP children. Height standard deviation score (SDS) was not different (p: 0.97). NC21OHD girls showed more advanced bone age than IPP girls (p<0.001). Earlier PP onset and bone age advance suggest NC21OHD, which requires confirmation by an ACTH stimulation test. Later, PP appearance in overweight children suggests IPP and could merit only clinical monitoring.

Birth weight influences the clinical phenotype and the metabolic control of patients with type 1 diabetes (T1D)

High birth weight has been related to an increased risk of type 1 diabetes (T1D), while suboptimal birth weight (both high and low) has been related to obesity, insulin resistance and type 2 diabetes. Insulin resistance, as a consequence of poor metabolic control, has been described in T1D patients. The aims of the study were to analyse the distribution of birth size for gestational age in a large group of T1D patients and to investigate the effect of birth weight on clinical phenotype.

ZnT8 antibodies in patients with cystic fibrosis: An expression of secondary beta-cell damage?

Cystic Fibrosis-Related Diabetes (CFRD) is caused by a severe insulin deficiency with associated different degrees of insulin resistance. Data concerning the potential impact of autoimmunity are conflicting. Ninety subjects with cystic fibrosis (CF) were tested for glucose tolerance and autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA2) and zinc transporter 8 (Znt8A). Eighty-three subjects showed a normal glucose tolerance (92.2%), 6 subjects (6.6%) impaired glucose tolerance and 1 subject (1.1%) newly diagnosed CFRD. Four subjects were found positive for both IAA and GADA (4.4%), one subject (1.1%) for both IA2 and GADA, and one subject (1.1%) for isolated GADA. Three subjects (3.3%) showed isolated ZnT8A positivity. ZnT8A positivity in CF patients is uncommon and not associated with other autoantibodies. ZnT8A may not represent a specific indicator of a primary autoimmune beta-cell destruction, but possibly the expression of a secondary damage of the pancreatic islets with autoantigen release.

La steatosi epatica in età pediatrica: è parte intégrante della sindrome metabolica?

RiassuntoLa crescita esponenziale dell’eccesso ponderale registratasi nelle ultime decadi anche in età pediatrica ha fatto drammaticamente aumentare l’incidenza di complicanze metaboliche quali sindrome metabolica (SM) ed epatopatia steatosica (NAFLD). Recenti evidenze dimostrano l’esistenza di una stretta correlazione tra SM e NAFLD, suggerendo che esse rappresentino l’espressione clinica di un comune disarray metabolico, nel quale l’insulino-resistenza e l’accumulo di grasso intraepatocitario svolgerebbero un ruolo chiave.