Giuliana Valerio

The Lumbar Bone Mineral Density Is Affected by Long-Term Poor Metabolic Control in Adolescents with Type 1 Diabetes mellitus

Aim: To analyze whether bone mineral density (BMD) and bone resorption status are influenced by long-term metabolic control and duration of disease in adolescents with long-standing type 1 diabetes mellitus. Methods: Twenty-seven adolescents (age 13.1 ± 1.7 years, duration of diabetes 6.9 ± 3.0 years) were studied. The BMD, expressed as z score, was measured at the lumbar spine (L1–L4) using dual-energy X-ray absorptiometry, while the urinary excretion of total deoxypiridinoline (Dpyd), a marker of bone resorption, was measured by immunoassay and was corrected by creatinine (Cr). Linear and multivariate correlations between lumbar BMD z score or Dpyd/Cr excretion and age and disease variables [short-term (Hb A1clatest) or long-term (Hb A1cwholeduration) metabolic control, duration, ‘diabetes impact index’ (mean Hb A1cwholeduration x duration of disease in months)] were sought. Results: In diabetic subjects the mean BMD z score was –0.44 ± (SD) 1.02 (95% CI: –0.03; –0.84), and the Dpyd/Cr excretion was not increased. A negative correlation was found between lumbar BMD z score and age (r –0.59; p = 0.001), duration (r –0.39; p = 0.04), and the diabetes impact index (r –0.4; p = 0.04). The Dpyd/Cr ratio correlated negatively with age (r –0.40; p = 0.04) and positively with height velocity (r 0.42; p = 0.04). By using multiple linear regression, age showed a significant inverse correlation with lumbar BMD z score (β = –0.39; p = 0.0005). A negative correlation was found between lumbar BMD z score and Hb A1cwholeduration (β = –0.40; p = 0.02) or diabetes impact index (β = –0.001; p = 0.01). Conclusions: Poor metabolic control may expose adolescents with long-standing type 1 diabetes to the risk of developing osteopenia in adult age. Optimization of metabolic control in growing diabetic children may prevent osteoporosis in later life.

Lack of efficacy of ursodeoxycholic acid for the treatment of liver abnormalities in obese children

OBJECTIVE To determine whether ursodeoxycholic acid (UDCA) is effective for treatment of obesity-related liver abnormalities in children. STUDY DESIGN Thirty-one children (21 bboys; mean age, 8.7 years) had obesity-related persistent elevation of aminotransferase levels, which was associated with ultrasonographic images of bright liver in 27. A preliminary interview determined which patients were (n = 18) or were not (n = 13) likely to comply with a balanced low-calorie diet. Four subgroups emerged: patients who followed the diet (n = 11), patients treated with UDCA (10 mg/kg/d) given alone (n = 7) or added to the diet (n = 7), and untreated control patients (n = 6). RESULTS Diet alone determined weight loss and resolved biochemical liver abnormalities in all patients. Addition of UDCA to the diet was no more efficacious than weight loss alone. UDCA alone was ineffective for the treatment of liver abnormalities in all cases, and results did not differ from those observed in the untreated control group. Improvement of ultrasonographic abnormalities was observed in patients who lost weight, irrespective of UDCA administration. CONCLUSIONS UDCA is not effective for the treatment of obesity-related liver abnormalities in children.

One-year glargine treatment can improve the course of lung disease in children and adolescents with cystic fibrosis and early glucose derangements

Background:  Diabetes increases morbidity and mortality in cystic fibrosis (CF) patients, but several studies indicate that also prediabetic status may have a potential impact on both nutrition and lung function.

Celiac disease in type 1 diabetes mellitus

Celiac Disease (CD) occurs in patients with Type 1 Diabetes (T1D) ranging the prevalence of 4.4-11.1% versus 0.5% of the general population. The mechanism of association of these two diseases involves a shared genetic background: HLA genotype DR3-DQ2 and DR4-DQ8 are strongly associated with T1D, DR3-DQ2 with CD. The classical severe presentation of CD rarely occurs in T1D patients, but more often patients have few/mild symptoms of CD or are completely asymptomatic (silent CD). In fact diagnosis of CD is regularly performed by means of the screening in T1D patients. The effects of gluten-free diet (GFD) on the growth and T1D metabolic control in CD/T1D patient are controversial. Regarding of the GFD composition, there is a debate on the higher glycaemic index of gluten-free foods respect to gluten-containing foods; furthermore GFD could be poorer of fibers and richer of fat. The adherence to GFD by children with CD-T1D has been reported generally below 50%, lower respect to the 73% of CD patients, a lower compliance being more frequent among asymptomatic patients. The more severe problems of GFD adherence usually occur during adolescence when in GFD non compliant subjects the lowest quality of life is reported. A psychological and educational support should be provided for these patients.

Severe clinical onset of diabetes and increased prevalence of other autoimmune diseases in children with coeliac disease diagnosed before diabetes mellitus

Abstract Aims/hypothesis. To analyse whether the time of diagnosis of coeliac disease with respect to the clinical onset of diabetes could differentiate subgroups of varying severity in patients with both diseases. Methods. We investigated 383 patients with Type I (insulin-dependent) diabetes mellitus for coeliac disease. Sex distribution, age at diagnosis of diabetes, prevalence of ketoacidosis at the onset of diabetes and prevalence of other autoimmune diseases were compared in patients. We divided these patients according to whether coeliac disease was diagnosed before (Group A, n=8) or after (Group B, n=24) diabetes onset and whether they had presented clinical symptoms of coeliac disease. Group C (n=351) included diabetic patients without coeliac disease. Results. Out of 383 Type I diabetic patients we found 32 coeliac subjects (8.3%). There was a higher number of girls (p=0.003), but similar age and prevalence of ketoacidosis compared with Group C; 18.7% had a third autoimmune disorder. The higher number of girls was confirmed in Groups A and B in comparison to Group C (p=0.013), while higher prevalence of both ketoacidosis (p=0.009) and other autoimmune diseases (p=0.001) was found only in Group A. Compared with symptomatic patients, asymptomatic subjects in Group B had a lower number of girls, older age at diabetes onset, lower prevalence of ketoacidosis and no other associated autoimmune disease. Conclusions/interpretation. A wide clinical spectrum characterises the association of coeliac disease and diabetes mellitus, with a severe clinical presentation (higher prevalence of ketoacidosis at the onset and occurrence of other autoimmune diseases) when coeliac disease is diagnosed before diabetes. Distinct phenotypes might imply the contribution of a peculiar genetic background.

Long-Term Follow-Up of Diabetes in Two Patients With Thiamine-Responsive Megaloblastic Anemia Syndrome

OBJECTIVE To describe a 15-year follow-up of diabetes and to present data regarding pancreatic β-cell function in two adolescents affected by the thiamine-responsive megaloblastic anemia (TRMA) syndrome. CASE REPORTS The first patient (PMR) is a 17.5-year-old Italian girl who presented megaloblastic anemia at 7.5 months of age. At age 2.5 years, because of the presence of diabetes and sensorineural deafness, she was diagnosed with TRMA syndrome and started treatment with thiamine-HCl, followed very early by benzoyloxymethyl-thiamine (BOM-T). The second patient (PF) is a 16.8-year-old Italian boy born to consanguineous parents. Sensorineural deafness was diagnosed at age 1.5 years, while diabetes with ketoacidosis and megaloblastic anemia were diagnosed at age 3 years. Treatment with thiamine HCl was started immediately after diagnosis and changed to BOM-T 2 months later. Subsequent to the initiation of the vitamin, the two patients did not require insulin for ∼ 7 and 10 years, respectively. Puberty was determinant in deteriorating the metabolic control in these patients, leading to treatment with an oral hypoglycemic agent and finally to a reinstitution of insulin therapy. CONCLUSIONS The hormonal assessment in our patients (normal insulin response to oral glucose in childhood, preserved C-peptide secretion in case 2) and the good response to an oral hypoglycemic agent would indicate that the pancreatic disease may initiate as type 2 diabetes and may progress after several years to an insulin-requiring diabetes, as indicated by the exhaustion of the insulin secretory capacity.

Continuous Glucose Monitoring System in the Screening of Early Glucose Derangements in Children and Adolescents with Cystic Fibrosis

BACKGROUND In cystic fibrosis (CF), diabetes mellitus (DM) is associated with progression of pulmonary disease and nutritional impairment. AIM To compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in patients with CF with early glucose derangements. PATIENTS AND METHODS Thirty-two patients with CF (5-20 years) with intermediate glucose values > 7.7 mmol/l during OGTT received a CGMS registration. Patients were classified into those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM, according to glucose values at 120 min of OGTT and during CGMS. Furthermore BMI z-scores, forced expiratory volume in 1 second (FEV1%), number of respiratory infections/year, enzyme supplementation, and HbA1c were evaluated. RESULTS OGTT and CGMS derangements were in agreement in 43.7% of the patients. BMI z-scores, FEV1%, number of respiratory infections/ year, enzyme supplementation, and HbA1c did not differ among the three groups. HbA1c, correlated positively with 120 min OGTT (r = 0.34; p = 0.059), CGMS area (r = 0.35; p = 0.048) and the number of respiratory infections, and negatively with FEV1%. CONCLUSIONS Intermediate glucose values during OGTT should be considered as a screening test in patients with CF. CGMS can be useful in studying the early occurrence of glucose derangements in selected patients.

Obesity Duration Is Associated to Pulmonary Function Impairment in Obese Subjects

Obesity is associated with pulmonary function disturbances. We hypothesized that lung function decreases with increasing duration of obesity. We evaluated pulmonary function tests (PFTs) in 188 nonsmoking subjects with primary obesity (aged 8–76 years; 36% with systemic hypertension). Duration of obesity was assessed by questionnaire in adults, and by height and weight growth patterns in children. Asthma and/or other allergic diseases were investigated by standardized questionnaires. BMI and BMI‐standard deviation scores (SDS) were 38.7 and 2.4 kg/m2, respectively. Forty‐six percent of patients were atopic. Among subjects with ever asthma (33%), 20 had current asthma (11% of the total). Forced vital capacity (FVC), forced expiratory volume in 1 s, total lung capacity (TLC), and functional residual capacity (FRC) were 103, 104, 95, and 76% predicted, respectively. Mean duration of obesity was 8.3 years. Compared with subjects who had been obese for ≤5 years, patients who had been obese for >15 years had significantly lower values on PFTs (P < 0.05). In subjects with systemic hypertension, PFTs were lower than in patients without hypertension (P < 0.01). Duration of obesity was significantly related to all PFTs (P ≤ 0.001). In a multiple regression analysis where duration and severity of obesity, hypertension, atopy, asthma, and family history of atopic diseases were independent variables, duration of obesity was a predictor of lower PFTs (P < 0.01). Of the remaining variables, only hypertension contributed to lower lung volumes. In obese individuals, lung function was significantly lower in subjects with greater years of obesity. Fat loss programs should be encouraged to prevent late pulmonary function impairment.

Prevalence of overweight in children with bone fractures: a case control study.

BackgroundChildrens fractures have been enlisted among orthopaedics complaints of childhood obesity. Unhealthy lifestyle behaviours may contribute to increased risk. This study described the prevalence of overweight/obesity in children and adolescents reporting a recent fracture in relation to gender, dynamic of trauma, and site of fracture.MethodsFour-hundred-forty-nine children and adolescents with fracture and 130 fracture-free controls were recruited from a large children’s hospital. The interaction between overweight and gender, dynamic of trauma, site of fracture was explored. Sports participation, television viewing, and calcium intake were also investigated.ResultsOverweight/obesity rate was increased in girls with fracture either at the upper or the lower limb (p= 0.004), while it was increased only in boys with fracture at the lower limb (p <0.02). Overweight/obesity rate did not differ between groups with low or moderate trauma. TV viewing ≥ 2 hrs was more frequent in children with fractures than controls (61.5% vs 34.5%, p =0.015) in the overweight/obese group.ConclusionsThe increased prevalence of overweight/obesity in children with fractures is related to gender and site of fracture. Higher levels of sedentary behaviours characterize overweight children reporting fractures.

Atypical celiac disease presenting as obesity-related liver dysfunction.

Asymptomatic liver involvement is more and more recognized in otherwise healthy, obese children (1–3). Loss of weight in these patients is an important target to achieve because it is most often followed by normalization of liver function tests, imaging, and histologic examination, thus reasonably confirming the causal role of weight excess with no need of further particular investigations. In the case of persisting liver disease despite a successful diet program, other causes of hypertransaminasemia and fatty liver should be ruled out. Hitherto, celiac disease has not been described as a condition possibly contributing to liver disease in obese patients. This may depend either on a true rarity of the association of these two conditions or on an insufficient correct investigation resulting from the bias of the seemingly improbable coexistence of celiac disease and obesity. However, there is some evidence that celiac disease is both an established cause of liver disease (4) and a condition possibly associated with obesity as well (5–7). Herein, we report for the first time a case of an obese child with weight-loss–resistant, longstanding liver disease. Liver abnormalities completely resolved only after gluten was withdrawn from diet after an unexpected diagnosis of celiac disease.