Type 1 diabetes (T1DM) in children and adolescents of immigrated families in Emilia-Romagna (Italy).

BACKGROUND AND AIM OF THE WORK: The etiology and natural history of T1DM are still unknown but certainly both genetics and environmental factors contribute to the development of the disease. Migration studies are an important tool to better understand the role of the environment. The aim of this study was to investigate some variables in diabetic children of immigrant families living in Emilia-Romagna compared with Italian diabetic children living in the same region. METHODS: We recruited 73 diabetic children from immigrant families and 707 Italian diabetic children. All children were cared by Pediatric Diabetes Units of Emilia-Romagna (10 centers). The investigated variables were: gender, current age, place of birth, parents' country of origin, age at diagnosis, HbA1c and insulin regimen. RESULTS: No significant difference with reference to gender neither among the two ethnic groups, nor in the current mean age was observed. Mean age at diagnosis in the Italian children was lower than in immigrant patients born outside Italy--group A- (7.4 vs. 9.6, p < 0.000) and higher compared to those born in Italy--group B- (7.4 vs. 5.7 p < 0.003; A vs. B p < 0.000). The immigrant patients showed higher mean HbA1c than Italian patients (8.8 vs. 8.2, p < 0.009). CONCLUSIONS: A younger age at diagnosis of T1DM in immigrant children, born in Italy compared with those born in the country of origin, and with Italian patients, suggests the existence of some environmental determinants acquired with a more westernised lifestyle. Immigrant children have significantly poorer metabolic control compared with western patients. (www.actabiomedica.it)

Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene.

Glucokinase is essential for glucose-stimulated insulin release from the pancreatic beta-cell, serving as glucose sensor in humans. Inactivating or activating mutations of glucokinase lead to different forms of glucokinase disease, i.e. GCK-monogenic diabetes of youth, permanent neonatal diabetes (inactivating mutations), and congenital hyperinsulinism, respectively. Here we present a novel glucokinase gene (GCK)-activating mutation (p.E442K) found in an infant with neonatal hypoglycemia (1.5 mmol/liter) and in two other family members suffering from recurrent hypoglycemic episodes in their childhood and adult life. In contrast to the severe clinical presentation in the index case, functional studies showed only a slight activation of the protein (relative activity index of 3.3). We also report on functional studies of two inactivating mutations of the GCK (p.E440G and p.S441W), contiguous to the activating one, that lead to monogenic diabetes of youth. Interestingly, adult family members carrying the GCK pE440G mutation show an unusually heterogeneous and progressive diabetic phenotype, a feature not typical of GCK-monogenic diabetes of youth. In summary, we identified a novel activating GCK mutation that although being associated with severe neonatal hypoglycemia is characterized by the mildest activation of the glucokinase enzyme of all previously reported.

The continuous glucose monitoring system (CGMS) in patients with beta-thalassemia major and impaired glucose homeostasis: preliminary results.

Impaired glucose tolerance (IGT) and diabetes mellitus (DM) are well known complications in ?-thalassemia major (TM). In recent years new technologies have become available for the management of these conditions, including the continuous glucose monitoring system (CGMS). We implanted CGMS in six TM patients with abnormal glucose homeostasis after an oral glucose tolerance test (OGTT). Two-hour OGTT glucose values and CGMS fluctuations were classified as normal if <7.8 mmol/l, impaired if 7.8 to 11.1 mmol/l, diabetic if >11.1 mmol/l. All participants completed the study. The length of recording ranged from 69:30 hours to 94:35 hours. The TM patients spent from 1 to 23% of the time with a blood glucose level from 7.8 to 11.1 mmol/l. In five patients the CGMS confirmed the impaired glucose tolerance diagnosis and in one patient the CGMS excluded the diagnosis of diabetes. Our results demonstrate that the CGMS is a useful method to detect the variability of glucose fluctuations and offers the opportunity for better assessment of glucose homeostasis in TM patients.