The IMPROVE study--a multinational, multicentre, observational study in type 2 diabetes: results from the Italian cohort.

AIMS: The IMPROVE study evaluated the safety and effectiveness of biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients in the routine practice. Here we present the results for patients from Italy. METHODS: Adverse events, hypoglycaemia, glycaemic control, patient treatment satisfaction and physician resource utilisation were assessed at baseline and 26 weeks. RESULTS: Out of the 1371 patients enrolled, 84.1% (n=1153) were receiving BIAsp 30 at baseline (in accordance with local regulations), and were included in the study. Mean HlbA, reduction was--0.63% after 26 weeks (p < 0.001); 26.5% and 13.5% of patients reached the HbA(1c) targets of < 7% and < 6.5%, respectively. Fasting and postprandial blood glucose significantly decreased; 65% of patients were using BIAsp 30 once daily and 32% twice daily at final visit. Rates of major and minor hypoglycaemic events also significantly decreased. Small weight increase was observed, and total insulin daily dose increased from 0.29 IU/kg pre-study to 0.32 IU/kg at final visit. CONCLUSIONS: In Italy, BIAsp 30 in the routine care improved glycaemic control and reduced hypoglycaemia; however, there was little intensification and titration. This may partly explain the relatively small improvement in glycaemic control in Italy compared with other countries in the IMPROVE study.

Linkage studies for T2D in Chop and C/EBPbeta chromosomal regions in Italians.

The genes causing type 2 diabetes (T2D), a complex heterogeneous disorder, differ and/or overlap in various populations. Among others there are two loci in linkage to T2D, the chromosomes 20q12-13.1 and 12q15. These two regions harbor two genes, C/EBPbeta and CHOP, which are excellent candidate genes for T2D. In fact, C/EBPbeta protein cooperates with HNF4alpha (MODY1, monogenic form of diabetes) and 1alpha (MODY3, monogenic form of diabetes). C/EBPbeta mediates suppression of insulin gene transcription in hyperglycemia and may contribute to insulin-resistance. It interacts in a complex pathway with the CHOP protein. CHOP may play a role in altered beta-cell glucose metabolism, in beta-cell apoptosis, and in lack of beta-cell replication. Thus, both C/EBPbeta and CHOP genes may independently and interactively contribute to T2D. The chromosomal regions targeting C/EBPbeta and CHOP genes have never been previously explored in T2D. We planned to identify their potential contribution to T2D in Italians. We have genotyped a group of affected siblings/families with both late- and early-onset T2D around the C/EBPbeta and the CHOP genes. We have performed non-parametric linkage analysis in the total T2D group, in the late-onset and the early-onset group, separately. We have identified a suggestive linkage to T2D in the CHOP gene locus in the early-onset T2D group (P = 0.04). We identified the linkage to T2D in the chromosome 12q15 region in the early-onset T2D families and specifically target the CHOP gene. Our next step will be the identification of CHOP gene variants, which may contribute to the linkage to T2D in Italians.