BACKGROUND AND AIM: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). METHODS AND RESULTS: Questionnaires investigating the organisation of diabetes care centres, individuals' clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. <58 mmol/mol for age <18 years and <53 mmol/mol for age >18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. CONCLUSIONS: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia.

To investigate the role of IRS1 locus on failure to oral antidiabetes drugs (OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326 (tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R amino acid substitution) in 2662 patients with T2D. Although no association with OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93-1.16 and OR: 0.97, 95% CI: 0.87-1.09 respectively), a significant association was observed for rs1801278 (OR: 1.34, 95% CI: 1.08-1.66). When meta-analyzed with previous published data, an allelic OR of 1.41 (1.15-1.72; P=0.001) was obtained, so that homozygous R972R individuals have >80% higher risk of failing to OADs as compared with their G972G counterparts. In all, though further studies are needed for confirming this finding, our present data point to IRS1 rs1801278 as a potential biomarker for pursuing the goal of stratified medicine in the field of antihyperglycemic treatment in T2D.

There are contrasting views on whether familial non-medullary thyroid carcinomas (FNMTCs) are characterized by aggressive behavior, and limited evidence exists on the prognostic value of BRAF and RAS mutations in these tumors. Thus, in the present study, clinicopathological features were analyzed in 386 non-medullary thyroid carcinomas (NMTCs), subdivided in 82 familial and 304 sporadic cases. Furthermore, the RAS and BRAF mutational statuses were investigated in a subgroup of 34 FNMTCs to address their clinical and biological significance. The results demonstrated that, compared with sporadic NMTCs, FNMTCs are characterized by significantly higher rates of multicentricity and bilaterality and are more frequently associated with chronic autoimmune thyroiditis. Notably, a statistically significant difference in the rates of multicentricity was observed by subgrouping familial tumors according to the number of relatives involved; those with ≥3 affected relatives were more likely to be multicentric. Furthermore, the FNMTC cohort exhibited higher rates of tumors >4 cm in size with extrathyroidal or lymph node involvement. However, no significant difference was observed. Similarly, no differences were observed with respect to the age of onset or the patient outcome. The mutational profiling exhibited a rate of 58.8% for BRAF V600E mutations in familial tumors, which is at the upper limit of the mutational frequency observed in historical series of sporadic thyroid cancer. A high rate of NRAS mutations (17.6%) was also observed, mostly in the follicular variant histotype. Notably, compared with BRAF/RAS-wild type FNMTCs, the familial carcinomas bearing BRAF or NRAS mutations exhibited slightly higher rates of bilaterality and multicentricity, in addition to increased frequency of locally advanced stage or lymph node involvement. The present data support the theory that FNMTCs are characterized by clinicopathological features that resemble a more aggressive phenotype and suggest that RAS/BRAF mutational analysis deserves to be further evaluated as a tool for the identification of FNMTCs with a potentially unfavorable prognosis.