Significant lower VVH7-like immunoreactivity serum level in diabetic patients: evidence for independence from metabolic control and three key enzymes in hemorphin metabolism, cathepsin D, ACE and DPP-IV.

Low circulating VVH7-like immunoreactivity (VVH7 i.r) level was amazingly observed in human diabetic sera. Here, we examined the impact of diabetes type, clinico-biological features and metabolic control on circulating VVH7 i.r level in this disease. ELISA test was used to measure VVH7 i.r in sera of 120 diabetic patients (type 1 diabetes in 64, type 2 diabetes in 56). Three enzymatic tests were also applied to determine serum cathepsin D (CD), dipeptidyl peptidase IV (DPP-IV) and angiotensin-converting enzyme (ACE) activities. A subgroup of 24 type 1 diabetic patients negative for microalbuminuria and hypertension were submitted to an ambulatory blood pressure monitoring to evaluate the relationship between VVH7 i.r level and blood pressure parameters. The mean serum concentration of VVH7 i.r was drastically reduced in diabetic patients (0.91+/-0.93 micromol/l versus 5.63+/-1.11 micromol/l in controls) (p<0.001). A negative correlation between VVH7 i.r level and daytime diastolic blood pressure existed in type 1 diabetic patients. There was no association of low VVH7 i.r with either type of diabetes or HbA1c level. An increase of cathepsin D activity was found in serum of diabetic patients compared to controls (0.47 U/ml versus 0.15 U/ml, respectively) whereas DPPIV activity was significantly decreased in diabetic sera (50.81 U/ml versus 282.10 U/l respectively). Diminution of VVH7 i.r in sera of diabetic patients was confirmed but still remained unexplained. Relationships between higher systolic blood pressure and decrease of VVH7 i.r reinforce the need to investigate this pathway in this disease to elucidate its role in macro- and micro-angiopathy.

Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: a retrospective 35-year study of 12 patients.

AIM: Sporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI. METHODS: Every patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded. RESULTS: The ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up. CONCLUSION: Aggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.