Italian guidelines for the management of adult individuals with overweight and obesity and metabolic comorbidities that are resistant to behavioral treatment.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

Use of neutral protamine lispro insulin (NPL) in patients with hyperglycemia receiving parenteral nutrition.

AIMS: Nutritional support with parenteral nutrition (PN), a key component in the care of critically ill patients, usually requires insulin therapy in patients with diabetes or may require insulin treatment in patients not known to be diabetic. We wanted verify whether it is possible to use neutral protamine lispro (NPL) in double administration monotherapy in patients receiving artificial nutrition (AN) and if the same NPL is capable of obtaining and maintaining acceptable glycemic control without inducing hypoglycemia. PATIENTS AND METHODS: We studied 18 consecutive patients, who were not taking insulin, they needed to start artificial nutrition, and presenting at least two consecutive blood glucose > 120 mg/dL. Each patient was given at least 1 U of insulin for every 10 grams of glucose infused. RESULTS: Eighteen consecutive patients, not stratified in any way, were judged eligible in the last 24 months, with a mean age of 71 years (range 54-85 yrs). All patients were evaluated after 2, 3 and 5 days of treatment; only 1 patient has not been evaluated to 5 days. Mean glycemic values on days 2, 3, 5 were in range between 145 and 180 mg/dL. Any adjustments in NPL dose were carried out by the team of nutrition and there was no hypoglycemia that required medical intervention in emergency. CONCLUSIONS: Our impression is that also lispro protamine insulin (NPL) in double subcutaneous administration may contribute to improving the glycemic values in patients receiving parenteral nutrition with hyperglycemia.

Myenteric neuronal loss in rats with experimental colitis: role of tissue transglutaminase-induced apoptosis.

BACKGROUND AND AIMS: Transglutaminases are tissue enzymes involved in different neuronal processes including maintenance and signalling. However, their up-regulation elicited by a variety of noxae contributes to neurodegeneration. This study tested the hypothesis that experimental inflammation evoked transglutaminase up-regulation in myenteric neurons and that this event had an impact on neuronal survival. METHODS: Rats with or without trinitro-benzene-sulphonic acid-induced colitis were used. One week after colitis induction, longitudinal muscle-myenteric plexus preparations were obtained from left colon to assess tissue-transglutaminase activity, protein and mRNA expression. Double labelling immunofluorescence using antibodies to neuron-specific enolase and transglutaminase was performed to identify myenteric neurons expressing transglutaminase. Additional sets of experiments evaluated the involvement of transglutaminase in the apoptotic process of cultured myenteric neurons. RESULTS: Compared to controls, rats with colitis showed several tranglutaminase/neuron-specific enolase positive myenteric neurons. Western blot analysis and RT-PCR confirmed that in rats with colitis, the increased neuronal transglutaminase-immunoreactivity was associated with an increased enzyme expression. Similarly, transglutaminase activity was significantly higher than in controls (1100+/-280 m U/g vs. 725+/-119 m U/g, p<0.05). In cultured myenteric neurons incubation with the specific transglutaminase inducer, retinoic acid, significantly increased neuronal apoptosis, whereas the presence of cystamine significantly reduced the number of apoptotic neurons. CONCLUSIONS: Experimental colitis evoked transglutaminase up-regulation and increased activity in myenteric neurons. This mechanism enhances neuronal susceptibility to apoptosis and could contribute to neuropathic changes during gut inflammation.