Maria Chiara Masoni

Malnutrition, anorexia and cachexia in cancer patients: A mini-review on pathogenesis and treatment

Malnutrition, anorexia and cachexia are a common finding in cancer patients. They become more evident with tumor growth and spread. However, the mechanisms by which they are sustained often arise early in the history of cancer. For malnutrition, these mechanisms can involve primary tumor or damage by specific treatment such as anticancer therapies (surgery, chemotherapy, radiotherapy) also in cancers that usually are not directly responsible for nutritional and metabolic status alterations (i.e. bone tumors). For anorexia, meal-related neural or hormonal signals and humoral signals related to body fat or energy storage and the interaction of these signals with the hypothalamus or the hypothalamic inappropriate response play a pathogenetic role. Some cytokines are probably involved in these mechanisms. For cachexia, the production of proinflammatory cytokines by tumour cells is the initial mechanism; the main biochemical mechanisms involved include the ubiquitine proteasome-dependent proteolysis and heat shock proteins. Treatment includes pharmaceutical and nutritional interventions.

Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes.

Background Sitagliptin has been proven to be effective and safe as add-on to insulin in adult patients with type 2 diabetes and absolute insulin deficiency. Recently, it has been suggested to extend the use of dipeptidyl-peptidase-4 inhibitors to type 1 diabetes. The aim of this study was to evaluate and compare the effects of a long-term, fixed-dose combination of sitagliptin and metformin as add-on to insulin on body mass index, fasting plasma glucose, fructosamine, HbA1c, lipids, and daily dose of insulin in both type 1 diabetes and insulin-treated type 2 diabetes. Methods We recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively. Results After 21 ± 9 weeks, patients with type 1 diabetes had a significantly lower body mass index, fasting plasma glucose, fructosamine, HbA1c, and daily insulin requirement. After 49 ± 17 weeks, they maintained their weight loss and total daily insulin dose and showed a significant reduction in low-density lipoprotein cholesterol levels, whereas their HbA1c had returned to baseline values. In patients with type 2 diabetes, long-term treatment remained weight-neutral but had persistent beneficial effects on short-term, intermediate-term, and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement. Conclusion Clinical outcomes differed according to type of diabetes in terms of quality and over time. In type 2 diabetes, the combination therapy significantly improved metabolic control and the lipid profile, and decreased insulin requirements, even in the absence of clinically significant weight loss. In type 1 diabetes, the combined therapy only temporarily improved metabolic control, but significantly decreased body weight, low-density lipoprotein cholesterol levels, and insulin requirements.

Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer

BackgroundNormotensive non-diabetic relatives of type 1 diabetes (T1D) patients have an abnormal blood pressure response to exercise testing that is associated with indices of metabolic syndrome and increased oxidative stress. The primary aim of this study was to investigate the circadian variability of blood pressure and the ambulatory arterial stiffness index (AASI) in healthy siblings of T1D patients vs healthy control subjects who had no first-degree relative with T1D. Secondary aims of the study were to explore the influence of both cardiovascular autonomic function and erythrocyte electron transfer activity as oxidative marker on the ambulatory blood pressure profile.MethodsTwenty-four hour ambulatory blood pressure monitoring (ABPM) was undertaken in 25 controls, 20 T1D patients and 20 siblings. In addition to laboratory examination (including homeostasis model assessment of insulin sensitivity) and clinical testing of autonomic function, we measured the rate of oxidant-induced erythrocyte electron transfer to extracellular ferricyanide (RBC vfcy).ResultsSystolic blood pressure (SBP) midline-estimating statistic of rhythm and pulse pressure were higher in T1D patients and correlated positively with diabetes duration and RBC vfcy; autonomic dysfunction was associated with diastolic BP ecphasia and increased AASI. Siblings had higher BMI, lower insulin sensitivity, larger SBP amplitude, and higher AASI than controls. Daytime SBP was positively, independently associated with BMI and RBC vfcy. Among non-diabetic people, there was a significant correlation between AASI and fasting plasma glucose.ConclusionsSiblings of T1D patients exhibited a cluster of sub-clinical metabolic abnormalities associated with consensual perturbations in BP variability. Moreover, our findings support, in a clinical setting, the proposed role of transplasma membrane electron transport systems in vascular pathobiology.

Exploring Leukocyte Mitochondrial Membrane Potential in Type 1 Diabetes Families

Proper cellular function requires the maintenance of mitochondrial membrane potential (MMP) sustained by the electron transport chain. Mitochondrial dysfunction is believed to play a role in the development of diabetes and diabetic complications possibly because of the active generation of free radicals. Since MMP can be investigated in clinical settings using fluorescent probes and living whole blood cells, mitochondrial membrane alterations have been observed in some chronic disorders. We have used the mitochondrial indicator 5,5′,6,6′-tetra chloro-1,1′,3,3′-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) in conjunction with flow cytometry to measure the MMP in peripheral blood granulocytes from type 1 diabetes (T1D) families. The intracellular ROS levels and the respiratory burst activity were also measured. Leukocyte MMP was elevated in 20 T1D patients and their 20 non-diabetic siblings compared with 25 healthy subjects without family history of T1D. Fasting plasma glucose was the only correlate of MMP. If confirmed by further observations, the functional implications of mitochondrial hyperpolarisation (probably different among different cells) will require extensive investigation.

The Effect of Low-dose Orlistat (60 mg Twice Daily) on Weight-loss and Markers of Metabolic Disease in Obese Subjects: A Preliminary Report

Aims: The use of Orlistat as an aid for weight loss has increased among obese individuals over recent years. Although the most frequently administered dosage is 120 mg three times daily, data on the metabolic effects of this drug are inconclusive. The primary aim of the present study was to determine the effectiveness of chronic, low-dose Orlistat administration on weight reduction and metabolic profile among individuals who present for weight loss. Methods: We report here results from a three month study at a low-dose (60 mg twice daily) in 15 obese subjects with metabolic syndrome characteristics (hyperglycaemia, dyslipidaemia, hypertension) with no change of diet and physical habits and no other drugs. Results and Conclusion: We observed a significant decrease of weight, BMI, glucose and glycated haemoglobin, diastolic pressure, total cholesterol, LDL cholesterol, non-HDL cholesterol, triglycerides, with a mild significant rise of HDL cholesterol. Of relevance, the decrease of non-HDL fraction was double of that of LDL (13 vs 7%), possibly suggesting effectiveness not only on LDL

Plasma Levels of Neuropeptide Y and Peptide YY in Patients Diagnosed with Anorexia Nervosa and Type 2 Diabetes Morbid Obese Subjects

Anorexia Nervosa (AN) and Obesity are prevalent in modern societies. This study evaluate circulating levels of Neuropeptide Y (NPY) and of Peptide Tyrosine-Tyrosine (PYY) in 60 women: 20 affected by AN (Body Mass Index = BMI 15.74 ± 2.09 kg/m2, age 30.19 ± 10.52 yr), 10 restrictor (BMI 14.89 ± 1.64 kg/m2) and 10 binge-purge subtype (BMI 18.27 ± 0.81 kg/m2); 20 affected by severe Obesity (BMI>40 kg/m2; age 33.56 ± 5.2 yr) with type II diabetes with no therapy, and 20 healthy controls (BMI 22.06 ± 0.93 kg/m2, age 32.44 ± 4.35 yr). NPY is higher in AN than obese and controls (70.17 ± 20.84 vs 25.12 ± 7.26 and 52.20 ± 10.88 pmol/L; p<0.001) and lower in obese than controls (p<0.001). PYY is higher in AN than obese and controls (219.77 ± 83.51 vs 116.42 ± 41.42 and 94.97 ± 12.74 pg/ml; p<0.001), with no differences between obese and controls. In AN, NPY and PYY are quite higher (p=0.059; p=0.06) in restrictor (75.77 ± 20.86 pmol/L; 241.78 ± 84.6 pg/ml) than in binge-purge subtype (53.39 ± 8.72 pmol/L; 153.73 ± 29.45 pg/ml). Increase of NPY despite simultaneous PYY increase in AN might be related to reduced sensitivity to PYY inhibitory effect on NPY production or increased production of NPY from sympathetic peripheral nervous system, a finding evident mainly in restrictor AN. In obese PYY is close to controls suggesting a reduced intestinal production of this peptide because of the stimulus of continuous overfeeding, whereas the reduced NPY production could be explained by increased levels of insulin and leptin. Reduced NPY levels suggest that in these obese the overfeeding is not dependent on increased hungry signal, but on inadequate satiety signal.