The Journal of clinical endocrinology and metabolism, Jan 11, 2015
Alström syndrome is characterised by increased risk of cardiovascular disease from childhood. To ... more Alström syndrome is characterised by increased risk of cardiovascular disease from childhood. To explore the association between risk factors for cardiovascular disease, aortic pulse wave velocity and vascular events in Alström syndrome. Cross-sectional analyses with 5 year follow up. The UK NHS nationally commissioned specialist clinics for Alström syndrome. Thirty one Alström patients undertook vascular risk assessment, cardiac studies and aortic pulse wave velocity measurement. Subsequent clinical outcomes were recorded. Insulin resistance was treated with lifestyle intervention and Metformin; diabetes with the addition of glitazones, GLP1 agonists and/or insulin. Thyroid and testosterone deficiencies were corrected. Dyslipidaemia was treated with statins and nicotinic acid derivatives. Cardiomyopathy was treated with standard therapy as required. The associations of age, gender and risk factors for cardiovascular disease with aortic pulse wave velocity was assessed, and correlat...
Alström Syndrome, a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically ch... more Alström Syndrome, a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multi-system involvement including early cone-rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of Alström Syndrome. Mutational analysis in a world-wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with Alström Syndrome, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all A...
Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bi... more Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices ...
Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribut... more Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced i...
Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma h... more Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma have been reported to date. Diagnosis of insulinoma could be difficult if the functional activity is incomplete, possibly leading to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by histological examination after surgery, characterized by a high intracystic insulin concentration despite normal blood basal levels of the hormone. New diagnostic findings from dynamic tests and cystic fluid examination have been carefully focused on.
The Journal of Clinical Endocrinology & Metabolism, 2004
Glucose transporter 4 (GLUT4) seems to be involved in the mechanism of insulin resistance in poly... more Glucose transporter 4 (GLUT4) seems to be involved in the mechanism of insulin resistance in polycystic ovary syndrome (PCOS) patients (PCOSs) in both muscular and adipose tissue. The observation that insulin stimulates glucose oxidation in endometrial cells led us to investigate the presence of GLUT4 in this tissue and whether a defect of GLUT4 is present at the endometrial level in PCOSs. We also investigated whether body weight influences GLUT4 expression in this syndrome. GLUT4 mRNA content was examined by real-time quantitative RT-PCR and immunostaining reaction in the endometrial tissue of nine normal subjects, nine lean and eight obese hyperinsulinemic (h-INS), and eight lean and 10 obese normoinsulinemic (n-INS) PCOSs. GLUT4 mRNA and its positive immunostaining reaction were present in epithelial cell level in the endometrium of both normal and PCOS subjects. Significantly higher levels of GLUT4 were observed in normal and lean n-INS PCOSs in comparison with other groups. In both n-INS and h-INS obese PCOSs, GLUT4 was significantly lower than in lean subjects. However, obese n-INS and lean h-INS PCOSs showed a similar low GLUT4 expression, whereas obese h-INS PCOSs showed the lowest expression when compared with other groups. In conclusion, our data demonstrate that GLUT4 is present in the endometrium of normal and PCOS subjects and that hyperinsulinism and obesity seem to have a negative effect on endometrial GLUT4 expression in PCOS.
Abstract The case of a female patient with a large multinodular goiter and severe primary hyperpa... more Abstract The case of a female patient with a large multinodular goiter and severe primary hyperparathyroidism (PHPT) is reported. She was treated with total thyroidectomy. At bilateral neck exploration, only 3 normal-sized parathyroid glands were found so that she ...
This is a case of a 48-year-old man treated with surgery and (131)I for papillary thyroid carcino... more This is a case of a 48-year-old man treated with surgery and (131)I for papillary thyroid carcinoma: a follow-up (18)F-FDG PET/CT incidentally evidenced pituitary uptake, also seen in (111)In-octreoscan as increased uptake in the sellar area. MRI confirmed a pituitary mass. The patient did not show any signs or symptoms related to this lesion; 1 year later, both PET/CT and MRI findings remained unchanged. Surgery confirmed nonfunctioning benign pituitary adenoma. This single case observed in 12,873 consecutive patients scanned in our center confirms the possibility that nonfunctioning benign pituitary adenomas may be FDG-avid: uptake mechanisms remain unknown, and targeted studies are needed.
The Journal of clinical endocrinology and metabolism, Jan 11, 2015
Alström syndrome is characterised by increased risk of cardiovascular disease from childhood. To ... more Alström syndrome is characterised by increased risk of cardiovascular disease from childhood. To explore the association between risk factors for cardiovascular disease, aortic pulse wave velocity and vascular events in Alström syndrome. Cross-sectional analyses with 5 year follow up. The UK NHS nationally commissioned specialist clinics for Alström syndrome. Thirty one Alström patients undertook vascular risk assessment, cardiac studies and aortic pulse wave velocity measurement. Subsequent clinical outcomes were recorded. Insulin resistance was treated with lifestyle intervention and Metformin; diabetes with the addition of glitazones, GLP1 agonists and/or insulin. Thyroid and testosterone deficiencies were corrected. Dyslipidaemia was treated with statins and nicotinic acid derivatives. Cardiomyopathy was treated with standard therapy as required. The associations of age, gender and risk factors for cardiovascular disease with aortic pulse wave velocity was assessed, and correlat...
Alström Syndrome, a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically ch... more Alström Syndrome, a recessive, monogenic ciliopathy caused by mutations in ALMS1, is typically characterized by multi-system involvement including early cone-rod retinal dystrophy and blindness, hearing loss, childhood obesity, type 2 diabetes mellitus, cardiomyopathy, fibrosis and multiple organ failure. The precise function of ALMS1 remains elusive, but roles in endosomal and ciliary transport and cell cycle regulation have been shown. The aim of our study was to further define the spectrum of ALMS1 mutations in patients with clinical features of Alström Syndrome. Mutational analysis in a world-wide cohort of 204 families identified 109 novel mutations, extending the number of known ALMS1 mutations to 239 and highlighting the allelic heterogeneity of this disorder. This study represents the most comprehensive mutation analysis in patients with Alström Syndrome, identifying the largest number of novel mutations in a single study worldwide. Here, we also provide an overview of all A...
Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bi... more Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type 1 diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular part, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/ poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices ...
Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribut... more Dysregulation of signaling pathways in adipose tissue leading to insulin resistance can contribute to the development of obesity-related metabolic disorders. Alström Syndrome, a recessive ciliopathy, caused by mutations in ALMS1, is characterized by progressive metabolic alterations such as childhood obesity, hyperinsulinemia, and type 2 diabetes. Here we investigated the role of Alms1 disruption in AT expansion and insulin responsiveness in a murine model for Alström Syndrome. A gene trap insertion in Alms1 on the insulin sensitive C57BL6/Ei genetic background leads to early hyperinsulinemia and a progressive increase in body weight. At 6 weeks of age, before the onset of the metabolic disease, the mutant mice had enlarged fat depots with hypertrophic adipocytes, but without signs of inflammation. Expression of lipogenic enzymes was increased. Pre-adipocytes isolated from mutant animals demonstrated normal adipogenic differentiation but gave rise to mature adipocytes with reduced i...
Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma h... more Cystic endocrine tumors of the pancreas rarely occur, and only a few cases of cystic insulinoma have been reported to date. Diagnosis of insulinoma could be difficult if the functional activity is incomplete, possibly leading to blunted symptoms of hypoglycemia and failure in the laboratory to provide evidence of hyperinsulinemia. We report a clinical case of cystic insulinoma confirmed by histological examination after surgery, characterized by a high intracystic insulin concentration despite normal blood basal levels of the hormone. New diagnostic findings from dynamic tests and cystic fluid examination have been carefully focused on.
The Journal of Clinical Endocrinology & Metabolism, 2004
Glucose transporter 4 (GLUT4) seems to be involved in the mechanism of insulin resistance in poly... more Glucose transporter 4 (GLUT4) seems to be involved in the mechanism of insulin resistance in polycystic ovary syndrome (PCOS) patients (PCOSs) in both muscular and adipose tissue. The observation that insulin stimulates glucose oxidation in endometrial cells led us to investigate the presence of GLUT4 in this tissue and whether a defect of GLUT4 is present at the endometrial level in PCOSs. We also investigated whether body weight influences GLUT4 expression in this syndrome. GLUT4 mRNA content was examined by real-time quantitative RT-PCR and immunostaining reaction in the endometrial tissue of nine normal subjects, nine lean and eight obese hyperinsulinemic (h-INS), and eight lean and 10 obese normoinsulinemic (n-INS) PCOSs. GLUT4 mRNA and its positive immunostaining reaction were present in epithelial cell level in the endometrium of both normal and PCOS subjects. Significantly higher levels of GLUT4 were observed in normal and lean n-INS PCOSs in comparison with other groups. In both n-INS and h-INS obese PCOSs, GLUT4 was significantly lower than in lean subjects. However, obese n-INS and lean h-INS PCOSs showed a similar low GLUT4 expression, whereas obese h-INS PCOSs showed the lowest expression when compared with other groups. In conclusion, our data demonstrate that GLUT4 is present in the endometrium of normal and PCOS subjects and that hyperinsulinism and obesity seem to have a negative effect on endometrial GLUT4 expression in PCOS.
Abstract The case of a female patient with a large multinodular goiter and severe primary hyperpa... more Abstract The case of a female patient with a large multinodular goiter and severe primary hyperparathyroidism (PHPT) is reported. She was treated with total thyroidectomy. At bilateral neck exploration, only 3 normal-sized parathyroid glands were found so that she ...
This is a case of a 48-year-old man treated with surgery and (131)I for papillary thyroid carcino... more This is a case of a 48-year-old man treated with surgery and (131)I for papillary thyroid carcinoma: a follow-up (18)F-FDG PET/CT incidentally evidenced pituitary uptake, also seen in (111)In-octreoscan as increased uptake in the sellar area. MRI confirmed a pituitary mass. The patient did not show any signs or symptoms related to this lesion; 1 year later, both PET/CT and MRI findings remained unchanged. Surgery confirmed nonfunctioning benign pituitary adenoma. This single case observed in 12,873 consecutive patients scanned in our center confirms the possibility that nonfunctioning benign pituitary adenomas may be FDG-avid: uptake mechanisms remain unknown, and targeted studies are needed.
Uploads
Papers by Pietro Maffei