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Biomedical subjects

C M Rotella

Publications and source records attributed to C M Rotella.

At least 19 recordsLinked to original sources
PubMed2006

Diabetic microangiopathy: IGFBP control endothelial cell growth by a common mechanism in spite of their species specificity and tissue peculiarity.

Endothelial cells (EC) play a role in many diseases including diabetes mellitus. EC share common functions, such as angiogenesis and vascular remodeling both regulated by proliferation and apoptosis, anti-thrombotic properties, regulation of vascular tone, control in the passage of nutrients and secretion of peptides and growth factors. However, EC are characterized by site-specificity so their characteristics depend on the organs and tissues where they are. The IGF system induces important growth factors that control cell growth in different microvascular EC (mEC). This family includes IGF-I and IGF-II peptides, their receptors and regulatory proteins IGF-binding proteins (IGFBP-1 to IGFBP-6). The IGFBP modulate their interaction with the IGF membrane receptors and might be regulated at a transcriptional and post-transcriptional level, thus determining the biological IGF-dependent effects on target cells. The IGF system is also a mediator of vascular diseases, and its altered balance might contribute to endothelial dysfunction with the development and evolution of diabetic microangiopathy. We reported here the reviewed literature of IGFBP production from various sources of mEC, showing that they predominantly express IGFBP-2 through IGFBP-5 mRNA. The different pattern of IGFBP secretion depends on the anatomical district and on the species of the tissues. Nevertheless, based on our and other experimental observations, we suggested that a common mechanism of IGFBP regulation in mEC could be hypothized. In retinal and glomerular EC the IGFBP4/IGFBP5 ratio controls the response of these cells to IGF-I and high levels of glucose, in terms of cellular growth.

Animals↗
PubMed2006

Clinical phenotype and beta-cell autoimmunity in Italian patients with adult-onset diabetes.

OBJECTIVE: To characterize the phenotype of a large population of Italian patients with adult onset (> or =40 years) diabetes who were attending outpatient clinics and who were screened for glutamic acid decarboxylase 65 autoantibodies (GADA), protein tyrosine phosphatase IA-2 (IA-2A) and IA-2beta/phogrin (IA-2betaA). DESIGN AND METHODS: This was a cross-sectional study comprising a total of 881 patients, aged < or = 70 years, diagnosed with type 2 diabetes after the age of 40 years, and consecutively recruited in five clinics located in different geographic areas of Italy (Milan, Florence, Rome, Naples and Catania). Their mean disease duration was 8.1 (6.9; s.d.) years. GADA, IA-2A and IA-2betaA were measured with radiobinding assays with in vitro translated S-methionine-labelled glutamic acid decarboxylase 65 (GAD65) or IA-2 or IA-2beta. Anthropometric and clinical data were collected and compared amongst patients with or without autoantibodies. RESULTS: Sixty-three (7.1%) patients had one or more autoantibodies, 58 (6.6%) had GADA, 22 (2.5%) had IA-2A, six (0.7%) had IA-2betaA and 19 (2.15%) had two or more autoantibodies. IA-2A or IA-2betaA, in the absence of GADA, were found in only five patients. Autoantibody-positive patients were more often female (63.5 vs 36.5%; P < 0.009), had higher glycated haemoglobin (Hb A1c) (P < 0.001), lower body mass index (BMI; P < 0.0005) and waist/hip ratio (WHR; P < 0.01); female gender being the main contributor to BMI and WHR. We did not observe any differences in age at diagnosis or duration of disease with respect to the presence or absence of islet autoantibodies. The proportion of patients on insulin therapy was higher in patients with two or more antibodies, compared with those with one antibody only, and no antibodies (P for trend < 0.001), and among patients with GADA, in those with higher antibody titre (73.9% in those with > 10 units vs 42.0% in those with < or = 10 units; P < 0.007). CONCLUSIONS: Patients with adult onset diabetes characterized by autoimmunity to beta-cells showed a clinical phenotype with anthropometric features that differed from those classically observed in patients with type 2 diabetes. The number and titre of autoantibodies, which reflect the severity of autoimmunity and beta-cell impairment, amplified this difference. The usefulness of autoantibody screening in adult-onset diabetes is further emphasized by these findings.

Aged↗
PubMed2005

Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus.

AIMS/HYPOTHESES: Chronic hyperglycaemia increases dipeptidyl peptidase IV (DPP-IV) activity in endothelial cells in vitro. The present study was designed to assess the effect of high glucose on circulating DPP-IV activity in patients with type 1 and type 2 diabetes. METHODS: Plasma DPP-IV activity was measured in 29 patients with type 1 diabetes and 29 age-, sex- and BMI-matched control subjects. We also assessed DPP-IV activity in 31 type 2 diabetic patients with HbA1c > 8.5% and in plasma from matched groups of 31 newly diagnosed diabetic subjects with HbA1c < 7.5%, 31 subjects with IGT and 62 subjects with NGT. In a further sample of 66 type 2 diabetic patients, a longitudinal study was also performed to evaluate variations in DPP-IV activity and HbA1c over 3 months. RESULTS: DPP-IV activity in type 1 diabetic patients was not significantly different from that in control subjects; however, a significant correlation between DPP-IV and HbA1c was observed in diabetic subjects (r = 0.47; p < 0.01). Type 2 diabetic patients with HbA1c > 8.5% showed significantly (p < 0.05) higher DPP-IV activity (mean+/-SD 27.7+/-7.1 U/l) than newly diagnosed diabetic patients and subjects with IGT (22.1+/-6.0 and 18.8+/-8.8 U/l, respectively). Variations in DPP-IV activity over 3 months in type 2 diabetic patients showed a significant positive correlation with variations in HbA1c (r = 0.26; p < 0.05). CONCLUSIONS/INTERPRETATION: Chronic hyperglycaemia induces a significant increase in DPP-IV activity in type 1 and type 2 diabetes. This phenomenon could contribute to the reduction in circulating active glucagon-like peptide-1 and to the consequent postprandial hyperglycaemia in type 2 diabetic patients with poor metabolic control.

Adult↗
PubMed2005

Eating disorders in patients with type 1 diabetes: a meta-analysis.

A meta-analysis of controlled studies on prevalence of eating disorders in Type 1 diabetes was performed in order to assess differences between diabetic and non-diabetic female subjects. All controlled studies using the Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised (DSM Ill-R) or the DSM Fourth Edition (DSM IV) criteria for interview-based diagnosis were included in the analysis. The total sample was composed of 748 and 1587 female subjects with and without diabetes, respectively. The prevalence of anorexia nervosa (AN) in Type 1 diabetic subjects was not significantly different from that of controls (0.27 vs 0.06%), while that of bulimia nervosa and of the two conditions combined was significantly higher in diabetic patients (1.73 vs 0.69%, and 2.00 vs 0.75%, respectively; both p < 0.05). Type 1 diabetes is associated with a higher prevalence of bulimia nervosa in females.

Adolescent↗
PubMed2005

Glucagon-like peptide 1 (GLP-1) and metabolic diseases.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone, mainly secreted after meals, which enhances glucose-induced insulin secretion and induces satiety. It has been reported that GLP-1 levels after a mixed meal and after an oral glucose load are reduced in patients with Type 2 diabetes. The reduction of oral glucose-stimulated active GLP-1 levels in patients with Type 2 diabetes has also been observed during euglycemic iperinsulinemic clamp. The reduction of post-prandial circulating active GLP-1 in Type 2 diabetic subjects, as a consequence of chronic hyperglycemia, could contribute to the reduction of early post-prandial insulin secretion; in fact, the administration of GLP-1 receptor antagonists to healthy volunteers elicits both an impairment of meal-induced insulin secretion and an increase of post-prandial glycemia similar to that observed in Type 2 diabetes. GLP-1 is rapidly inactivated by dipeptidyl peptidase IV (DPP-IV), an enzyme produced by endothelial cells in different districts and that circulates in plasma. It is still not clear whether the reduction of mealor oral-glucose stimulated GLP-1 levels in Type 2 diabetic patients is due to impairment of secretion, increase of degradation, or both. The major limitation of using GLP-1 to treat diabetic patients is the short half-life of the native compound. There are now several compounds in various stages of pre-clinical or clinical development for the treatment of Type 2 diabetes that utilize the GLP-1 signaling pathway; these include GLP-1 receptor agonists with extended half-lives, and inhibitors of DPP-IV that increase circulating levels of endogenous, intact and bioactive GLP-1.

Diabetes Mellitus, Type 2↗
PubMed2005

Long-term interactive group education for type 1 diabetic patients.

The aim of this study was to assess the feasibility and efficacy of an Interactive Educational and Support Group programme (IESG) for patients with type 1 diabetes. A sample of 96 type 1 diabetic outpatients was studied measuring the effects of participation in IEGS on metabolic control and diabetes-related quality of life (QoL). Those refusing to participate (n = 48) and a sample of 37 patients who were not invited to IESG (control) where studied for comparison. After one year, participants showed a significant (p < 0.05) improvement of HbA(1c) from 7.7+/-1.6 to 7.2+/-1.5%, whereas no variation of HbA(1c) was observed in non-participants and controls. No significant variation of QoL was observed in any of the three groups. At two-years follow-up, HbA(1c) of the patients attending IESG was not significantly different from that at one-year follow-up, and it was significantly lower than that observed at enrolment. QoL showed a significant improvement at 2 years with respect to baseline and one-year follow-up. In conclusion, this programme appears to be effective in the improvement of medium term metabolic control and QoL.

Adolescent↗
PubMed2004

The Eating Disorder Examination as a retrospective interview.

UNLABELLED: The purpose of this study was to determine the validity of the Eating Disorder Examination 12.0D (EDE) when administered retrospectively. METHODS: Twenty-five female patients suffering from an eating disorder [(10 with anorexia nervosa (AN), 10 with bulimia nervosa (BN), 5 with eating disorders not otherwise specified (EDNOS)] were investigated using the EDE at the time of the first referral to our outpatient ward (T1). Afterwards (mean 1.4 +/- 0.6 years later) each patient was administered again the EDE by the same assessor (T2). At this time the interviewer asked the patients to answer the questions referring to the symptoms and behaviours at the time of the first interview. RESULTS: Test-retest correlation factors were 0.7 or greater for all subscales of the EDE (p < 0.0001) and 0.5 or greater for every single item of the EDE (p < 0.001), except for EDE 1.5 (snack after dinner) and EDE 9A.6 (maximum time free from objective bulimic episodes in the last two months). DISCUSSION: Our results provide evidence that the EDE 12.0D is a reliable interview even when administered retrospectively, suggesting the use of this instrument for the retrospective assessment of eating disorders.

Adult↗
PubMed2004

Effects of metformin on glucagon-like peptide-1 levels in obese patients with and without Type 2 diabetes.

Metformin has been shown to increase glucagon-like peptide-1 (GLP-1) levels after an oral glucose load in obese non-diabetic subjects. In order to verify if this effect of the drug was also present in obese Type 2 diabetic patients who have never been treated with hypoglycemic drugs, 22 Type 2 diabetic and 12 matched non-diabetic obese patients were studied. GLP-1 was measured before and after a 100 g glucose load at baseline, after a single oral dose of 850 mg of metformin, and after 4 weeks of treatment with metformin 850 mg three times daily. Post-load GLP-1 levels were significantly lower in diabetic patients. A single dose of metformin did not modify GLP-1 levels. After 4 weeks of treatment, fasting GLP-1 increased in diabetic patients (3.8 vs 4.9 pmol/l; p<0.05), while the incremental area under the curve of GLP-1 significantly increased in both diabetic [93.6 (45.6-163.2) vs 151.2 (36.0-300.5) pmol x min/l; p<0.05] and non-diabetic [187.2 (149.4-571.8) vs 324.0 (238.2-744.0) pmol x min/l; p<0.05] subjects. In conclusion, GLP-1 levels after an oral glucose load in obese type 2 diabetic patients were increased by 4 weeks of metformin treatment in a similar fashion as in obese subjects with normal glucose tolerance.

Adult↗
PubMed2003

Adherence to structured physical exercise in overweight and obese subjects: a review of psychological models.

Regular physical exercise is a widely accepted means of reducing mortality and improving a number of health outcomes, which is also efficacious in the treatment of obesity. Unfortunately, despite the evidence of favourable short- and long-term effects, the results seem to be affected by a lack of adherence, particularly over the long term. It is very important to evaluate and predict good adherence in order to be able to assess the real efficacy of physical activity in the treatment of various diseases. In this paper, we describe most of the psychological models used to evaluate such adherence, and investigate the physiological and psychological bases of physical activity, the most suitable type of exercise for obese patients and some useful strategies for ensuring long-term adherence.

Exercise↗
PubMed2003

Fasting plasma glucose and glycated haemoglobin in the screening of diabetes and impaired glucose tolerance.

The use of fasting plasma glucose (FPG) only has been proposed for the screening and diagnosis of diabetes, but its sensitivity has been reported to be unsatisfactory. The use of HbA1C, alone or combined with FPG, has been suggested for the screening of diabetes and impaired glucose tolerance (IGT). In a sample of 1215 adult subjects without previously known diabetes, we assessed the sensitivity and specificity of FPG and HbA1C in diagnosing diabetes and IGT, determined by oral glucose tolerance test (OGTT). All lean diabetic patients, and 85% of overweight and obese diabetic individuals, had FPG > or =7 mmol/l. FPG >6.1 mmol/l had a sensitivity of 98.8% and a specificity of 32.9%; HbA1C had a lower specificity and sensitivity for the screening of diabetes. A screening strategy for diabetes based on FPG, with OGTT in all overweight subjects with FPG >6.1 mmol/l, is suggested. Neither FPG nor HbA1C is effective in the screening of IGT; although combined FPG and HbA1C could be useful for case finding, screening for IGT with OGTT is advisable in all subjects at high risk.

Adult↗
PubMed2003

Eating behavior and thyroid disease in female obese patients.

It has been suggested that preexisting thyroid disease (TD) could be a risk factor for the development of eating disorders. The aim of this study was to compare eating attitudes and behavior in female obese patients with and without TD. Thyrotropin (TSH) was determined in 256 patients aged 44.9+/-14.7 years with body mass index (BMI) >30 kg/m(2); eating attitudes and behavior were assessed with the Eating Disorder Examination (EDE). EDE Shape Concern score was significantly higher in patients with previous or current hypothyroidism (N=30) than in the rest of the sample. Among patients without known TD, no difference in eating attitudes was observed between patients with elevated TSH (N=24; 11%) and those with normal thyroid function. The prevalence of binge eating disorder (BED) in the total sample was 9.7%; no difference in prevalence was observed between patients with and without a history of hypothyroidism, and between those with and without previously unknown hypothyroidism. In conclusion, known hypothyroidism is associated with increased shape concern; this does not appear to be related to differences in current levels of thyroid hormones or related hormones.

Journal Article↗
PubMed2003

Comparison among different insulin sensitivity indices in obese patients.

AIMS: Recently, several indices have been proposed for the measurement of insulin sensitivity (IS). We set out to make a comparison between fasting insulin, and different IS indices in obese subjects. PATIENTS AND METHODS: Fasting and post load (75 g) glucose and insulin were measured in a consecutive series of 767 (626 F, 141 M) obese (body mass index > 30 kg/m(2)) out-patients, with no known history of diabetes (DM). Mean (+/- sd) age was 46.7 +/- 13.8 years in females and 45.6 +/- 14.3 years in males. Indices of IS based on fasting homeostasis assessment model (HOMA) and post-load (ISI) glucose and insulin and either parameter (1A, and 1B scores) were determined. RESULTS: DM was diagnosed in 21.4% of females, and 20.6% of males, and impaired glucose tolerance in 24% females and 21.3% males. Fasting and post-load glucose, triglyceride and HDL-cholesterol were correlated with all indices in both sexes (P < 0.05). The relative risk of different conditions in the upper quartile of ISI was similar to that observed in the upper quartile of HOMA. The HOMA index was similarly associated with low HDL-cholesterol and hypertriglyceridaemia as fasting insulin, while it showed a greater association with diabetes; ISI was similarly associated with all three conditions as the HOMA index. CONCLUSIONS: Indices of IS based on fasting glucose and insulin show a greater association with diabetes, but not with other abnormalities related to insulin resistance, when compared with fasting insulin levels. Indices based on post-load glucose and insulin do not offer any advantage over those based on fasting values.

Adult↗
PubMed2002

Sibutramine lost and found.

Obesity has now been identified as a chronic disease, a global epidemic (globesity) and a serious public health issue that leads to reduced life expectancy, an increased risk for many serious medical conditions and enormous healthcare costs. The prevalence of obesity and overweight in Italy in 2000 was respectively 9% and 33%, and has grown by 25% over the last five years. Even moderate weight loss can improve obesity-related morbidity and mortality. In November 1997, the US Food and Drug Administration approved sibutramine, a serotonin and noradrenaline reuptake inhibitor, for the treatment of pathological obesity and the management and maintenance of weight loss. In March 2002, sibutramine was temporarily withdrawn from the Italian market on the basis of 47 adverse event reports received between April and December 2001. However, a worldwide review of efficacy and safety data has shown that the overall risk/benefit profile of sibutramine remains favourable, with the rate of fatal reports involving patients receiving sibutramine being 200 times less than the obese women's mortality rate in the Nurses' Health Study. There is strong evidence supporting the usefulness of the correct use of sibutramine in the management of obesity.

Antidepressive Agents↗
PubMed2002

Eating behavior in obese patients with and without type 2 diabetes mellitus.

OBJECTIVE: Aim of this study was the assessment of the prevalence of eating disorders, and of eating disorder symptoms, in obese patients with type 2 diabetes, compared to non-diabetic subjects. DESIGN: Three samples of individuals were studied: a series of 156 (76 male, 80 female) overweight and obese type 2 diabetic patients, aged 30-65 y, with a body mass index (BMI)>28 kg/m(2) (DM); a series of 192 (20 male, 172 female) obese (BMI>30 kg/m(2)) non-diabetic patients aged 30-65 y seeking treatment for weight loss (OC); and a non-clinical sample of 48 (22 male, 26 female) obese (BMI>30 kg/m(2)) subjects aged 30-65 y selected from the lists of two general practices (OP). Eating behavior was assessed using the Eating Disorder Examination (EDE 12.0D). RESULTS: The prevalence of Binge Eating Disorder was lower than 5% in all the three samples. Median EDE scores in females were significantly higher in OC (3.0) and OP (3.4) than in DM (1.7), while diabetic patients showed higher scores on Restraint than both non-diabetic samples. Among diabetic patients, a significant correlation of EDE scores with HbA(1)c was observed. CONCLUSIONS: Type 2 diabetes is unlikely to induce relevant eating disturbances in obese patients, apart from an increase in restraint. Abnormalities of eating attitudes and behavior are associated with an impairment of metabolic control.

Adult↗
PubMed2002

The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.

Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

Adolescent↗
PubMed2001

Psychopathological and clinical features of outpatients with an eating disorder not otherwise specified.

In order to investigate similarities and differences between Eating Disorder Not Otherwise Specified (EDNOS) and Anorexia Nervosa (AN) and Bulimia Nervosa (BN), we studied a consecutive series of 189 female outpatients attending two Eating Disorder Units. The data were collected by means of interviews (Eating Disorder Examination, EDE 12.0D), the Structured Diagnostic Interview for DSM III-R, (SCID), and self-reported questionnaires (Beck Depression Inventory, BDI, and State and Trait Anxiety Inventory, STAI 1-2). The diagnosis of EDNOS was as frequent as that of AN and BN (43.8% versus 43.2%). There were no significant differences between EDNOS and AN/BN patients in terms of their general and specific psychopathological features, but significant differences were observed between bulimic-like and anorectic-like EDNOS patients, as well as between those with AN and BN. In conclusion, in our clinical setting, the patients with EDNOS and those with typical eating disorders have similar psychopathological features, thus suggesting that EDNOS patients should be further divided into two groups, anorectic-like (similar to AN) and bulimic-like (similar to BN) patients.

Adolescent↗
PubMed2001

Direct measurement of IGF-I and IGFBP-3 in bronchoalveolar lavage fluid from idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterized by the rearrangement of extracellular matrix and progressive increase in the amount of fibrotic tissue in the lung. IGF-I is a potent profibrogenic molecule and its bioavailability is dependent on at least 6 binding proteins called IGFBPs. Among these, IGFBP-3 is the most represented in serum and in different connective tissues. The purpose of this study was to identify and characterize IGFBP-3 in bronchoalveolar lavage (BAL) fluids. We studied 11 patients with IPF and 6 normal subjects by performing baseline pulmonary function test and BAL. IGF-I and IGFBP-3 were measured by RIA in BAL and serum. No significant differences were observed between serum IGF-I and IGFBP-3 from IPF patients and normal subjects. Instead, the direct measurement in BAL revealed a significant increase of IGF-I and IGFBP-3 in IPF patients compared to normal subjects. BAL IGF-I and IGFBP-3 concentrations were significantly related to inspiratory vital capacity (IVC) and carbon dioxide partial pressure (PaCO2): the higher the value of IVC and the lower the value of PaCO2, the higher the level of IGF-I and IGFBP-3. In conclusion, IGFBP3 and IGF-I could be important local mediators of IPF. Their direct measurement in BAL in IPF patients could be used as a clinical marker of the disease, since high levels of IGFBP-3 and IGF-I in BAL are associated to the initial phase of the disease.

Aged↗