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Biomedical subjects

C M Rotella

Publications and source records attributed to C M Rotella.

At least 37 records · Page 2Linked to original sources

IGFBPs modulate IGF-I- and high glucose-controlled growth of human retinal endothelial cells.

Insulin-like growth factor binding proteins (IGFBPs) are important local factors in the development of proliferative diabetic retinopathy. We investigated the effects of IGF-I and increased glucose concentrations on the release of IGFBPs and the growth of human retinal endothelial cells (HRECs). HRECs secrete IGFBPs-2 to -5. IGF-I stimulated thymidine incorporation and modified the pattern of IGFBPs, decreasing the inhibitory IGFBP-4 through down-regulation of its mRNA, and increasing IGFBP-5 which, per se, was able to modulate HREC growth, exerting post-transcriptional control. Studies using an antibody (alpha IR3) against the IGF-I receptor, and compounds with low affinity for IGFBPs, such as insulin and des(1-3)IGF-I, showed that an interaction between IGF-I and IGFBP-5 was necessary to detach this IGFBP from its binding sites. The dose of IGF-I that significantly decreased the IGFBP-4/IGFBP-5 ratio was the same that stimulated HREC growth. Chronic exposure to high concentrations of glucose was able to reduce HREC mitogenesis, interacting with the IGF system through a decrease in the stimulatory IGFBPs-2, -3 and -5, leaving the concentration of the inhibitory IGFBP-4 constant. These results extend our previous observations in endothelial cells and suggest that the IGFBP-4/IGFBP-5 ratio regulates IGF-I-induced growth of HRECs, whereas a general decrease in IGFBPs (except for IGFBP-4) was the anti-proliferative effect of chronic exposure to high glucose concentrations.

Analysis of Variance↗

Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects.

OBJECTIVE: To evaluate the effects of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels. RESEARCH DESIGN AND METHODS: A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects. On days 0 and 15, leptin and GLP-1(7-36)amide/(7-37) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion. The effects of metformin on GLP-1(7-36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV (DPP-IV) were also studied. RESULTS: Leptin levels were not affected by the oral glucose load, and they were not modified after metformin treatment. Metformin induced a significant (P < 0.05) increase of GLP-1(7-36)amide/(7-37) at 30 and 60 min after the oral glucose load (63.8 +/- 29.0 vs. 50.3 +/- 15.6 pmol/l and 75.8 +/- 35.4 vs. 46.9 +/- 20.0 pmol/l, respectively), without affecting baseline GLP-1 levels. No variations of GLP-1 levels were observed in the control group. In pooled human plasma, metformin (0.1-0.5 microg/ml) significantly inhibited degradation of GLP-1(7-36)amide after a 30-min incubation at 37 degrees C; similar results were obtained in a buffer solution containing DPP-IV. CONCLUSIONS: Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects; this effect could be due to an inhibition of GLP-1 degradation.

Adolescent↗

Anorexia nervosa and celiac disease: two case reports.

OBJECTIVE: Anorexia nervosa (AN) has been reported to be associated with several chronic medical illnesses. In this study, we report two cases of women suffering from AN and celiac disease. The former received the diagnosis of celiac disease before the onset of the eating disorder. For the latter, the diagnosis of celiac disease followed that of AN. Authors discuss the complex relationships between celiac disease and AN. They suggest that in the first case the dietary restriction could act as a trigger for the eating disorder, whereas in the second case, the onset of celiac disease could have exacerbated the clinical symptoms of AN.

Adult↗

Eating attitudes and behavior throughout the menstrual cycle in obese women: a case-control study.

Premenstrual variations of eating behavior are reported in several studies, but their relationship with mood is unclear. Eating behavior and physical and psychological complaints during the menstrual cycle were studied in 107 obese patients and 93 matched controls using retrospective (Weekly Bulimic Test Edinburgh, W-BITE and Premenstrual Assessment Form, PAF) and prospective (Daily Rating Form, DR) questionnaires. Eating disorder symptoms increased in the premenstrual phase, as shown by the W-BITE scores both in patients (6.2 +/- 5.3 premenstrual week vs 4.9 +/- 4.4 postmenstrual week, p < 0.05) and in control subjects (4.9 +/- 4.1 premenstrual week vs 4.2 +/- 3.0 postmenstrual week, p < 0.05) and were correlated to premenstrual complaints in control subjects (r = 0.5; p < 0.05) but not in obese women (r = 0.2; p = NS). A close relationship between physical and psychological premenstrual disturbances was observed in obese patients only. Premenstrual variation of eating behavior could be the target of specific treatment.

Adult↗

Glucagon-like peptide (GLP)-1 and leptin concentrations in obese patients with Type 2 diabetes mellitus.

AIMS: To assess differences in circulating leptin and glucagon-like peptide (GLP)-1 concentrations before and after an oral glucose load, in euglycaemic and isoinsulinaemic conditions, between obese patients with and without Type 2 diabetes mellitus. METHODS: Ten male obese (body mass index (BMI) > 30 kg/m2) patients with Type 2 diabetes and 20 matched non-diabetic subjects were studied. Leptin, GLP-1(7-36)amide and GLP-1(7-37) concentrations were measured 0, 30, 60, and 90 min after a 50-g oral glucose load administered 90 min after the beginning of a euglycaemic hyperinsulinaemic clamp. RESULTS: GLP-1(7-36)amide concentrations before the glucose load were significantly lower in diabetic patients than in controls (median (quartiles): 50.5 (44.7-53.2) vs. 128.7(100-172.5) pg/ml; P < 0.01), while no difference was observed in baseline GLP-1(7-37). In non-diabetic subjects, GLP-1(7-36)amide and GLP-1(7-37) concentrations increased significantly after the oral glucose load, while no glucose-induced increase in GLP-1 concentration was observed in diabetic patients. GLP-1(7-36)amide at 30, 60, and 90 min, and GLP-1(7-37) at 30 min, of the glucose challenge, were significantly lower in diabetic patients. Leptin concentrations were not significantly different in diabetic patients when compared to non-diabetic subjects, and they did not change after the oral glucose load. DISCUSSION: Leptin concentrations are not significantly modified in obese Type 2 diabetic patients. GLP-1(7-36)amide baseline concentrations are reduced in Type 2 diabetes; moreover, diabetic subjects show an impaired response of GLP-1 to oral glucose in euglycaemic, isoinsulinaemic conditions. This impairment, which is not the result of differences in glycaemia or insulinaemia during assessment, could contribute to the pathogenesis of hyperglycaemia in Type 2 diabetes mellitus.

Blood Glucose↗

5-HT2A receptor gene polymorphisms in anorexia nervosa and bulimia nervosa.

To examine the distribution of different polymorphisms in genes of the 5-HT system in patients with anorexia nervosa (AN) and bulimia nervosa (BN), we analyzed the distribution of a polymorphism (-1438G/A) and the presence of known mutations in 5-HT2A and 5-HT2C receptor genes in 168 Italian female patients affected by AN and BN. Patients with AN restricting type (ANr) only, unlike those with AN binge eating/purging type (ANp) and BN purging type (BNp), showed a statistically significant difference in 5-HT2A-1438A/A genotype frequency with respect to controls. With regard to the other polymorphisms, no differences were found in the studied groups with respect to controls. 5-HT2A promoter polymorphism is probably implicated in the susceptibility to eating disorders and its involvement is more significant in ANr, when compared with ANp and BNp.

Adolescent↗

Human glomerular endothelial cells IGFBPs are regulated by IGF-I and TGF-beta1.

The release of insulin-like growth factor binding proteins (IGFBPs) and their regulation in human glomerular endothelial cells (GENC) was characterised. GENC produce IGFBP-4, IGFBP-2 and IGFBP-3 and express mRNA for IGFBP-2 to IGFBP-5. Due to the fact that IGF-I and TGF-beta1 modulate glomerular hypertrophy, their action on IGFBP release and GENC growth was studied. IGF-I increased IGFBP-3, IGFBP-2 and decreased IGFBP-4, while TGF-beta1 decreased IGFBP-3 and apparently increased IGFBP-4. All of the IGFBPs, except the TGF-beta1-regulated IGFBP-4, were modulated at mRNA level. IGF-I stimulated GENC proliferation, while TGF-beta1 inhibited their growth. It was demonstrated that an IGFBP-3 antibody reduced GENC proliferation. However, rhIGFBP-3 alone had no effect on GENC, but after 48 h pre-incubation the IGF-I stimulated GENC growth was increased, suggesting that IGFBP-3 could modulate the IGF-I induced GENC proliferation. It was concluded that the stimulatory IGFBP-3 and the inhibitory IGFBP-4 could regulate GENC growth, although the IGFBP-3 seems to have a predominant effect in this control.

Cell Division↗

Failure of acupuncture in the treatment of obesity: a pilot study.

Acupuncture has been anecdotally reported to induce weight loss in obese patients. This pilot study examines its efficacy in a randomised, placebo-controlled clinical trial. Forty (33 F, 7 M) obese (BMI > 30 kg/m2) outpatients were randomised to either placebo or acupuncture (12 weekly sessions of minimal acupuncture and somatic moxibustion-acupuncture associated with auriculopuncture respectively). BMI, eating attitudes (BES), anxiety (STAI), depression (BDI), and obesity-related quality of life (ORWELL 97) were measured at the beginning and end of the treatment. Six (30%) patients in the treatment group and 12 (60%) in the placebo group dropped out. Intention-to-treat analysis did not show any significant effect of acupuncture on BMI and obesity-related quality of life; eating attitudes improved in both groups, possibly because of the placebo effect. A significant improvement in anxiety and depression was only observed in the acupuncture group. In conclusion, acupuncture does not promote weight loss and is not recommendable in the treatment of obesity. It may, however, improve the psychological status of obese patients.

Acupuncture Therapy↗

Venlafaxine versus fluoxetine in the treatment of atypical anorectic outpatients: a preliminary study.

The efficacy of venlafaxine and fluoxetine in the treatment of atypical anorexia nervosa (AN) was compared in a controlled trial. A consecutive series of 24 atypical anorectic females was assigned to either venlafaxine (75 mg/day) or fluoxetine (40 mg/day) plus cognitive-behavioural therapy (CBT). Eating Disorder Examination (EDE12.0D), Beck Depression Inventory (BDI) and State and Trait Anxiety Inventory (STAI) scores were compared before and after 6 months of treatment. Venlafaxine and fluoxetine determined an increase of body mass index (BMI) and a significant reduction of EDE12.0D and BDI scores; venlafaxine alone reduced STAI scores. It would seem that venlafaxine is as effective as fluoxetine when combined with CBT in the treatment of atypical AN.

Adolescent↗

Comparison of ADA and WHO screening methods for diabetes mellitus in obese patients. American Diabetes Association.

AIMS: To compare the performance of fasting glycaemia (FG) and oral glucose tolerance testing (OGTT) in screening for diabetes mellitus in obese patients. METHODS: A consecutive series of 528 (445 female, 83 male) obese (body mass index > 30 kg/m2) outpatients, aged 45.2 +/- 14.3 years, was studied with FG and OGTT. The association of categories of glucose tolerance (diabetes and impaired glucose tolerance (IGT)) and fasting glycaemia (diabetes and impaired fasting glucose (IFG)) with hypertension and hyperlipidaemia were also assessed. RESULTS: Prevalence of diabetes and IGT were 20.1 and 22.9%, respectively. FG (> 7 mmol/l) had a sensitivity of 56.7%. Using FG > 6.1 mmol/l, and OGTT in those above the threshold, the sensitivity for diabetes would have been 89.6%, with a positive predictive value of 59.0%, but 68.8% of cases of IGT would not have been detected. Patients with impaired fasting glucose (FG of 6.1-7.0 mmol/l) showed lower insulin sensitivity and impaired beta cell function, and a weaker association to hypertriglyceridaemia, when compared to IGT. CONCLUSION: FG > 7.0 mmol/l does not show a sufficient sensitivity for the screening of diabetes in obese patients. FG > 6. mmol/l has a satisfactory sensitivity for diabetes, but not for IGT. IFG has different pathophysiological features than IGT and cannot be assumed to have the same prognostic value of IGT.

Adult↗

Relationship between leptin and oestrogens in healthy women.

OBJECTIVE: Leptin. a protein secreted by white adipocytes, plays a relevant role in the regulation of body weight and food intake. A possible role for sex hormones in the regulation of leptin secretion has been suggested; however, the effect of variations in oestrogen concentration on serum leptin levels has not been described so far. METHODS: In study 1, serum leptin concentrations were measured on days 3, 10, 17 and 24 of the menstrual cycle in 18 healthy, lean, regularly menstruating women, aged 18-35 years. Serum oestradiol, progesterone, testosterone. Delta4-androstenedione, dehydroepiandrosterone sulphate (DHEAS). LH and FSH concentrations were also determined. In study 2, serum leptin and oestradiol levels were measured on the 5th and 7th day of ovarian stimulation with human FSH (225 IU daily) during an in vitro fertilisation programme for infertility in 20 women aged 25-45 years. RESULTS: The results from study 1 show a physiological fluctuation of leptin levels during the menstrual cycle, which has not been described previously. Leptin levels are significantly lower in the early follicular phase. The results of study 2 show a parallel increase in serum oestrogen and leptin concentrations during FSH administration. CONCLUSIONS: The fluctuation in leptin levels during the menstrual cycle observed in study 1 is compatible with the hypothesis of a stimulatory effect of oestrogen on leptin secretion. The results of study 2 support the hypothesis of a relevant role for oestrogen in the regulation of leptin secretion. Leptin fluctuations during the menstrual cycle are consistent with reported perimenstrual variations in food craving and consumption.

Adolescent↗

Clinical features of binge eating disorder in type I diabetes: a case report.

Eating disorders in patients with type I diabetes show some peculiar clinical features. We report the case of a young type I diabetic woman with binge eating disorder and dysthymic disorder. The patient shows a poor metabolic control and her body mass index is within the normal range. The eating disorder has been present for 3 years, and it developed after recurrent nocturnal hypoglycemic episodes. The authors discuss the complex relationships between binge eating disorder and hypoglycemic reactions and underline the diagnostic problems typical of comorbidity between type I diabetes and binge eating disorder.

Adult↗