Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). AIMS: To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. METHODS: One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL-6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). RESULTS: By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003-1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023-2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771-8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231-6.757, P = 0.01) were correlated with significant fibrosis (F2-F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). CONCLUSIONS: In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis.

La intususcepción en el adulto como causa de oclusión intestinal / Bowel oclusion by adult intussusception

Antecedentes. La intususcepción en el adulto representa el 1 por ciento de las causas de oclusión intestinal. La presentación más frecuente es la oclusión intestinal. En la mayoría de los casos, el diagnóstico se realiza en la intervención. Objetivo. Describir los resultados de nuestra serie. Lugar de aplicación. Hospital universitario. Diseño. Estudio retrospectivo. Población. Se realizó una revisión retrospectiva de las historias clínicas de los pacientes admitidos por oclusión intestinal entre 2002-2004. De los casos en los que la causa de oclusión fue una intususcepción de intestino delgado se analizaron la edad, sexo, presentación, intervención realizada y anatomía patológica de estos pacientes. Método. Recopilación retrospectiva de casos. Se revisaron 186 historias clínicas. Resultados. Se recopilaron los datos de cuatro pacientes en los que la causa de oclusión intestinal fue una intususcepción de intestino delgado. La edad promedio fue de 51 años. Dos pacientes eran hombvres. La forma de presentación fue en dos casos una oclusión intestinal aguda, y en dos casos como suboclusión crónica. Se analizaron dos resecciones segmentarias, una hemi-colectomía derecha y una polipectomía por enterotomía. No hubo complicaciones postoperatorias. La anatomía patológica informó lipoma, linfoma, adenoma velloso y pólipo hiperplásico. Conclusiones. La oclusión intestinal por intususcepción en el adulto es infrecuente. La técnica operatoria depende de la localización de la lesión, el compromiso de la vitalidad del asa, y la patología de base del enfermo (AU)

La intususcepción en el adulto como causa de oclusión intestinal / Bowel oclusion by adult intussusception

Antecedentes. La intususcepción en el adulto representa el 1 por ciento de las causas de oclusión intestinal. La presentación más frecuente es la oclusión intestinal. En la mayoría de los casos, el diagnóstico se realiza en la intervención. Objetivo. Describir los resultados de nuestra serie. Lugar de aplicación. Hospital universitario. Diseño. Estudio retrospectivo. Población. Se realizó una revisión retrospectiva de las historias clínicas de los pacientes admitidos por oclusión intestinal entre 2002-2004. De los casos en los que la causa de oclusión fue una intususcepción de intestino delgado se analizaron la edad, sexo, presentación, intervención realizada y anatomía patológica de estos pacientes. Método. Recopilación retrospectiva de casos. Se revisaron 186 historias clínicas. Resultados. Se recopilaron los datos de cuatro pacientes en los que la causa de oclusión intestinal fue una intususcepción de intestino delgado. La edad promedio fue de 51 años. Dos pacientes eran hombvres. La forma de presentación fue en dos casos una oclusión intestinal aguda, y en dos casos como suboclusión crónica. Se analizaron dos resecciones segmentarias, una hemi-colectomía derecha y una polipectomía por enterotomía. No hubo complicaciones postoperatorias. La anatomía patológica informó lipoma, linfoma, adenoma velloso y pólipo hiperplásico. Conclusiones. La oclusión intestinal por intususcepción en el adulto es infrecuente. La técnica operatoria depende de la localización de la lesión, el compromiso de la vitalidad del asa, y la patología de base del enfermo

Experiencia con la cirugía radioguiada mínimamente invasiva de paratiroides / Minimally invasive radioguided parathyroidectomy

Antecedentes: El hiperparatiroidismo primario es causado por un adenoma único en alrededor del 90 por ciento de los casos; debido a la más precisa localización preoperatoria, se ha cuestionado la exploración cervical bilateral en todos los enfermos. Objetivos: Presentar la técnica y los resultados de la paratiroidectomia radioguiada mínimamente invasiva (PRM) en el tratamiento del hiperparatiroidismo primario. Lugar y aplicación: Servicio de cirugía oncológica. Diseño: Observacional retrospectivo. Población: 54 pacientes consecutivos operados por hiperparatiroidismo primario: 49 para tratamiento primario y 5 por recidiva. Método: Ecografía y centellograma con Sesta MIBI preoperatorios y paratiroidectomía radioguiada con cámara manual para detección de radiaciones gamma. Resultados: La cámara manual localizó al adenoma en el 88,8 por ciento de los casos, mientras que la ecografía y el centellograma lo hicieron en el 76 y 87 por ciento respectivamente. La combinación de los tres métodos permitió ubicar el adenoma en toda la serie; en 15 oportunidades fue necesario prolongar la cervicotomía por patología tiroidea sincrónica y en 2 por carcinoma de paratiroides. Conclusiones: La PRMI es una técnica complementaria de los estudios preoperatorios (AU)

Experiencia con la cirugía radioguiada mínimamente invasiva de paratiroides / Minimally invasive radioguided parathyroidectomy

Antecedentes: El hiperparatiroidismo primario es causado por un adenoma único en alrededor del 90 por ciento de los casos; debido a la más precisa localización preoperatoria, se ha cuestionado la exploración cervical bilateral en todos los enfermos. Objetivos: Presentar la técnica y los resultados de la paratiroidectomia radioguiada mínimamente invasiva (PRM) en el tratamiento del hiperparatiroidismo primario. Lugar y aplicación: Servicio de cirugía oncológica. Diseño: Observacional retrospectivo. Población: 54 pacientes consecutivos operados por hiperparatiroidismo primario: 49 para tratamiento primario y 5 por recidiva. Método: Ecografía y centellograma con Sesta MIBI preoperatorios y paratiroidectomía radioguiada con cámara manual para detección de radiaciones gamma. Resultados: La cámara manual localizó al adenoma en el 88,8 por ciento de los casos, mientras que la ecografía y el centellograma lo hicieron en el 76 y 87 por ciento respectivamente. La combinación de los tres métodos permitió ubicar el adenoma en toda la serie; en 15 oportunidades fue necesario prolongar la cervicotomía por patología tiroidea sincrónica y en 2 por carcinoma de paratiroides. Conclusiones: La PRMI es una técnica complementaria de los estudios preoperatorios

Haemorheological profile in metabolic Syndrome.

Metabolic Syndrome (MetS) has been defined as a clinical condition including impaired glucose tolerance or diabetes mellitus and/or insulin-resistance, associated with two or more of the following components: arterial hypertension, central obesity, dyslipidaemia, microalbuminuria. In a group of subjects with MetS we examined the macrohaemorheological profile, demonstrating a significant increase of blood, plasma and serum viscosity and a decrease of whole blood filterability. The results show that in these subjects a secondary hyperviscosity condition is present, but also that several significant correlations are present between the haemorheological variables and some aspects of MetS, especially those reflecting central obesity (waist to hip ratio) and insulin-resistance. The altered haemorheological profile likely contributes to explain the high cardiovascular risk present in MetS, but it may also participate, through its influence on haemodynamic pattern, in the pathogenesis of insulin-resistance.

Polymorphonuclear leukocyte membrane fluidity, at baseline and after in vitro activation, in obesity with or without diabetes mellitus.

We studied a group of 28 obese subjects (mean age 38.2+/-13.5 years, body mass index 35.0+/-5.6 kg/m2) with insulin resistance demonstrated employing an euglycemic hyperinsulinemic clamp, subdivided into a subgroup with normal glucose tolerance (NGT) and a subgroup with type 2 diabetes mellitus (DM). We examined the polymorphonuclear leukocyte (PMN) membrane fluidity at baseline and after activation with 4-phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl-leucylphenylalanine (fMLP). At baseline, PMN membrane fluidity was significantly decreased in both subgroups compared to normals. In obese subjects with NGT no correlation was found between this PMN determinant and the parameters reflecting the insulin-resistance degree (glucose disposal [M] and metabolic clearance rate of glucose [MCR]), while in type 2 DM subjects the PMN membrane fluidity was correlated to M and MCR. After activation with PMA and fMLP, no variation in PMN membrane fluidity was observed in normals, while in obese subjects with NGT an early decrease was present only after fMLP activation, and in obese subjects with type 2 DM there was a constant and significant decrease of this PMN parameter after activation with PMA and fMLP. Our interest in the study of the PMN membrane fluidity emerges from its known role in PMN function, especially considering that PMN cells, together with monocytes, may be mediators of vascular damage.

Metabolic syndrome and breast cancer risk.

States of hyperinsulinemia with insulin resistance are frequently associated with proliferative tissue abnormalities, via stimulation of DNA synthesis and cell proliferation through the IGF-1 receptor. Such elements of metabolic syndrome (hyperinsulinemia/insulin-resistance, obesity, type 2 diabetes mellitus, hypertension, dyslipidemia) are explored in a population of 125 women (n. 50 with histologically confirmed diagnosis of breast cancer, Group A; n. 50 with benign breast pathology, Group B; n. 25 with no breast pathology, Group C, controls), affering to a Center for the prevention of breast cancer, in order to investigate for an eventual relationship between these pathologies. The prevalence of type 2 diabetes mellitus, hypertension, dyslipidemia, was higher in group of women affected by breast cancer vs. benign breast pathology and controls. This finding is in agreement with the hypothesis of the interrelationship of hyperinsulinism/insulin resistance with the growth-related abnormalities of breast cancer.

Polycystic ovary syndrome: an endocrine and metabolic disease.

Polycystic ovary syndrome (PCOS) is a common disorder occurring during female reproductive years, characterized by a number of heterogeneous clinical and biochemical features. Clinical presentation is characterized by hirsutism, acne, androgen-dependent alopecia, menstrual dysfunction, infertility and ultrasonographically-documented cystic ovaries. Tonic elevation of luteinizing hormone (LH) secretion is a regular feature of PCOS. Abnormal secretion of estrogen and high serum levels of free testosterone are also present. In addition to these endocrine abnormalities, specific metabolic alterations, such as hyperinsulinemia and insulin resistance are more frequent. Metabolic derangements associated with PCOS may predispose the patient to a range of diseases with attendant morbidity and mortality risks, so it is important to consider the syndrome in terms of both endocrine and metabolic aspects, achieving a correct hormone equilibrium and preventing metabolic alterations.

Polymorphonuclear leukocyte membrane fluidity before and after activation in subjects with insulin resistance.

The aim of this research was the evaluation of polymorphonuclear leukocyte (PMN) membrane fluidity in subjects with insulin resistance. Insulin sensitivity, in fact, may be influenced by plasma membrane fluidity. We enrolled 19 subjects with insulin resistance previously demonstrated during an euglycemic hyperinsulinemic clamp. PMN membrane fluidity was studied by labeling intact cells with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene and calculating the fluorescence polarization degree. The measurement was made before and after incubation of PMNs with two activating agents: 4-phorbol 12-myristate 13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). The baseline data showed a reduction of PMN membrane fluidity in subjects with insulin resistance. After PMN activation with PMA and fMLP, no significant variation in membrane fluidity was present in PMNs from normals, while in those from subjects with insulin resistance a slight decrease in PMN membrane fluidity was found only after activation with fMLP. The behavior of PMN membrane fluidity, before and after activation, distinguishes insulin-resistant subjects from normal controls, although the effect cannot be directly correlated with the degree of insulin resistance.

Effects of insulin-oral hypoglycemic agents combined therapy in outpatients with type 2 diabetes.

To evaluate the efficacy of combined insulin-OHAs therapy in subjects with NIDDM who received treatment with OHAs and insulin alone, we selected 60 outpatients divided in two groups: Group A: 36 subjects treated with OHAs therapy that received insulin treatment for secondary failure; Group B: 24 subjects in which OHAs therapy was added to insulin regimen to avoid the effects of hyperinsulinization. In the group A body weight increased significantly (+1.94 +/- 2.80 kg, p < 0.001 vs baseline), while in group B no gain of body weight was observed. Both groups showed a similar improvement of glycemic control. For the group A, the FPG and HbA1c decreased, respectively, from 14.64 +/- 3.76 to 8.72 +/- 2.92 mmol/l and from 9.10 +/- 0.30 to 7.20 +/- 0.53% at 6 months (p < 0.001). For the group B FPG and HbA1c decreased, respectively, from 12.05 +/- 3.49 to 8.24 +/- 3.01 mmol/l and from 8.3 +/- 0.1 to 6.8 +/- 0.13% (p < 0.001). Plasma cholesterol, triglycerides and uric acid concentrations did not show significant changes in either group. Insulin requirement in group A was 0.21 +/- 0.13 U/Kg/day. Despite of improvement of glycemia, total insulin requirement decreased in Group B from 0.53 +/- 0.25 to 0.34 +/- 0.2 U/Kg/day after OHAs therapy (p < 0.001). In the group A the bedtime insulin administration was prevalent (52.68%), while the most patients of group B needed a second or a third daily insulin injection (83.33%). In conclusion, in type 2 diabetic patients, therapy with combination of OHAs and insulin was associated with lower insulin doses and less weight gain.

The diabetic cataract: an unusual presentation in a young subject: case report.

This case report concerns a 14-year-old female patient, whose insulin-dependent diabetes mellitus was displayed by one infrequent complication, the cataract. This is an unusual manifestation in a 14-year-old patient; indeed, there are many findings in experimental animals demonstrating the development of this complication by maintaining blood glucose levels above 12 mM. After surgical therapy, complete vision was recovered, but we think that an earlier diagnosis and therapy of metabolic derangement of diabetes may have avoided this complication.

[Etiopathogenetic aspects and clinical implications of insulin resistance in polycystic ovary syndrome]. / Aspetti etiopatogenetici ed implicazioni cliniche dell'insulino-resistenza nella sindrome dell'ovaio policistico.

Polycystic ovary syndrome (PCOS) is a heterogeneous pathological condition characterized by a number of clinical, endocrine and pathological anatomic aspects. The heterogeneity of these factors and the variability of their presence makes it difficult to classify the syndrome and define it precisely as a separate nosographic entity. It is also difficult to position it with precision among the insulin-resistant syndromes in view of the multiple pathogenetic hypotheses that have been proposed over the years which are still the subject of numerous studies and deserve further confirmation. Data regarding beta-cell secretion in PCOS are also discordant; numerous experimental findings are therefore required to define this aspect correctly. On the basis of the most recent data reported in the international literature, the authors affirm the importance of considering this syndrome both from a purely endocrine point of view and in metabolic terms, for the therapeutic purpose of restoring hormone status and preventing, where possible, the onset of metabolic changes.

[Serum protein changes in diabetes mellitus]. / Alterazioni sieroproteiche nel diabete mellito.

AIM: To evaluate the serum protein pattern in a wide sample of diabetic patients using the simple method of electrophoresis, identifying the characteristics for each condition and correlating the various components. EXPERIMENTAL DESIGN: A retrospective study was made using medical records. SETTING: The Institute of Clinical Medicine I at Palermo University Hospital during the years 1990, 1991 and 1992. PATIENTS: 156 patients suffering from diabetes mellitus, of whom 68 were Type 1 (IDDM) and 88 Type 2 (NIDDM). The latter were divided into non-obese (NO-NIDDM), obese (O-NIDDM) and "secondary failures" (SF-NIDDM) to oral hypoglycemic agents (receiving mixed treatment, TM-NIDDM, or insulin alone, I-NIDDM). PARAMETERS: In addition to personal and anthropometric data and clinical data, in particular dysmetabolic data, an electropherogram was performed in each patient. RESULTS: Higher serum albumin concentrations were found in patients with IDDM, NIDDM compared to I-NIDDM, with an overall inverse correlation between the duration of diabetes and albumin serum levels. On the contrary, serum levels of alpha-2 globulins were higher in I-NIDDM patients compared to IDDM, and directly correlated with the age and duration in the overall series. beta-globulin levels were lower in IDDM patients compared to all other groups, and were directly correlated with age and body mass index (BMI) in the overall series. No statistical significance or correlation was found between the two groups in relation to alpha 1 and gamma-globulins. CONCLUSIONS: The study showed a characteristic serum protein pattern for each group of diabetic patients examined, analysing the role of insulin but also the duration and typical pathological events of the natural history of diabetes on protein metabolism, not only with regard to the amino acid metabolism but also on the distribution of circulating proteins.

Feedback inhibition of insulin secretion and insulin resistance in polycystic ovarian syndrome with and without obesity.

Hyperinsulinemia/insulin resistance is a well-known feature of polycystic ovarian (PCO) syndrome. In this study, the comparative roles of the peripheral tissues and the pancreatic beta-cells in its pathogenesis were evaluated. We determined basal serum C-peptide values (index of insulin secretion) and in vivo insulin action on peripheral glucose utilization (by the euglycemic hyperinsulinemic clamp technique) in obese (n = 5) and nonobese (n = 5) PCO women compared to obese (n = 5) and nonobese (n = 5) normal ovulatory women. During the clamp, feed-back inhibition of insulin on insulin secretion was studied by C-peptide percentage suppression. Serum C-peptide basal values did not differ significantly between the four groups. Insulin stimulated glucose utilization, expressed as M-value, was significantly decreased in both PCO groups compared to normal ovulatory women (p < 0.005). The metabolic clearance rate of glucose (MCR) and insulin (M/I) had the same behaviour. No differences were found between M, MCR and M/I values and the two groups of PCO subjects (obese/nonobese). The C-peptide percentage suppression was similar in all the groups. We conclude that PCO women have a significant insulin resistance that is independent of obesity, while basal and insulin-inhibited insulin secretion do not differ from normal-cycle subjects.

Serum uric acid, insulin secretion and resistance in nonhyperuricemic and hyperuricemic obese female subjects.

In order to study the relationships between obesity, serum uric acid, insulin secretion and insulin resistance in female subjects, we evaluated serum C-peptide and glucose-induced insulin utilization (euglycemic hyperinsulinemic clamp) in 16 obese (8 nonhyperuricemic and 8 hyperuricemic) and 10 nonobese control subjects. Baseline C-peptide levels were significantly higher in hyperuricemic compared to both nonhyperuricemic obese subjects and controls (P < 0.001). M values, a measure of glucose disposal and insulin sensitivity, were significantly lower in hyperuricemic obese compared to nonhyperuricemic obese subjects and controls (P < 0.001) and, for all subjects were inversely correlated with the serum uric acid values (r = -0.821, P < 0.001). In conclusion, in this group of subjects the serum uric acid values were directly related to insulin resistance independently of age, sex, excess body weight, fat distribution and blood pressure.