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.

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.

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.

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.

[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.

[Inhibition of pancreatic beta-cell secretion during "glucose clamp" in patients with polycystic ovary syndrome]. / Inibizione della secrezione beta-cellulare pancreatica durante "glucose clamp" in soggetti affetti da sindrome dell'ovaio policistico.

Insulin-resistance is a well-known feature of polycystic ovary syndrome (PCOS) and the present paper investigates the comparative roles of the peripheral tissues and the pancreatic beta-cells in its pathogenesis. The study was conducted on 5 young women with PCOS, all of normal weight and glucose tolerance in whom the glucose-insulin clamp test had revealed reduced peripheral glucose uptake that was not influenced by other conditions typically associated with insulin-resistance. Beta-cell function was investigated in these patients and 5 healthy controls via the assessment of the efficiency of the insulin/insulin feedback which involved studying the suppression of plasma C peptide during the glucose clamp. The results suggested that the insulin/insulin beta-cell feedback mechanism had retained its efficiency despite proven peripheral insulin-resistance. These data do not therefore support the hypothesis advanced by others that there is some sort of beta-cell insulin resistance parallel to the insulin resistance of the peripheral tissues. On the basis of those results it is rather believed that in PCOS the insulin-resistance is generated peripherally while the insulin/insulin feedback in the beta-cell is unimpaired. This obliges us to rethink the role of the hyperinsulinism encountered in PCOS and suggests that the changed sensitivity of the peripheral tissues to insulin activity may constitute a primary event in the genesis of insulin-resistance. This type of behavior has been demonstrated in the obese and in people with acanthosis nigricans, all with normal glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

[Residual hyperinsulinism after glucose oral load in obese subjects with normal glucose tolerance]. / Iperinsulinismo residuo dopo carico orale di glucosio in obesi a normale tolleranza glicidica.

Forty-five NGT obese subjects were submitted to OGTT with IRI and CPR determinations and to euglycemic hyperinsulinemic clamp, and divided into two groups: A) those with return of insulinemia toward basal values, and B) those with residual hyperinsulinism, in order to evaluate possible differences in insulin secretion and/or insulin action among them. Our data show the younger age of those with residual hyperinsulinism, that also seems related to insulin secretion, represented by IRI and CPR basal values, but not to insulin resistance parameters.

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.

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.

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.

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.

[Inhibition of pancreatic beta-cell secretion during a "glucose-clamp" in subjects with acanthosis nigricans]. / Inibizione della secrezione beta-cellulare pancreatica durante "glucose-clamp" in soggetti affetti da Acanthosis Nigricans.

It has long been known that acanthosis nigricans is accompanied by insulin resistance. In certain insulin-resistant states, including obesity, a more sluggish response to the insulin/insulin inhibition feedback normally present in pancreatic beta cells has been documented. Some have claimed a sort of beta-cell insulin resistance "parallel" to that of the peripheral tissues. The present study assesses the efficiency of the insulin/insulin feedback in acanthosis nigricans patients, measuring the inhibition of the production of C-peptide (the indicator of beta cell secretion) induced by the administration of exogenous insulin during glucose clamping. This was done in order to compare the roles of the peripheral tissues and the beta cells in producing the insulin resistance typical of acanthosis nigricans. The study using the glucose-insulin clamp technique was conducted on 4 Acanthosis Nigricans patients with normal glucose tolerance and 4 healthy controls, the drop in C-peptide levels after the administration of exogenous insulin being assessed in the course of both steady states. The results showed that the acanthosis nigricans patients retained a beta cell response to the exogenous insulin through their peripheral tissues presented a reduced sensitivity to insulin as revealed by the glucose-insulin clamp. It therefore seems reasonable to attribute the endocrine metabolic alteration found in Acanthosis Nigricans to a peripheral receptor and/or post receptor alteration rather than central alterations in the beta cells that have yet to be demonstrated. It is concluded that in acanthosis nigricans the peripheral insulin resistance is primarily independent phenomenon and not "parallel" to insulin/insulin feedback.

[Comparison of intensified traditional insulin therapy and micropump therapy in pregnant women with type 1 diabetes mellitus]. / Confronto fra terapia insulinica tradizionale ottimizzata e con microinfusore in gravide affette da diabete mellito di tipo I.

Ten pregnant women, affected by type I diabetes mellitus, observed for the first time during the II-III month of pregnancy, were examined. These patients were divided in two groups at random: group A underwent continuous subcutaneous insulin infusion with micropump CPI 9100 Lilly; group B underwent intensified insulin therapy with three daily doses of MC rapid insulin, two of which associated with MC intermediate insulin. All the patients were able to monitor their own blood glucose levels at home by means of reactive strips and reflectometer. In both the groups the mean glycemic values during fast and two hours after meals, and the eventual presence of urinary keton bodies and hypoglycemic crisis were evaluated during the course of pregnancy: these parameters turned out to be identical in the two groups. The increased need of insulin, the maternal body weight gain, the week and mode of delivery, the neonatal weight and the maternal and fetal complications also turned out to be identical in the two groups. To conclude, a good maternal metabolic control can be obtained either with the intensified conventional insulin therapy of with micropumps, if the patients, being properly instructed, are responsible for the monitoring of their own blood glucose levels at home.

[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.

[Obesity and arterial hypertension. Relation between insulin secretion, peripheral insulin resistance and pressure indices]. / Obesità ed ipertensione arteriosa. Relazioni tra secrezione insulinica, sensibilità periferica all'ormone e valore pressori.

The association between obesity and hypertension has been well documented. Both conditions are often linked to an insulin resistance state. In a group of homogeneously obese hypertensive subjects, the presence of a significant correlation between degree of insulin resistance and severity of hypertension was found. These results confirm that, independently of obesity and insulin secretion, equally present in all the subjects, high blood pressure is inversely correlated to hormone sensitivity.

[Semifasting and type II diabetes mellitus]. / Semidigiuno e diabete mellito di tipo II.

The author discusses the very low calorie diet and its physiopathological effects, in the treatment of NIDDM with obesity. In the latter condition the very low calorie diet can be utilized in order to obtain the desired body weight decrease, and consequently to improve glucose tolerance; however, this goal can only be reached by including in the diet sufficient amounts of carbohydrates, and by following some identified parameters of the treated patient.

[Insulin resistance: related clinical syndromes]. / Insulino-resistenza: sindromi cliniche correlate.

The authors, after having defined and listed the pathogenetic mechanisms of insulin resistance, describe the main, more or less frequent, syndromes with accompany this condition, classified on the basis of the prevalent etiology (dismetabolic, disendocrine, genetic, mixed), identifying of each one, when possible, the modes of determining the same insulin resistance. The more frequent diseases, whose common feature is the insulin resistance (obesity, non insulin dependent diabetes mellitus, acanthosis nigricans, polycystic ovarian syndrome) are particularly considered on the basis of recent literature and of personal data.

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.