Evaluation of a large set of patients with Autoimmune Polyglandular Syndrome from a single reference centre in context of different classifications.

PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.

Multiscale homogenization for dual porosity time-dependent Darcy-Brinkman/Darcy coupling and its application to the lymph node.

We study the coupling between time-dependent Darcy-Brinkman and the Darcy equations at the microscale subjected to inhomogeneous body forces and initial conditions to describe a double porosity problem. We derive the homogenized governing equations for this problem using the asymptotic homogenization technique, and as macroscopic results, we obtain a coupling between two Darcy equations, one of which with memory effects, with mass exchange between phases. The memory effects are a consequence of considering the time dependence in the Darcy-Brinkman equation, and they allow us to study in more detail the role of time in the problem under consideration. After the formulation of the model, we solve it in a simplified setting and we use it to describe the movement of fluid within a vascularized lymph node.

Costs of treatment and complications of adult type 1 diabetes.

BACKGROUND AND AIMS: Costs associated with diabetes represent a large burden for patients and the health-care system. However, few studies examined the costs for diabetes treatment in adults with type 1 diabetes (T1DM). This analysis was aimed to assess the costs of treatment associated with T1DM among adults in Italy from the national health-care system perspective. METHODS AND RESULTS: Data were collected using a questionnaire assessing resource consumption retrospectively (drugs, visits, diagnostics, hospitalisations and self-monitoring of blood glucose (SMBG)). One-year costs were calculated for the 12 months preceding the survey. Cost estimation, referred to 2006, was carried out using univariate and multivariate Poisson regression models. Fifty-eight centres enrolled 1193 patients (49.5% women; aged between 18 and 55 years, average diabetes duration was 16.1 ± 9.8 years). The average annual cost for an adult patient with TDM1 was € 2450 (95% confidence interval (CI): 2358-2544). Insulin therapy and SMBG accounted together for 71.2% of total costs (35.6% and 35.6%, respectively); the remainder was shared by hospitalisations (18%), visits (4.0%), diagnostics (3.9%) and other drugs (2.9%). Univariate analyses showed that the presence of complications was associated with excess of costs, mainly related to the hospitalisation and drugs. Multivariate analyses confirmed these results showing that the presence of micro-vascular plus macrovascular complications doubles the cost of treatment. CONCLUSION: Strategies of care for T1DM that can improve disease management and prevent or delay the onset of complications could represent the most important tool to reduce costs in the long term while improving clinical outcomes and quality of life.

Eggshell membrane as feedstock in enzyme immobilization.

Eggshell membrane, an eco-compatible, safe and cheap by-product was employed as carrier for the laccase from Trametes versicolor immobilization. In order to evaluate the best protocol to apply for the syringic acid degradation, two different types of laccase loading on eggshell membrane were used by incubation in solution or by enzyme-dropping. Chemicals (covalent) and physicals (adsorption) immobilizations were tested for both procedure using native or periodate-oxidized laccase. It is shown that immobilization of periodate-oxidized laccase on NiCl2-pretreated eggshell membrane was the best method for the first procedure (immobilized activity 1300 U/Kg, a residual activity of 30 % for 6 reuse). For the enzyme-dropping protocol a covalent method with the bifunctional cross linker (glutaraldehyde) was the best method (immobilized activity 3500 U/Kg, a residual activity of 45 % for 6 reuse).

Design of bioreactor based on immobilized laccase on silica-chitosan support for phenol removal in continuous mode.

A silica-chitosan support was employed for laccase immobilization. The hybrid support was obtained using calcium ion as linking agent that coordinates silanol and hydroxyl groups of chitosan. The insoluble biocatalyst was then packed in a column and used in a flow system for phenol removal. The immobilized enzyme reactor (IMER) showed a good storage stability (70 % of activity in 70 days) and good reusability (90-50 % of catalytic activity at the 4th reuse in function of chitosan type). The best performance for the phenol removal was obtained with a low molecular weight chitosan from crab shells at pH 5 and with a flow rate of 0.7 mL/min. The apparent Michaelis-Menten (Vmaxapp, Kmapp) and the inherent (Vmaxinh, Kminh) constants were also determined to evaluate the influence of the phenol structure on the performance of the system. The enzymatic oxidation of a phenol mixture (4-methylcatechol, catechol, caffeic acid, syringic acid, vanillic acid, p-coumaric acid, and tyrosol) was followed for 21 h in a continuous mode by HPLC. The phenol mixture removal of 90 % was also confirmed by Folin-Ciocalteu assay.

Spent grain as a sustainable and low-cost carrier for laccase immobilization.

Spent grain is promising lignocellulosic by-product support for laccase immobilization. The waste digestion with two different approaches (HCl/NaOH and H2SO4/NaOH) was performed. Different procedures (soaking and dropping), based on chemical and physical reactions, were also used to obtain the highest immobilized activity. Results showed that H2SO4/NaOH digestion guaranteed an immobilized activity five times higher than HCl/NaOH digestion. The best immobilization conditions with physical dropping procedure resulted in the highest immobilized activity on digested spent grain (2500 U/Kg). Good reusability (42% of activity retained after four cycles), and lower catalytic efficiency (Vmax/Km) of 0.053 min-1 than free laccase (0.14 min-1) with ABTS as substrate, were also obtained. Besides, when 20 mg of biocatalyst (0.02 U) were tested for syringic acid removal, complete oxidation of the phenol was achieved in just 4 h.

Correlates of quality of life in adults with type 1 diabetes treated with continuous subcutaneous insulin injection.

BACKGROUND AND AIMS: Aim of this study was to identify subgroups of adults with Type 1 Diabetes Mellitus (T1DM) treated with Continuous Subcutaneous Insulin Infusion (CSII) at higher risk of poor quality of life (QoL). A sample of consecutive patients completed the Diabetes Specific Quality of Life Scale (DSQOLS), investigating the daily burden and restrictions related to diabetes. Lower DSQOLS scores indicate worse QoL perception. METHODS AND RESULTS: The main results were obtained by using a regression-tree technique (RECursive Partitioning and AMalgamation - RECPAM) and multivariate logistic regression. Overall, 472 patients aged between 18 and 55 years were recruited by 43 Italian centers. RECPAM analysis led to the identification of 5 classes characterized by a marked difference in QoL. Male patients not reporting episodes of ketoacidosis and using CSII for >2 years had the lowest likelihood of scoring in the lower tertile of the DSQOLS summary score, and thus represented the reference category. Patients who reported > or =1 ketoacidosis episodes (OR = 5.4; 95% CI 2.4-12.1) and female patients with a duration of diabetes of <10 years (OR = 5.9; 95% CI 2.6-13.5) had the highest likelihood of reporting poor QoL, while females with longer diabetes duration (OR = 2.4; 95% CI 1.3-4.7) and males treated with CSII for < or =2 years (OR = 2.2; 95% CI 1.1-4.6) showed a two-fold risk of poor QoL. Patient age, diabetic complications and civil status were globally predictive variables associated with poor QoL. CONCLUSION: We identified subgroups of T1DM individuals treated with CSII showing a major impairment in QoL. Specific strategies are needed to help the patient cope with this therapeutic modality, especially during the initial phase of treatment.

Silica-chitosan hybrid support for laccase immobilization.

The aim of this study was to optimize the laccase immobilization on a silica/chitosan composite support. The innovative method proposed is based on the use of Ca(II) as a linker of the support precursors. In addition for the laccase immobilization the glycosidic part of enzyme is oxidized by periodate in order to form aldehydes reactive towards the NH2 groups of chitosan. The immobilized laccase presents a good storage stability (7 months 40% residual activity) and a good affinity towards ABTS substrate (Kmapp 0.008 mM, Vmaxapp = 0.0034 µmol/min). Furthermore, the biocatalyst showed optimum pH 3 and optimum incubation temperature of 50 °C.

Quality of life and treatment satisfaction in adults with Type 1 diabetes: a comparison between continuous subcutaneous insulin infusion and multiple daily injections.

AIMS: The aim of this case-control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). METHODS: Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes-Specific Quality-of-Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF-36 Health Survey (SF-36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. RESULTS: Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA(1c) were similar. Of control subjects, 90% followed glargine-based MDI regimens and 10% used NPH-based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions (beta = 5.96; P < 0.0001), daily hassles (beta = 3.57; P = 0.01) and fears about hypoglycaemia (beta = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score (beta = 4.13; P < 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine- or NPH-based MDI regimens. CONCLUSIONS: This large, non-randomized, case-control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine-based or NPH-based MDI regimens.

In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine.

AIMS: The superiority of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) with glargine is uncertain. In this randomized cross-over study, we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII. The primary end-point was glucose variability. METHODS: Thirty-nine patients [38.1 +/- 9.3 years old (mean +/- sd), diabetes duration 16.6 +/- 8.2 years, glycated haemoglobin (HbA(1c)) 7.6 +/- 0.8%], already on CSII for at least 6 months, were randomly assigned to CSII with lispro or MDI with lispro and glargine. After 4 months they were switched to the alternative treatment. During the last month of each treatment blood glucose variability was analysed using glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). As secondary end-points we analysed blood glucose profile, HbA(1c), number of episodes of hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction. RESULTS: During CSII, glucose variability was 5-12% lower than during MDI with glargine. The difference was significant only before breakfast considering glucose standard deviation (P = 0.011), significant overall using MAGE (P = 0.016) and lability index (P = 0.005) and not significant using ADRR. Although HbA(1c) was similar during both treatments, during CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was less, FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments. CONCLUSIONS: During CSII, glucose variability is lower, glycaemic control better and treatment satisfaction higher than during MDI with glargine.

Survey on the use of insulin pumps in Italy: comparison between pediatric and adult age groups (IMITA study).

AIMS: The aim of the study was to evaluate and compare continuous subcutaneous insulin infusion (CSII) use in pediatric and adult age groups. METHODS: Data were collected with a questionnaire sent by e-mail to CSII-experienced Diabetes Centers. The questionnaire assessed: (1) number of CSII-treated patients; (2) patient demographic data and characteristics; (3) structure and organization of Diabetes Centers providing CSII therapy; (4) pump characteristics (conventional pump, sensor-augmented pump); and (5) CSII dropouts. RESULTS: A total of 217 out of 1093 Italian centers participated: 51 pediatric (23.5 %) and 166 (76.5 %) adult centers (AP). Compared to a survey performed in 2005, there was a significant increase in the number of pediatric units when compared to adult units (112 vs 37 %, respectively, p < 0.05). Pediatric age is characterized by a greater concern for quality of life and injections, and a higher dropout rate (10.6 vs 8.9 %) mainly related to pump wearability and site reactions. A complete diabetes-care team is associated with a superior use of technology (fewer dropouts, increased CGM and advanced bolus use) which is, however, still used in a small percentage of patients. CONCLUSIONS: In Italy, the number of CSII-treated pediatric patients (PP) is growing more significantly when compared to adults. Only 60 % of all patients are using advanced functions and 20 % are using CGMs continuously. This confirms the great interest in diabetes technology that is growing in pediatric diabetologists. However, much improvement is warranted in the organization and specialized training of pediatric, adult and transitional facilities.

Variations of hepatic dolichols during rat development.

The content and the percent distribution of dolichol and dolichyl phosphate homologues were measured by high-performance liquid chromatography in perinatal rat livers. Short dolichol chains and no dolichyl phosphate are detectable in the liver at foetal stages; dolichol content progressively increases during liver development. A good correlation is observable between the changes of the dolichol, dolichyl phosphate and the activity of dolichyl-phosphate phosphatase.

Structural alterations in subcutaneous small arteries of normotensive and hypertensive patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: It is not presently known whether non-insulin-dependent diabetes mellitus (NIDDM) is associated with the presence of structural alterations in small arteries or whether the combination of hypertension and NIDDM may have an additive effect on endothelial dysfunction. Therefore, we investigated subcutaneous small arteries in 12 normotensive subjects (NT group), 18 patients with essential hypertension (EH group), 13 patients with NIDDM, and 11 patients with NIDDM and EH (NIDDM+EH group). METHODS AND RESULTS: Subcutaneous small arteries were evaluated by a micromyographic technique. The internal diameter, the media-to-lumen ratio, remodeling and growth indices, and the collagen-to-elastin ratio were calculated. Concentration-response curves to acetylcholine, bradykinin, the endothelium-independent vasodilator sodium nitroprusside, and endothelin-1 were performed. The media-to-lumen ratio was higher in the EH, NIDDM, and NIDDM+EH groups compared with the NT group. EH patients showed the presence of eutrophic remodeling, whereas NIDDM and NIDDM+EH patients showed 40% to 46% cell growth. The collagen-to-elastin ratio was significantly increased in the EH and NIDDM+EH groups compared with the NT group. The vasodilatation to acetylcholine and bradykinin was similarly reduced in EH, NIDDM, and NIDDM+EH groups compared with the NT group. The contractile responses to endothelin-1 were similarly reduced in EH, NIDDM, and NIDDM+EH patients. CONCLUSIONS: Our data suggest that the effects of NIDDM and EH on small artery morphology are quantitatively similar but qualitatively different and that the presence of hypertension in diabetic patients has little additive effect on small artery morphology and none on endothelial dysfunction.

Efficacy, safety and acceptability of the new pen needle 33G × 4 mm. AGO 01 study.

OBJECTIVES: Adherence to insulin therapy can be threatened by pain and needle fear. This cross-over randomized non-inferiority trial evaluated a new Pic Insupen 33G × 4 mm needle vs. a 32G × 4 mm needle in terms of metabolic control, safety and acceptability in patients with diabetes treated with insulin. RESEARCH DESIGN AND METHODS: We used a centralized, permuted block randomization, stratified by center and maximum insulin dose per single injection. Subjects used the two needles in two 3 week treatment periods. The primary endpoint was the absolute percentage variation of the blood fructosamine between the two treatments (% |ΔFru|). Additional endpoints were: glycemic variability, total insulin doses, body weight, severe hypoglycemic episodes, leakage at injection sites and pain measured by visual analogue scale. Equivalent glycemic control was defined a priori as % |ΔFru| (including 95% CI) within 20%. RESULTS: Of 87 subjects randomized, 77 completed the study (median age 53.1 [IR 42.3-61.2], median BMI 24.3 Kg/m(2) [IR 21.3-28.5], median duration of insulin therapy [in months] 141.4 (IR 56.3-256.9), median baseline HbA1c 7.9% [IR 7.2-8.8]). The % |ΔFru| was 7.93% (95% CI 6.23-9.63), meeting the non-inferiority criterion. The fasting blood glucose standard deviation was 46.2 (mean 154.6) with the 33G needle and 42.8 (mean 157.3) with the 32G needle (p=0.42). Insulin daily dose and patients' weight did not show any statistically significant variation. We observed 95 episodes of symptomatic hypoglycemia with the 33G needle and 96 with the 32G needle. One episode of severe hypoglycemia was documented in the latter group. As for insulin leakage we observed 37.55 episodes per 100 patient-days with the 33G needle and 32.21 episodes per 100 patient-days with the 32G needle (p=0.31). Patients reported less pain with the 33G × 4 mm needle (p=0.05). STUDY LIMITATIONS: Study sample was mainly composed of adults with type 1 diabetes and study was not blinded. CONCLUSIONS: The 33G needle is not inferior to the 32G needle in terms of efficacy and safety, with reduced pain and no difference in insulin leakage. CLINICAL TRIAL REGISTRATION: NCT01745549.

Effects of sex and age on the growth hormone response to galanin in healthy human subjects.

The aim of our study was to analyze the effects of sex and age on the GH response to galanin infusion in healthy subjects. We have studied 12 young (age, < 40 yr) nonobese healthy volunteers [6 females: age, 31.0 +/- 2.5 yr; body mass index (BMI), 21.6 +/- 0.9 kg/m2; 6 males: age, 29.2 +/- 1.4 yr; BMI, 23.3 +/- 0.4 kg/m2] and 11 old (age, > 65 yr) healthy subjects (5 females: age, 83.8 +/- 3.8 yr; BMI, 23.4 +/- 1.4 kg/m2; 6 males: age, 79.7 +/- 4.6 yr; BMI, 23.3 +/- 0.2 kg/m2). All subjects received an infusion of synthetic porcine galanin (500 micrograms, iv) in 100 mL saline from 0-45 min. Blood samples for GH measurement were drawn at -15, 0, 15, 30, 45, 60, 90, and 120 min. The GH peaks after galanin treatment in young females (11.9 +/- 2.9 micrograms/L) were significantly (P < 0.05) higher than those in the young males (5.1 +/- 1.8 micrograms/L). Old males showed significantly higher peak GH levels after galanin treatment (8.6 +/- 3.1 micrograms/L) than old females (2.4 +/- 0.6 micrograms/L). The GH peaks and areas under the curve after galanin treatment were significantly (P < 0.05) higher in young than in old females. On the contrary, no significant differences were observed after galanin treatment in young and old males. The magnitude of galanin-induced GH secretion significantly correlated with estradiol levels in young women. Our data seem to suggest that circulating estrogen levels play a crucial permissive role in galanin-induced GH secretion in humans.

Arginine normalizes the growth hormone (GH) response to GH-releasing hormone in adult patients receiving chronic daily immunosuppressive glucocorticoid therapy.

Glucocorticoids are thought to inhibit GH secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effect of arginine, a secretagogue that increases GH secretion acting at the hypothalamic level, probably by decreasing somatostatin tone, on GH-releasing hormone (GHRH)-induced GH secretion in three male and five female adult patients with nonendocrine disease who were receiving daily immunosuppressive glucocorticoid therapy. Six normal subjects (four males and two females) served as controls. GHRH-induced GH secretion was evaluated after 30-min iv infusion of saline (100 mL) or arginine (30 g) in 100 mL saline. After saline administration, steroid-treated patients showed a blunted GH response to GHRH (GH peak, 8.7 +/- 2.4 micrograms/L) compared to that of normal subjects (GH peak, 23.8 +/- 3.9 micrograms/L). The GH responses to GHRH increased (P less than 0.05) after pretreatment with arginine compared to saline pretreatment in both normal subjects (GH peak, 36.6 +/- 4.0 micrograms/L) and steroid-treated patients (GH peak, 28.4 +/- 5.5 micrograms/L). The GH responses to GHRH plus arginine were not significantly different in steroid-treated and normal subjects. Thus, arginine is able to normalize the GH response to GHRH in patients receiving chronic glucocorticoid treatment. Our data are evidence that the stimulatory action of arginine and the inhibitory action of glucocorticoids on GH secretion are mediated by opposite effects on hypothalamic somatostatin tone.

Pyridostigmine blocks the inhibitory effect of glucocorticoids on growth hormone-releasing hormone stimulated growth hormone secretion in normal man.

Glucocorticoids have been shown to inhibit GH secretion in normal man when acutely and chronically administered in pharmacological amounts. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate the influence of glucocorticoids on the GH response to PD administered either alone or in combination with GHRH in normal adult subjects. Six healthy adult volunteers underwent six experimental protocols. They received 1) human (h) GHRH(1-29)NH2, 100 micrograms injected as an iv bolus; 2) cortisone acetate, 50 mg administered orally (po) 60 min before an hGHRH iv bolus injection; 3) PD, 120 mg administered po, 60 min before an hGHRH iv bolus injection; 4) PD and cortisone acetate, administered po 60 min before an hGHRH iv bolus injection; 5) PD, administered po 60 min before a saline iv bolus injection; 6) PD and cortisone acetate administered po 60 min before a saline iv bolus injection. Mean GH levels, peak GH levels, and GH area under the curves (AUCs) were significantly lower after GHRH + cortisone as compared to GHRH alone. However, these parameters were not significantly different after PD + GHRH + cortisone when compared to PD + GHRH and after PD + cortisone when compared to PD alone. We conclude that acute administration of pharmacological amounts of glucocorticoids cannot inhibit the GH response to PD alone or in combination with GHRH. Thus, we hypothesize that the inhibitory action of glucocorticoids on the GH response to GHRH in man may be mediated by an enhancement of either somatostatin release by the hypothalamus or somatostatin action on the pituitary.

Left ventricular diastolic function and responses to adrenergic stimuli in borderline arterial hypertension.

OBJECTIVE: To detect the existence of a possible relationship between arterial hypertension and adrenergic reactivity to pressure stimuli, and changes in left ventricular diastolic function (LVDF). PATIENTS: Fifty-nine young subjects with borderline arterial hypertension and ten sex- and age-matched controls were investigated. After three medical examinations, the subjects were divided into hypertensive and borderline groups on the basis of the blood pressure reading at visit 3. A complete echocardiographic study was performed in 25 of the 59 subjects. DESIGN: Blood pressure was measured in baseline conditions and during pressure stimuli (mental stress, handgrip and cold pressor tests). LVDF was evaluated primarily by means of filling velocities during diastolic phases taken from the left ventricular volume curve (obtained from a complete echocardiographic study). RESULTS: No significant changes in blood pressure responses were observed for the borderline or hypertensive groups during the adrenergic test. The echocardiographic indices of diastolic function were statistically different for the two groups when compared with the control group. The LVDF parameters correlated significantly with systolic blood pressure and diastolic blood pressure measured at the time of the echocardiogram, but not with blood pressure measured occasionally. CONCLUSIONS: Blood pressure increases similarly during adrenergic stimuli in both the hypertensive and borderline groups. The correlation between systolic blood pressure, diastolic blood pressure and LVDF parameters may indicate a very early onset of reduced compliance of the left ventricle, even in a preclinical phase of hypertension.

Endothelial dysfunction in small resistance arteries of patients with non-insulin-dependent diabetes mellitus.

OBJECTIVE: Arterial hypertension is frequently associated with the presence of endothelial dysfunction in human subcutaneous small resistance arteries, as evaluated by responses to acetylcholine or bradykinin; however it is not known whether patients with diabetes mellitus show similar alterations. Therefore, we have investigated endothelial function in subcutaneous arteries of normotensive subjects (NT), of patients with essential hypertension (EH), of patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as of patients with both essential hypertension and non-insulin-dependent diabetes mellitus (NIDDM+EH). PATIENTS AND METHODS: All subjects were submitted to a biopsy of the subcutaneous fat Small arteries were dissected and mounted on a micromyograph. The media to lumen ratio (M/L) was calculated. A concentration-response curve to acetylcholine, to bradykinin as well as to the endothelium-independent vasodilator sodium nitroprusside were performed. We also evaluated the contractile response to endothelin-1. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) plasma levels were also measured. RESULTS: The vasodilatation to acetylcholine and bradykinin (but not to sodium nitroprusside) was significantly and similarly reduced in EH, in NIDDM, and in NIDDM+EH compared with NT. The contractile response to endothelin-1 was similarly reduced in EH, in NIDDM and in NIDDM+EH. Plasma ICAM-1 and VCAM-1 concentrations were higher in EH, NIDDM and NIDDM+EH than in NT. CONCLUSIONS: An evident endothelial dysfunction was detected in patients with NIDDM, and the simultaneous presence of EH did not seem to exert an additive effect. The contractile responses to endothelin-1 were reduced possibly as a consequence of ET(A) receptor down-regulation.

Effect of pyridostigmine on the growth hormone response to growth hormone-releasing hormone in lean and obese type II Diabetic patients.

A suppressed growth hormone (GH) response to GH-releasing hormone (GHRH) in both lean and overweight type II diabetics has been reported. Pyridostigmine (PD), an acetylcholinesterase inhibitor, elicits GH secretion when administered alone and enhances the GH response to GHRH in normal subjects. The aim of our study was to evaluate the effect of PD on GHRH-stimulated GH secretion in both lean and obese type II diabetic patients. We studied 16 patients with type II diabetes mellitus (seven lean and nine obese). Eleven nondiabetic subjects (six lean and five obese) served as controls. Each subjects underwent treatment with (1) 120 mg PD orally or (2) 2 tablets of placebo orally, 60 minutes before intravenous (IV) injection of 100 micrograms GHRH-(1-29)NH2. We have found no significant differences in GH responses to GHRH between obese diabetics and obese controls. On the other hand, the absolute GH levels were significantly suppressed in lean type II diabetics compared with lean controls at 15 and 30 minutes after GHRH injection. Obese diabetic subjects had slightly but not significantly decreased GH responses to GHRH+PD compared with obese nondiabetic subjects (8.36 +/- 1.62 v 14.4 +/- 7.62 micrograms/L). Lean type II diabetics showed a blunted GH release after GHRH+PD compared with normal-weight healthy subjects (GH peaks, 15.77 +/- 2.17 v 40.88 +/- 6.17 micrograms/L, P < .05). PD enhanced significantly the GH response to GHRH in obese diabetics, obese controls, and non-obese controls (P < .05), but not in non-obese type II diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)