Carotid intima-media thickness measurement through semi-automated detection software and analysis of vascular walls.

AIM: The aim of the present study was to compare the semi-automatic measurement of carotid intima thickness (RFQIMT - Esaote, Italy), with the conventional method. METHODS: We enrolle 81 patients, mean age 46 years ±15, with no history of cardio-cerebrovascular events and we assessed the traditional cardiovascular risk factors. We examined the IMT of the common carotid artery with manual and RFQIMT method (based on the "Radio Frequency" signal), according to the ASE protocol. RESULTS: Semi-automatic measurement was on average lower than manual measurement (617 µm ±191 vs. 676 µm ± 222) with a statistically significant difference (P<0.01). In agreement with manual measurements, the values of RFQIMT increased with increasing age and presence of cardiovascular risk factors. CONCLUSION: The RFQIMT measurement was, on average, lower than manual measurement, this means that probably, age- and gender-related reference values of RFQIMT need to be revised.

Motion Index: a new parameter to evaluate the diastole by M-Mode imaging.

AIM: Heart failure with normal left ventricle (LV) ejection fraction is commonly understood as diastolic heart failure because this expression implies the presence of LV diastolic dysfunction diagnosed by specific echocardiographic findings, such as slow LV relaxation and increased LV stiffness. In this work the authors propose a new parameter named Motion Index, which is measurable by M-Mode technique and it is likely linked to diastolic dysfunction. METHODS: A patient population composed by 134 subjects was enrolled. They all were in New York Heart Association (NYHA) functional class II. Echocardiogram carried out in all patients allowed the authors to distinguish 2 patient arms depending on the presence or absence of diastolic dysfunction, evaluated by flow Doppler and tissue Doppler. RESULTS: After carrying out every echocardiographic examination, the authors also measured the new parameter that called Motion Index, and found that it had an average value of 46 in patients with normal diastolic function and 33.5 in patients with diastolic dysfunction. This parameter did not depend on systolic dysfunction. CONCLUSIONS: Data obtained showed a statistically significant correlation between Motion Index and means of diastolic function assessed by both flow and tissue Doppler.

Role of ARBs in the blood hypertension therapy and prevention of cardiovascular events.

Hypertension has a worldwide high incidence in the general population and undoubtedly it is the most important risk factor for cardiovascular morbidity and mortality, in industrialized countries. In this Review we investigated the role of angiotensin II receptor antagonists (ARBs) therapy in the treatment of essential hypertension. We selected in the PubMed and in a list of selected sources the most significant clinical trials and meta-analysis carried out from 1999 to now, to assess, in adult patients populations, ARBs' efficacy, safety and tolerability profile, in comparison with the efficacy of the other common antihypertensive drugs, with particular regard to both the prevention of disabling consequences of hypertension (like cerebrovascular events, coronary events and heart failure) and the influence of an adequate antihypertensive therapy on comorbidities which strongly influence the outcome of hypertensive patients (like atherosclerosis, kidney damage, type II diabetes mellitus and arrhythmias). We also evaluated, in a detailed pharmacological and pharmaco-economic analysis, the basilar differences between ACE-inhibitors and ARBs in the control of the RAA system, and we assessed the possible benefits of their associated use, according to the new evidences concerning the treatment of arterial hypertension.

Impaired glucose metabolism in patients with acute stroke and no previous diagnosis of diabetes mellitus.

BACKGROUND: About a third of patients with acute stroke and no prior diagnosis of diabetes have hyperglycaemia during the acute phase of stroke. Whether this is an acute stress response or a reflection of underlying diabetes is controversial. AIM: To assess whether impaired glucose metabolism in patients with acute ischaemic stroke and no previous diagnosis of diabetes persists after 3 months, and whether such persistence can be predicted. DESIGN: Prospective observational study. METHODS: We enrolled 106 patients with acute ischaemic stroke and no history of diabetes. Fasting blood glucose, serum insulin and the insulin resistance index HOMA were recorded during hospital stay. A standard oral glucose tolerance test was performed at discharge and 3 months later. RESULTS: Ten patients did not complete the study. Eighty-one patients (84.4%) had abnormal glucose metabolism at discharge and 62 (64.6%) after 3 months. Thirty-seven (38.5%) had impaired glucose tolerance at discharge and 26 (27.1%) after 3 months. Forty-four (45.8%) had diabetes at discharge, and 36 (37.5%) at 3 months. Post-load hyperglycaemia at discharge was a predictor of diabetes after 3 months. A plasma glucose cut-off of 11.7 mmol/l (210 mg/dl) had a specificity of 90.0% and a positive predictive value of 81.3%. HOMA increased progressively from patients with normal glucose metabolism to those with newly diagnosed diabetes. DISCUSSION: Impaired glucose tolerance and previously unrecognized diabetes could be detected early in the stroke course, and persisted after 3 months in more than two-thirds of our patients. Post-load hyperglycaemia during the acute phase of stroke may be useful in identifying patients with abnormal glucose metabolism, which places them at risk for adverse outcomes, including cardiovascular disease.

Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits.

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.

Effect of octreotide on insulin requirement, hepatic glucose production, growth hormone, glucagon and c-peptide levels in type 2 diabetic patients with chronic renal failure or normal renal function.

Aim of this study was to investigate whether octreotide, a synthetic somatostatin analogue that inhibits growth hormone, insulin and glucagon secretion and improves glycaemic control in insulin dependent diabetic patients was able to exert similar effects in insulin treated type 2 diabetic patients with chronic renal failure who have high plasma glucagon levels. For this purpose saline or octreotide was randomly administered by continuous subcutaneous infusion (100 mcg/daily) in addition to usual insulin treatment for 5 days to six type 2 insulin treated diabetic patients with chronic renal failure and to six type 2 patients with normal renal function, as a control group. At day 3 of insulin plus saline or insulin plus octreotide treatment, total glucose uptake and hepatic glucose production (HGP) were investigated during an euglycemic clamp; at day 5 GH, glucagon and C-peptide plasma levels were evaluated. Octreotide treatment lowered endogenous insulin secretion (evaluated by C-Peptide levels assay), GH and glucagon in all patients, but caused a significant reduction of daily insulin requirement (32 +/- 14 I.U. vs 41 +/- 19 I.U., P<0.02) only in patients with renal failure. HGP was significantly (P<0.05) lowered in patients with renal failure but glucose uptake remained unchanged. The lowering effect of octreotide on insulin requirement in diabetic patients with renal failure in spite of the contemporaneous inhibition on insulin secretion could be explained on the basis of the greater reduction of glucagon levels which are very elevated in these patients as compared to patients with normal renal function. The lowering of glucagon could decrease HGP and, consequently, insulin requirement.

Effects of the treatment with acarbose in elderly overweight type 2 diabetic patients in poor glycemic control with oral hypoglycemic agents or insulin.

The aim of this study was to evaluate the efficacy of acarbose, an inhibitor of alpha-glucosidase, on glycemic control in elderly overweight type 2 diabetic patients poorly controlled by oral hypoglycemic agents (OHA) or insulin. Our study included 22 overweight patients, 60-75-years-old, treated with OHA and/or insulin who, after a period of 4 weeks of controlled diet, showed a poor metabolic control. They were divided into two groups: Group I (nine patients) on OHA treatment; Group II (13 patients) undergoing treatment with insulin alone or in combination with OHA. Acarbose was administered to all the patients (100 mg three times a day at meal times) for 6 months in addition to their previous treatment. The addition of acarbose caused a significant reduction in both groups with regard to fasting glycemia (after 3 and 6 months, respectively, 20.7 and 21.9%, P<0.04 in Group I; 19.1 and 21.8%, P<0.04 in Group II), and postprandial glycemia (after 3 and 6 months, respectively, 41.6 and 42.5%, P<0.0001 in Group I; 35.6 and 38%, P<0.0006 in Group II). There was also a significant reduction in the values of HBA(1c) in Group I after 6 months of treatment (24.3%, P<0.05) and in Group II after 3 and 6 months (respectively 13.4%, P<0.02 and 20.6%, P<0.01). Three months after treatment with acarbose ended, fasting and postprandial glycemia and HBA(1c) values returned to original baseline values. In conclusion, the addition of acarbose to the OHA in elderly overweight type 2 diabetic patients poorly controlled by OHA or insulin regimes improved metabolic control.

Increased frequency of HCV and HBV infection in type 2 diabetic patients.

The aim of our study was to verify if the diabetic population can be considered at risk for HBV (B hepatitis virus) and/or HCV (C hepatitis virus) correlated viral hepatitis. We examined 1514 diabetic patients, 668 males and 846 females. In patients who had, on at least two occasions, pathological transaminase values (AST and/or ALT), the markers for HBV and HCV infection were determined. Of the 1514 patients studied, 295 (19.48%) had pathological values of ALT and /or AST. Among the hypertransaminase patients (295), 69 were not tested for the markers because they refused to give informed consent; of the remaining 226 patients, 54 were negative and 172 (76.6%) were positive for at least one of the hepatitis markers (HBV, HCV or both). Those who were anti-HCV positive were 115 (38.98%), of which 50 were also positive to hepatitis B (16.9%), while those positive only to the B markers were 57 (19.3%). If we compare the patients with positive markers (172) to the total number of diabetic patients studied (1514), we find that there is a hepatitis B and/or C prevalence of 11.36%, with no statistically significant difference between females (95/846, 11.23%) and males (77/668, 11.53%). The prevalence of only hepatitis C was 7.6%, while only hepatitis B was 7.1%. In conclusion, our study shows an increasing prevalence of hepatitis C and B, often associated, in type 2 diabetic patients that allows us to define them as a group at risk for viral hepatitis.

Hypertension and related risk factors in type 2 diabetes mellitus.

METHODS: The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001). RESULTS: Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waisthip ratio. CONCLUSIONS: In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Macrophage-derived cytokines in the follicular fluids of women with infertility due to immunological causes. Elevated levels of interleukin 6 and low levels of granulocyte-macrophage colony-stimulating factor.

The cytokines are (glyco)proteins secreted by lymphoid and non-lymphoid cells which modulate several biological responses including the ovarian function. Interleukin (IL)-1 and tumour necrosis factor (TNF)-alpha suppress 17beta-estradiol (E2) and progesterone release from granulosa and luteal cells in vitro. TNF-alpha affects negatively folliculogenesis and ovarian maturation. Additional in vivo evidence for a role of this macrophage-derived cytokine came from our recent observation that women with infertility due to immunological causes have elevated intrafollicular fluid levels of TNF-alpha and decreased levels of E2 compared to women with a tubal factor of infertility. Because the macrophages are a primary component of the intrafollicular compartment, the present study was undertaken to evaluate whether other macrophage-derived cytokines are also released in the human follicular fluid. To accomplish this, we measured the levels of IL-1beta, IL-6, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the follicular fluids of two groups of infertile women undergoing to an in vitro fertilization program. The first group of women had a significant titre of anti-spermatozoon antibodies in the serum and/or the mucus as the only cause of infertility, whilst the second group of women was infertile because of non patent fallopian tubes. Intrafollicular cytokines levels were measured by solid-phase ELISA and steroid concentrations by radioimmunoassay. Whilst IL-1beta, IL-6, IL-10, and GLM-CSF were all measurable in the follicular fluid of both groups of women, the levels of IL-6 were found to be significantly more elevated and those of GM-CSF lower in patients with infertility due to immunological causes as compared to those with tubal infertility. The former had also decreased intrafollicular E2 levels and increased progesterone concentrations. No difference was seen in the follicular fluid levels of testosterone and androstenedione. In conclusion, several macrophage-derived cytokines are present in the follicular fluids of infertile women. Patients with infertility due to immunological causes had higher levels of IL-6 and lower concentrations of GM-CSF as compared to patient with a tubal factor of infertility. We speculate that this abnormal cytokine profile may contribute to the altered intrafollicular steroid milieu.

Hypertension and related risk factors in type 2 diabetes mellitus.

METHODS: The correlation between hypertension and related risk factors has been studied in 733 type 2 diabetic patients. Hypertension was more frequent in women (65.35%) than in men (50.35%) (p < 0.0001). RESULTS: Hypertensive patients showed older age (p < 0.0001) and greater Body Mass Index (BMI) (p < 0.03) than normotensive. In the diabetic group on diet only basal insulinaemia was higher (p < 0.05) in hypertensive than in normotensive diabetic men, but not in women. Such a difference, was not seen in patients of both sexes treated with oral hypoglycaemic agents; besides there was no difference in fasting C-peptide levels between hypertensive and normotensive insulin treated patients. In both sexes hypertension was independently correlated with age, BMI, increased urinary albumin excretion, triglycerides. The strongest correlation was with the family history of hypertension. On the contrary there was no correlation between hypertension and waist-hip ratio. CONCLUSIONS: In conclusion, the association between hypertension and type 2 diabetes depends on various risk factors, but a relationship with insulin levels is not surely demonstrable.

Different effects of octreotide by continuous night infusion at increasing rate or by evening injections at different times on morning hyperglycemia and growth hormone levels in insulin-dependent diabetic patients.

The effect of octreotide on morning hyperglycemia and GH levels was evaluated in eight insulin-dependent diabetic patients. Octreotide (50 mcg) was administered through subcutaneous injections at different hours (20:00, 22:00 and 24:00 h) or through continuous subcutaneous night infusion from midnight to 08:00 at increasing rate between 03:00 and 08:00 h. After octreotide injection at midnight we noticed a sharp decrease of both glycemia (p < 0.005) and GH (p < 0.05) at 04:00 h, but not at 08:00 h. Only the night continuous infusion at increasing rate was able to reduce glycemia and GH at 04:00 and at 08:00 h (p < 0.001 and p < 0.01 respectively). The injections of octreotide at 20:00 and 22:00 h lowered GH values at 24:00 h (p < 0.01 and p < 0.05 vs insulin alone) but did not show any significant effect on blood glucose levels and GH at 04:00 and 08:00 h. In conclusion, only the continuous subcutaneous night infusion of octreotide at increasing rate during the last hours of the night was able to reduce simultaneously morning hyperglycemia and GH levels in insulin-dependent diabetic patients, whereas evening subcutaneous injections at different times did not show any appreciable effect.

Increased urinary albumin excretion is a marker of risk for retinopathy and coronary heart disease in patients with type 2 diabetes mellitus.

The prevalence of increased urinary albumin excretion (UAE) (micro- and macroalbuminuria) and its association with diabetic retinopathy (DR) (evaluated by fluorescent angiography), coronary heart disease (CHD), and various related risk factors were studied in 320 type 2 diabetic patients. In this subsample of type 2 diabetic patients, microalbuminuria was present in 15% of the patients; macroalbuminuria in 4.8%, CHD in 9.9%, DR in 53.4%, and arterial hypertension in 46%. UAE was independently related to CHD (P < 0.05), retinopathy (P < 0.001), hypertension (P < 0.001), and triglycerides (P < 0.02). We conclude that increased UAE is associated to a greater frequency of retinopathy and CHD in type 2 diabetic patients.

Sodium fusidate in Gillain-Barré syndrome: a case report.

A patient with Guillain-Barré syndrome is reported on who responded favourably to a short course treatment with the novel immunosuppressant sodium fusidate (Fucidin), given at a daily dose of 1.5 g for one week. Along with prompt and clear cut clinical improvement, treatment with Fucidin was associated with a rapid decline in the blood concentrations of inflammatory cytokines presumably implicated in the pathogenesis of Guillain-Barré syndrome such as interleukin-2, interferon-gamma, and tumor necrosis factor-alpha. The ex vivo production of these cytokines was also markedly diminished compared with pretreatment values. Fucidin was well tolerated and no clinical or biochemical side effects were seen.

A simplified diagnostic test for ambulatory screening of peripheral diabetic neuropathy.

The reliability and reproducibility of Michigan Neuropathy Screening Instrument (MNSI), a recently proposed simple test for ambulatory screening of peripheral diabetic neuropathy (PDN), was evaluated on 80 diabetic patients. MNSI was carried out by two diabetologists and repeated after a week. It consisted of the sum of scores varying from 0 to 1 for each abnormality revealed in foot appearance, achilles reflexes presence and vibratory threshold (VPT) by tuning fork (maximum score = 8). Then patients had to go to neurologist for PDN diagnosis by a quantitative neurological examination and electrophysiological evaluation, the so named Michigan Diabetic Neuropathy Score (MDNS) and the results compared with MNSI score according to one of the two observers. The inter-observer reproducibility of MNSI was 88.75% the within observer reproducibility was 95 and 94%, respectively, for each observer with good correlation between the two measurements (P < 0.001). The MNSI score of 2.5 as a cut-off appeared to be reliable for ambulatory screening of suspected PDN (false positive and false negative = 2.5%; specificity and sensitivity = 75% and 78.6%, respectively). In conclusion MNSI by using 2.5 score as cut-off may be considered a rapid, simple, reproducible and reliable test for rapid ambulatory screening of PDN from the diabetologists.

Lack of pharmacological effect of subcutaneous octreotide in an insulin-dependent diabetic patient: reversal after mixing with aprotinin.

Octreotide, a synthetic analogue of somatostatin, may improve metabolic control and reduce GH and glucagon levels in insulin-dependent diabetic patients. We report hereto the case of an insulin-dependent diabetic patient in whom the subcutaneous continuous infusion of octreotide (150 micrograms/daily for six days) resulted ineffective on blood glucose levels, GH and glucagon. However, when octreotide was administered mixed together with aprotinin-an inhibitory of proteolytic enzymes (10,000 I.U. daily), it had lowering effect on blood glucose levels, GH and glucagon. We suggest the possibility that a local subcutaneous enzymatic degradation of octreotide may have occurred and that this degradation was blocked by aprotinin.

Diabetic neuropathy: prevalence, concordance between clinical and electrophysiological testing and impact of risk factors.

UNLABELLED: The aim of this study was to assess the prevalence of various forms of diabetic neuropathy (DN), by clinical and electrophysiological tests, on 374 diabetic patients (66 with type 1 and 308 with type 2 diabetes mellitus) and the concordance between clinical and electroneurological alterations and relative risk factors impact. The overall prevalence of DN, according to the Saint Antonio Conference criteria, was 44.9% (28.88% somatic, 14.44% mixed and 1.60% autonomic) without statistical difference between type 2 and type 1 diabetes (46.43% and 37.88% respectively). In 32.24% of patients nerve conduction velocity (NCV) abnormalities were present together with clinical signs or symptoms of neuropathy, while 12.68% presented only signs and/or symptoms. In addition 9.36% of patients showed alterations of NCV in the absence of clinical signs or symptoms of neuropathy. The most frequent form was asymptomatic (30.21%), followed by symptomatic neuropathy (12.83%); rare was the severe neuropathy. Relative risk increased for diabetes duration > 20 years (p < 0.0001). IN CONCLUSION: 1) the Saint Antonio Consensus Conference criteria can be considered the most complete test for neuropathy diagnosis; 2) NCV alterations may not be concordant with signs-symptoms of neuropathy; 3) the duration of diabetes seems to be the most important risk factor.