Giuseppe Seghieri

Abnormalities of pulmonary function tests have been described in type 1 (insulin-dependent) diabetes mellitus (IDDM). To better characterise such abnormalities and to verify whether these latter are associated with the presence of diabetic microvascular disease we compared 23 non-smoking patients who had IDDM with 24 non-smoking healthy control subjects strictly matched for sex, age, and body mass index. Compared with controls, diabetic patients had a reduced forced vital capacity (FVC) (87.5 +/- 13.1% vs. 96.4 +/- 13.6% of the predicted; P = 0.03) and forced expiratory volume in 1 s (FEV1) (90.5 +/- 17.7% vs. 101.2 +/- 13.2% of the predicted; P = 0.02). While within the group of patients the presence of retinopathy and autonomic neuropathy were not associated with modifications of pulmonary function tests, those with altered urinary albumin excretion rate (AER > or = 20 micrograms/min; range 21-589) (n = 7) had a significantly lower pulmonary diffusion capacity (DLCO) than the 16 normoalbuminuric subjects (62.6 +/- 7.2% vs. 88.7 +/- 20.1% of the predicted; P = 0.01). Moreover, in the group of patients, DLCO was inversely related with AER (r = -0.43; P = 0.04). In conclusion, IDDM is characterised by reduced FVC and FEV1, while a significant decrease in DLCO may be considered as selectively associated with renal disease.

As diabetes mellitus represents a situation in which production of peroxides is increased, the aim of this study was to investigate the relationship between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides, both assayed using high-performance liquid chromatography (HPLC), in 59 patients with insulin-dependent diabetes mellitus (IDDM) compared with 51 healthy control subjects matched for sex, age, smoking habits, as well as for dietary intake of energy, alcohol and vitamin C. Mean plasma and platelet MDA were significantly higher in the patients affected with IDDM than in control subjects. Moreover, the diabetic group was characterized by a huge decrease in plasma AA [8.45 +/- 5.5 mumol L-1 (SD) vs. 33.4 +/- 7.6 mumol L-1, P = 0.0001], mirrored by a significant increase in plasma DHA (11.9 +/- 3.9 mumol L-1 vs. 3.9 +/- 2.5 mumol L-1, P = 0.0001). No detectable DHA was observed in the platelets from both diabetic and control subjects, whereas AA was significantly increased in platelets from diabetic patients compared with control subjects (42.6 +/- 7.4 vs. 34.8 +/- 5.1 nmol 10(-9) platelets, P = 0.0001). Platelet AA in the diabetic group was significantly inversely correlated with glycated haemoglobin (r = -0.34; P = 0.04) and directly with plasma AA (r = 0.39; P = 0.02), the sum of plasma AA + DHA (r = 0.44; P = 0.009) and with platelet MDA (r = 0.38; P = 0.02). (a) The ratio plasma AA/DHA is significantly lowered in IDDM in association with an increase in MDA levels; (b) only AA is detected in platelets, being augmented in the diabetic group; (c) plasma ascorbate depletion does not reflect platelet levels of AA; and, finally, (d) metabolic control, as well as intracellular lipoperoxides, modulates platelet AA in IDDM.

Neurofibromatosis (NF) is a heterogeneous disorder clinically characterized by the presence of neurofibromas, multiple café au lait spots, intertriginous freckles and Lisch nodules. We describe an unusual case of NF with cutaneous neurofibromas localized on the anterior chest, in a bilateral dermatomal distribution. No other signs were detected. The family history was negative for NF. The different subsets of NF are briefly discussed, with particular emphasis on the segmental type.

The increase in urinary albumin excretion rate (AER), a hallmark of both diabetic nephropathy and hypertension, has also been described in patients affected with diffuse psoriasis. The aim of this study was to investigate whether such an increase is independent of the coexistence of diabetes or hypertension and whether it may be related to the extension and severity of skin lesions. Median AER, determined by radioimmunoassay, was significantly higher in a group of 32 normotensive nondiabetic psoriatic patients than in 36 age- and sex-matched controls (9.6 vs. 5.3 micrograms/min; p = 0.0006). AER was related with grading of skin involvement (r = 0.65; p = 0.001); patients with the most widespread skin lesions (psoriasis area and severity index: PASI greater than 11) were characterized by a significantly raised median AER (14.9 micrograms/min) compared with those with PASI scores between 4 and 11 (9.8 micrograms/min) or less (5.6 micrograms/min) and controls (F = 10.58; p = 0.0001), independent of other covariates such as age, sex and blood pressure (p = 0.001). This latter finding was confirmed by the prevalence of microalbuminuria (AER greater than 10 micrograms/min) which was present in 2 out of 8 patients with PASI less than 4, 0 out of 12 patients with PASI ranging between 4 and 11 and in 5 out of 12 psoriatics with PASI greater than 11 (p = 0.038 by two-tailed Fisher's exact test).

A 43-year-old man, affected with alopecia universalis and vitiligo since his childhood, developed erythrodermic pityriasis rubra pilaris followed then by lichen planus; chronic viral hepatitis C was diagnosed. This appears to be a unique constellation of cutaneous diseases implying both autoimmunity and hepatitis C virus.

Much evidence suggests sexual dimorphism in the relationship linking blood pressure (BP) to both left ventricular mass (LVM) and geometry in hypertension. To better evaluate gender-associated characteristics in the relation BP-LVM among newly diagnosed hypertension (24-h average ambulatory BP monitoring, ABPM, > 125/80 mmHg), we measured indexed LVM and relative wall thickness (RWT) by standardized echographic methods in 209 Caucasian drug-naïve subjects, of whom 162 (100M/62F) were recognized to be hypertensive. Mean office systolic (SBP)/diastolic (DBP), 24-h average and night-time BP values were similar between sexes and significantly related to indexed LVM in both genders. Daytime SBP was significantly related to indexed LVM only in females (r =0.41; p =0.0008 in women; r =0.11; p = NS in males), while LVM was more sensitive to day-to-night SBP change in females. RWT was, on the contrary, significantly related to ABPM values only in males. All these findings were confirmed after adjusting for possible confounders. Percentage of LVM variance explained by 24-h average, daytime or night-time SBP values were higher in females than in males (17% vs 3%; 11% vs 1%; and 17% vs 8%). In conclusion, in early hypertension, LVM was significantly associated with daytime BP and more sensitive to reduced percentage of night BP fall in females. LVM variance explained by ABPM SBP was much higher in females than in males. RWT, expressing concentric LVM remodelling was, conversely, more related to BP increase in males.

To determine the rate and clinicopathologic factors predictive of sentinel lymph node (SLN) positivity, regional lymph node recurrence, and survival in a large series of patients with thin primary cutaneous melanoma who underwent SLN biopsy (SLNB). Patients with thin (≤1 mm) melanomas who underwent SLNB between 1992 and 2009 at Melanoma Institute Australia were identified from the Melanoma Institute Australia database. The association of clinicopathologic features with SLN status, lymph node recurrence, and survival was analyzed. In 432 patients [226 men, 206 women; median age 49.5 years (range: 14.4-85.0 years)], SLNB was positive for metastatic melanoma in 29 (6.7%) patients. No SLN positivity was detected in 37 patients with primary tumor thickness 0.50 mm or less. Breslow thickness (P = 0.012) and presence of lymphovascular invasion (P = 0.018) were the only factors significantly associated with SLN positivity. Regional lymph node recurrence was significantly more common in tumors located in the head/neck region (4/33, 12%) than in extremities (3/245, 1.2%) and trunk (2/154, 1.3%) (P < 0.001). Primary tumor mitotic rate was a significant predictor of melanoma-specific survival (Hazard Ratio [HR] = 1.2, 95% confidence interval: 1.09-1.35, P < 0.001). There is a low but significant rate of SLN positivity in patients with primary melanomas 0.51 to 1.0 mm in thickness. Given its prognostic importance, SLNB should be considered in such patients, particularly if there is lymphatic permeation by melanoma at the primary tumor site. More frequent regional node field recurrences…

Background: The aim of this study was to clarify any gender differences in the mortality risk of people with DFD since patients with diabetic foot disease (DFD) are at a high risk of mortality and, at the same time, are more likely to be men. Methods: From regional administrative sources, the survival probability was retrospectively evaluated by the Kaplan-Meier method and using the Cox proportional-hazards model comparing people with DFD to those without DFD across the years 2011–2018 in Tuscany, Italy. Gender difference in mortality was evaluated by the ratio of hazard ratios (RHR) of men to women after initial DFD hospitalizations (n = 11,529) or in a cohort with prior history of DFD hospitalizations (n = 11,246). Results: In both cohorts, the survival probability after DFD was lower among women. Compared to those without DFD, after initial DFD hospitalizations, the mortality risk was significantly (18%) higher for men compared to women. This excess risk was particularly high aft...

The aim of this study was to evaluate the risk of death after hospitalizations for diabetic foot (DF) complications, comparing two different cohorts of people with or without a prior history of DF hospitalizations across the years 2011 to 2018 in Tuscany, Italy. The DF complications were categorized by administrative source datasets such as: amputations (both major and minor), gangrene, ulcers, infections, Charcot and revascularizations. A further aim was to present the trend over time of the first ever incidents of diabetic foot hospitalizations in Tuscany. The eight-year-mortality rate was higher in the cohort with prior hospitalizations (n = 6633; 59%) compared with the cohort with first incident DF hospitalizations (n = 5028; 44%). Amputations (especially major ones) and ulcers had the worst effect on survival in people without basal history of DF hospitalizations and respectively in those with a history of prior DF hospitalizations. In both cohorts, revascularization procedures...

To provide data on hospitalization and incidence rates of Charcot neuroarthropathy (CN) and its relation to lower limbs' amputations/revascularizations in population with diabetes of Italy as well as of one of its regions (Tuscany). Hospitalizations with CN diagnosis (codes ICD-9-CM: 7130, 7135, 7138) have been recorded in people with diabetes over years 2003-2013 in Italy and 2008-2015 in Tuscany. Amputations, peripheral vascular disease, revascularizations and infections were likewise evaluated. Between 2003 and 2013 CN hospitalizations were very infrequent in Italy ranging between 14×100,000 and 11×100,000 patients with diabetes. In Tuscany they declined to a minimum of 7×100,000 patients in 2015, after a previous increase to a maximum of 22×100,000 (p=NS for both). Yearly CN incidence remained constant in Italy, declining in Tuscany to a minimum of 3.4×100,000 diabetic patients in 2015 (p=0.047). CN patients were younger and with longer length of hospital stay than those with non-Charcot diabetic foot (p<0.05 for both). Amputation and infection rates were manifold higher in CN patients than in those with non-Charcot diabetic foot, while the revascularization rate was similar in both. Over last decade, in Italy and Tuscany yearly CN incidence and hospitalization rates concerned only a small percentage of patients, remaining constant over years and declining in Tuscany in the last couple of years. CN was significantly associated to younger age, longer hospital stay and greater risk of amputations and infections while the need of revascularization was similar to that of non-Charcot diabetic foot.

... 1994;359:419-24. Taurine levels in plasma and platelets in insulin-dependent and non-insulin-dependent diabetes mellitus: correlation with platelet aggregation. Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Milan M, Gironi A, Bartomomei G, Anichini R, Seghieri ...

... 1992;315:181-6. Taurine potentiates the antiaggregatory action of aspirin and indomethacin. Franconi F, Miceli M, Bennardini F, Mattana A, Covarrubias J, Seghieri G. Istituto di Chímica Biologica, University of Sassari, Italy. PMID: 1509937 [PubMed - indexed for MEDLINE]. ...

To evaluate the effect of diabetes by gender on the peak-risk of first-ever-ischemic stroke and its recurrence. Administrative datasets including all hospital discharges for ischemic stroke (N=43,332) in the diabetic (N=207,568) and non-diabetic (N=2,808,554) population of the Tuscany region, Italy were used to calculate Hazard ratios (HR) after Cox-regression, of first-ever and recurrent ischemic strokes, between 2005 and 2011. Overall, diabetes increased the HR of first-ever ischemic stroke by about 50% in both genders. However, this risk significantly declined with age and was higher in women aged 55-74yr than in men of the same age (HR; 95% CI: 1.392; 1.228-1.579 in age-class 55-64yr and 1.203; 1.110-1.304 in age class 65-74yr; p<0.001). Diabetes also increased the adjusted risk of three-year-stroke recurrence (N=5,998) in women, independently of age, whereas this was the case in men <70yr. Diabetes is associated with increased risk of ischemic stroke although it declines with age though at lower rate among women than men. Moreover, diabetic women have greater risk of recurrence than in men>70yrs old, supporting a high-risk "time-window" in postmenopausal-elderly diabetic women.

Incidence of ischemic stroke and associated in-hospital mortality is decreasing in Western populations, while the prevalence of diabetes, a well-known risk factor for ischemic stroke, is progressively rising. This study was aimed at evaluating the effect of diabetes on ischemic stroke hospitalization and in-hospital mortality after ischemic stroke. Discharges with diagnosis of ischemic stroke were identified in a database containing all hospitalizations of resident population of Tuscany, Italy, over years 2004-2011. Cases with diabetes were identified through specific drug prescriptions, official certifications or previous hospital diagnosis. Rates of annual ischemic stroke incidence and related in-hospital mortality were separately calculated for gender and age class, in subjects with and without diabetes. Sixty-five thousand one hundred sixty-five hospital discharges with ischemic stroke diagnosis were identified. Diabetes was associated with increased risk of stroke odds ratio(95% confidence interval):1.31(1.28-1.34) in men and 1.24(1.21-1.37) in women. Diabetic women, compared with men, had a higher in-hospital mortality risk after ischemic stroke (odds ratio:1.32; 1.06-1.64), whereas in non-diabetic subjects, there was no difference between genders. Incidence of ischemic stroke has declined in non-diabetic subjects, except for women aged ≤70 years; a similar reduction was observed for in-hospital mortality. Among diabetic patients, conversely, annual incidence of ischemic stroke rose by 3% in the elderly people (>70 years), and annual mortality trend remained unchanged. In the last decade, the incidence of ischemic stroke and of related in-hospital mortality declined in persons without diabetes, while increasing among diabetic patients of advanced age. Women with diabetes, compared with men, had a higher in-hospital mortality risk. Copyright © 2014 John Wiley & Sons, Ltd.

Objective: Evidences have recently accrued about a ‘gender effect’ on the relationship linking blood pressure (BP) and left ventricular mass (LVM) and consequently the question asked by this study is to evaluate the effect of gender on the relationship BP-LVM in subjects who had never used antihypertensive drugs and who were enrolled to a standardised protocol aimed at diagnosing unknown arterial hypertension. Design and Methods: We studied 114 people (58 M/56F), who consecutively came to Hospital's hypertension unit to diagnose/confirm the presence of arterial hypertension as well as to measure LVM in not previously treated patients. Males and females were matched for mean(±SD) age (46±8yr in males and 49±12yr in females) while men were fattier than women (BMI was 28±4Kg/m2 in males,26±5Kg/m2 in females;p = 0.03). LVM was studied by a standardised echographic method and indexed for body area while BP was monitored by ABPM. Results: Hypertensive patients (those with 24hr-mean-ABPM>125/80mmHg) were 47/58 males and 35/56 females. Mean indexed LVM was larger in hypertensive males (n = 47; 105±19 g/m2) than in females (n = 35; 91±19 g/m2;p = 0.001). In the hypertensive population 24-hr-mean-systolic-BP, night- or day-systolic-BP and pulse-BP were similar in both sexes and LVM was related to 24-hr-mean-systolic-BP, night- or day-systolic-BP, and pulse-BP only in females (r = 0.53; 0.51; 0.53; and 0.55;p < 0.05 in all) while no relation was observed with 24-hr-diastolic-BP in both sexes. On the contrary in males only night-24-hr-BP was weakly related to LVM (r = 0.29;p = 0.05). After adjusting for age and BMI, LVM was significantly related to 24-hr-mean-systolic-BP, night- or day-systolic-BP and pulse-BP in hypertensive females and only to night-systolic-BP in males. During the night the adjusted slope of line linking BP and LVM increase was similar in both sexes (0.574 g/m2 in women and 0.560 g/m2 in men for each 1mmHg increase in night-systolic-BP). Conclusions: These data obtained in non-treated-newly-diagnosed hypertensive patients indicate a significant relationship between LVM and 24-hr-BP only in females, while in men only night-systolic-BP seems to exert a significant independent impact on LVM increase.

Context: Dipeptidyl peptidase IV (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes. The underlying mechanisms (incretin effect, β-cell function, endogenous glucose production) are not well known. Objective: The aim of the study was to examine mechanisms of the antihyperglycemic effect of DPP-4 inhibitors. Design, Setting, and Patients: We administered a mixed meal with glucose tracers ([6,6-2H2]-glucose infused, [1-2H]-glucose ingested), and on a separate day, a glucose infusion matched the glucose responses to the meal (isoglycemic test) in 50 type 2 diabetes patients (hemoglobin A1c = 7.4 ± 0.8%) and seven controls; 47 diabetic completers were restudied after 6 wk. Glucose fluxes were calculated, and β-cell function was assessed by mathematical modeling. The incretin effect was calculated as the ratio of oral to iv insulin secretion. Intervention: We conducted a 6-wk, double-blind, randomized treatment with sitagliptin (100 mg/d; n = 25) or placebo (n = ...

The question asked by this study was whether β-cell function expressed by insulin secretion/sensitivity measured during pregnancy in women with gestational diabetes (GDM) predicts post-partum long-term derangement in glucose metabolism. Seventy-four Caucasian women with previous GDM were retested through a 75 g-2-h-OGTT after 8 [6] years (median[interquartile range]) from index pregnancy, measuring at pregnancy and follow-up insulin sensitivity, insulin secretion (1-h-incremental-insulin-area/incremental-glucose-area: ΔAUC60 (I)/ΔAUC60 (G)) as well as the product of Stumvoll-first-phase - secretion x insulin sensitivity (insulin-secretion-sensitivity index (ISSI). At follow-up 47 women were normotelerant to glucose and 27 had altered glucose metabolism (AGM:10 with type 2 diabetes and 17 with IGT). Women progressed to AGM had at their index pregnancy higher mean 2-h-OGTT-glucose area (1.15±0.09 VS. 1.09±0.09 mol l 2-h (-1);p=0.014), and lower ΔAUC60 (I)/ΔAUC60 (median [interquantile range]) (54.4 [51.7] vs. 73.4 [60] pmol mmol (-1)) and ISSI (2 977 [766] vs. 3 708 [1 141]; p<0.05 for both), but similar insulin sensitivity index 2.9 [2.5] VS. 3.2 [2.2] ml min (-1) m (-2);p=NS). Two-h-OGTT-glucose area, or decrease in ΔAUC60 (I)/ΔAUC60 (G) and ISSI were significantly associated with glucose tolerance impairment and with raised adjusted risk for AGM while insulin sensitivity at pregnancy did no predict AGM development. In this group of women increased post-load plasma glucose and impaired β-cell function assessed during GDM pregnancy predict long-term post-partum AGM, while insulin sensitivity measured at the same time does not.

Taurine plays a role in neuronal development. In this study, we examined whether postnatal taurine administration influences the long-term consequences induced by mild neonatal stressors (10 min maternal deprivation plus sham injection, applied daily to neonatal mice up to 21 days). At 30 days of age stressed mice showed higher pain threshold both in the tail-flick--which measures mostly the spinal mechanisms of pain--and in the hot-plate test--which reflects mainly the supraspinal mechanisms of pain. The latter effect was prevented completely by neonatal taurine administration, while the tail-flick test was not affected, thus suggesting that spinal pain is not sensitive to taurine treatment. At 140 days of age, mice which were stressed during the neonatal period showed consistent decrease in immobility time in forced swimming test, and taurine did not influence this parameter. At the same age, the fear/anxiety axis, measured with elevated plus maze test, did not show any consistent changes. Electrophysiological experiments in brain slices obtained from adult mice showed that input-output curves in hippocampal CA1 were increased by taurine administration in lactation. Hence, neonatal administration of taurine might permanently modify the functioning of hippocampus, a brain area which is known to be crucial for learning and memory.

To examine risk of adverse pregnancy outcomes, mothers’ characteristics and incidence rate over time of pregestational type 1 (T1D), type 2 (T2D) or gestational diabetes (GDM). The study included all singleton live births born from women aged 15–45 year, in Tuscany, Italy from 2010 to 2018. Pregnancy outcomes were retrieved by certificates of care at delivery compiled by midwives. Pregestational diabetes and GDM were identified by regional administrative databases. Time course of pregestational diabetes and GDM across last decade was assessed by Poisson analysis. Logistic regression analysis was used to calculate adjusted odds ratios (OR; 95% CI) for maternal characteristics or neonatal outcomes. Among 206,917 singleton live births, GDM was diagnosed in 21,613 pregnancies (10.46%) and pregestational diabetes in 979, being T2D more prevalent than T1D (606; 0.29% vs. 373; 0.18%). Pregestational T2D incidence progressively decreased over last decade, T1D remained stable while GDM progr...