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Biomedical subjects

Giovanni Ghirlanda

Publications and source records attributed to Giovanni Ghirlanda.

17 recordsLinked to original sources

Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study.

BACKGROUND AND AIM: Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up. METHODS: Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG. RESULTS: During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 +/- 30.14 min at baseline and 92.10 +/- 24.52 min at the end of follow-up) and without AN (135.14 +/- 17.09 min and 92.68 +/- 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho - 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values. CONCLUSIONS: Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control.

3-Iodobenzylguanidine↗

Taurine in women with a history of gestational diabetes.

Taurine is the most abundant amino acid in the human body and seems to play an important role in increasing glucose-mediated insulin secretion, as well as in programming beta-cell maturation during the prenatal life in utero. To test the hypothesis that plasma taurine is related to glucose tolerance, insulin sensitivity and insulin secretion in subjects with history of beta-cell dysfunction such as women with history of gestational diabetes (GDM), we studied 72 non-diabetic women with history of GDM (n=43), impaired glucose tolerance (IGT; n=7), and normal glucose tolerance (NGT; n=22) as previously classified by a 100g-3h-OGTT performed between the 24th and the 28th gestational week. Insulin sensitivity (ISIogtt, calculated through Matsuda-DeFronzo index) and a proxy for insulin secretion (basal plasma C-peptide/fasting plasma glucose; CP/glucose) were measured during and after pregnancy. Plasma taurine was measured after a median period of 6 years (2-11 years) from index pregnancy, when glucose tolerance was retested by a 75 g-2h-OGTT. Plasma taurine was significantly lower in women who had experienced GDM and was unrelated to ISIogtt. Moreover, plasma taurine was inversely related to previous gestational area-under-curve of glucose and directly related to post-gestational CP/glucose, as well to CP/glucose measured during pregnancy (p<0.05 for both). The relative risk of altered glucose metabolism during previous pregnancies (IGT+GDM) was higher as plasma taurine decreased, even after adjusting for age, time-lag from pregnancy, body mass index and family history of diabetes (OR: 0.980; CI 95%: 0.963-0.999, p=0.003). In conclusion plasma taurine seems to be a fair marker of altered glucose metabolism during past pregnancies in women with antecedent GDM and appears to be inversely related to the previous as well as to the actual insulin secretion in these subjects.

Adult↗

Inverse correlation between serum free IGF-I and IGFBP-3 levels and blood pressure in patients affected with type 1 diabetes.

BACKGROUND: Even though the gene encoding for IGF-I is considered of most importance amongst blood pressure-regulating genes in mouse models, little and discordant data are available in literature for what concerns a possible relationship between blood pressure and serum free IGF-I values in humans. In addition, no information is available on type 1 diabetes patients. AIM: Our aim is to analyze the relationship between systolic and diastolic blood pressure and serum free IGF-I and IGFBP-3 levels in subjects suffering from type 1 diabetes. RESULTS: A highly significant inverse correlation was observed between serum free IGF-I levels and both systolic and diastolic blood pressure in subjects affected with type 1 diabetes. Similar but less significant relationships were observed for IGFBP-3, whose levels were also significantly and directly correlated with those of free IGF-I. The correlation between systolic and diastolic blood pressures with free IGF-I and between systolic blood pressure and IGFBP-3 levels were confirmed after adjusting for age, gender, age at diagnosis, disease duration, familial history, HBA1c, and amount of insulin administered by multivariate logistic regression analysis. A decrease in free IGF-I and IGFBP-3 levels, along with increases in blood pressure, significantly influenced the presence of diabetic complications, confirming how these molecules may be considered as severity markers for patients with type 1 diabetes as well as risk factors for altered pressure control linked diseases.

Adult↗

Taurine supplementation and diabetes mellitus.

PURPOSE OF REVIEW: Taurine is a semi-essential sulphur amino acid derived from methionine and cysteine metabolism. It has been evaluated either in experimental or clinical type 1 and 2 diabetes mellitus and insulin resistance. One form of experiment has included the possibility that perinatal taurine administration could prevent diabetes mellitus and/or insulin resistance. RECENT FINDINGS: Experimental data suggest strongly that taurine could have beneficial effects in type 1 diabetes mellitus, and could generally reduce organ lipid peroxidation and plasma lipids. Interestingly, retina, lens and nerves seem to respond better to taurine than other organs such as kidneys. It has been shown in some experimental models that in type 2 diabetes mellitus and insulin resistance there is alteration in taurine homeostasis. Taurine could prevent the onset of diabetes mellitus in NOD mice and postnatal taurine modifies the glucose-loading curves in adults. However, the clinical studies are too small and too short to have any real significance. SUMMARY: Further experimental and clinical studies are required to evaluate taurine's possible therapeutic potential. Careful attention has to be paid in the selection of animal species, in standardization of taurine concentrations and patient selection. Moreover, care must also be given to the metabolic state, presence of complications, duration of supplementations and selection of the right end-points.

Adult↗

Association between serum free IGF-I and IGFBP-3 levels in type-I diabetes patients affected with associated autoimmune diseases or diabetic complications.

BACKGROUND: Patients with type 1 diabetes (T1DM) present lower serum free IGF and IGFBP-3 values than healthy people. T1DM patients often present with associated autoimmune diseases such as thyroiditis or coeliac disease, and over time they frequently develop proliferative retinopathy, neuropathy or nephropathy in different combinations. OBJECTIVE: The aim of this study was to evaluate the effect of two associated autoimmune diseases or three diabetic complications on the serum free IGF-I or IGFBP-3 levels in T1DM patients, who also have a family history of T1DM. Design. 246 T1DM patients were enrolled, and then subdivided into groups according to diabetic complications or associated autoimmune diseases. Demographic and clinical data were recorded. Serum free IGF-I and IGFBP-3 levels were determined by IRMA. RESULTS: IGF-I and IGFBP-3 generally present correlated serum values as confirmed in this study. Those patients with autoimmune thyroiditis and coeliac disease presented with significantly lower serum values of IGFBP-3, whereas free IGF-I was significantly lower in patients with the different diabetic complications. Retinopathy presented a slightly significant reduction in serum free IGF-I, while neuropathy and nephropathy showed a more pronounced fall. The number of complications was related to progressively decreasing free IGF-I levels. T1DM family history was associated with lower serum free IGF-I concentrations. These findings were confirmed after correction for age, glycosylated haemoglobin levels, insulin treatment protocol, body mass index, serum creatinine and sex. CONCLUSION: Despite a direct correlation between serum free IGF-I and IGFBP-3, the correlation between the two molecules in patients with associated autoimmune diseases was lost, possibly due to different mechanisms of metabolic regulation.

Adult↗

Overweight and metabolic and hormonal parameter disruption are induced in adult male mice by manipulations during lactation period.

Neonatal manipulations (10 min of maternal separation plus s.c. sham injection, daily for the first 21 d of life) determine overweight in male adult mice. In this work, we investigated the mechanisms underlying mild obesity and the alteration of caloric balance. Neonatally manipulated mice become overweight after onset of maturity, showing increased fat tissue and hypertrophic epididymal adipocytes. Increase in body weight occurs in the presence of a small increase in daily food intake (significant only in the adult period) and the absence of a decrease in spontaneous locomotor activity, while the calculated caloric efficiency is higher in manipulated mice, especially in adulthood. Fasting adult animals show hyperglycemia, hyperinsulinemia, hypertriglyceridemia, hypercholesterolemia, and hyperleptinemia. Soon after weaning and in the adulthood, plasma corticosterone and adrenocorticotropin (ACTH) are also significantly increased. Thus, neonatal manipulations in nongenetically susceptible male mice program mild obesity, with metabolic and hormonal alterations that are similar to those found in experimental models of diabetes mellitus, suggesting that this metabolic derangement may have at least part of its roots early on in life and, more interestingly, that psychological and nociceptive stimuli induce these features.

Animals↗

Is taurine beneficial in reducing risk factors for diabetes mellitus?

Taurine is a semiessential amino acid, and its deficiency is involved in retinal and cardiac degenerations. In recent years, it was found that diabetes mellitus (DM) is associated with taurine, and many in vivo experimental studies showed that taurine administration is able to reduce the alterations induced by DM in the retina, lens, and peripheral nerve, although its effects on diabetic kidney are dubious. Interestingly, long-term taurine supplementation reduces the mortality rate in diabetic rats. The mechanisms by which taurine exerts beneficial effects in DM are discussed below. Recently, it has been suggested that taurine deficiency may alter the endocrine pancreas "fetal programming," increasing the risk of insulin resistance in adult life. The bulk of experimental data suggests that taurine administration could be useful in the treatment of type 1 DM and in the prevention of insulin resistance.

Diabetes Mellitus, Type 2↗

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations.

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.

Animals↗

A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8).

In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis.

Analysis of Variance↗

Neuroadrenergic denervation of the lung in type I diabetes mellitus complicated by autonomic neuropathy.

STUDY OBJECTIVE: To verify whether autonomic neuropathy (AN) complicating type I, insulin-dependent diabetes mellitus affected neuroadrenergic bronchopulmonary innervation. PATIENTS: Twenty nonsmoking diabetic patients without respiratory diseases were studied: 11 patients with AN (group AN) and 9 patients without AN (control; group C) diagnosed by standardized criteria. DESIGN: Patients underwent respiratory function tests and ventilatory scintigraphies with (123)I-metaiodobenzylguanidine (MIBG) and with (99m)Tc-diethylenetriaminepenta-acetic acid (DTPA) to assess both bronchopulmonary neuroadrenergic innervation and also permeability of the alveolar-capillary barrier to water-soluble tracers. Rates of pulmonary clearance of the two tracers were computed, and correlates were identified by nonparametric statistics. SETTING: University hospital. RESULTS: The AN and C groups had normal respiratory function test results and comparable duration of diabetes and quality of metabolic control. (99m)Tc-DTPA clearance did not distinguish the groups. (123)I-MIBG clearance was faster in the AN group than in the C group (mean +/- SD half-time of the radiotracer time-activity curve [T(1/2)], 116.1 +/- 22.8 min in the AN group vs 139.5 +/- 18.3 min in the C group, p = 0.022), which is consistent with neuroadrenergic denervation in the AN group. (123)I-MIBG clearance was independent from (99m)Tc-DTPA clearance. Faster (123)I-MIBG clearance was significantly associated with worse performance in three of the four autonomic tests. CONCLUSIONS: Neuroadrenergic bronchopulmonary denervation may occur in diabetic patients with AN despite normal clinical and respiratory function findings. Further research is needed to identify clinical and prognostic implications of these findings.

3-Iodobenzylguanidine↗

Early increase of oxidative stress and reduced antioxidant defenses in patients with uncomplicated type 1 diabetes: a case for gender difference.

OBJECTIVE: Diabetes increases the risk of coronary heart disease (CHD) to a greater extent in women than in men. We investigated whether type 1 diabetic patients with short duration of disease and without complications have an altered oxidative status and whether there are differences between men and women. RESEARCH DESIGN AND METHODS: We investigated oxidative status in 29 control subjects and 37 patients with uncomplicated type 1 diabetes with duration of 6 +/- 3 years. RESULTS: Compared with control subjects, type 1 diabetic patients had lower total plasma antioxidant capacity (TRAP) (720.3 +/- 111.2 vs. 972.5 +/- 97.7 micromol/l in men, P < 0.001; 579.8 +/- 95.4 vs. 930.1 +/- 84.2 in women, P < 0.001), higher lipid hydroperoxide (ROOH) levels (6.4 +/- 2.2 vs. 2.0 +/- 0.7 micromol/l in men, P < 0.001; 8.1 +/- 1.9 vs. 2.2 +/- 0.6 in women, P < 0.001), higher total conjugated diene (CD) levels (0.037 +/- 0.003 vs. 0.033 +/- 0.002 A.U. in men, P < 0.001), lower 246-nm CD levels (0.0032. +/- 0.0010 vs. 0.0070 +/- 0.0012 A.U. in men, P < 0.001; 0.0022 +/- 0.0011 vs. 0.0072 +/- 0.0014 A.U. in women, P < 0.001), and higher 232-nm CD levels (0.0348 +/- 0.0041 vs. 0.0257 +/- 0.0022 A.U. in men, P < 0.001; 0.0346 +/- 0.0031 vs. 0.0246 +/- 0.0074 A.U. in women, P < 0.001). Compared with diabetic men, diabetic women had lower TRAP (P < 0.01), higher ROOH levels (P < 0.01), and lower 246-nm CD levels (P < 0.05). Plasma concentration of uric acid was significantly lower in patients with type 1 diabetes than in control subjects (3.3 +/- 0.3 vs. 4.3 +/- 0.2 mg/dl; P = 0.009) with a significant difference between women and men with type 1 diabetes (2.6 +/- 0.3 vs. 3.9 +/- 0.3, respectively; P = 0.009). CONCLUSIONS: Our findings suggest that reduced antioxidant activity and increased oxidative stress occur early after the diagnosis of type 1 diabetes, especially in women, and this might explain, at least in part, the increased susceptibility of diabetic women to cardiovascular complications.

Adult↗

[Clinical and diagnostic approach to erectile dysfunction].

Erectile dysfunction (ED), defined as the inability to achieve and/or maintain an erection sufficiently long for a satisfactory sexual performance or intercourse, is an important and common medical problem. ED is not a life-threatening disorder, but it influences the daily routine, social interactions, well-being and quality of life of the patient. Recent epidemiological data have shown a high prevalence and incidence of ED. The Massachusetts Male Aging Study found that 52% of men between the ages of 40 and 70 years reported ED with 9.6% having mild, 22.2% moderate and 17.2% complete or severe ED. In a large Italian cross-sectional study the overall prevalence of self-reported ED was 12.8% and the frequency of ED increases with age. ED may signal serious underlying and potentially life-threatening diseases, such as diabetes, hypertension, cardiovascular disease, peripheral vascular disease and other neurological and endocrine disorders. Also well documented is the role of some drug groups, certain types of surgery, injuries and the role of risk factors related to lifestyle such as smoking, alcohol consumption and inappropriate dietary habits accompanied by an abnormal serum level of cholesterol. The current availability of effective and safe oral drugs for ED in conjunction with the tremendous media interest in the condition, have resulted in an increasing number of men seeking help for ED. As a consequence, many physicians without background knowledge and clinical experience in the diagnosis of ED are involved in making decisions concerning the evaluation of such patients. The result of this is that some males with ED may undergo little or no evaluation before treatment is initiated and, in such circumstances, the disease causing the symptom (ED) may remain untreated. Baseline diagnostic evaluation for ED can identify the underlying pathological condition or the risk factors associated with ED in 80% of patients. This article reports a sequential approach for the diagnosis of ED that may diagnose reversible causes of ED and also unmask medical conditions that manifest with ED as the first symptom.

Algorithms↗