Publications by authors named "Ilaria Giordani"

12 Publications

  • Page 1 of 1

The Footprints of Poly-Autoimmunity: Evidence for Common Biological Factors Involved in Multiple Sclerosis and Hashimoto's Thyroiditis.

Front Immunol 2018 20;9:311. Epub 2018 Feb 20.

Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano, Turin, Italy.

Autoimmune diseases are a diverse group of chronic disorders and affect a multitude of organs and systems. However, the existence of common pathophysiological mechanisms is hypothesized and reports of shared risk are emerging as well. In this regard, patients with multiple sclerosis (MS) have been shown to have an increased susceptibility to develop chronic autoimmune thyroid diseases, in particular Hashimoto's thyroiditis (HT), suggesting an autoimmune predisposition. However, studies comparing such different pathologies of autoimmune origin are still missing till date. In the present study, we sought to investigate mechanisms which may lead to the frequent coexistence of MS and HT by analyzing several factors related to the pathogenesis of MS and HT in patients affected by one or both diseases, as well as in healthy donors. In particular, we analyzed peripheral blood mononuclear cell gene-expression levels of common candidate genes such as TNFAIP3, NR4A family, BACH2, FOXP3, and PDCD5, in addition to the regulatory T cell (Treg) percentage and the 25-hydroxy vitamin D serum levels. Our findings support the plausibility of the existence of common deregulated mechanisms shared by MS and HT, such as BACH2/PDCD5-FOXP3 pathways and Tregs. Although the biological implications of these data need to be further investigated, we have highlighted the relevance of studies comparing different autoimmune pathologies for the understanding of the core concepts of autoimmunity.
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http://dx.doi.org/10.3389/fimmu.2018.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829620PMC
March 2019

Measuring procalcitonin to overcome heterophilic-antibody-induced spurious hypercalcitoninemia.

Clin Chem Lab Med 2018 07;56(8):e191-e193

Department of Nuclear Medicine and Competence Centre for Thyroid Disease, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.

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http://dx.doi.org/10.1515/cclm-2017-0993DOI Listing
July 2018

Retinal neurodegeneration in patients with type 1 diabetes mellitus: the role of glycemic variability.

Acta Diabetol 2017 May 25;54(5):489-497. Epub 2017 Feb 25.

Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

Aims: Recent studies have identified neuroretinal abnormalities in persons affected by diabetes mellitus, before the onset of microvascular alterations. However, the role of glycemic variability (GV) on early retinal neurodegeneration is still not clarified.

Methods: To explore the relationship between glycemic control and neuroretinal characteristics, 37 persons with Type 1 diabetes mellitus (Type 1 DM) divided into two groups with no signs (noRD) and with mild non-proliferative diabetic retinopathy (NPDR) compared to 13 healthy control participants (C) were recruited. All persons underwent an optical coherence tomography with automatic segmentation of all neuroretinal layers. Measurements of mean of nasal (N)/temporal (T)/superior (S)/inferior (I) macular quadrants for individual layer were also calculated. Metabolic control was evaluated by glycated hemoglobin (HbA1c), and indexes of GV were calculated from continuous glucose monitoring.

Results: The difference among the three groups in terms of RNFL thickness was significantly dependent on quadrant (F(6;132) = 2.315; p = 0.037). This interaction was due to a specific difference in RNFL-N thickness, where both Type 1 DM groups showed a similar reduction versus C (-3.9 for noDR and -4.9 for NPDR), without any relevant difference between them (-1.0). Inner nuclear layer (INL) was increased in all quadrants in the two Type 1 DM groups compared to C (mean difference = 7.73; 95% CI: 0.32-15.14, p = 0.043; mean difference = 7.74; 95% CI: 0.33-15.15, p = 0.043, respectively). A negative correlation between RNFL-N and low blood glucose index (r = -0.382, p = 0.034) and positive correlation between INL and continuous overall net glycemic action -1, -2, -4 h (r = 0.40, p = 0.025; r = 0.39, p = 0.031; r = 0.41, p = 0.021, respectively) were observed in Type 1 DM patients. The triglycerides were positively and significantly correlated to INL (r = 0.48, p = 0.011), in Type 1 DM subjects. GV and triglycerides resulted both independent predictors of increased INL thickness. No correlation was found with HbA1c.

Conclusions: Early structural damage of neuroretina in persons with Type 1 DM patients is related to glucose fluctuations. GV should be addressed, even in the presence of a good metabolic control.
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http://dx.doi.org/10.1007/s00592-017-0971-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385321PMC
May 2017

Severe hypoglycemia in patients with known diabetes requiring emergency department care: A report from an Italian multicenter study.

J Clin Transl Endocrinol 2016 Sep 20;5:46-52. Epub 2016 Aug 20.

Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.

Aims: To describe the characteristics and associated risk factors of patients with established diabetes who required Emergency Department (ED) care for severe hypoglycemia.

Methods: We performed an observational retrospective study to identify all cases of severe hypoglycemia among attendees at the EDs of three Italian University hospitals from January 2010 to December 2014.

Results: Overall, 520 patients with established diabetes were identified. Mean out-of-hospital blood glucose concentrations at the time of the hypoglycemic event were 2.2 ± 1.3 mmol/L. Most of these patients were frail and had multiple comorbidities. They were treated with oral hypoglycemic drugs (43.6%), insulin (42.8%), or both (13.6%). Among the oral hypoglycemic drugs, glibenclamide (54.5%) and repaglinide (25.7%) were the two most frequently used drugs, followed by glimepiride (11.3%) and gliclazide (7.5%). Hospitalization rates and in-hospital deaths occurred in 35.4% and in 2.3% of patients, respectively. Cirrhosis (odds ratio [OR] 6.76, 95% confidence interval [CI] 1.24-36.8, p < 0.05), chronic kidney disease (OR 2.42, 95% CI 1.11-8.69, p < 0.05) and center (Sapienza University OR 3.70, 95% CI 1.57-8.69, p < 0.05) were the strongest predictors of increased rates of hospital admission.

Conclusions: Severe hypoglycemia is a remarkable burden for patients with established diabetes and increases the risk of adverse clinical outcomes (in-hospital death and hospitalization), mainly in elderly and frail patients. This study further reinforces the notion that careful attention should be taken by health care providers when they prescribe drug therapy in elderly patients with serious comorbidities.
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http://dx.doi.org/10.1016/j.jcte.2016.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644438PMC
September 2016

Acute hyperglycemia reduces cerebrovascular reactivity: the role of glycemic variability.

J Clin Endocrinol Metab 2014 Aug 30;99(8):2854-60. Epub 2014 May 30.

Unit of Endocrinology, Diabetes, and Metabolism (I.G., A.D.F., F.P., I.M., D.Y., S.F.); Department of Neurology (P.Pal., F.P.); and Fatebenefratelli Association for Research Unit of Internal Medicine (S.D., P.Pas.) and Service of Medical Statistics and Information Technology (S.D., P.Pas.), S. Giovanni Calibita Fatebenefratelli Hospital, 00186 Rome, Italy; Department of Systems Medicine (I.G., A.D.F., F.P., I.M., D.Y., D.L., S.F.), University of Rome Tor Vergata, 00133 Rome, Italy; Department of Neurology (P.Pal., R.A., F.V.), Campus Bio-Medico University, 00128 Rome, Italy; and Unit of Health Management (S.D.), Ministry of Health, Viale Giorgio Ribotta 5, 00144 Rome, Italy.

Context: Cerebral vasomotor reactivity (CVR) is reduced in patients with diabetes mellitus (DM), and glucose variability (GV) might be responsible for cerebrovascular damage.

Objective: Studying patients with insulin resistance without DM, we explored the role of GV in impairing CVR.

Patients: We studied 18 metabolic syndrome (MS) patients without DM, 9 controls (C), and 26 patients with DM.

Main Outcome Measures: Groups were compared in terms of CVR, GV, and 24-hour blood pressure. To evaluate the impact of acute hyperglycemia on CVR, a hyperglycemic clamp was performed in MS patients and controls.

Results: Baseline CVR was reduced in DM vs C and MS (C vs DM = 20.2, 95% CI = 3.5-36.9, P = .014; and MS vs DM = 22.2, 95% CI = 8.6-35.8, P = .001), but similar between MS and C (MS vs C = 2.0, 95% CI = -14.7 to 18.7, P = .643). During acute hyperglycemia, CVR fell in MS and C to values comparable to DM. GV progressively increased from C to MS to DM. In MS, CVR at 120 minutes and GV displayed a negative correlation (r = -0.48, P = .043), which did not change after controlling for mean 24-hour systolic and diastolic blood pressure. In MS, the CVR reduction was significantly correlated to GV (r = 0.55, P = .02).

Conclusions: GV is increased in patients with MS but without DM and is the major predictor of CVR reduction induced by acute hyperglycemia, possibly representing the earliest cause of cerebrovascular damage in DM.
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http://dx.doi.org/10.1210/jc.2014-1087DOI Listing
August 2014

Cerebral hemodynamics and systemic endothelial function are already impaired in well-controlled type 2 diabetic patients, with short-term disease.

PLoS One 2013 31;8(12):e83287. Epub 2013 Dec 31.

Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, University of Rome Tor Vergata, Rome, Italy.

Objective: Impaired cerebral vasomotor reactivity (VMR) and flow-mediated dilation (FMD) were found in selected subgroups of type 2 diabetes mellitus (T2DM) patients with long-term disease. Our study aimed to evaluate cerebral hemodynamics, systemic endothelial function and sympatho-vagal balance in a selected population of well-controlled T2DM patients with short-term disease and without cardiac autonomic neuropathy (CAN).

Research Design And Methods: Twenty-six T2DM patients with short-term (4.40±4.80 years) and well-controlled (HbA1C = 6.71±1.29%) disease, without any complications, treated with diet and/or metformin, were consecutively recruited. Eighteen controls, comparable by sex and age, were enrolled also.

Results: FMD and shear rate FMD were found to be reduced in T2DM subjects with short-term disease (8.5% SD 3.5 and 2.5 SD 1.3, respectively) compared to controls (15.4% SD 4.1 and 3.5 SD 1.4; p<.001 and p<.05). T2DM patients also displayed reduced VMR values than controls (39.4% SD 12.4 vs 51.7%, SD 15.5; p<.05). Sympatho-vagal balance was not different in T2DM patients compared to healthy subjects. FMD and shear rate FMD did not correlate with VMR in T2DM patients or in controls (p>.05).

Conclusions: In well-controlled T2DM patients with short-term disease cerebral hemodynamics and systemic endothelial function are altered while autonomic balance appeared to be preserved.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083287PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877017PMC
August 2014

Preliminary evidence that obese patients with obstructive sleep apnea/hypopnea syndrome are refractory to the acute beneficial metabolic effects of a very low calorie diet.

Acta Diabetol 2013 Aug 6;50(4):639-43. Epub 2013 Jun 6.

Department of Medicina dei Sistemi, University of Rome Tor Vergata, Rome, Italy.

Since obesity seems to play a causal role in both obstructive sleep apnea/hypopnea syndrome (OSAHS) and type 2 diabetes, the question arises whether diet-induced weight loss is equally efficacious in type 2 diabetic patients with and without OSAHS. The present study was aimed to investigate the effect of 1 week very low calorie diet (VLCD) on oxygen desaturation index (ODI) and on glucose regulation in OSAHS versus non-OSAHS patients. Fourteen patients with type 2 diabetes mellitus and morbid obesity were enrolled. According to ODI, patients were divided into 2 groups (with and without OSAHS) and evaluated by a hyperglycemic clamp study, before and after a 7 day-VLCD. After a VLCD, a significant reduction of anthropometric parameters, in the overall group and in subgroups, was observed. M-value and acute insulin response increased significantly only in patients without obstructive sleep apnea (990.10 ± 170.19 vs. 1,205.22 ± 145.73 μmol min(-1) m(-2), p = 0.046; -1.05 ± 8.40 vs. 48.26 ± 11. 90 pmol/L, p = 0.028, respectively). The average 24-h heart rate (24-h HR) fell significantly (p = 0.05), primarily because of a decrease during daytime (p = 0.041), in the whole group. In conclusion, we observed that morbidly obese patients with type 2 diabetes and OSAHS are specifically resistant to the acute beneficial effects of VLCD on metabolic parameters. Our preliminary observation deserves further investigation to clarify the pathogenetic mechanisms involved.
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http://dx.doi.org/10.1007/s00592-013-0487-5DOI Listing
August 2013

A new clustering approach for learning transcriptional modules.

Int J Data Min Bioinform 2012 ;6(3):304-23

DISCO - Department of Computer Science, Systems and Communication, University of Milano Bicocca, Consorzio Milano Ricerche, Milan, Italy.

In modern biology, we had an explosion of genomic data from multiple sources, like measurements of RNA levels, gene sequences, annotations or interaction data. These heterogeneous data provide important information that should be integrated through suitable learning methods aimed at elucidating regulatory networks. We propose an iterative relational clustering procedure for finding modules of co-regulated genes. This approach integrates information concerning known Transcription Factors (TFs)--gene interactions with gene expression data to find clusters of genes that share a common regulatory program. The results obtained on two well-known gene expression data sets from Saccharomyces cerevisiae are shown.
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http://dx.doi.org/10.1504/ijdmb.2012.049248DOI Listing
January 2013

Very-low-calorie diet: a quick therapeutic tool to improve β cell function in morbidly obese patients with type 2 diabetes.

Am J Clin Nutr 2012 Mar 8;95(3):609-13. Epub 2012 Feb 8.

Department of Medicine, University of Rome Tor Vergata, Rome, Italy.

Background: Caloric restriction in obese diabetic patients quickly improves glucose control, independently from weight loss. However, the early effects of a very-low-calorie diet (VLCD) on insulin sensitivity and insulin secretion in morbidly obese patients with type 2 diabetes are still unclear.

Objective: The objective was to study the relative contributions of insulin sensitivity, insulin secretion, or both to improvement in glucose metabolism, after 1 wk of caloric restriction, in severely obese diabetic patients.

Design: Hyperglycemic clamps were performed in 14 severely obese (BMI, in kg/m(2): >40) patients with type 2 diabetes in good glucose control (glycated hemoglobin < 7.5%) before and after 7 d of a VLCD (400 kcal/d).

Results: The VLCD caused a 3.22 ± 0.56% weight loss (P < 0.001), 42.0% of which was fat loss, accompanied by decreases in fasting plasma glucose (P < 0.05) and triglycerides (P < 0.01). In parallel, the Disposition Index, which measures the body's capability to dispose of a glucose load, increased from 59.0 ± 6.3 to 75.5 ± 6.3 mL· min(-1) · m(-2) body surface area (P < 0.01), because of improvements in indexes of both first- and second-phase insulin secretion (P < 0.02), but with no changes in insulin sensitivity (P = 0.33).

Conclusion: The marked improvement in metabolic profile, observed in severely obese patients with type 2 diabetes after a 7-d VLCD, was primarily due to the amelioration of β cell function, whereas no contribution of insulin sensitivity was shown. This trial was registered at www.clinicaltrials.gov as NCT01447524.
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http://dx.doi.org/10.3945/ajcn.111.023697DOI Listing
March 2012

Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients.

Diabetes Care 2011 Jul 24;34(7):1605-9. Epub 2011 May 24.

Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, University of Rome Tor Vergata, Rome, Italy.

Objective: The effect of glycemic variability (GV) on cardiovascular risk has not been fully clarified in type 2 diabetes. We evaluated the effect of GV, blood pressure (BP), and oxidative stress on intima-media thickness (IMT), left ventricular mass index (LVMI), flow-mediated dilation (FMD), and sympathovagal balance (low frequency [LF]/high frequency [HF] ratio) in 26 type 2 diabetic patients (diabetes duration 4.41±4.81 years; HbA1c 6.70±1.25%) receiving diet and/or metformin treatment, with no hypotensive treatment or complications.

Research Design And Methods: Continuous glucose monitoring (CGM) data were used to calculate mean amplitude of glycemic excursion (MAGE), continuous overall net glycemic action (CONGA)-2, mean blood glucose (MBG), mean postprandial glucose excursion (MPPGE), and incremental area under the curve (IAUC). Blood pressure (BP), circadian rhythm, and urinary 15-F2t-isoprostane (8-iso-prostaglandin F2α [PGF2α]) were also evaluated. Subjects were divided into dipper (D) and nondipper (ND) groups according to ΔBP.

Results: IMT and LVMI were increased in ND versus D (0.77±0.08 vs. 0.68±0.13 [P=0.04] and 67±14 vs. 55±11 [P=0.03], respectively). MBG, MAGE, and IAUC were significantly associated with LF/HF ratio at night (r=0.50, P=0.01; r=0.40, P=0.04; r=0.41, P=0.04, respectively), MPPGE was negatively associated with FMD (r=-0.45, P=0.02), and CONGA-2 was positively associated with LVMI (r=0.55, P=0.006). The Δsystolic BP was negatively associated with IMT (r=-0.43, P=0.03) and with LVMI (r=-0.52, P=0.01). Urinary 8-iso-PGF2α was positively associated with LVMI (r=0.68 P<0.001).

Conclusions: An impaired GV and BP variability is associated with endothelial and cardiovascular damage in short-term diabetic patients with optimal metabolic control. Oxidative stress is the only independent predictor of increased LV mass and correlates with glucose and BP variability.
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http://dx.doi.org/10.2337/dc11-0034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120198PMC
July 2011