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1.
J Endocrinol Invest ; 45(1): 105-114, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34170488

RESUMO

PURPOSE: The C-X-C motif chemokine ligand 10 (CXCL10) participates in diabetes and diabetic cardiomyopathy development from the early stages. Rosiglitazone (RGZ) exhibits anti-inflammatory properties and can target cardiomyocytes secreting CXCL10, under interferon (IFN)γ and tumor necrosis factor (TNF)α challenge. Cardiomyocyte remodeling, CD4 + T cells and dendritic cells (DCs) significantly contribute to the inflammatory milieu underlying and promoting disease development. We aimed to study the effect of RGZ onto inflammation-induced secretion of CXCL10, IFNγ, TNFα, interleukin (IL)-6 and IL-8 by human CD4 + T and DCs, and onto IFNγ/TNFα-dependent signaling in human cardiomyocytes associated with chemokine release. METHODS: Cells maintained within an inflammatory-like microenvironment were exposed to RGZ at near therapy dose (5 µM). ELISA quantified cytokine secretion; qPCR measured mRNA expression; Western blot analyzed protein expression and activation; immunofluorescent analysis detected intracellular IFNγ/TNFα-dependent trafficking. RESULTS: In human CD4 + T cells and DCs, RGZ inhibited CXCL10 release likely with a transcriptional mechanism, and reduced TNFα only in CD4 + T cells. In human cardiomyocytes, RGZ impaired IFNγ/TNFα signal transduction, blocking the phosphorylation/nuclear translocation of signal transducer and activator of transcription 1 (Stat1) and nuclear factor-kB (NF-kB), in association with a significant decrease in CXCL10 expression, IL-6 and IL-8 release. CONCLUSION: As the combination of Th1 biomarkers like CXCL10, IL-8, IL-6 with classical cardiovascular risk factors seems to improve the accuracy in predicting T2D and coronary events, future studies might be desirable to further investigate the anti-Th1 effect of RGZ.


Assuntos
Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Miócitos Cardíacos , Rosiglitazona/farmacologia , Anti-Inflamatórios/farmacologia , Células Cultivadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatias Diabéticas/imunologia , Cardiomiopatias Diabéticas/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Inflamação/metabolismo , Interferon gama/metabolismo , Interleucina-8/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Prognóstico , Linfócitos T Auxiliares-Indutores/imunologia , Tiazolidinedionas/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
2.
J Endocrinol Invest ; 44(1): 105-110, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32350824

RESUMO

PURPOSE: The hepatokine fetuin-A might have a role as molecular link between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the association between fetuin-A and the prevalence and severity of NAFLD in a population of young adults. METHODS: Ninety-seven adults (age 35.7 ± 12.4 years, female 64.9%), enrolled in a previous study evaluating NAFLD prevalence in the presence or absence of family history of T2DM, were included. Serum levels of fetuin-A (ELISA BioVendor, Czech Republic) and the main biochemical parameters were assessed. Presence and severity of NAFLD were evaluated by ultrasonography (Toshiba, Japan). A linear regression was run to predict fetuin-A levels and a logistic regression was performed to predict moderate-severe steatosis. RESULTS: Fetuin-A associated inversely with age (ß - 0.12, p = 0.03) and directly with body mass index (BMI) (ß 0.5, p = 0.048), waist circumference (WC) (ß 0.3, p = 0.027), triglycerides (TG) (ß 0.1, p = 0.001) and uric acid (ß 1.7, p = 0.018), after adjustment for age and sex. In a model including age, BMI, WC, TG and uric acid, age (ß - 0.2, p = 0.002) and TG (ß 0.04, p = 0.02) were independent predictors of fetuin-A. Prevalence of steatosis was 66%. The rates of mild and moderate-severe steatosis were 50.5% and 15.5%, respectively. In the logistic model, the independent predictors of moderate-severe steatosis were fetuin-A (OR 1.22, p = 0.036), age (OR 1.17, p = 0.01) and BMI (OR 2.75, p = 0.011). CONCLUSION: In a sample of young adults, circulating levels of fetuin-A correlated with moderate-severe NAFLD, independent of confounders, and with some metabolic parameters. Fetuin-A might be a useful marker to predict NAFLD and metabolic disorders.


Assuntos
Biomarcadores/sangue , Índice de Massa Corporal , Hepatopatia Gordurosa não Alcoólica/patologia , alfa-2-Glicoproteína-HS/análise , Adulto , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prognóstico , Adulto Jovem
3.
J Endocrinol Invest ; 44(6): 1159-1174, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33111214

RESUMO

BACKGROUND: Obesity, characterized by an increased amount of adipose tissue, is a metabolic chronic alteration which has reached pandemic proportion. Lifestyle changes are the first line therapy for obesity and a large variety of dietary approaches have demonstrated efficacy in promoting weight loss and improving obesity-related metabolic alterations. Besides diet and physical activity, bariatric surgery might be an effective therapeutic strategy for morbid obese patients. Response to weight-loss interventions is characterised by high inter-individual variability, which might involve epigenetic factors. microRNAs have critical roles in metabolic processes and their dysregulated expression has been reported in obesity. AIM: The aim of this review is to provide a comprehensive overview of current studies evaluating changes in microRNA expression in obese patients undergoing lifestyle interventions or bariatric surgery. RESULTS: A considerable number of studies have reported a differential expression of circulating microRNAs before and after various dietary and bariatric surgery approaches, identifying several candidate biomarkers of response to weight loss. Significant changes in microRNA expression have been observed at a tissue level as well, with entirely different patterns between visceral and subcutaneous adipose tissue. Interestingly, relevant differences in microRNA expression have emerged between responders and non-responders to dietary or surgical interventions. A wide variety of dysregulated microRNA target pathways have also been identified, helping to understand the pathophysiological mechanisms underlying obesity and obesity-related metabolic diseases. CONCLUSIONS: Although further research is needed to draw firm conclusions, there is increasing evidence about microRNAs as potential biomarkers for weight loss and response to intervention strategies in obesity.


Assuntos
Cirurgia Bariátrica/métodos , MicroRNA Circulante/sangue , Dietoterapia/métodos , Obesidade , Redução de Peso/fisiologia , Biomarcadores/sangue , Perfilação da Expressão Gênica/métodos , Humanos , Obesidade/dietoterapia , Obesidade/metabolismo , Obesidade/psicologia , Obesidade/cirurgia
4.
Ig Sanita Pubbl ; 77(3): 502-508, 2021.
Artigo em Italiano | MEDLINE | ID: mdl-34342599

RESUMO

The percentage of female doctors employed in the health sector is constantly increasing both in Europe and in Italy with repercussions on organizational and socio-family models, currently not conceived in terms of equal opportunities, career and quality of life. The published studies have mainly taken into consideration economic and career disparities, (1) however, to date no study combined with surveys has highlighted criteria for evaluating the quality of work through the direct and sincere experience of workers. This reflection gave rise to the idea of a survey organized by the ANAAO Medical Women Group with the patronage of the Tuscan Medical Orders Federation organized on a homogeneous sample, i.e. female doctors from a single Region, Tuscany, in order to evaluate and new approaches in the management of human resources that take into account the delicate balance between the real possibilities available to the doctor and the complexities of experiential work that arise over the course of a lifetime. Empirical evidence deriving from specific investigations conducted at trade union and ordinistic level still document the existence of a gender gap between male and female doctors with respect to the reference parameters of quality work, such as the economic and ergonomic dimension, in relation to the physical and psychological aspects of people.


Assuntos
Expectativa de Vida , Qualidade de Vida , Atenção à Saúde , Europa (Continente) , Feminino , Humanos , Itália , Masculino
5.
J Endocrinol Invest ; 43(8): 1053-1060, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32495299

RESUMO

BACKGROUND: The Coronavirus disease 2019 (COVID-19) and type 2 diabetes (T2D) are two pandemics that share the dramatic impact on global mortality and economic resources. COVID-19 largely exhibits mild to moderate clinical manifestations. However, severe pneumonia with high fatality rate may occur, especially in the elderly and in patients with underlying conditions, such as diabetes and cardiovascular disease. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) binds to the angiotensin-converting enzyme 2 (ACE2), a ubiquitous trans-membrane carboxypeptidase, to enter the cells. AIMS: This short review discusses some open questions about the link between COVID-19 and diabetes, principally focusing on the possible effects of commonly used drugs in patients with diabetes. RESULTS: Preclinical studies have reported that angiotensin receptor blockers (ARBs) and ACE inhibitors might increase ACE2 expression in several cell types. Hence, it has been speculated that the treatment with these agents might influence the course of the infection, and both harmful and beneficial effects have been supposed. Other pharmacological agents are thought to increase ACE2 expression, including statins and proliferator-activated receptor gamma (PPAR-γ) agonists. All these drug classes are broadly adopted in T2D. Besides ACE2, other unknown co-factors might be involved in cell infection. It has been recently observed that dipeptidyl peptidase-4 (DPP4), the receptor for MERS-CoV (Middle East respiratory syndrome-related coronavirus) and ACE2 have similar expression profiles in the lung. DPP4 has important metabolic and immune functions and is a target for commonly used therapies in T2D. CONCLUSIONS: Although clinical data supporting an influence of all these drugs on the course of the disease are limited, this is an interesting background for further research that might help unravel the complex mechanisms underlying the link between COVID-19 and diabetes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/efeitos adversos , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Antagonistas de Receptores de Angiotensina/efeitos adversos , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Animais , COVID-19 , Infecções por Coronavirus/induzido quimicamente , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/induzido quimicamente , SARS-CoV-2
6.
BJOG ; 126(8): 1043-1051, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30957402

RESUMO

OBJECTIVE: To perform a health economic analysis of an intervention designed to increase rates of vaginal birth after caesarean, compared with usual care. DESIGN: Economic analysis alongside the cluster-randomised OptiBIRTH trial (Optimising childbirth by increasing vaginal birth after caesarean section (VBAC) through enhanced women-centred care). SETTING: Fifteen maternity units in three European countries - Germany (five), Ireland (five), and Italy (five) - with relatively low VBAC rates. POPULATION: Pregnant women with a history of one previous lower-segment caesarean section; sites were randomised (3:2) to intervention or control. METHODS: A cost-utility analysis from both societal and health-services perspectives, using a decision tree. MAIN OUTCOME MEASURES: Costs and resource use per woman and infant were compared between the control and intervention group by country, from pregnancy recognition until 3 months postpartum. Based on the caesarean section rates, and maternal and neonatal morbidities and mortality, the incremental cost-utility ratios were calculated per country. RESULTS: The mean difference in costs per quality-adjusted life years (QALYs) gained from a societal perspective between the intervention and the control group, using a probabilistic sensitivity analysis, was: €263 (95% CI €258-268) and 0.008 QALYs (95% CI 0.008-0.009 QALYs) for Germany, €456 (95% CI €448-464) and 0.052 QALYs (95% CI 0.051-0.053 QALYs) for Ireland, and €1174 (95% CI €1170-1178) and 0.006 QALYs (95% CI 0.005-0.007 QALYs) for Italy. The incremental cost-utility ratios were €33,741/QALY for Germany, €8785/QALY for Ireland, and €214,318/QALY for Italy, with a 51% probability of being cost-effective for Germany, 92% for Ireland, and 15% for Italy. CONCLUSION: The OptiBIRTH intervention was likely to be cost-effective in Ireland and Germany. TWEETABLE ABSTRACT: The OptiBIRTH intervention (to increase VBAC rates) is likely to be cost-effective in Germany and Ireland.


Assuntos
Análise Custo-Benefício , Serviços de Saúde Materno-Infantil/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Nascimento Vaginal Após Cesárea/economia , Adulto , Análise por Conglomerados , Feminino , Alemanha , Humanos , Irlanda , Itália , Gravidez , Anos de Vida Ajustados por Qualidade de Vida
7.
J Endocrinol Invest ; 42(3): 295-301, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29916137

RESUMO

PURPOSE: Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. METHODS: Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. RESULTS: OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9-31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. CONCLUSIONS: In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Fraturas do Quadril/diagnóstico , Lipídeos/sangue , Osteopontina/sangue , Fraturas por Osteoporose/diagnóstico , Pós-Menopausa , Idoso , Glicemia/análise , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Fraturas do Quadril/sangue , Fraturas do Quadril/epidemiologia , Humanos , Itália/epidemiologia , Estudos Longitudinais , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Prevalência , Prognóstico
8.
J Endocrinol Invest ; 42(6): 715-725, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30415310

RESUMO

PURPOSE: Interleukin (IL)-8 is a proinflammatory C-X-C chemokine involved in inflammation underling cardiac diseases, primary or in comorbid condition, such diabetic cardiomyopathy (DCM). The phosphodiesterase type 5 inhibitor sildenafil can ameliorate cardiac conditions by counteracting inflammation. The study aim is to evaluate the effect of sildenafil on serum IL-8 in DCM subjects vs. placebo, and on IL-8 release in human endothelial cells (Hfaec) and peripheral blood mononuclear cells (PBMC) under inflammatory stimuli. METHODS: IL-8 was quantified: in sera of (30) DCM subjects before (baseline) and after sildenafil (100 mg/day, 3-months) vs. (16) placebo and (15) healthy subjects, by multiplatform array; in supernatants from inflammation-challenged cells after sildenafil (1 µM), by ELISA. RESULTS: Baseline IL-8 was higher in DCM vs. healthy subjects (149.14 ± 46.89 vs. 16.17 ± 5.38 pg/ml, p < 0.01). Sildenafil, not placebo, significantly reduced serum IL-8 (23.7 ± 5.9 pg/ml, p < 0.05 vs. baseline). Receiver operating characteristic (ROC) curve for IL-8 was 0.945 (95% confidence interval of 0.772 to 1.0, p < 0.01), showing good capacity of discriminating the response in terms of drug-induced IL-8 decrease (sensitivity of 0.93, specificity of 0.90). Sildenafil significantly decreased IL-8 protein release by inflammation-induced Hfaec and PBMC and downregulated IL-8 mRNA in PBMC, without affecting cell number or PDE5 expression. CONCLUSION: Sildenafil might be suggested as potential novel pharmacological tool to control DCM progression through IL-8 targeting at systemic and cellular level.


Assuntos
Cardiomiopatias Diabéticas/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Interleucina-8/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Feminino , Seguimentos , Humanos , Técnicas In Vitro , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico
9.
Pharmacogenomics J ; 18(3): 431-435, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-28696414

RESUMO

To investigate the role of IRS1 locus on failure to oral antidiabetes drugs (OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326 (tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R amino acid substitution) in 2662 patients with T2D. Although no association with OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93-1.16 and OR: 0.97, 95% CI: 0.87-1.09 respectively), a significant association was observed for rs1801278 (OR: 1.34, 95% CI: 1.08-1.66). When meta-analyzed with previous published data, an allelic OR of 1.41 (1.15-1.72; P=0.001) was obtained, so that homozygous R972R individuals have >80% higher risk of failing to OADs as compared with their G972G counterparts. In all, though further studies are needed for confirming this finding, our present data point to IRS1 rs1801278 as a potential biomarker for pursuing the goal of stratified medicine in the field of antihyperglycemic treatment in T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Predisposição Genética para Doença , Proteínas Substratos do Receptor de Insulina/genética , Metformina/administração & dosagem , Administração Oral , Idoso , Alelos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Farmacogenética , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , População Branca
10.
J Endocrinol Invest ; 41(6): 671-676, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29150756

RESUMO

PURPOSE: In this study, we evaluated the impact of risk factors for gestational diabetes on clinical/biochemical parameters and maternal/fetal outcomes. METHODS: One hundred eighty-three (n 183) women (age 33.8 ± 5.5 years, 59% Caucasians, 41% non-Caucasians) with gestational diabetes were included in the study. Anamnestic information, anthropometric and laboratory parameters, and maternal and fetal outcomes at delivery were collected. RESULTS: Insulin therapy prevalence was higher in Asians vs Caucasians (p = 0.006), despite lower pre-pregnancy BMI in Asians (p = 0.0001) and in pre-pregnancy overweight vs normal weight patients (p = 0.04). Insulin-treated patients had higher fasting OGTT glucose than patients on diet therapy (p = 0.003). In multivariate analysis, Asian ethnicity, age ≥ 35 years and pre-pregnancy BMI ≥ 25 kg/m2 were independent predictors of insulin therapy. Cesarean section occurred more in women aged ≥ 35 years than < 35 years (p = 0.02). Duration of pregnancy and age showed inverse correlation (r - 0.3 p = 0.013). Week of delivery was lower in patients ≥ 35 years vs patients < 35 years (p = 0.013). Fasting OGTT glucose was higher in overweight than in normal weight patients (p = 0.016). 1-h OGTT glucose was lower in obese vs normal weight (p = 0.03) and overweight patients (p = 0.03). Prevalence of prior gestational diabetes was higher in overweight/obese women (p = 0.002). CONCLUSIONS: Ethnicity, age, and BMI have the heaviest impact on pregnancy outcomes.


Assuntos
Biomarcadores/análise , Diabetes Gestacional/etiologia , Intolerância à Glucose , Obesidade/complicações , Sobrepeso/complicações , Adulto , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Feminino , Seguimentos , Humanos , Gravidez , Resultado da Gravidez , Fatores de Risco
11.
J Reprod Infant Psychol ; 36(1): 30-41, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29517301

RESUMO

OBJECTIVE: The present study represents a qualitative research aimed to explore the obstetricians' psychological experiences of birth. BACKGROUND: During labour the role of obstetricians assumes a fundamental importance in hospitalised childbirth. However, literature analysis has shown that the psychological side of birth has been investigated only considering the woman's and midwife's points of view. The obstetricians' psychological experiences have not been considered enough and only a few studies at a quantitative level have been performed. METHODS: Seven focus groups for a total of 72 obstetricians were conducted in hospital contexts in Italy. The qualitative methodology of grounded theory was adopted. FINDINGS: The results were divided into three different core themes: obstetricians' approaches to delivery, critical aspects about relationships in the delivery room, and obstetricians' feelings and emotions in the delivery room. Each theme was subdivided into different subthemes. CONCLUSION: The results highlight different ways obstetricians approach their profession, the complex and multifaceted relationship with the woman and the extraordinary variety of feelings and emotions, which enrich, but also may complicate, life in the delivery room. Further studies could provide more details to help researchers to develop new and more effective strategies to support obstetricians' training and work.


Assuntos
Emoções , Trabalho de Parto , Obstetrícia , Parto/psicologia , Médicos/psicologia , Parto Obstétrico , Feminino , Grupos Focais , Teoria Fundamentada , Humanos , Itália , Relações Médico-Paciente , Gravidez , Pesquisa Qualitativa
13.
J Endocrinol Invest ; 40(9): 999-1005, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28386795

RESUMO

PURPOSE: Physical activity is an effective therapeutic tool for cardiovascular risk prevention. However, exercise aerobic capacity of patients with type 1 diabetes (T1DM) has not been thoroughly investigated. Aim of the present study is to evaluate exercise aerobic capacity in patients with T1DM compared to a normal control population. METHODS: This observational study included 17 T1DM patients and 17 matched healthy volunteers. Cardiopulmonary exercise test (CPET) was conducted on an electronically-braked cycle ergometer. Blood samples were collected for evaluation of glycemia and lactate levels. RESULTS: Mean oxygen uptake at peak exercise (V'O2,peak) was significantly lower in T1DM subjects (V'O2,peak T1DM 2200 ± 132ml/min vs V'O2,peak Healthy subjects of 2659 ± 120 ml/min p = 0.035). Cardiovascular response analysis did not show statistically significant differences. Respiratory exchange ratio (RER) was significantly higher in healthy subjects at peak exercise and at the first minute of recovery (p = 0.022, p = 0.024). Peak exercise lactate levels were significantly higher in healthy subjects. There was no statistical correlation between CPET results and diabetes-related parameters. CONCLUSIONS: Patients affected by T1DM have a worse exercise tolerance than normal subjects. The two groups differed by RER which can be greatly influenced by the substrate type utilized to produce energy. Because of the impaired carbohydrate utilization, T1DM subjects may use a larger amount of lipid substrates, such hypothesis could be strengthened by the lower lactate levels found in T1DM group at peak exercise. The lack of correlation between exercise tolerance and disease-related variables suggests that the alterations found could be independent from the glycemic levels.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Teste de Esforço/métodos , Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Frequência Cardíaca/fisiologia , Adulto , Diabetes Mellitus Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Consumo de Oxigênio/fisiologia
14.
Nutr Metab Cardiovasc Dis ; 26(2): 109-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26712708

RESUMO

BACKGROUND AND AIMS: In a previous study, the single-nucleotide polymorphism (SNP) rs9677, mapped in the 3'-UTR of vasoactive intestinal peptide receptor 1 (VPAC1) gene, was found to be associated with type 2 diabetes (T2D) in Caucasian women. Moreover, the CC genotype correlated with a worse glycolipid profile. The objectives of this study were to confirm this correlation and assess the prevalence of coronary artery disease (CAD) in the previously investigated diabetic women after a follow-up of 4.6 years. METHODS AND RESULTS: A total of 143 women with T2D, with 53 carrying the CC genotype (age: 71.7 ± 7.4 years, diabetes duration: 17.2 ± 9.9 years) and 90 carrying the CT + TT genotypes (age: 69.4 ± 8.8 years, diabetes duration: 14.3 ± 8.2 years), were followed up for 4.6 ± 1.8 years. At follow-up, the clinical and haematochemical parameters were analysed. Twelve-lead electrocardiography, Doppler echocardiography and the percentage of patients with acute myocardial infarction (AMI) or of those subjected to coronary angioplasty and coronary artery bypass surgery were evaluated. At follow-up, there was no significant difference in terms of the clinical and haematochemical parameters between the two groups. However, despite a significantly increased use of statin therapy, no significant improvement in the LDL cholesterol levels was observed in CC female patients unlike those with CT + TT (P = 0.02). Moreover, the CC female patients presented a significantly higher percentage of echocardiographic abnormalities (P = 0.035), especially left ventricular (LV) diastolic dysfunction (P = 0.04). CONCLUSIONS: The rs9677 CC genotype could be correlated with a reduced response to statin therapy and seems to be involved in diabetes cardiomyopathy in female patients with T2D.


Assuntos
LDL-Colesterol/sangue , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/genética , Dislipidemias/genética , Polimorfismo de Nucleotídeo Único , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/genética , Regiões 3' não Traduzidas , Idoso , Angioplastia Coronária com Balão , Biomarcadores/sangue , Ponte de Artéria Coronária , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnologia , Angiopatias Diabéticas/etnologia , Angiopatias Diabéticas/fisiopatologia , Angiopatias Diabéticas/terapia , Cardiomiopatias Diabéticas/etnologia , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/terapia , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Dislipidemias/etnologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Seguimentos , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Itália/epidemiologia , Pessoa de Meia-Idade , Infarto do Miocárdio/etnologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/fisiopatologia , Fenótipo , Prevalência , Fatores de Risco , Fatores de Tempo , Disfunção Ventricular Esquerda/etnologia , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/fisiopatologia , População Branca/genética
15.
Nutr Metab Cardiovasc Dis ; 26(2): 103-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26698225

RESUMO

BACKGROUND AND AIMS: The rate of mortality in diabetic patients, especially of cardiovascular origin, is about twice as much that of nondiabetic individuals. Thus, the pathogenic factors shaping the risk of mortality in such patients must be unraveled in order to target intensive prevention and treatment strategies. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with type 2 diabetes mellitus (T2DM). METHODS/DESIGN: The "SUMMER study in diabetes" is an observational, prospective, and collaborative study conducted on at least 5000 consecutive patients with T2DM, recruited from several diabetes clinics of Central-Southern Italy and followed up for a minimum of 5 years. The primary outcome is all-cause mortality; the secondary outcomes are cardiovascular mortality, acute myocardial infarction, stroke, and dialysis. A biobank will be created for genomic, transcriptomic, and metabolomic analysis, in order to unravel new molecular predictors of mortality and vascular morbidity. DISCUSSION: The "SUMMER study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with T2DM. These novel pathogenic factors will most likely be instrumental in unraveling new pathways underlying such dramatic events. In addition, they will also be used as additional markers to increase the performance of the already existing risk-scoring models for predicting the above-mentioned outcomes in T2DM, as well as for setting up new preventive and treatment strategies, possibly tailored to specific pathogenic backgrounds. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02311244; URL https://clinicaltrials.gov/ct2/show/NCT02311244?term=SUMMER&rank=5.


Assuntos
Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Estações do Ano , Bancos de Espécimes Biológicos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Causas de Morte , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Projetos de Pesquisa Epidemiológica , Perfilação da Expressão Gênica , Marcadores Genéticos , Genômica/métodos , Humanos , Itália/epidemiologia , Metabolômica/métodos , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
16.
J Endocrinol Invest ; 39(11): 1295-1301, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27344308

RESUMO

AIM: Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic control and the production of specific pro-/anti-inflammatory adipokines in overweight patients with type 2 diabetes mellitus (T2D). METHODS: Eleven overweight T2D patients not in treatment with insulin were invited to follow their habitual diet for a total of 8 weeks. During the first 4 weeks (wash-out period), they were asked to consume refined olive oil (ROO, polyphenols not detectable) and then to replace ROO with HP-EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for the remaining 4 weeks. Anthropometric parameters, fasting glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein, plasma lipid profile, liver function and serum levels of TNF-α, IL-6, adiponectin, visfatin and apelin were assessed at the end of each 4-week period. RESULTS: HP-EVOO consumption significantly reduced fasting plasma glucose (P = 0.023) and HbA1c (P = 0.039) levels as well as BMI (P = 0.012) and body weight (P = 0.012). HP-EVOO ingestion determined a reduction in serum level of aspartate aminotransferase (AST, P = 0.0056) and alanine aminotransferase (ALT, P = 0.024). Serum visfatin levels strongly decreased after HP-EVOO ingestion (P = 0.0021). CONCLUSIONS: Daily consumption of polyphenol-rich EVOO might improve metabolic control and circulating inflammatory adipokines profile in overweight T2D patients.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 2/metabolismo , Nicotinamida Fosforribosiltransferase/sangue , Azeite de Oliva/química , Fenóis/administração & dosagem , Administração Oral , Citocinas/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações
18.
Nutr Metab Cardiovasc Dis ; 23(6): 505-10, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22402064

RESUMO

BACKGROUND AND AIMS: Several studies have reported that the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism (rs1044498) interacts with increased adiposity in affecting glucose homeostasis and insulin sensitivity. Conversely, one would expect that the amelioration of glucose homeostasis observed after weight loss is modulated by the ENPP1 K121Q polymorphism. The aim of our study was to test such hypothesis, in non-diabetic overweight-obese individuals. METHODS AND RESULTS: Two hundred eleven non-diabetic overweight-obese individuals were studied. Body mass index (BMI), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR index) and lipid levels were obtained before and after 6-week lifestyle intervention (LI; diet and exercise) and their changes calculated as baseline minus 6-week values. LI decreased BMI, glucose, HOMA-IR and triglyceride levels (p < 0.001 for all). No difference across genotype groups (160 KK and 51 KQ or QQ - named as XQ - individuals) was observed in these changes. In a multivariate model, BMI changes predicted fasting glucose changes (ß = 0.139 mmol/L (2.50 mg/dl) for 1 unit BMI change, p = 0.005). This correlation was not significant among KK individuals (ß = 0.082; p = 0.15), while much steeper and highly significant among XQ individuals (ß = 0.336; p = 0.00008) (p-value for Q121-by-weight loss interaction = 0.047). CONCLUSION: Individuals carrying the ENPP1 Q121 variant are highly responsive to the effect of weight loss on fasting glucose. This reinforces the previously suggested hypothesis that the Q121 variant interacts with adiposity in modulating glucose homeostasis.


Assuntos
Adiposidade , Glicemia/análise , Diester Fosfórico Hidrolases/genética , Polimorfismo Genético , Pirofosfatases/genética , Redução de Peso , Adulto , Índice de Massa Corporal , HDL-Colesterol/sangue , Diabetes Mellitus , Dieta , Exercício Físico , Jejum , Feminino , Genótipo , Homeostase , Humanos , Resistência à Insulina , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/sangue , Obesidade/genética , Sobrepeso/sangue , Sobrepeso/genética , Diester Fosfórico Hidrolases/metabolismo , Pirofosfatases/metabolismo , Triglicerídeos/sangue
19.
J Endocrinol Invest ; 32(6): 542-5, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19494717

RESUMO

OBJECTIVE: To investigate whether MS is associated with erectile dysfunction (ED) among obese non diabetic individuals. METHODS: A cross-sectional study was carried out to examine the association between the cluster of abnormalities related to the MS and ED as evaluated by the International Index of Erectile Function (IIEF). Fifty consecutive obese [i.e. body mass index (BMI) > or =30 kg/m2], nondiabetic whites (age 42.1+/-11.3 yr, BMI 43.3+/-8.7 kg/m2) were recruited. RESULTS: The prevalence of MS as well as that of any MS component were not different between subjects with or without ED. Neither the prevalence of ED (34.3% vs 33.4%, p=0.6), nor IIEF score (21.5+/-3.9 vs 21.7+/-3.7, p=0.8), were different between patients with or without MS. IIEF was similar across subgroups of individuals stratified according to the number of MS components and was not related to HOMAIR index. Hypogonadism was observed in 30.8% and 28.1% individuals with and without MS (p=0.58). Testosterone and BMI levels were inversely related (r=-0.3, p=0.04). CONCLUSION: Among obese non-diabetic individuals the risk of developing ED is independent of the presence of MS factors. Testosterone levels progressively decrease with increasing body weight.


Assuntos
Disfunção Erétil/complicações , Síndrome Metabólica/complicações , Obesidade/complicações , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Disfunção Erétil/sangue , Disfunção Erétil/fisiopatologia , Humanos , Insulina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Obesidade/sangue , Obesidade/fisiopatologia , Inquéritos e Questionários , Testosterona/sangue
20.
J Endocrinol Invest ; 31(6): 558-62, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18591891

RESUMO

Advanced glycation end products (AGE) increase as a consequence of diabetic hyperglycemia and, in nephropathic patients, following renal function loss. Protein-bound AGE behave as immunogens, inducing formation of specific antibodies (Ab-AGE). In this work AGE immunogenicity was studied in 42 diabetic patients, 26 nephropathic patients on hemodialysis and 26 patients with end-stage renal disease who underwent kidney transplantation and in 20 normal subjects. Non-oxidation-derived AGE (nox-AGE), oxidation-derived AGE (ox-AGE) and Ab-AGE were measured by competitive or direct enzyme-linked immunosorbent assay (ELISA) and circulating immune complexes (CIC) by C1q ELISA. Nox- AGE increased significantly in all patient groups (p < or = 0.05 to < or = 0.0001) except in patients on hemodialysis for less than 6 yr. Ox-AGE were only significantly increased in patients transplanted more than 3 yr previously (p < 0.05). Ab-AGE were significantly lower than controls in both diabetic groups and in patients on hemodialysis for more than 6 yr (p < 0.005 to < 0.0001) and not unlike controls in the other groups. These results demonstrate that hemodialysis or renal transplantation can, initially, reduce either nox- or ox-AGE levels, which however go back to being high in time. Renal transplantation fails to normalize nox-AGE. More importantly, plasma Ab-AGE levels are reduced or unchanged in all patient groups in comparison with controls, despite higher circulating AGE levels. This suggests the importance of tissue-bound AGE as Ab-AGE targets. Additional interventions are needed to control AGE levels in treated nephropathic patients. The search and quantification of specific Ab-AGE would give more meaningful results if performed over specific tissue specimens.


Assuntos
Diabetes Mellitus/imunologia , Glomerulonefrite Membranosa/imunologia , Produtos Finais de Glicação Avançada/imunologia , Transplante de Rim/imunologia , Diálise Renal , Adulto , Idoso , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Feminino , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/terapia , Produtos Finais de Glicação Avançada/genética , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/imunologia , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Diálise Renal/tendências , Fatores de Tempo
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