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1.
J Diabetes Complications ; 36(8): 108226, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35803839

RESUMEN

AIMS: The aim of this prospective study was to examine the relationship between controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) with the risk of developing a composite endpoint inclusive of incident acute myocardial infarction (AMI), cerebrovascular insult (CVI) or chronic kidney disease (CKD) in people with type 2 diabetes mellitus (T2DM). METHODS: This study included 238 T2DM outpatients without chronic liver diseases. RESULTS: The patient population was followed for a median period of 7.6 years. Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the aforementioned composite outcome (P < 0.001 by the log-rank test), as well as CKD (P < 0.001) or AMI alone (P = 0.014) among those with elevated CAP values (≥238 dB/m) at baseline. Similarly, Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the composite outcome (P < 0.001), as well as CKD (P < 0.001), or AMI alone (P < 0.001) among those with elevated LSM values (≥7.0/6.2 kPa). In multivariable regression analyses, the presence of elevated CAP (adjusted-hazard ratio 2.34, 95% CI 1.32-4.15) and elevated LSM (adjusted-hazard ratio 2.84, 95% CI 1.92-4.21), independently of each other, were associated with a higher risk of developing the composite outcome, as well as incident AMI or CKD alone after adjusting for traditional cardiovascular risk factors and diabetes-related variables. CONCLUSIONS: Our study shows that the elastographic parameters of liver steatosis and fibrosis independently predict the long-term risk of developing chronic vascular complications in T2DM patients.


Asunto(s)
Diabetes Mellitus Tipo 2 , Diagnóstico por Imagen de Elasticidad , Infarto del Miocardio , Enfermedad del Hígado Graso no Alcohólico , Insuficiencia Renal Crónica , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/epidemiología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/patología
2.
J Endocrinol Invest ; 45(7): 1277-1288, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35147926

RESUMEN

PURPOSE: Chronic plaque psoriasis is associated with the presence of non-alcoholic fatty liver disease (NAFLD), but the magnitude of this association remains currently uncertain. We aimed to investigate the magnitude of the association between psoriasis and the risk of prevalent and incident NAFLD, and to assess whether psoriasis severity and/or psoriatic arthritis are associated with a greater risk of NAFLD. METHODS: A systematic review and meta-analysis of observational studies evaluating the association between psoriasis and NAFLD, as diagnosed by imaging or International Classification of Diseases codes was performed. Literature search on PubMed, Scopus and Web of Science on May 3, 2021 was undertaken. Studies using liver biopsy were not available. For the meta-analysis, the random-effects modelling was adopted. RESULTS: We identified 15 observational (case-control and cross-sectional) studies for a total of 249,933 patients with psoriasis (49% with NAFLD) and 1,491,402 controls (36% with NAFLD). Psoriasis was associated with prevalent NAFLD (n = 11 studies; pooled random-effects odds ratio [OR] 1.96, 95% CI 1.70-2.26; I2 = 97%, p < 0.01). Psoriatic patients with NAFLD had a higher mean psoriasis area and severity index (PASI) than their counterparts without NAFLD (n = 8 studies, pooled weighted mean difference: 3.93, 95% CI 2.01-5.84; I2 = 88%, p < 0.01). The risk of NAFLD was marginally higher in patients with psoriatic arthritis than in those with psoriasis alone (n = 5 studies, pooled random-effects OR 1.83, 95% CI 0.98-3.43; I2 = 64%, p = 0.03). Sensitivity analyses did not alter these findings. Funnel plot did not show any significant publication bias. A major limitation of the study was the high degree of heterogeneity across studies. CONCLUSION: Psoriasis is associated with prevalent NAFLD and this risk parallels the severity of psoriasis.


Asunto(s)
Artritis Psoriásica , Enfermedad del Hígado Graso no Alcohólico , Psoriasis , Artritis Psoriásica/complicaciones , Artritis Psoriásica/epidemiología , Estudios de Casos y Controles , Estudios Transversales , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Psoriasis/complicaciones , Psoriasis/epidemiología
3.
Diabetes Res Clin Pract ; 177: 108884, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34082054

RESUMEN

AIMS: The aim of this study was to investigate whether controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as assessed by vibration-controlled transient elastography (VCTE), are associated with chronic vascular complications of diabetes mellitus type 2 (T2DM). METHODS: We studied 442 outpatients with established T2DM, and who underwent VCTE and extensive assessment of chronic vascular complications of diabetes. RESULTS: A quarter of analyzed patients had a previous history of myocardial infarction and/or ischemic stroke, and about half of them had at least one microvascular complication (chronic kidney disease (CKD), retinopathy or polyneuropathy). The prevalence of liver steatosis (i.e., CAP ≥ 238 dB/m) and significant liver fibrosis (i.e., LSM ≥ 7.0/6.2 kPa) was 84.2% and 46.6%, respectively. Significant liver fibrosis was associated with an increased likelihood of having myocardial infarction (adjusted-odds ratio 6.61, 95%CI 1.66-37.4), peripheral polyneuropathy (adjusted-OR 4.55, 95%CI 1.25-16.6), CKD (adjusted-OR 4.54, 95%CI 1.24-16.6) or retinopathy (adjusted-OR 1.81, 95%CI 1.62-1.97), independently of cardiometabolic risk factors, diabetes-related variables, and other potential confounders. Liver steatosis was not independently associated with any macro-/microvascular diabetic complications. CONCLUSIONS: Significant liver fibrosis is strongly associated with the presence of macro-/microvascular complications in patients with T2DM. These results offer a new perspective on the follow-up of people with T2DM.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática , Enfermedades Cardiovasculares/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Humanos , Hígado/diagnóstico por imagen , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Enfermedad del Hígado Graso no Alcohólico/patología
4.
Nutr Metab Cardiovasc Dis ; 31(5): 1548-1555, 2021 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-33810963

RESUMEN

BACKGROUND AND AIM: The association between non-alcoholic fatty liver (NAFL) and the variant rs641738 within the membrane bound O-acyltransferase domain-containing 7 (MBOAT7) gene is currently uncertain, especially in the paediatric population. We examined whether there is an association between this genetic variant and NAFL in a large multicentre, hospital-based cohort of Italian overweight/obese children. METHODS AND RESULTS: We studied 1760 overweight or obese children [mean age (SD): 11.1(2.9) years, z-body mass index (zBMI) 3.2(0.9)], who underwent ultrasonography for the diagnosis of NAFL. A subgroup of these children (n = 182) also underwent liver biopsy. Genotyping of the MBOAT7 rs641738 polymorphism was performed by TaqMan-Based RT-PCR system in each subject. Overall, 1131 (64.3%) children had ultrasound-detected NAFL; 528 (30%) had rs641738 CC genotype, 849 (48.2%) had rs641738 CT genotype, and 383 (21.8%) had rs641738 TT genotype, respectively. In the whole cohort, the interaction of MBOAT7 genotypes with zBMI was not associated with NAFL after adjustment for age, sex, serum triglycerides, serum alanine aminotransferase levels and patatin-like phospholipase domain-containing protein-3 (PNPLA3) genotype (adjusted-odds ratio 1.02 [95% CI 0.98-1.06]). Similarly, no association was found between MBOAT7 genotypes and NAFL after stratification by obesity status. MBOAT7 genotypes were not associated with the presence of non-alcoholic steatohepatitis or the stage of liver fibrosis in a subgroup of 182 children with biopsy-proven NAFLD. CONCLUSIONS: The results of this study did not show any significant contribution of MBOAT7 rs641738 polymorphism to the risk of having either NAFL on ultrasonography or NASH on histology in a large hospital-based cohort of Italian overweight/obese children.


Asunto(s)
Aciltransferasas/genética , Cirrosis Hepática/genética , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad Infantil/epidemiología , Polimorfismo de Nucleótido Simple , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Italia/epidemiología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Masculino , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Obesidad Infantil/diagnóstico , Fenotipo , Prevalencia , Medición de Riesgo , Factores de Riesgo
5.
J Endocrinol Invest ; 44(9): 1879-1889, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33432553

RESUMEN

AIM: Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI. METHODS: We collected data from 46 diabetes clinics (n = 281,381 T2D patients), extracted data to calculate HSI and validated it against ultrasound-detected hepatic steatosis. We then examined changes in HSI among patients with a follow-up visit within 1 year after initiating newer GLMs. RESULTS: MAFLD (defined by HSI > 36, i.e., a high probability of steatosis) was present in 76.3% of the 78,895 included patients, while only 2.7% had HSI < 30 (low probability of steatosis). After age- and sex-adjusting, higher HSI was associated with higher prevalence of chronic kidney disease (odds ratio 1.35; 95%CI 1.22-1.51) and macroangiopathy (odds ratio 1.18; 95%CI 1.07-1.30). Among 2,179 subjects in the validation cohort, the prevalence of MAFLD was 67.8% and was greater in those with high HSI. Performance of HSI for ultrasound-detected MAFLD was moderate (AUROC 0.70), yet steatosis prevalence was > threefold higher among subjects with HSI > 36 than among those with HSI < 30. Notably, HSI declined significantly ~ 6 months after initiation of dapagliflozin or incretin-based therapies, but not gliclazide. CONCLUSION: About three quarters of patients with T2D have HSI values suggestive of MAFLD, a condition associated with macroangiopathy and nephropathy. Treatment with dapagliflozin or incretin therapies might improve MAFLD in T2D.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Hígado Graso/complicaciones , Hígado Graso/epidemiología , Hipoglucemiantes/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Hígado Graso/terapia , Femenino , Estudios de Seguimiento , Gliclazida/uso terapéutico , Humanos , Incretinas/uso terapéutico , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Ultrasonografía , Adulto Joven
6.
Diabetes Metab ; 47(1): 101152, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32283179

RESUMEN

AIM: Plasma levels of certain ceramides are increased in patients with ischemic heart disease (IHD). Many risk factors for IHD are also risk factors for chronic kidney disease (CKD), but it is currently uncertain whether plasma ceramide levels are increased in patients with CKD. METHODS: We measured six previously identified high-risk plasma ceramide concentrations [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 415 middle-aged individuals who attended our clinical Cardiology and Diabetes services over a period of 9 months. RESULTS: A total of 97 patients had CKD (defined as e-GFRCKD-EPI<60ml/min/1.73m2 and/or urinary albumin-to-creatinine ratio≥30mg/g), 117 had established IHD and 242 had type 2 diabetes. Patients with CKD had significantly (P=0.005 or less) higher levels of plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) compared to those without CKD. The presence of CKD remained significantly associated with higher levels of plasma ceramides (standardized beta coefficients ranging from 0.124 to 0.227, P<0.001) even after adjustment for body mass index, smoking, hypertension, diabetes, prior IHD, plasma LDL-cholesterol, hs-C-reactive protein levels and use of any lipid-lowering medications. Notably, more advanced stages of CKD and abnormal albuminuria were both associated (independently of each other) with increased levels of plasma ceramides. These results were consistent in all subgroups considered, including patients with and without established IHD or those with and without diabetes. CONCLUSION: Increased levels of plasma ceramides are associated with CKD independently of pre-existing IHD, diabetes and other established cardiovascular risk factors.


Asunto(s)
Ceramidas , Isquemia Miocárdica , Insuficiencia Renal Crónica , Ceramidas/sangre , Humanos , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo
7.
J Endocrinol Invest ; 44(3): 547-555, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32588382

RESUMEN

OBJECTIVE: Previous studies showed a significant association between lower plasma adiponectin levels and higher risk of adverse cardiovascular outcomes in patients with and without type 2 diabetes mellitus (T2DM). Presently, it is uncertain whether lower plasma adiponectin levels are associated with greater plasma thrombin generation in patients with T2DM. PATIENTS AND METHODS: We studied 82 middle-aged men with non-insulin-treated T2DM [mean age ± SD: 64.1 ± 8 years; median duration of diabetes: 12.5 (inter-quartile range 6-19) years; mean hemoglobin A1c 7.0 ± 0.7%], consecutively attending our diabetes outpatient service over a 6-month period. Using the newly developed fully automated thrombin generation analyzer ST Genesia®, we measured the plasma parameters lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP) in all participants. RESULTS: In univariable linear regression analyses, lower plasma adiponectin levels were significantly associated with higher plasma thrombin generation parameters, as reflected by higher values of PH (Pearson's r coefficient = - 0.228, p = 0.039) and EPT (r = - 0.293, p = 0.007). Plasma adiponectin levels were not significantly associated with other thrombin generation parameters (LT and TP). Notably, the significant associations of plasma adiponectin levels with thrombin PH and EPT values persisted after adjustment for age and adiposity measures, but they were lost after additional adjustment for plasma triglycerides. CONCLUSION: Our findings show for the first time the existence of a significant association between lower levels of plasma adiponectin and greater plasma thrombin generation (as assessed by the ST Genesia® analyzer) in men with non-insulin-treated T2DM, which appears to be largely mediated by plasma triglycerides.


Asunto(s)
Adiponectina/sangre , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/patología , Trombina/análisis , Triglicéridos/sangre , Anciano , Glucemia/análisis , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos
9.
Eur Rev Med Pharmacol Sci ; 24(9): 5028-5035, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32432766

RESUMEN

OBJECTIVE: Right ventricle and pulmonary artery pressure have always received less attention in type 1 diabetes than left ventricle. The aim of this study is to compare the right heart performance and the estimated peak systolic pulmonary artery pressure (EPSPAP) in young type 1 diabetes patients with healthy controls. PATIENTS AND METHODS: Subjects affected by type 1 diabetes without cardiovascular and respiratory diseases (n=93) and healthy controls (n=56) were evaluated with a comprehensive transthoracic echocardiography. The pulmonary peak systolic arterial pressure was calculated with an established formula based on pulmonary artery acceleration time. RESULTS: The left ventricle's function was found to be normal in all the subjects under study. The estimated peak systolic pulmonary artery pressure was significantly higher in patients with type 1 diabetes compared to the controls (38.5 ± 8.6 vs. 35.4 ± 6.7, p = 0.019). The highest value of EPSPAP was observed in smoking female patients with type 1 diabetes. Basal and mid cavity diameter of the right ventricle were higher in patients with type 1 diabetes. Factors associated with EPSPAP were sex, body mass index, mid cavity diameter and, with an inverse correlation, HDL-cholesterol. CONCLUSIONS: The present study suggests that young, uncomplicated patients with type 1 diabetes have a higher estimated peak systolic pulmonary artery pressure. Further studies are needed to define the mechanisms underlying this alteration and its clinical consequences.


Asunto(s)
Presión Sanguínea , Diabetes Mellitus Tipo 1/fisiopatología , Arteria Pulmonar/fisiopatología , Adulto , Femenino , Humanos , Masculino , Función Ventricular Izquierda
11.
Diabetes Metab ; 46(6): 496-503, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32035968

RESUMEN

AIM: We aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism. MATERIALS AND METHODS: We enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a 'strict-normal' TSH group (TSH level 0.4 to 2.5mIU/L; n=283) and a 'high-normal' TSH group (TSH level 2.5 to 5.3mIU/L with normal thyroid hormones; n=44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes. RESULTS: Compared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298-8.284; P=0.012). CONCLUSION: In euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.


Asunto(s)
Lipasa/genética , Proteínas de la Membrana/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Tirotropina/sangre , Adulto , Alelos , Femenino , Predisposición Genética a la Enfermedad , Humanos , Hígado/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Polimorfismo de Nucleótido Simple , Índice de Severidad de la Enfermedad
12.
Diabetes Metab ; 46(6): 427-441, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-31923578

RESUMEN

AIM: There are no approved drugs for the treatment of non-alcoholic fatty liver disease (NAFLD). However, many randomized controlled trials (RCT) have examined the effect of anti-hyperglycaemic agents on NAFLD in patients with and without type 2 diabetes mellitus (T2DM), since both T2DM and insulin resistance are closely linked to this burdensome liver disease. METHODS: We systematically searched publication databases using predefined keywords to identify head-to-head or placebo-controlled RCTs (published until September 30, 2019) of NAFLD individuals testing the efficacy of anti-hyperglycaemic drugs to specifically treat NAFLD or non-alcoholic steatohepatitis (NASH). Outcomes of interest included changes in serum liver enzyme levels, liver fat, liver fibrosis, or histologic resolution of NASH. RESULTS: We included 29 RCTs involving a total of 2,617 individuals (∼45% had T2DM) that have used metformin (n=6 studies), glitazones (n=8 studies), glucagon-like peptide-1 receptor agonists (n=6 studies), dipeptidyl peptidase-4 inhibitors (n=4 studies) or sodium-glucose cotransporter-2 inhibitors (n=7 studies) to treat NAFLD. Although most anti-hyperglycaemic drugs improved serum liver enzyme levels, only glitazones (especially pioglitazone) and liraglutide showed an improvement of histologic features of NAFLD, with a mild beneficial effect also on liver fibrosis for pioglitazone only. CONCLUSION: RCT evidence supports the efficacy of some anti-hyperglycaemic agents (especially pioglitazone) in patients with NAFLD or NASH, though weight gain with pioglitazone may warrant caution. Further well-designed RCTs are needed to better characterize the efficacy and safety of monotherapy and combination therapy with anti-hyperglycaemic agents in patients with NAFLD.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Receptor del Péptido 1 Similar al Glucagón/agonistas , Humanos , Metformina/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/patología , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Tiazolidinedionas/uso terapéutico , Resultado del Tratamiento
13.
J Diabetes Complications ; 34(3): 107512, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31882273

RESUMEN

AIMS: To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ±â€¯11.7 months. RESULTS: During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23-2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients. CONCLUSION: This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.


Asunto(s)
Diagnóstico por Imagen de Elasticidad , Cirrosis Hepática/diagnóstico , Hígado/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Anciano , Calibración , Progresión de la Enfermedad , Diagnóstico por Imagen de Elasticidad/métodos , Diagnóstico por Imagen de Elasticidad/normas , Femenino , Estudios de Seguimiento , Humanos , Hígado/patología , Hígado/fisiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/patología , Estudios Prospectivos , Factores de Riesgo
15.
Diabetes Metab ; 46(4): 326-330, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31185304

RESUMEN

AIM: Emerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, scarce information is currently available on the association between distinct plasma ceramides (that have been associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group of individuals at high risk of developing CVD and other chronic inflammation-related conditions. METHODS: We measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] in 92 postmenopausal women with T2DM attending the diabetes outpatient service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. RESULTS: Plasma hs-CRP levels were positively associated with all measured ceramides in univariable linear regression analyses. However, only plasma Cer(d18:1/16:0) (standard ß coefficient: 0.27, P=0.015), Cer(d18:1/22:0) (standard ß coefficient: 0.25, P=0.032) and Cer(d18:1/24:1) (standard ß coefficient: 0.30, P=0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA1c, insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs. CONCLUSION: In postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors.


Asunto(s)
Proteína C-Reactiva/metabolismo , Ceramidas/sangre , Diabetes Mellitus Tipo 2/sangre , Posmenopausia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad
16.
Diabetes Metab ; 46(2): 150-157, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31386900

RESUMEN

AIM: Recent prospective studies have identified distinct plasma ceramides as strong predictors of major adverse cardiovascular events in patients with established or suspected coronary artery disease (CAD). Currently, it is uncertain whether higher levels of distinct plasma ceramides are associated with greater angiographic severity of coronary-artery stenoses in this patient population. METHODS: We measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD, who underwent urgent or elective coronary angiography. RESULTS: Approximately 77% of patients had a significant stenosis (≥50%) in one or more of the main coronary arteries, the majority of whom (∼60%) had a significant stenosis in the left anterior descending (LAD) artery. Of the six measured plasma ceramides, higher levels of plasma Cer(d18:1/20:0) (adjusted-odds ratio 1.39, 95%CI 1.0-1.99), Cer(d18:1/22:0) (adjusted-odds ratio 1.57, 95%CI 1.08-2.29) and Cer(d18:1/24:0) (adjusted-odds ratio 1.59, 95%CI 1.08-2.32) were significantly associated with the presence of LAD stenosis≥50%, after adjustment for age, sex, smoking, pre-existing CAD, hypertension, diabetes, dyslipidaemia, lipid-lowering therapy, estimated glomerular filtration rate and plasma C-reactive protein levels. Almost identical results were found even after excluding patients (n=15) with acute ST-elevation myocardial infarction. Similar results were also found when patients were categorized according to the Gensini severity score. CONCLUSION: Our cross-sectional study shows for the first time that higher levels of specific plasma ceramides are independently associated with a greater severity of coronary-artery stenoses in the LAD artery in patients who had suspected or established CAD.


Asunto(s)
Ceramidas/sangre , Estenosis Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Estenosis Coronaria/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad
17.
Diabetes Metab ; 46(4): 288-295, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31786360

RESUMEN

AIM: The association between Liver fibrosis (LF), as assessed by either histology or Liver stiffness measurement (LSM), and the presence of Early kidney dysfunction (EKD) was investigated in this study, as was also the diagnostic performance of LSM for identifying the presence of EKD in patients with Non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: A total of 214 adults with non-cirrhotic biopsy-proven NAFLD were recruited from two independent medical centres. Their histological stage of LF was quantified using Brunt's criteria. Vibration-controlled Transient elastography (TE), using M-probe (FibroScan®) ultrasound, was performed in 154 patients and defined as significant when LSM was≥8.0kPa. EKD was defined as the presence of microalbuminuria with an estimated glomerular filtration rate≥60mL/min/1.73 m2. Logistic regression modelling was used to estimate the likelihood of having EKD with NAFLD (LSM-EKD model). RESULTS: The prevalence of EKD was higher in patients with vs without LF on histology (22.14% vs 4.82%, respectively; P<0.001) and, similarly, EKD prevalence was higher in patients with LSM≥8.0kPa vs LSM<8.0kPa (23.81% vs 6.59%, respectively; P<0.05). The area under the ROC curve of the LSM-EKD model for identifying EKD was 0.80 (95% CI: 0.72-0.89). LF detected by either method was associated with EKD independently of established renal risk factors and potential confounders. CONCLUSION: LF was independently associated with EKD in patients with biopsy-proven NAFLD. Thus, TE-measured LSM, a widely used technique for quantifying LF, can accurately identify those patients with NAFLD who are at risk of having EKD.


Asunto(s)
Albuminuria/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Cirrosis Hepática/diagnóstico por imagen , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Insuficiencia Renal/epidemiología , Adulto , Diagnóstico por Imagen de Elasticidad , Femenino , Tasa de Filtración Glomerular , Humanos , Cirrosis Hepática/epidemiología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Índice de Severidad de la Enfermedad
18.
Diabetes Metab ; 46(4): 296-303, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31786361

RESUMEN

AIM: Despite the high prevalence and serious clinical implications of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), NAFLD is usually overlooked during routine diabetes care. This study explored the proportion of NAFLD cases and increased liver fibrosis (LF), and the association between LF and either chronic kidney disease (CKD) or cardiovascular complications in T2DM patients. METHODS: The study included 137 patients with non-insulin-treated T2DM and no known liver disease consecutively attending our diabetes outpatients' service who underwent liver ultrasonography and liver stiffness measurement (LSM) using vibration-controlled transient elastography (FibroScan®). RESULTS: The proportion of patients with hepatic steatosis on ultrasonography was 73.7%, and the proportion with significant LF was 17.5% with an LSM cut-off ≥7kPa or 10.2% with an LSM cut-off ≥8.7kPa. The presence of CKD (estimated GFR <60mL/min/1.73m2 and/or abnormal albuminuria) increased significantly across LSM tertiles (from around 15% in tertile 1 to 45% in tertile 3). Cardiovascular complications (previous ischaemic heart disease, ischaemic stroke, permanent atrial fibrillation) also tended to increase across LSM tertiles (from around 15% to 30%). After adjusting for established risk factors and potential confounders, LSM tertile 3 remained significantly associated with an approximately threefold higher risk of prevalent CKD (adjusted OR: 3.28, 95% CI: 1.22-8.90; P=0.019), but not for cardiovascular complications. CONCLUSION: These results suggest that NAFLD and significant LF (as assessed by FibroScan®) are very commonly seen in T2DM outpatients with no known liver disease attending a secondary-care diabetes service, and that increased LF is associated with a greater proportion of chronic vascular complications, especially CKD.


Asunto(s)
Fibrilación Atrial/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Nefropatías Diabéticas/epidemiología , Accidente Cerebrovascular Isquémico/epidemiología , Isquemia Miocárdica/epidemiología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Insuficiencia Renal Crónica/epidemiología , Anciano , Enfermedades Cardiovasculares/epidemiología , Complicaciones de la Diabetes/epidemiología , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/epidemiología
19.
Eur Rev Med Pharmacol Sci ; 23(15): 6700-6706, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31378913

RESUMEN

OBJECTIVE: To compare different methods assessing the burden of cardiovascular mortality in diabetes mellitus, which is usually underestimated by standard mortality statistics based on the underlying cause of death. PATIENTS AND METHODS: All residents in the Veneto Region (Italy) aged 30-89 years with co-payment exemption for diabetes in January 2010 (n=185,341) were identified and linked with mortality records (2010-2015). The underlying causes of death, as well as all the diseases mentioned in the death certificate (multiple causes), were extracted. The standardized mortality ratios (SMR) were computed with regional rates as a reference. RESULTS: After grouping diabetes and circulatory diseases as the underlying cause of death, the mortality rates were highly increased, especially among patients aged 30-54 years: SMR 4.24 (95% confidence interval 3.57-5.00) and 9.84 (7.47-12.72) in males and females, respectively. After re-assignment of the underlying cause in deaths from diabetes, the percentage of overall mortality caused by circulatory diseases increased from 33.8% to 41.7%. Based on multiple causes, the risk of death was increased for several cardiovascular diseases, including causes rarely emerging from standard mortality statistics such as atrial fibrillation/flutter. CONCLUSIONS: The re-assignment of the underlying cause and the analyses of the multiple causes of death allowed to estimate the whole burden of mortality associated with cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Costo de Enfermedad , Complicaciones de la Diabetes/mortalidad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad
20.
Diabetes Metab ; 45(6): 536-544, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31067493

RESUMEN

AIM: Recent observational studies assessed the association between non-alcoholic fatty liver disease (NAFLD) and lung function in adults, but the magnitude of this association remains uncertain. We estimated the magnitude of the association between NAFLD and lung function on spirometry (predicted forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]). METHODS: We searched publication databases using predefined keywords to identify studies (published up to October 4, 2018), in which NAFLD was diagnosed by imaging or biochemistry (no studies with biopsy-proven NAFLD were available). Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. RESULTS: Six observational studies (5 cross-sectional and 1 longitudinal) with aggregate data on 133,707 individuals (27.8% with NAFLD) of predominantly Asian ethnicity (74.6%) were included in the final analysis. There were significant differences in predicted FEV1 (n = 5 studies; pooled weighted mean difference [WMD]: -2.43%, 95% CI: -3.28 to -1.58; I2 = 69.7%) and predicted FVC (pooled WMD: -2.96%, 95% CI: -4.75 to -1.17; I2 = 91.7%) between individuals with and without NAFLD. Decreased FEV1 and FVC at baseline were also independently associated with a ∼ 15% increased risk of incident NAFLD (n = 1 study in Korean individuals). Subgroup analyses did not materially modify these findings. CONCLUSIONS: NAFLD is associated with significant reductions of both FEV1 and FVC in Asian and United States adults, and such small, but significant, reductions of lung volumes at baseline may be also associated with increased NAFLD incidence in Asian individuals. Further research is needed to better elucidate the link between NAFLD and impaired lung volumes.


Asunto(s)
Enfermedades Pulmonares/epidemiología , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Adulto , Estudios Transversales , Humanos , Incidencia , Estudios Longitudinales , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/epidemiología , Pruebas de Función Respiratoria , Factores de Riesgo , Espirometría , Estados Unidos/epidemiología , Capacidad Vital
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