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The incidence of osteoporosis in children is increasing because of the increased survival rate of children with chronic diseases and the increased use of bone-damaging drugs. As childhood bone fragility has several etiologies, its management requires a thorough evaluation of all potentially contributing pathogenetic mechanisms. This review focuses on the main causes of primary and secondary osteoporosis and on the benefits and limits of the different radiological methods currently used in clinical practice for the study of bone quality. The therapeutic and preventive strategies currently available and the most novel diagnostic and treatment strategies are also presented. Optimal management of underlying systemic conditions is key for the treatment of bone fragility in childhood. DXA still represents the gold standard for the radiologic evaluation of bone health in children, although other imaging techniques such as computed tomography and ultrasound evaluations, as well as REMS, are increasingly studied and used. Bisphosphonate therapy is the gold standard for pharmacological treatment in both primary and secondary pediatric osteoporosis. Evidence and experience are building up relative to the use of monoclonal antibodies such as denosumab in cases of poor response to bisphosphonates in specific conditions such as osteogenesis imperfecta, juvenile Paget's disease and in some cases of secondary osteoporosis. Lifestyle interventions including adequate nutrition with adequate calcium and vitamin D intake, as well as physical activity, are recommended for prevention.
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Gaucher Disease (GD) is a condition resulting from an autosomal recessive inheritance pattern, characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase. This leads to the accumulation of glucocerebroside and other glycolipids in multiple tissues, causing damage to various organ systems. The diagnosis of GD can be challenging due to its heterogeneity, non-specific symptoms, and variability across different geographic regions and age groups. Although GD is suspected based on symptoms or signs, the diagnosis is confirmed through the measurement of deficient b-glucocerebrosidase activity and the identification of biallelic pathogenic variants in the GBA gene. Intravenous enzyme replacement therapy (ERT) is recommended for GD patients. In this paper, we report a case of a 2-year and 8-month-old girl with massive splenomegaly and radiological finding of hepatic gaucheroma, in whom a genetic study showed homozygous mutation on the GBA gene at c.1448T>C (p.Leu483Pro) and certified the diagnosis of GD. This patient represents the youngest child reported to have gaucheroma and also the first one presenting with gaucheroma at the diagnosis and not during the follow up, highlighting that GD should be routinely included in the differential diagnosis of children presenting with splenomegaly and hepatomegaly, taking into account that the early start of ERT can change the natural history of the disease-preventing serious complications.
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BACKGROUND: Type 2 diabetes may alter cardiac structure and function. Many patients with type 2 diabetes have diastolic dysfunction with preserved ejection fraction (EF). Recently, this latter measure was criticised. Thus, this research looked at the impact of left ventricular end-diastolic volume and E/e' ratio variations in patients with type 2 diabetes and preserved EF with the aim to recognise different clinical phenotypes. METHODS: In this cross-sectional study, we evaluated 176 men affected by type 2 diabetes with transthoracic echocardiography. All subjects have preserved EF (>50%). Patients were stratified into four groups based on the median value of both left ventricular end-diastolic volume and E/e' ratio, and the clinical variables were registered. The independent predictors associated with the groups were analysed by a multinomial logistic regression model. RESULTS: Diabetes duration, age, estimated glomerular filtration rate and antihypertensive treatments were significantly different among the groups as were EF, left atrial volume index (LAVI), E/A, septum thickness and s' mean wave. Multinomial regression analysis showed that the groups significantly differed for age, diabetes duration, EF, LAVI, septum thickness and s' mean wave. The main result of this study was that patients with higher left ventricular volume and higher E/e' ratio (group 2) showed the worse clinical profile. CONCLUSIONS: Our study might suggest that variations of left ventricular end-diastolic volume along with E/e' ratio variations, even in the normal range, may allow to recognise phenotypes of patients with type 2 diabetes with worse clinical characteristics. This finding should be tested in prospective studies to assess the predictive roles of these phenotypes.
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BACKGROUND: Type 2 diabetes is strongly associated with the occurrence of cardiovascular diseases, especially heart failure. Some studies have suggested that subclinical systolic dysfunction as assessed by tissue Doppler imaging (TDI) is already present in uncomplicated diabetic patients with normal left ventricular ejection fraction (LVEF). Considering the importance of this aspect, the aim of this cross-sectional study was to examine the relationship between glycated hemoglobin and mean s' wave velocity (a reliable measure of early LV systolic dysfunction) in a cohort of type 2 diabetic outpatients with preserved LVEF and without ischemic heart disease. METHODS: Forty-four male patients with newly diagnosed and 172 male patients with established type 2 diabetes were recruited for this cross-sectional study. All patients were evaluated with a transthoracic echocardiographic Doppler. The statistical analysis was conducted by a linear multivariate regression analysis, including several potential confounders. RESULTS: The mean values of mean s' wave velocity were lower in patients with a worse glycemic control and progressively decreased across the quartiles of glycated hemoglobin. The multivariate linear regression analysis showed that mean s' wave velocity was inversely and independently associated with glycated hemoglobin (standardized beta coefficient -0.178; p = 0.043) after adjustment for age, duration of diabetes, body mass index, pulse pressure, estimated glomerular filtration rate, microvascular complication status, and indexed cardiac mass. CONCLUSIONS: These results suggest that s' wave velocity, as evaluated by TDI echocardiography, was an early marker of systolic dysfunction in type 2 diabetic patients with preserved LVEF and without prior ischemic heart disease. Moreover, early systolic dysfunction was independently associated with poor glycemic control in these patients. Future studies are needed to elucidate the pathogenic role of chronic hyperglycemia in the development of early LV systolic dysfunction.
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Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Idoso , Doenças Assintomáticas , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Progressão da Doença , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/diagnósticoRESUMO
AIMS: It is known that type 2 diabetic patients are at high risk of atrial fibrillation (AF). However, the early echocardiographic determinants of AF vulnerability in this patient population remain poorly known. METHODS: We followed-up for 2years a sample of 180 consecutive outpatients with type 2 diabetes, who were free from AF and ischemic heart disease at baseline. All patients underwent a baseline echocardiographic-Doppler evaluation with tissue Doppler and 2-D strain analysis. Standard electrocardiograms were performed twice per year, and a diagnosis of incident AF was confirmed in affected patients by a single cardiologist. RESULTS: Over the 2-year follow-up period, 14 (7.8%) patients developed incident AF. In univariate analyses, echocardiographic predictors of new-onset AF were greater indexed cardiac mass, larger indexed left atrial volume (LAVI), lower global longitudinal strain (LSSYS), lower global diastolic strain rate during early phase of diastole (SRE), lower global diastolic strain rate during late phase of diastole (SRL), and higher E/SRE ratio. Multivariate logistic regression analysis showed that lower LSSYS remained the only significant predictor of new-onset AF (adjusted-odds ratio 1.63, 95%CI 1.17-2.27; p<0.005) after adjustment for age, sex, diabetes duration, indexed cardiac mass and LAVI. Results were unchanged even after adjustment for body mass index, hypertension and glycemic control. CONCLUSIONS: This is the first prospective study to show that early LSSYS impairment independently predicts the risk of new-onset AF in type 2 diabetic patients with preserved ejection fraction and without ischemic heart disease. Future larger prospective studies are needed to confirm these findings.
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Fibrilação Atrial/complicações , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/fisiopatologia , Ventrículos do Coração/fisiopatologia , Disfunção Ventricular Esquerda/complicações , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Cardiomiopatias Diabéticas/diagnóstico por imagem , Diagnóstico Precoce , Ecocardiografia Doppler , Feminino , Seguimentos , Ventrículos do Coração/diagnóstico por imagem , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
OBJECTIVE: Recent studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of heart rate-corrected QT interval prolongation and atrial fibrillation in patients with type 2 diabetes. Currently, no data exist regarding the relationship between NAFLD and ventricular arrhythmias in this patient population. RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data of 330 outpatients with type 2 diabetes without preexisting atrial fibrillation, end-stage renal disease, or known liver diseases who had undergone 24-h Holter monitoring for clinical reasons between 2013 and 2015. Ventricular arrhythmias were defined as the presence of nonsustained ventricular tachycardia (VT), >30 premature ventricular complexes (PVCs) per hour, or both. NAFLD was diagnosed by ultrasonography. RESULTS: Compared with patients without NAFLD, those with NAFLD (n = 238, 72%) had a significantly higher prevalence of >30 PVCs/h (19.3% vs. 6.5%, P < 0.005), nonsustained VT (14.7% vs. 4.3%, P < 0.005), or both (27.3% vs. 9.8%, P < 0.001). NAFLD was associated with a 3.5-fold increased risk of ventricular arrhythmias (unadjusted odds ratio [OR] 3.47 [95% CI 1.65-7.30], P < 0.001). This association remained significant even after adjusting for age, sex, BMI, smoking, hypertension, ischemic heart disease, valvular heart disease, chronic kidney disease, chronic obstructive pulmonary disease, serum γ-glutamyltransferase levels, medication use, and left ventricular ejection fraction (adjusted OR 3.01 [95% CI 1.26-7.17], P = 0.013). CONCLUSIONS: This is the first observational study to show that NAFLD is independently associated with an increased risk of prevalent ventricular arrhythmias in patients with type 2 diabetes.
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Diabetes Mellitus Tipo 2/complicações , Eletrocardiografia Ambulatorial , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Taquicardia Ventricular/complicações , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Índice de Massa Corporal , Colesterol/sangue , Estudos Transversais , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Prevalência , Estudos Retrospectivos , Fatores de Risco , Taquicardia Ventricular/diagnóstico , Triglicerídeos/sangue , Função Ventricular Esquerda , gama-Glutamiltransferase/sangueRESUMO
Accumulating evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with left ventricular diastolic dysfunction (LVDD) in nondiabetic individuals. To date, there are very limited data on this topic in patients with type 2 diabetes and it remains uncertain whether NAFLD is independently associated with the presence of LVDD in this patient population. We performed a liver ultrasonography and trans-thoracic echocardiography (with speckle-tracking strain analysis) in 222 (156 men and 66 women) consecutive type 2 diabetic outpatients with no previous history of ischemic heart disease, chronic heart failure, valvular diseases and known hepatic diseases. Binary logistic regression analysis was used to examine the association between NAFLD and the presence/severity of LVDD graded according to the current criteria of the American Society of Echocardiography, and to identify the variables that were independently associated with LVDD, which was included as the dependent variable. Patients with ultrasound-diagnosed NAFLD (n = 158; 71.2% of total) were more likely to be female, overweight/obese, and had longer diabetes duration, higher hemoglobin A1c and lower estimated glomerular filtration rate (eGFR) than those without NAFLD. Notably, they also had a remarkably greater prevalence of mild and/or moderate LVDD compared with those without NAFLD (71% vs. 33%; P<0.001). Age, hypertension, smoking, medication use, E/A ratio, LV volumes and mass were comparable between the two groups of patients. NAFLD was associated with a three-fold increased odds of mild and/or moderate LVDD after adjusting for age, sex, body mass index, hypertension, diabetes duration, hemoglobin A1c, eGFR, LV mass index and ejection fraction (adjusted-odds ratio 3.08, 95%CI 1.5-6.4, P = 0.003). In conclusion, NAFLD is independently associated with early LVDD in type 2 diabetic patients with preserved systolic function.
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Diabetes Mellitus Tipo 2/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/complicações , Disfunção Ventricular Esquerda/complicações , Idoso , Índice de Massa Corporal , Estudos Transversais , Complicações do Diabetes , Ecocardiografia , Feminino , Taxa de Filtração Glomerular , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão , Fígado/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade , Razão de Chances , Sobrepeso , Ultrassonografia Doppler , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
AIMS: We assessed whether left atrial volume index (LAVI) was associated with the presence of microvascular complications in patients with type 2 diabetes, and whether this association was independent of hemodynamic and non-hemodynamic factors. METHODS: We studied 157 consecutive outpatients with type 2 diabetes with no previous history of ischemic heart disease, chronic heart failure and valvular diseases. A transthoracic echocardiography and myocardial perfusion scintigraphy were performed in all participants. Presence of microvascular complications was also recorded. RESULTS: Overall, 51 patients had decreased estimated glomerular filtration rate and/or abnormal albuminuria, 24 had diabetic retinopathy, 22 had lower-extremity sensory neuropathy, and 67 (42.7%) patients had one or more of these microvascular complications (i.e., combined endpoint). After stratifying patients by LAVI, those with LAVI ≥32 ml/m(2) had a greater prevalence of microvascular complication, lower left ventricular (LV) ejection fraction, higher LV mass index and higher E/e' ratio than those with LAVI <32 ml/m(2). Logistic regression analyses revealed that microvascular complications (singly or in combination) were associated with increased LAVI, independently of age, sex, diabetes duration, hemoglobin A1c, hypertension, LV-ejection fraction, LV mass index and the E/e' ratio. CONCLUSIONS: These results indicate that microvascular diabetic complications are associated with increased LAVI in well-controlled type 2 diabetic patients with preserved systolic function and free from ischemic heart disease, independently of multiple potential confounders.
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Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico , Átrios do Coração/diagnóstico por imagem , Microvasos/fisiopatologia , Idoso , Volume Cardíaco/fisiologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/etiologia , Ecocardiografia , Feminino , Átrios do Coração/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do MiocárdioRESUMO
PURPOSE: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are two powerful predictors of adverse cardiovascular outcomes in patients with type 2 diabetes, but the etiology of valvular calcification is uncertain. Nonalcoholic fatty liver disease (NAFLD) is an emerging cardiovascular risk factor and is very common in type 2 diabetes, but whether NAFLD is associated with valvular calcification in this group of patients is presently unknown. METHODS: We undertook a cross-sectional study of 247 consecutive type 2 diabetic outpatients with no previous history of heart failure, valvular heart diseases (aortic stenosis, mitral stenosis, moderate or severe aortic and mitral regurgitation) or hepatic diseases. Presence of MAC and AVS was detected by echocardiography. NAFLD was diagnosed by ultrasonography. RESULTS: Overall, 139 (56.3%) patients had no heart valve calcification (HVC-0), 65 (26.3%) patients had one valve affected (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). 175 (70.8%) patients had NAFLD and the prevalence of this disease markedly increased in patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1% vs. 83.1% vs. 60.4%, respectively; p < 0.001). NAFLD was significantly associated with AVS and/or MAC (unadjusted-odds ratio 3.51, 95% CI 1.89-6.51, p < 0.001). Adjustments for age, sex, waist circumference, smoking, blood pressure, hemoglobin A1c, LDL-cholesterol, kidney function parameters, medication use and echocardiographic variables did not appreciably weaken this association (adjusted-odds ratio 2.70, 95% CI 1.23-7.38, p < 0.01). CONCLUSIONS: Our results show that NAFLD is an independent predictor of cardiac calcification in both the aortic and mitral valves in patients with type 2 diabetes.
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Calcinose/etiologia , Diabetes Mellitus Tipo 2/complicações , Doenças das Valvas Cardíacas/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Idoso , Valva Aórtica , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/patologia , Esclerose/patologiaRESUMO
BACKGROUND AND AIMS: The relationship between nonalcoholic fatty liver disease (NAFLD) and prolonged heart rate-corrected QT (QTc) interval, a risk factor for ventricular arrhythmias and sudden cardiac death, is currently unknown. We therefore examined the relationship between NAFLD and QTc interval in patients with type 2 diabetes. METHODS AND RESULTS: We studied a random sample of 400 outpatients with type 2 diabetes. Computerized electrocardiograms were performed for analysis and quantification of QTc interval. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. Mean QTc interval and the proportion of those with increased QTc interval (defined as either QTc interval above the median, i.e. ≥416 ms, or QTc interval >440 ms) increased steadily with the presence and ultrasonographic severity of NAFLD. NAFLD was associated with increased QTc interval (odds ratio [OR] 2.16, 95% CI 1.4-3.4, p < 0.001). Adjustments for age, sex, smoking, alcohol consumption, BMI, hypertension, electrocardiographic left ventricular hypertrophy, diabetes-related variables and comorbid conditions did not attenuate the association between NAFLD and increased QTc interval (adjusted-OR 2.26, 95% CI 1.4-3.7, p < 0.001). Of note, the exclusion of those with established coronary heart disease or peripheral artery disease from analysis did not appreciably weaken this association. CONCLUSION: This is the first study to demonstrate that the presence and severity of NAFLD on ultrasound is strongly associated with increased QTc interval in patients with type 2 diabetes even after adjusting for multiple established risk factors and potential confounders.
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Arritmias Cardíacas/etiologia , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Idoso , Arritmias Cardíacas/complicações , Arritmias Cardíacas/epidemiologia , Estudos de Coortes , Estudos Transversais , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Cardiomiopatias Diabéticas/epidemiologia , Eletrocardiografia , Feminino , Humanos , Itália/epidemiologia , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Ambulatório Hospitalar , Fatores de Risco , Índice de Gravidade de Doença , Processamento de Sinais Assistido por Computador , UltrassonografiaRESUMO
BACKGROUND: Recent epidemiological data suggest that non-alcoholic fatty liver disease (NAFLD) is closely associated with aortic valve sclerosis (AVS), an emerging risk factor for adverse cardiovascular outcomes, in nondiabetic and type 2 diabetic individuals. To date, nobody has investigated the association between NAFLD and AVS in people with type 2 diabetes, a group of individuals in which the prevalence of these two diseases is high. METHODS AND RESULTS: We recruited 180 consecutive type 2 diabetic patients without ischemic heart disease, valvular heart disease, hepatic diseases or excessive alcohol consumption. NAFLD was diagnosed by liver ultrasonography whereas AVS was determined by conventional echocardiography in all participants. In the whole sample, 120 (66.7%) patients had NAFLD and 53 (29.4%) had AVS. No patients had aortic stenosis. NAFLD was strongly associated with an increased risk of prevalent AVS (odds ratio [OR] 2.79, 95% CI 1.3-6.1, p<0.01). Adjustments for age, sex, duration of diabetes, diabetes treatment, body mass index, smoking, alcohol consumption, hypertension, dyslipidemia, hemoglobin A1c and estimated glomerular filtration rate did not attenuate the strong association between NAFLD and risk of prevalent AVS (adjusted-OR 3.04, 95% CI 1.3-7.3, pâ=â0.01). CONCLUSIONS: Our results provide the first demonstration of a positive and independent association between NAFLD and AVS in patients with type 2 diabetes mellitus.
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Estenose da Valva Aórtica/complicações , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/complicações , Idoso , Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico por imagem , Diabetes Mellitus Tipo 2/sangue , Ecocardiografia , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Análise de RegressãoRESUMO
The association between serum uric acid (SUA) levels and atrial fibrillation (AF) is currently poorly known. We examined the association between SUA levels and risk of incident AF in patients with type 2 diabetes mellitus. We followed for 10 years a random sample of 400 type 2 diabetic outpatients, who were free from AF at baseline. A standard 12-lead electrocardiography was undertaken annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist. Over 10 years, there were 42 incident AF cases (cumulative incidence of 10.5%). Elevated SUA level was associated with an increased risk of incident AF (odds ratio 2.43, 95% confidence interval 1.8 to 3.4, p <0.0001 for each 1-SD increase in SUA level). Adjustments for age, gender, body mass index, hypertension, chronic kidney disease, electrocardiographic features (left ventricular hypertrophy and PR interval), and use of diuretics and allopurinol did not attenuate the association between SUA and incident AF (adjusted odds ratio 2.44, 95% confidence interval 1.6 to 3.9, p <0.0001). Further adjustment for variables that were included in the 10-year Framingham Heart Study-derived AF risk score did not appreciably weaken this association. Results remained unchanged even when SUA was modeled as a categorical variable (stratifying by either SUA median or hyperuricemia), and when patients with previous coronary heart disease or heart failure were excluded from analysis. In conclusion, our findings suggest that elevated SUA levels are strongly associated with an increased incidence of AF in patients with type 2 diabetes mellitus even after adjustment for multiple clinical risk factors for AF.
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Fibrilação Atrial/sangue , Fibrilação Atrial/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Ácido Úrico/sangue , Idoso , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Tipo 2/tratamento farmacológico , Eletrocardiografia , Feminino , Humanos , Incidência , Itália/epidemiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Risco , Fatores de Risco , População BrancaRESUMO
BACKGROUND: The relationship between non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) in type 2 diabetes is currently unknown. We examined the relationship between NAFLD and risk of incident AF in people with type 2 diabetes. METHODS AND RESULTS: We prospectively followed for 10 years a random sample of 400 patients with type 2 diabetes, who were free from AF at baseline. A standard 12-lead electrocardiogram was undertaken annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist. At baseline, NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. During the 10 years of follow-up, there were 42 (10.5%) incident AF cases. NAFLD was associated with an increased risk of incident AF (odds ratio [OR] 4.49, 95% CI 1.6-12.9, p<0.005). Adjustments for age, sex, hypertension and electrocardiographic features (left ventricular hypertrophy and PR interval) did not attenuate the association between NAFLD and incident AF (adjusted-OR 6.38, 95% CI 1.7-24.2, pâ=â0.005). Further adjustment for variables that were included in the 10-year Framingham Heart Study-derived AF risk score did not appreciably weaken this association. Other independent predictors of AF were older age, longer PR interval and left ventricular hypertrophy. CONCLUSIONS: Our results indicate that ultrasound-diagnosed NAFLD is strongly associated with an increased incidence of AF in patients with type 2 diabetes even after adjustment for important clinical risk factors for AF.
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Fibrilação Atrial/complicações , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/complicações , Idoso , Fígado Gorduroso/diagnóstico por imagem , Feminino , Humanos , Incidência , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Estudos Prospectivos , UltrassonografiaRESUMO
OBJECTIVE: To examine whether baseline pulse pressure (PP), a marker of arterial stiffness, is associated with subsequent development of atrial fibrillation (AF) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 350 type 2 diabetic patients, who were free from AF at baseline, were followed for 10 years. A standard electrocardiogram was performed annually and a diagnosis of incident AF was confirmed in affected participants by a single cardiologist. RESULTS: During the follow-up, 32 patients (9.1% of total) developed incident AF. After adjustments for age, sex, BMI, diabetes duration, presence of left ventricular hypertrophy, hypertension treatment, kidney dysfunction, and pre-existing history of coronary heart disease, heart failure, and mild valvular disease, baseline PP was associated with an increased incidence of AF (adjusted odds ratio 1.76 for each SD increment [95% CI 1.1-2.8]; P < 0.01). CONCLUSIONS: Our findings suggest that increased PP independently predicts incident AF in patients with type 2 diabetes.
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Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Data on cardiac function in patients with nonalcoholic fatty liver disease (NAFLD) are limited and conflicting. We assessed whether NAFLD is associated with abnormalities in cardiac function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We studied 50 consecutive type 2 diabetic individuals without a history of ischemic heart disease, hepatic diseases, or excessive alcohol consumption, in whom NAFLD was diagnosed by ultrasonography. A tissue Doppler echocardiography with myocardial strain measurement was performed in all patients. RESULTS: Thirty-two patients (64%) had NAFLD, and when compared with the other 18 patients, age, sex, BMI, waist circumference, hypertension, smoking, diabetes duration, microvascular complication status, and medication use were not significantly different. In addition, the left ventricular (LV) mass and volumes, ejection fraction, systemic vascular resistance, arterial elasticity, and compliance were also not different. NAFLD patients had lower e' (8.2 ± 1.5 vs. 9.9 ± 1.9 cm/s, P < 0.005) tissue velocity, higher E-to-e' ratio (7.90 ± 1.3 vs. 5.59 ± 1.1, P < 0.0001), a higher time constant of isovolumic relaxation (43.1 ± 10.1 vs. 33.2 ± 12.9 ms, P < 0.01), higher LV-end diastolic pressure (EDP) (16.5 ± 1.1 vs. 15.1 ± 1.0 mmHg, P < 0.0001), and higher LV EDP/end diastolic volume (0.20 ± 0.03 vs. 0.18 ± 0.02 mmHg, P < 0.05) than those without steatosis. Among the measurements of LV global longitudinal strain and strain rate, those with NAFLD also had higher E/global longitudinal diastolic strain rate during the early phase of diastole (E/SR(E)). All of these differences remained significant after adjustment for hypertension and other cardiometabolic risk factors. CONCLUSIONS: Our data show that in patients with type 2 diabetes and NAFLD, even if the LV morphology and systolic function are preserved, early features of LV diastolic dysfunction may be detected.
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Diabetes Mellitus Tipo 2/fisiopatologia , Fígado Gorduroso/fisiopatologia , Disfunção Ventricular Esquerda/patologia , Idoso , Ecocardiografia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Disfunção Ventricular Esquerda/etiologiaRESUMO
BACKGROUND: Abnormal microvolt T-wave alternans (MTWA), a marker of ventricular arrhythmic risk, is a highly prevalent condition in patients with type 2 diabetes mellitus (T2DM) and is correlated with glycemic control. However, there is uncertainty as to whether central or peripheral hemodynamic factors are associated with abnormal MTWA in T2DM individuals. METHODS AND RESULTS: We studied 50 consecutive, well-controlled T2DM outpatients without a history of ischemic heart disease and with normal systolic function. All patients underwent a complete echocardiographic Doppler evaluation with spectral tissue Doppler analysis. MTWA analysis was performed noninvasively during submaximal exercise. Effective arterial elastance, arterial compliance, and heart rate variability were also measured. Compared with patients with MTWA negativity (n = 38), those with MTWA abnormality (n = 12, 24%) had significantly lower e' (7.6 ± 1.3 versus 9.1 ± 1.7 cm/s; P < 0.01), a' (10.2 ± 1.6 versus 12.7 ± 1.9 cm/s; P < 0.001) and s' velocities (8.7 ± 1.1 versus 10.2 ± 1.5 cm/s; P = 0.001) and higher indexed left ventricular mass (121.3 ± 16.4 versus 107.5 ± 16.5 g/m2; P = 0.016), indexed left atrial volume (33.5 ± 11.9 versus 23.6 ± 5.6 mL/m2; P < 0.001), and E/e' ratio (8.8 ± 1.4 versus 6.5 ± 1.3; P < 0.001). Multivariable logistic regression analysis revealed that higher E/e' ratio was the only independent correlate of abnormal MTWA (adjusted odds ratio, 3.52; 95% confidence interval, 1.19 to 10.6; P = 0.02) after controlling for glycemic control and other potential confounders. CONCLUSIONS: In this pilot study, we found that early diastolic dysfunction, as measured by tissue Doppler imaging, is independently associated with MTWA abnormality in T2DM individuals with normal systolic function. Further larger studies are needed to examine the reproducibility of these results.
Assuntos
Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/etiologia , Diabetes Mellitus Tipo 2/complicações , Ecocardiografia Doppler , Idoso , Arritmias Cardíacas/fisiopatologia , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 2/fisiopatologia , Diástole/fisiologia , Feminino , Testes de Função Cardíaca , Frequência Cardíaca/fisiologia , Humanos , Modelos Logísticos , Masculino , Projetos Piloto , Análise de Regressão , Medição de Risco , Estatísticas não Paramétricas , Sístole/fisiologia , Resistência Vascular/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: We assessed whether nonalcoholic steatohepatitis (NASH) diagnosed by liver biopsy is associated with decreased kidney function and whether such association is independent of insulin resistance and features of the metabolic syndrome. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: We enrolled 80 consecutive overweight patients with biopsy-proven NASH and 80 nonsteatotic control subjects who were matched for age, gender, and body mass index. Chronic kidney disease (CKD) was defined as the presence of estimated GFR (eGFR) of ≤60 ml/min per 1.73 m(2) and/or abnormal albuminuria (i.e., urinary albumin/creatinine ratio ≥30 mg/g). RESULTS: NASH patients had significantly (P < 0.001) lower eGFR (75.3 ± 12 versus 87.5 ± 6 ml/min per 1.73 m(2)) and a greater frequency of abnormal albuminuria (14 versus 2.5%) and CKD (25 versus 3.7%) than control subjects. The significant differences in eGFR, albuminuria, and CKD that were observed between the two groups were only slightly weakened after adjustment for age, gender, body mass index, smoking status, insulin resistance (by homeostasis model assessment), and components of the metabolic syndrome. Notably, histologic severity of NASH (i.e., fibrosis stage) was strongly associated with either decreasing eGFR or increasing albuminuria (P < 0.01 or less), independently of potential confounding factors. CONCLUSIONS: Our findings suggest that patients with biopsy-proven NASH have moderately decreased eGFR and a higher frequency of abnormal albuminuria and CKD than matched control subjects and that the severity of NASH histology is associated with decreased kidney function, independently of traditional risk factors, insulin resistance, and components of the metabolic syndrome.
Assuntos
Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Rim/fisiopatologia , Fígado/patologia , Doença Crônica , Estudos Transversais , Fígado Gorduroso/complicações , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND & AIMS: To estimate the prevalence of non-alcoholic fatty liver disease (NAFLD) in type 1 diabetic individuals, and to evaluate whether NAFLD is associated with increased prevalence of cardiovascular disease (CVD). METHODS: All patients with diagnosed type 1 diabetes with available liver ultrasound data (n=250), who regularly attended our diabetes clinic, were enrolled. Main study measures were detection of NAFLD (by patient history and liver ultrasound) and asymptomatic/symptomatic CVD (by patient history, chart review, electrocardiogram, and echo-Doppler scanning of carotid and lower limb arteries). RESULTS: The prevalence of NAFLD was 44.4%, and NAFLD was the most common cause (69.8%) of hepatic steatosis on ultrasound examination. Patients with NAFLD had a remarkably higher (p<0.001) age- and sex-adjusted prevalence of coronary (10.8% vs. 1.1%), cerebrovascular (37.3% vs. 5.5%) and peripheral (24.5% vs. 2.5%) vascular disease than their counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with prevalent CVD (as composite endpoint), independently of age, sex, diabetes duration, hemoglobin A(1c), smoking history, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and medication use (adjusted odds ratio 7.36, 95% confidence intervals 1.60-34.3, p<0.01). CONCLUSIONS: Our findings suggest that NAFLD is very common in type 1 diabetic subjects and is associated, independently of several confounding factors, with a higher prevalence of CVD. Future prospective studies are needed to evaluate whether NAFLD predicts incident CVD events in type 1 diabetes.
Assuntos
Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/epidemiologia , Adulto , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Prevalência , UltrassonografiaRESUMO
It is unknown whether chronic kidney disease (CKD) is associated with nonalcoholic fatty liver disease among patients with type 2 diabetes. We followed 1760 outpatients with type 2 diabetes and normal or near-normal kidney function and without overt proteinuria for 6.5 yr for the occurrence of CKD (defined as overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m(2)). During follow-up, 547 participants developed incident CKD. Nonalcoholic fatty liver disease, diagnosed by liver ultrasound and exclusion of other common causes of chronic liver disease, was associated with a moderately increased risk for CKD (hazard ratio 1.69; 95% confidence interval 1.3 to 2.6; P < 0.001). Adjustments for gender, age, body mass index, waist circumference, BP, smoking, diabetes duration, glycosylated hemoglobin, lipids, baseline estimated GFR, microalbuminuria, and medications (hypoglycemic, lipid-lowering, antihypertensive, or antiplatelet drugs) did not appreciably attenuate this association (hazard ratio 1.49; 95% confidence interval 1.1 to 2.2; P < 0.01). In conclusion, our findings suggest that nonalcoholic fatty liver disease is associated with an increased incidence of CKD in individuals with type 2 diabetes, independent of numerous baseline confounding factors.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Fígado Gorduroso/epidemiologia , Falência Renal Crônica/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/complicações , Humanos , Incidência , Itália/epidemiologia , Falência Renal Crônica/etiologia , Estudos Prospectivos , Fatores de RiscoRESUMO
We assessed the differential contribution of nonalcoholic steatohepatitis (NASH) and visceral adiposity to nontraditional cardiovascular risk biomarkers in adult men. We enrolled 45 consecutive, overweight, male patients with biopsy-proven NASH, 45 overweight male patients without ultrasound-diagnosed hepatic steatosis, and 45 healthy male volunteers. All participants were matched for age; NASH and overweight patients were also matched for BMI and visceral adiposity (as estimated by abdominal ultrasonography). Nontraditional cardiovascular risk biomarkers were measured in all participants. Plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity, and adiponectin were markedly different among the groups; the lowest values (the highest for adiponectin) were in nonobese healthy subjects, intermediate in overweight nonsteatotic patients, and the highest (the lowest for adiponectin) in those with biopsy-proven NASH. The marked differences in these cardiovascular risk biomarkers that were observed between overweight and NASH patients were only slightly weakened after adjustment for age, BMI, smoking, plasma triglycerides, and insulin resistance (IR) as assessed by homeostasis model assessment (HOMA). In multivariate regression analysis, NASH and visceral adiposity predicted cardiovascular risk biomarkers independently of potential confounders. In conclusion, our results suggest that NASH can predict a more atherogenic risk profile in a manner that is partly independent from the contribution of visceral adiposity in adult men.