Excess diabetes-related deaths: The role of comorbidities through different phases of the COVID-19 pandemic.

BACKGROUND AND AIMS: Diabetes confers an excess risk of death to COVID-19 patients. Causes of death are now available for different phases of the pandemic, encompassing different viral variants and COVID-19 vaccination. The aims of the present study were to update multiple causes of death data on diabetes-related mortality during the pandemic and to estimate the impact of common diabetic comorbidities on excess mortality. METHODS AND RESULTS: Diabetes-related deaths in 2020-2021 were compared with the 2018-2019 average; furthermore, age-standardized rates observed during the pandemic were compared with expected figures obtained from the 2008-2019 time series through generalized estimating equation models. Changes in diabetes mortality associated with specific comorbidities were also computed. Excess diabetes-related mortality was +26% in 2020 and +18% in 2021, after the initiation of the vaccination campaign. The presence of diabetes and hypertensive diseases was associated with the highest mortality increase, especially in subjects aged 40-79 years, +41% in 2020 and +30% in 2021. CONCLUSION: The increase in diabetes-related deaths exceeded that observed for all-cause mortality, and the risk was higher when diabetes was associated with hypertensive diseases. Notably, the excess mortality decreased in 2021, after the implementation of vaccination against COVID-19.

Diabetes as a cause of death across different COVID-19 epidemic waves.

AIMS: The aim of this study is to assess the role of diabetes as a cause of death through different epidemic waves of COVID-19. METHODS: The annual percentage change in age-standardized rates (APC) was estimated for diabetes as the underlying (UCOD) and as multiple causes of death (MCOD) in 2008-2019. Diabetes-related deaths in 2020 were compared to the 2018-2019 average. SARIMA models were applied to monthly excess in mortality considering seasonality and long-term trends. RESULTS: 2018-2019-Age-standardized mortality rates decreased, especially among females (MCOD: APC -2.49, 95%CI -3.01/-1.97%). In 2020, deaths increased by 19% (95%CI 13-25%) for UCOD, and by 27% (95%CI 24-30%) for MCOD. Diabetes and COVID-19 accounted for 74% of such excess. During the first epidemic wave, the increase in observed rates vs predicted by the model was larger in males (March +39%, April +46%) than in females (+30% and +32%). In the second wave, a huge excess of similar magnitude was observed in the two sexes; rates in December exceeded those predicted by more than 100%. CONCLUSIONS: The COVID-19 pandemic abruptly interrupted a long-term declining trend in mortality associated to diabetes. MCOD analyses are warranted to fully estimate the impact of epidemic waves on diabetes-related mortality.

Thyroidectomies in Italy: A Population-Based National Analysis from 2001 to 2018.

Background: The incidence of thyroid disease is generally increasing, and it is subject to major geographic variability, between and within countries. Moreover, the incidence rates and the proportion of overdiagnosis for thyroid cancer in Italy are among the highest worldwide. This study aimed to estimate population-based frequency and trends of thyroidectomies in Italy by type of surgical procedure (total/partial), indication (tumors/other conditions), sex, age, and geographical region. Materials and Methods: Age-standardized rates (ASRs) of thyroidectomies were estimated from 2001 to 2018 using the national hospital discharges database. Results: In Italy, ASRs of thyroidectomies were nearly 100 per 100,000 women in 2002-2004 and decreased to 71 per 100,000 women in 2018. No corresponding variation was shown in men (ASR 27 per 100,000 men) in the overall period. A more than twofold difference between Italian regions emerged in both sexes. The proportion of total thyroidectomies (on the sum of total and partial thyroidectomies) in the examined period increased from 78% to 86% in women and from 72% to 81% in men. Thyroidectomies for goiter and nonmalignant conditions decreased consistently throughout the period (from 81 per 100,000 women in 2002 to 49 in 2018 and from 22 to 16 per 100,000 men), while thyroidectomies for tumors increased until 2013-2014 up to 24 per 100,000 women (9 per 100,000 men) and remained essentially stable thereafter. Conclusions: The decrease in thyroidectomies for nonmalignant diseases since early 2000s in Italy may derive from the decrease of goiter prevalence, possibly as a consequence of the reduction of iodine deficiency and the adoption of conservative treatments. In a context of overdiagnosis of thyroid cancer, recent trends have suggested a decline in the diagnostic pressure with a decrease in geographic difference. Our results showed the need and also the possibility to implement more conservative surgical approaches to thyroid diseases, as recommended by international guidelines.

SARS-CoV-2 and COVID-19 in diabetes mellitus. Population-based study on ascertained infections, hospital admissions and mortality in an Italian region with ∼5 million inhabitants and ∼250,000 diabetic people.

BACKGROUND AND AIMS: Diabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19. METHODS AND RESULTS: Diabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19-1.45], 2.11 [1.83-2.44], 2.45 [1.96-3.07], 1.87 [1.68-2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20-39 years: 1.90 [1.04-3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40-59 years: 3.47 [2.00-5.70] and 5.54 [2.23-12.1], respectively. CONCLUSIONS: These data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.

Glomerular filtration rate decline in T2DM following diagnosis. The Verona newly diagnosed diabetes study-12.

AIMS: Nephropathy is a complication of type 2 diabetes, with increased albuminuria and reduced glomerular filtration rate (GFR) as biomarkers. Rates of progression to end-stage-renal disease are variable among patients. In this study we have examined the GFR decline in newly diagnosed T2DM. METHODS: A cohort of 410 patients with newly diagnosed T2DM and with at least four serum creatinine during the follow-up period were recruited. A linear model was used to calculate the decline in eGFR. A multivariable logistic model was used to identify independent predictors of rapid eGFR decline. RESULTS: Average follow-up was 12.4 years. The eGFR change was -0.80 ±â€¯2.23 ml/min/1.73 m2 per year. Patients were arbitrarily stratified into rapid decliners (≤-3.0 ml/min/1.73 m2 per year), moderate decliners (-2.9/-1 ml/min/1.73 m2 per year) and slow/no decliners (>-1.0 ml/min/1.73 m2 per year). Subjects in the 3 categories were 11.4%, 27.3%, and 61.3%, respectively. Albuminuria was the stronger predictor of rapid eGFR decline. CONCLUSIONS: A rapid decline in eGFR occurs in approximately 1 out of 10 newly diagnosed subjects. This rapid decline can be predicted by widely accessible clinical features, such as albuminuria. Identification of rapid decliners may help to reduce progression toward advanced stages of nephropathy.

Echocardiographic parameters according to insulin dose in young patients affected by type 1 diabetes.

Insulin dose has been found to associate to several cardiometabolic risk factors in type 1 diabetes. Changes over time in body weight and composition may partly explain this association. However, no data are available on the relationship between insulin dose and echocardiographic parameters of both systolic and diastolic function in type 1 diabetes. Therefore, the aim of the present study was to examine systolic and diastolic echocardiographic parameters in relation to insulin dose in young patients with type 1 diabetes. The study was carried out on 93 consecutive outpatients with type 1 diabetes with a mean age of 32.8 ± 9.8 years. All patients were examined with a transthoracic echocardiography. Clinical and laboratory data were collected. The median value of daily insulin dose was used to categorized patients in two groups: high and low insulin dose group. Patients belonging to the high insulin dose group showed higher levels of cardiometabolic risk factors such as BMI, triglycerides and TG/HDL cholesterol ratio. Indexes of both systolic and diastolic function were similar in both groups except isovolumetric relaxation time (IVRT), that was significantly prolonged in patients of the high insulin group (94.4 ± 15.0 vs 86.7 ± 13.1 ms, p = 0.008). In the multivariate regression analysis, insulin dose was positively and significantly associated with IVRT. In this study we report an association between insulin dose and impaired active diastolic myocardial relaxation. Future studies are needed to further explore this observation.

Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9.

INTRODUCTION: We explored the presence of chronic complications in subjects with newly diagnosed type 2 diabetes referred to the Verona Diabetes Clinic. Metabolic (insulin secretion and sensitivity) and clinical features associated with complications were also investigated. RESEARCH DESIGN AND METHODS: The comprehensive assessment of microvascular and macrovascular complications included detailed medical history, resting ECG, ultrasonography of carotid and lower limb arteries, quantitative neurological evaluation, cardiovascular autonomic tests, ophthalmoscopy, kidney function tests. Insulin sensitivity and beta-cell function were assessed by state-of-the-art techniques (insulin clamp and mathematical modeling of glucose/C-peptide curves during oral glucose tolerance test). RESULTS: We examined 806 patients (median age years, two-thirds males), of whom prior clinical cardiovascular disease (CVD) was revealed in 11.2% and preclinical CVD in 7.7%. Somatic neuropathy was found in 21.2% and cardiovascular autonomic neuropathy in 18.6%. Retinopathy was observed in 4.9% (background 4.2%, proliferative 0.7%). Chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) was found in 8.8% and excessive albuminuria in 13.2% (microalbuminuria 11.9%, macroalbuminuria 1.3%).Isolated microvascular disease occurred in 30.8%, isolated macrovascular disease in 9.3%, a combination of both in 9.1%, any complication in 49.2% and no complications in 50.8%.Gender, age, body mass index, smoking, hemoglobin A1c and/or hypertension were independently associated with one or more complications. Insulin resistance and beta-cell dysfunction were associated with macrovascular but not microvascular disease. CONCLUSIONS: Despite a generally earlier diagnosis for an increased awareness of the disease, as many as ~50% of patients with newly diagnosed type 2 diabetes had clinical or preclinical manifestations of microvascular and/or macrovascular disease. Insulin resistance might play an independent role in macrovascular disease. TRIAL REGISTRATION NUMBER: NCT01526720.

Nonalcoholic Fatty Liver Disease and Implications for Older Adults with Diabetes.

Nonalcoholic fatty liver disease (NAFLD) is common in older patients with type 2 diabetes. In older patients with type 2 diabetes, the presence of NAFLD is associated with a higher risk of hepatic (eg, nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma) and extrahepatic (eg, cardiovascular disease, sarcopenia, and dementia) complications than that observed in other patient groups. For this reason, appropriate identification and management of NAFLD are clinically relevant particularly in the group of older patients with type 2 diabetes. In this regard, clinicians should consider the peculiar characteristics of elderly patients, such as frailty, multimorbidity, and polypharmacy.

Association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease: An updated meta-analysis.

BACKGROUND: Recent studies that have examined the association between Helicobacter pylori infection and risk of nonalcoholic fatty liver disease (NAFLD) have produced conflicting data. We have performed a systematic review and meta-analysis to assess the association between H. pylori infection and risk of NAFLD. METHODS: We searched PubMed, Web of Science and Scopus databases using predefined keywords to identify observational studies (published up to November 2018), in which NAFLD was diagnosed by histology, imaging or biochemistry. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling. The statistical heterogeneity among studies (I2-index), subgroup analyses and the possibility of publication bias were assessed. RESULTS: Thirteen observational (11 cross-sectional/case-control and 2 longitudinal) studies involving a total of 81,162 middle-aged individuals of predominantly Asian ethnicity (47.5% of whom had H. pylori infection diagnosed by urea breath test, faecal or serological tests) were included in the final analysis. Meta-analysis of data from cross-sectional and case-control studies showed that H. pylori infection was associated with increased risk of prevalent NAFLD (n = 11 studies; random-effects odds ratio [OR] 1.20, 95% CI 1.07-1.35; I2 = 59.6%); this risk remained significant in those studies where analysis was fully adjusted for age, sex, smoking, adiposity measures, diabetes or dyslipidemia (random-effects OR 1.19, 95% CI 1.07-1.32, I2 = 0%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was also associated with increased NAFLD incidence (n = 2 studies; random-effects hazard ratio 1.14, 95% CI 1.05-1.23; I2 = 0%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias. CONCLUSIONS: H. pylori infection is associated with mildly increased risk of both prevalent and incident NAFLD in middle-aged individuals. More prospective studies, particularly in non-Asian populations, and mechanistic studies are required to better elucidate the link between chronic H. pylori infection and NAFLD.

Association Between Nonalcoholic Fatty Liver Disease and Reduced Bone Mineral Density in Children: A Meta-Analysis.

Recent cross-sectional studies have examined the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in children or adolescents, but these have produced conflicting results. We performed a systematic review and meta-analysis of these published studies to quantify the magnitude of the association, if any, between NAFLD and BMD. We searched publication databases from January 2000 to September 2018, using predefined keywords to identify relevant observational studies conducted in children or adolescents in whom NAFLD was diagnosed either by imaging or by histology and BMD Z score was measured by dual-energy X-ray absorptiometry. Data from selected studies were extracted, and a meta-analysis was performed using random-effects modeling. A total of eight observational cross-sectional or case-control studies enrolling 632 children and adolescents (mean age 12.8 years), 357 of whom had NAFLD, were included in the final analysis. Meta-analysis showed significant differences in whole-body or lumbar BMD Z scores between children/adolescents with and without NAFLD (n = 6 studies; pooled weighted mean difference [WMD], -0.48; 95% confidence interval [CI], -0.74 to -0.21; I2 = 55.5%), as well as between those with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and those with no-NASH (n = 4 studies; pooled WMD, -0.27; 95% CI, -0.40 to -0.13; I2 = 0%). The aforementioned WMDs in BMD Z scores were independent of common clinical risk factors, such as age, sex, race/ethnicity, and body mass index. Sensitivity analyses did not modify these findings. Funnel plot and Egger test did not reveal significant publication bias. Conclusion: This meta-analysis shows that the presence and severity of NAFLD are significantly associated with reduced whole-body BMD Z scores in children and adolescents; however, the observational design of the studies included does not allow for proving causality.

Association between non-alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta-analysis.

BACKGROUND & AIMS: Recent studies examined the association between non-alcoholic fatty liver disease (NAFLD) and risk of atrial fibrillation (AF) in adults, but the findings have been inconsistent. We provided a quantitative estimate of the magnitude of the association between NAFLD and risk of AF. METHODS: We searched publication databases using predefined keywords to identify observational studies (published up to December 14, 2018), in which NAFLD was diagnosed by biopsy, imaging or biochemistry and AF was diagnosed by medical history and electrocardiograms. Data from selected studies were extracted and meta-analysis was performed using random-effects modelling. RESULTS: Nine cross-sectional and longitudinal studies were included in the final analysis (n = 364 919 individuals). Meta-analysis of data from 5 cross-sectional studies showed that NAFLD was associated with an increased risk of prevalent AF (random-effects odds ratio 2.07, 95% CI 1.38-3.10; I2  = 54.7%), independent of age, sex, body mass index, hypertension and other common AF risk factors. This risk was particularly high among patients with established diabetes (n = 1 study; random-effects odds ratio 5.17, 95% CI 2.05-13.02). Meta-analysis of data from 4 longitudinal studies showed that NAFLD was independently associated with a 10-year increased risk of incident AF only in type 2 diabetic patients (n = 1 study; random-effects hazard ratio 4.96, 95% CI 1.42-17.28). Sensitivity analyses did not modify these findings. Funnel plots did not reveal significant publication bias. CONCLUSIONS: NAFLD is associated with an increased risk of AF in middle-aged and elderly individuals (especially in those with type 2 diabetes). However, the observational design of the eligible studies does not allow for proving causality.

Systematic review with meta-analysis: non-alcoholic fatty liver disease is associated with a history of osteoporotic fractures but not with low bone mineral density.

BACKGROUND: Several studies have explored the effect of non-alcoholic fatty liver disease (NAFLD) on bone mineral density (BMD) and risk of osteoporotic fractures in adults. However, the extent to which NAFLD adversely affects bone health remains uncertain. AIM: To provide a quantitative estimation of the magnitude of the association of NAFLD with BMD or history of osteoporotic fractures in adults. METHODS: We searched PubMed, Web of Science, and Scopus using predefined keywords to identify all observational studies, published up to 31 August 2018, in which NAFLD was diagnosed by imaging or histology; BMD was measured by dual energy X-ray absorptiometry; and a self-reported history of osteoporotic fractures was collected with interviewer-assisted questionnaires. Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling. RESULTS: Twelve cross-sectional or case-control studies with aggregate data on 30 041 adults of predominantly Asian ethnicity (30% with NAFLD) were included in the final analysis. No significant differences in BMD at different skeletal sites (whole body, lumbar spine, or femur) were observed between individuals with and without NAFLD. Conversely, NAFLD was associated with increased odds of osteoporotic fractures, especially in older Chinese men (n = 2 studies; random-effects odds ratio 2.10, 95% CI 1.36-3.25; I2  = 0%). Sensitivity analyses did not alter these findings. The funnel plot and Egger test did not reveal significant publication bias. CONCLUSIONS: This meta-analysis suggests that imaging-defined or biopsy-proven NAFLD is associated with a self-reported history of osteoporotic fractures (principally in Chinese men), but not with low BMD, in middle-aged and elderly individuals.

The E/e' ratio difference between subjects with type 2 diabetes and controls. A meta-analysis of clinical studies.

Type 2 diabetes is associated with an increased risk of heart failure. Left ventricular diastolic dysfunction and type 2 diabetes are frequently associated. Using echocardiography, we know that tissue Doppler imaging E/e' ratio is a reliable predictor of left ventricular filling pressure. We performed a systematic review and meta-analysis to investigate the averaged E/e' ratio value in patients with type 2 diabetes compared to non-diabetic controls. In the analysis we included cross-sectional studies providing the averaged E/e' ratio. Subgroup/sensitivity analyses were conducted according to variables known to influence E/e' ratio measurements. The analysis included 15 cross sectional studies with 877 type 2 diabetes patients and 1193 controls. The weighted mean difference showed higher values in diabetes (WMD 2.02; 95% CI 1.35, 2.70; p<0.001). The result was consistent in the subgroup/sensitivity analyses. Visual inspection of the funnel plot did not identify substantial asymmetry and the Egger test for funnel plot asymmetry showed a p value of 0.36. In conclusion, our assessment suggests that averaged E/e' ratio is consistently increased in patients with type 2 diabetes compared to non-diabetic controls in the absence of cardiovascular diseases and complicated hypertension. This alteration may be a precocious diastolic alteration in the diabetic cardiomyopathy.

Association Between Primary Hypothyroidism and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: It is currently uncertain whether primary hypothyroidism is associated with nonalcoholic fatty liver disease (NAFLD). We performed a meta-analysis of relevant studies to quantify the magnitude of association between primary hypothyroidism and risk of NAFLD. METHODS: We searched PubMed, Web of Science and Scopus databases from January 2000 to March 2018 using predefined keywords to identify observational cross-sectional, case-control, and longitudinal studies in which NAFLD was diagnosed by imaging or biopsy. Data from selected studies were extracted and meta-analysis was performed using random-effects modeling. RESULTS: A total of 12 cross-sectional and 3 longitudinal studies enrolling 44,140 individuals were included in the final analysis. Hypothyroidism (defined either by self-reported history of hypothyroidism with use of levothyroxine replacement therapy or by presence of abnormal thyroid function tests) was associated with an increased risk of prevalent NAFLD (n = 12 studies; random-effects odds ratio 1.42 [95% confidence interval (CI) 1.15-1.77]; I2 = 51.2%), independently of age, sex, body mass index and other common metabolic risk factors. The magnitude of risk paralleled the underlying severity of NAFLD histology (n = 3 studies; random-effects odds ratio 2.73 [CI 1.90-3.93]; I2 = 0%), and tended to increase across the different definitions used for diagnosing hypothyroidism. Meta-analysis of data from the three longitudinal studies showed that subclinical hypothyroidism was not independently associated with risk of incident ultrasound-defined NAFLD over a median of 5 years (random-effects hazard ratio 1.29 [CI 0.89-1.86]; I2 = 83.9%). Sensitivity analyses did not alter these findings. Funnel plot did not reveal significant publication bias. CONCLUSIONS: This large and updated meta-analysis shows that the presence of variably defined hypothyroidism is significantly associated with the presence and severity of NAFLD. However, the observational design of the eligible studies does not allow for proving causality.

A renal genetic risk score (GRS) is associated with kidney dysfunction in people with type 2 diabetes.

This study aims to investigate whether renal and cardiovascular phenotypes in Italian patients with type 2 diabetes (T2D) could be influenced by a number of disease risk SNPs recently found in genome-wide association studies (GWAS). In 1591 Italian subjects with T2D: (1) 47 SNPs associated to kidney function and/or chronic kidney disease (CKD) and 49 SNPs associated to cardiovascular disease (CVD) risk were genotyped; (2) urinary albumin/creatinine (A/C) ratio, glomerular filtration rate (eGFR) and lipid profile were assessed; (3) a standard electrocardiogram was performed; (4) two genotype risk scores (GRS) were computed (a renal GRS calculated selecting 39 SNPs associated with intermediate traits of kidney damage and a cardiovascular GRS determined selecting 42 SNPs associated to CVD risk phenotypes). After correction for multiple comparisons, the renal GRS was not associated to A/C ratio (p = 0.33), but it was significantly related to decreased eGFR (p = 0.005). No association between the cardiovascular GRS and electrocardiogram was detected. Thus, in Italian patients with T2D a renal GRS might predict the decline in glomerular function, suggesting that the clock of diabetes associated CKD starts ticking long before hyperglycemia. Our data support the feasibility of gene-based prediction of complications in people with T2D.

Left ventricular chamber dilation and filling pressure may help to categorise patients with type 2 diabetes.

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.

Association between nonalcoholic fatty liver disease and colorectal tumours in asymptomatic adults undergoing screening colonoscopy: a systematic review and meta-analysis.

BACKGROUND: It is currently uncertain whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of colorectal tumours. We performed a meta-analysis of relevant observational studies to quantify the magnitude of the association between NAFLD and risk of colorectal adenomas and cancer. METHODS: We searched PubMed, Scopus and Web of Science from January 2000 to November 2017 using pre-defined keywords to identify observational studies of asymptomatic adults undergoing screening colonoscopy, in which NAFLD was diagnosed by imaging or histology. Data from selected studies were extracted and meta-analysis was performed using random-effects modelling. RESULTS: Eleven observational studies (8 cross-sectional and 3 longitudinal) with aggregate data on 91,124 asymptomatic adults (32.1% with NAFLD) of predominantly Asian descent accounting for a total of 14,911 colorectal adenomas and 1684 cancers were included in the final analysis. NAFLD was associated with an increased risk of prevalent colorectal adenomas (n = 7 studies using liver imaging techniques; random-effects odds ratio [OR] 1.28, 95% CI 1.11-1.48; I2 = 82.9% or n = 1 study using liver biopsy; random-effects OR 1.61, 95% CI 0.90-2.89) and cancer (n = 4 studies using liver imaging techniques; random-effects OR 1.56, 95% CI 1.25-1.94; I2 = 65.6% or n = 1 study using liver biopsy; random-effects OR 3.04, 95% CI 1.29-7.18). NAFLD was also associated with an increased risk of incident colorectal adenomas (n = 3 studies; random-effects hazard ratio [HR] 1.42, 95% CI 1.18-1.72; I2 = 0%) and cancer (n = 1 study; random-effects HR 3.08, 95% CI 1.02-9.03). These risks were independent of age, sex, smoking, body mass index and diabetes (or metabolic syndrome). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias. CONCLUSIONS: This meta-analysis of observational studies (involving asymptomatic individuals of predominantly Asian descent undergoing screening colonoscopy) suggests that NAFLD (detected by imaging or biopsy) is independently associated with a moderately increased prevalence and incidence of colorectal adenomas and cancer. However, the observational design of the studies does not allow for proving causality, and the possibility of residual confounding by some unmeasured factors cannot be ruled out. More prospective studies, particularly in European and American individuals, and mechanistic studies are required to better understand the association between NAFLD and colonic carcinogenesis.

Non-alcoholic fatty liver disease and increased risk of all-cause mortality in elderly patients admitted for acute heart failure.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for incident heart failure (HF). It is currently unknown whether NAFLD predicts all-cause mortality in patients admitted for acute HF. We aimed to assess whether NAFLD and its severity (diagnosed by ultrasonography and non-invasive fibrosis biomarkers) were associated with increased all-cause mortality in this particularly high-risk patient population. METHODS: We studied 264 elderly patients, who were consecutively admitted for acute HF to the hospital between years 2013 and 2015, after excluding those with acute myocardial infarction, severe valvular heart diseases, kidney failure, cancer, cirrhosis of any etiology or known chronic liver diseases. Follow-up of patients continued until November 1, 2017. RESULTS: Over a mean follow-up of 23.2 months (range: 1 day-58 months), there were 140 (53%) total deaths. Of these, 24 deaths occurred during the first hospital admission (in-hospital death) and 116 deaths occurred after the hospital discharge during the follow-up period. Patients with NAFLD at hospital admission had significantly higher cumulative incidence rates of in-hospital and post-discharge all-cause mortality (singly or in combination) compared with those without NAFLD. This mortality risk was particularly high among patients with advanced NAFLD fibrosis. In Cox regression analysis, NAFLD was associated with an increased risk of all-cause mortality (adjusted-hazard ratio 1.82, 95% confidence intervals 1.22-2.81, p < 0.005) even after adjustment for established risk factors and potential confounding variables. CONCLUSIONS: NAFLD and its severity were independently associated with increased risk of in-hospital and post-discharge all-cause mortality in elderly patients admitted for acute HF.

Long-Acting GLP-1 Receptor Agonist Exenatide Influence on the Autonomic Cardiac Sympatho-Vagal Balance.

Long-acting glucagon-like peptide 1 receptor agonists are increasingly used to treat type 2 diabetes. An increase of heart rate (HR) has been observed with their use. To elucidate the role of the cardiac sympatho-vagal balance as a possible mediator of the reported increase in HR, we performed power spectral analysis of HR variability (HRV) in patients receiving exenatide extended-release (ER). Twenty-eight ambulatory patients with type 2 diabetes underwent evaluation at initiation of exenatide-ER and thereafter at 3 and at 6 months. To obtain spectral analyses of HRV, a computerized acquisition of 10 minutes of RR electrocardiogram intervals (mean values of ~700 RR intervals) were recorded both in lying and in standing positions. All patients showed a substantial increase of HR both in lying and in standing positions. Systolic blood pressure, body weight, and glycated hemoglobin A1c significantly decreased both at 3 and 6 months compared with basal levels. The low-frequency/high-frequency ratio varied from 3.05 ± 0.4 to 1.64 ± 0.2 (P < 0.001) after 3 months and to 1.57 ± 0.3 (P < 0.001) after 6 months in a lying position and from 4.56 ± 0.8 to 2.24 ± 0.3 (P < 0.001) after 3 months and to 2.38 ± 0.4 (P < 0.001) after 6 months in a standing position compared with basal values, respectively. HR variations, induced by exenatide-ER treatment, do not appear to be related to sympathetic autonomic tone. Of note, we observed a relative increase of vagal influence on the heart.