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.

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.

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.

Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis.

BACKGROUND & AIMS: There have been many studies of the effects of non-alcoholic fatty liver disease (NAFLD) and the risk of cardiovascular disease (CVD), but these have produced conflicting results. We performed a meta-analysis of these studies to quantify the magnitude of the association between NAFLD (and NAFLD severity) and risk of CVD events. METHODS: We searched PubMed, Google scholar, and Web of Science databases using terms "NAFLD", "cardiovascular events", "cardiovascular mortality", "prognosis" and their combinations to identify observational studies published through January 2016. We included only observational studies conducted in adults >18years and in which NAFLD was diagnosed on imaging or histology. Data from selected studies were extracted and meta-analysis was then performed using random effects modelling. RESULTS: A total of 16 unique, observational prospective and retrospective studies with 34,043 adult individuals (36.3% with NAFLD) and approximately 2,600 CVD outcomes (>70% CVD deaths) over a median period of 6.9years were included in the final analysis. Patients with NAFLD had a higher risk of fatal and/or non-fatal CVD events than those without NAFLD (random effect odds ratio [OR] 1.64, 95% CI 1.26-2.13). Patients with more 'severe' NAFLD were also more likely to develop fatal and non-fatal CVD events (OR 2.58; 1.78-3.75). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias. CONCLUSIONS: NAFLD is associated with an increased risk of fatal and non-fatal CVD events. However, the observational design of the studies included does not allow to draw definitive causal inferences. LAY SUMMARY: The data on whether NAFLD by itself is associated with increased cardiovascular events and death remains an issue of debate. The findings of this updated and large meta-analysis of observational studies indicate that NAFLD is significantly associated with an increased risk of fatal and non-fatal cardiovascular events. However, the observational design of the studies included does not allow us to prove that NAFLD causes cardiovascular disease. Clinicians who manage patients with NAFLD should not focus only on liver disease but should also consider the increased risk of cardiovascular disease and undertake early, aggressive risk factor modification.

Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries.

BACKGROUND: Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. METHODS AND RESULTS: The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. CONCLUSIONS: Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Multiple causes of death analysis of chronic diseases: the example of diabetes.

BACKGROUND: Identifying a single disease as the underlying cause of death (UCOD) is an oversimplification of the clinical-pathological process leading to death. The multiple causes of death (MCOD) approach examines any mention of a disease in death certificates. Taking diabetes as an example, the study investigates: patterns of death certification, differences in mortality figures based on the UCOD and on MCOD, factors associated to the mention of diabetes in death certificates, and potential of MCOD in the analysis of the association between chronic diseases. METHODS: The whole mortality archive of the Veneto Region-Italy was extracted from 2008 to 2010. Mortality rates and proportional mortality were computed for diabetes as the UCOD and as MCOD. The position of the death certificate where diabetes was mentioned was analyzed. Conditional logistic regression was applied with chronic liver diseases (CLD) as the outcome and diabetes as the exposure variable. A subset of 19,605 death certificates of known diabetic patients (identified from the archive of exemptions from medical charges) was analyzed, with mention of diabetes as the outcome and characteristics of subjects as well as other diseases reported in the certificate as predictors. RESULTS: In the whole mortality archive, diabetes was mentioned in 12.3 % of death certificates, and selected as the UCOD in 2.9 %. The death rate for diabetes as the UCOD was 26.8 × 10(5) against 112.6 × 10(5) for MCOD; the UCOD/MCOD ratio was higher in males. The major inconsistencies of certification were entering multiple diseases per line and reporting diabetes as a consequence of circulatory diseases. At logistic regression the mention of diabetes was associated with the mention of CLD (mainly non-alcohol non-viral CLD). In the subset of known diabetic subjects, diabetes was reported in 52.1 %, and selected as the UCOD in 13.4 %. The probability of reporting diabetes was higher with coexisting circulatory diseases and renal failure and with long duration of diabetes, whereas it was lower in the presence of a neoplasm. CONCLUSIONS: The use of MCOD makes the analysis of mortality data more complex, but conveys more information than usual UCOD analyses.

Mortality from chronic liver diseases in diabetes.

OBJECTIVES: Mortality from chronic liver diseases (CLDs) is increased in diabetes, but little is known about the etiology. The aim of this study was to assess mortality rates from CLD by etiology in known diabetic subjects living in the Veneto Region, Northern Italy. METHODS: A total of 167,621 diabetic subjects, aged 30-89 years (54.6% men), were identified in the year 2007 and their vital status was assessed between 2008 and 2010. Standardized mortality ratios (SMR) with 95% confidence intervals (CIs) were computed with regional mortality rates as reference. The underlying cause of death and all comordidities reported on the certificate were scrutinized in order to identify CLD deaths and their main etiologies. The latter were grouped into the following three categories: (i) virus-related, (ii) alcohol-related, and (iii) non-virus, non-alcohol-related (mainly represented by nonalcoholic fatty liver disease, NAFLD). RESULTS: Analyses were based upon 473,374 person-years of follow-up and 17,134 deaths. We observed an increased risk of dying from CLD in diabetic subjects with an SMR of 2.47 (95% CI=2.19-2.78) in men and 2.70 (2.24-3.23) in women. SMRs were 2.17 (1.90-2.47), 2.25 (1.98-2.54), and 2.86 (2.65-3.08) for virus-related, alcohol-related, and non-virus, non-alcohol-related CLD, respectively. CONCLUSIONS: Diabetic patients have a twofold to threefold higher risk of dying of CLD, mainly associated with a non-virus and non-alcohol-related etiology, which is largely attributable to NAFLD. An early diagnosis and treatment of NAFLD, if any, may have a beneficial clinical impact on the survival of diabetic patients.

Hemostatic and fibrinolytic abnormalities in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility, affecting up to 10% of women of reproductive age. This syndrome was first described in 1935 when American gynecologists Stein and Leventhal associated the presence of ovarian cysts with anovulation, obesity, and hirsutism. For many years, the effects of PCOS on coagulation and fibrinolysis have remained largely unexplored. This review summarizes current knowledge of the effects of PCOS on coagulation and fibrinolysis, and the putative mechanisms by which PCOS may contribute to the development of coagulation and fibrinolytic disorders. To date, there is relatively strong evidence suggesting that PCOS is associated with increased platelet aggregation and decreased plasma fibrinolytic activity. However, whether these hemostatic disorders are linked to the abnormal hormonal system in PCOS remains to be elucidated. Moreover, it should be emphasized that PCOS is a heterogeneous endocrine condition, and that the number of published studies is limited, the sample size of most of these studies is relatively small, and the selection of control subjects has not been always appropriate. Furthermore, well-designed studies on larger cohorts of carefully characterized PCOS patients are needed to provide more comprehensive information on this issue.

Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial).

UNLABELLED: Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease (NAFLD), which is extremely common in people with type 2 diabetes, no intervention studies have compared the effects of aerobic (AER) or resistance (RES) training on hepatic fat content in type 2 diabetic subjects with NAFLD. In this randomized controlled trial, we compared the 4-month effects of either AER or RES training on insulin sensitivity (by hyperinsulinemic euglycemic clamp), body composition (by dual-energy X-ray absorptiometry), as well as hepatic fat content and visceral (VAT), superficial (SSAT), and deep (DSAT) subcutaneous abdominal adipose tissue (all quantified by an in-opposed-phase magnetic resonance imaging technique) in 31 sedentary adults with type 2 diabetes and NAFLD. After training, hepatic fat content was markedly reduced (P < 0.001), to a similar extent, in both the AER and the RES training groups (mean relative reduction from baseline [95% confidence interval] -32.8% [-58.20 to -7.52] versus -25.9% [-50.92 to -0.94], respectively). Additionally, hepatic steatosis (defined as hepatic fat content >5.56%) disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group). Insulin sensitivity during euglycemic clamp was increased, whereas total body fat mass, VAT, SSAT, and hemoglobin A1c were reduced comparably in both intervention groups. CONCLUSION: This is the first randomized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD.

Antidromic sensory nerve conduction study of the digital branches of the medial plantar nerve: a novel method to detect early diabetic sensory axonal polyneuropathy.

INTRODUCTION: Distal sensory neuropathy is the most common form of diabetic neuropathy. We developed a novel antidromic technique for assessment of distal nerve function for early diagnosis of diabetic neuropathy. METHODS: Diabetic and control groups underwent standard and more distal sensory nerve conduction studies (NCS); sensory nerve action potentials (SNAPs) of the proper digital branches of the medial plantar nerve were recorded with our method after stimulation at the sole and recording from digits I and II. RESULTS: Comparison between controls and diabetics showed a statistically significant difference in mean SNAP amplitudes for all nerves tested. A higher percentage of abnormal SNAPs was obtained with our technique than with either conventional or more distal NCS in all patients. CONCLUSIONS: As compared with clinical evaluation and other NCS, our antidromic stimulation was the most sensitive method to detect abnormal sensory nerve conduction in symptomatic and asymptomatic diabetic patients.

Association of nonalcoholic fatty liver disease with QTc interval in patients with type 2 diabetes.

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.

Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study.

BACKGROUND: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. METHODS: Serial (3-5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52 ± 0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine. RESULTS: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Median and interquartile range were 7.78 (7.04-8.56) and 7.49 (6.81-8.31), respectively, for HbA1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke, whereas both correlated with any lower limb vascular event and HbA1c-SD alone with ulceration/gangrene. All these associations were independent of known CVD risk factors and microvascular complications (DR and CKD). CONCLUSIONS: In patients with type 2 diabetes, HbA1c variability has not a major impact on macrovascular complications, at variance with average HbA1c, an opposite finding as compared with microvascular disease, and particularly nephropathy. TRIAL REGISTRATION: ClinicalTrials.Gov NCT00715481.

Non-alcoholic fatty liver disease is associated with an increased prevalence of atrial fibrillation in hospitalized patients with type 2 diabetes.

NAFLD (non-alcoholic fatty liver disease) and AF (atrial fibrillation) are two pathological conditions that are highly prevalent in developed countries and share multiple risk factors. The relationship between NAFLD and AF in Type 2 diabetes is currently unknown. We studied a hospital-based sample of 702 patients with Type 2 diabetes discharged from our Division of Endocrinology during 2007-2011. The diagnosis of AF was confirmed in affected participants on the basis of ECGs and medical history by experienced cardiologists. NAFLD was defined by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. Of the 702 hospitalized patients included in the study, 514 (73.2%) of them had NAFLD and 85 (12.1%) had persistent or permanent AF. NAFLD was associated with an increased risk of prevalent AF {OR (odds ratio), 3.04 [95% CI (confidence interval), 1.54-6.02]; P<0.001}. Adjustments for age, sex, systolic BP (blood pressure), HbA1c, (glycated haemoglobin), estimated GFR (glomerular filtration rate), total cholesterol, electrocardiographic LVH (left ventricular hypertrophy), COPD (chronic obstructive pulmonary disease), and prior history of HF (heart failure), VHD (valvular heart disease) or hyperthyroidism did not attenuate the association between NAFLD and AF [adjusted OR, 5.88 (95% CI, 2.72-12.7); P<0.001]. In conclusion, our results show that ultrasound-diagnosed NAFLD is strongly associated with an increased prevalence of persistent or permanent AF in patients with Type 2 diabetes, independently of several clinical risk factors for AF. The potential impact of NAFLD on AF deserves particular attention, especially with respect to the implications for screening and surveillance strategies in the growing number of patients with NAFLD.

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.

Risk of chronic kidney disease in patients with non-alcoholic fatty liver disease: is there a link?

Non-alcoholic fatty liver disease (NAFLD) has emerged as a growing public health problem worldwide. Increasing recognition of the importance of NAFLD and its association with the features of the metabolic syndrome has stimulated an interest in its putative role in the development and progression of chronic kidney disease (CKD). Accumulating evidence suggests that NAFLD and CKD share many important cardio-metabolic risk factors and common pathogenetic mechanisms and that NAFLD is associated with an increased prevalence and incidence of CKD. This association appears to be independent of obesity, hypertension, and other potentially confounding factors, and it occurs both in patients without diabetes and in those with diabetes. Although further research is needed to establish a definitive conclusion, these observations raise the possibility that NAFLD is not only a marker of CKD but also might play a part in the pathogenesis of CKD, possibly through the systemic release of several pro-inflammatory/pro-coagulant mediators from the steatotic/inflamed liver or through the contribution of NAFLD itself to insulin resistance and atherogenic dyslipidemia. However, given the heterogeneity and small number of observational longitudinal studies, further research is urgently required to corroborate the prognostic significance of NAFLD for the incidence of CKD, and to further elucidate the complex and intertwined mechanisms that link NAFLD and CKD. If confirmed in future large-scale prospective studies, the potential adverse impact of NAFLD on kidney disease progression will deserve particular attention, especially with respect to the implications for screening and surveillance strategies in the growing number of patients with NAFLD.

Hemostatic disorders in type 1 diabetes mellitus.

This review summarizes current knowledge of the adverse effects of type 1 diabetes mellitus on coagulation and fibrinolysis. Although further larger studies are needed to provide more definitive information, patients with type 1 diabetes exhibit a proinflammatory/procoagulant condition deriving from increased platelet adhesiveness, activation of the coagulation system, and decreased plasma fibrinolytic potential. This review also focuses on recent data from large prospective studies suggesting a strong association between procoagulant imbalance and development of chronic vascular complications in people with type 1 diabetes. It is likely that a greater appreciation of the intimate interactions between endothelial integrity, coagulation and fibrinolytic factors, and platelets in type 1 diabetes will provide a greater understanding of the risk of developing cardiovascular disease and microvascular complications such as nephropathy and retinopathy in this patient population.

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.

Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes.

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.