Several studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes ...remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.
We collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (
≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.
A total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio HR 2.22, 95% CI 1.84-2.60;
= 79.2%). Patients with more "severe" NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (
= 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (
= 1 study; random-effects HR 4.74, 95% CI 3.54-5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy.
NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.
Sommario
In Italia vivono circa 4 milioni di persone con il diabete e ogni anno ci sono circa 350 mila nuove diagnosi. Le persone con diabete ricevono prescrizioni di farmaci, esami di laboratorio e ...strumentali e richiedono ricoveri ospedalieri più spesso delle persone senza il diabete. Il diabete è gravato da aumentata mortalità e accorcia la vita, soprattutto nelle persone di media età. La qualità della cura nelle persone con diabete è subottimale, soprattutto fra chi non è assistito nei centri diabetologici (che, peraltro, rappresentano dei luoghi “salvavita”). Il diabete contribuisce fortemente alla spesa sanitaria e comporta ingenti spese, non tutte specificamente sanitarie. Nonostante tutto questo e nonostante leggi nazionali e regionali, documenti di indirizzo nazionali e regionali, PDTA regionali e locali, promesse e proponimenti di varia provenienza, la pandemia diabete non riceve le attenzioni che merita.
Recent studies examined the prognostic impact of nonalcoholic fatty liver disease (NAFLD) on the risk of incident chronic kidney disease (CKD). However, the extent to which NAFLD may confer risk of ...incident CKD is uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident CKD.
We searched PubMed, Scopus and Web of Science from January 1, 2000 to August 31, 2017 using pre-defined keywords to identify large observational cohort studies with a follow-up duration of at least 1year, in which NAFLD was diagnosed by biochemistry, fatty liver index or ultrasonography. No studies with biopsy-proven NAFLD were available for the analysis. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling.
A total of 9 observational studies with 96,595 adult individuals (34.1% with NAFLD) of predominantly Asian descent, and 4653 cases of incident CKD stage ≥3 (i.e., defined as occurrence of estimated glomerular filtration rate<60ml/min/1.73m2, with or without accompanying overt proteinuria) over a median period of 5.2years were included in the final analysis. Patients with NAFLD had a significantly higher risk of incident CKD than those without NAFLD (random-effects hazard ratio HR 1.37, 95% CI 1.20–1.53; I2=33.5%). Patients with more ‘severe’ NAFLD (according to ultrasonography and non-invasive fibrosis markers) were also more likely to develop incident CKD (n=2 studies; random-effects HR 1.50, 95% CI 1.25–1.74; I2=0%); this risk appeared to be even greater among those with ultrasound-diagnosed NAFLD and a high-intermediate NAFLD fibrosis score (n=1 study; random-effects HR 1.59, 95% CI 1.31–1.93). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias.
This largest and most updated meta-analysis to date shows that NAFLD (detected by biochemistry, fatty liver index or ultrasonography) is associated with a nearly 40% increase in the long-term risk of incident CKD. However, the observational nature of the eligible studies does not allow for proving causality. Our findings pave the way for future large, prospective, histologically-based studies.
MicroRNAs (miRNAs) have been implicated in the epigenetic regulation of key metabolic, inflammatory, and antiangiogenic pathways in type 2 diabetes (DM) and may contribute to common disease ...complications.
In this study, we explore plasma miRNA profiles in patients with DM.
Total RNA was extracted from plasma samples of the prospective population-based Bruneck study. A total of 13 candidate miRNAs identified by microarray screening and miRNA network inference were quantified by quantitative PCR in all diabetic patients of the Bruneck study and age- and sex-matched controls (1995 evaluation, n=80 each). Quantitative PCR assessment revealed lower plasma levels of miR-20b, miR-21, miR-24, miR-15a, miR-126, miR-191, miR-197, miR-223, miR-320, and miR-486 in prevalent DM, but a modest increase of miR-28-3p. Findings emerged as robust in multivariable analysis and were independent of the standardization procedure applied. For endothelial miR-126, results were confirmed in the entire Bruneck cohort (n=822) in univariate (odds ratio 95% confidence interval, 0.38 0.26 to 0.55; P=2.72 × 10(-7)) and multivariate analyses (0.57 0.37 to 0.86; P=0.0082). Importantly, reduced miR-15a, miR-29b, miR-126, miR-223, and elevated miR-28-3p levels antedated the manifestation of disease. Most differences in miRNA levels were replicated in plasma obtained from hyperglycemic Lep(ob) mice. High glucose concentrations reduced the miR-126 content of endothelial apoptotic bodies. Similarly in patients with DM, the reduction of miR-126 was confined to circulating vesicles in plasma.
We reveal a plasma miRNA signature for DM that includes loss of endothelial miR-126. These findings might explain the impaired peripheral angiogenic signaling in patients with DM.
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.
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).
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.
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.
This study examined predictors of the annual decline in estimated GFR (eGFR) in patients with type 2 diabetes and preserved kidney function.
In a prospective, observational cohort study, 1682 ...individuals with type 2 diabetes and baseline eGFR ≥60 ml/min per 1.73 m(2) (as estimated by the Chronic Kidney Disease Epidemiology Collaboration equation) were followed for 10 years. Linear regression was used to estimate participants' changes in eGFR over time.
During follow-up, 263 (15.6%) individuals had a rapid eGFR decline defined as >4.0% per year. Average eGFR decline was -5.8 ± 3 and -0.6 ± 2 ml/min per 1.73 m(2) per year in rapid decliners and nondecliners, respectively. Compared with normotensive, normoalbuminuric patients (-0.2 ± 0.2 ml/min per 1.73 m(2) per year), those with hypertension (-1.0 ± 0.1 ml/min per 1.73 m(2) per year), hemoglobin A(1c)≥7% (-1.0 ± 0.1 ml/min per 1.73 m(2) per year), longer diabetes duration (-1.0 ± 0.1 ml/min per 1.73 m(2) per year), obesity (-1.2 ± 0.1 ml/min per 1.73 m(2) per year), insulin treatment (-1.5 ± 0.1 ml/min per 1.73 m(2) per year), microalbuminuria (-1.3 ± 0.2 ml/min per 1.73 m(2) per year), or macroalbuminuria (-2.7 ± 0.4 ml/min per 1.73 m(2) per year) had significantly faster age-adjusted annual eGFR declines. Multivariable linear regression analyses revealed that albuminuria (P<0.001) was the strongest predictor of annual eGFR decline. Other independent predictors of annual eGFR decline were older age, hypertension, insulin treatment, and lower baseline eGFR.
Annual eGFR decline is predicted by multiple modifiable risk factors in patients with type 2 diabetes and preserved kidney function.
An overwhelming number of meta-analyses and reviews are published by scientific journals. In part this may reflect some preference of editors and publishers for these types of papers, which are more ...frequently cited and can increase the impact factor of their journals. Meta-analyses and reviews are also attractive for investigators looking for a greater chance of having successful publications with several citations, and therefore an improved personal
h
-index. This greater ‘promise of success’ might have a deleterious effect on the intellectual maturation of investigators, particularly early career investigators, who might neglect original research and concentrate their efforts on meta-analyses and reviews. However, while meta-analyses and reviews are useful for emphasising data and disseminating concepts, progress in science requires original ideas, original experiments and original papers. ‘Analysts’ and ‘novelists’ are welcome, but ‘scientists’ are indispensable.
Context/Objective:
Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each ...patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women.
Patients/Design:
A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique.
Results:
Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030).
Conclusions:
There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group.
Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are ...fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion–extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G × 5 mm and 32 G × 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G × 5 mm needle and p-value < 0.001 for 32 G × 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion–extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients.
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