Data are limited on the epidemiological implications of the recent change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction‐associated fatty liver disease (MAFLD). ...We therefore performed a cross‐sectional study of adults recruited in the 2017‐2018 National Health and Nutrition Examination Survey, a representative sample of the general US population. The prevalence of NAFLD and MAFLD based on controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) obtained through vibration‐controlled transient elastography (VCTE) were 37.1% (95% CI 34.0‐40.4) and 39.1% (95% CI 36.3‐42.1), respectively, with higher rates among Hispanic individuals. Agreement between the two definitions was high (Cohen's κ 0.92). Patients with NAFLD and MAFLD also showed similar risk of advanced liver fibrosis (7.5% and 7.4% respectively). Our results suggest that the recent change in diagnostic criteria did not affect the prevalence of the condition in the general United States population.
Several studies reported an association between nonalcoholic fatty liver disease (NAFLD) and the risk of incident hypertension. The objective of this systematic review and meta-analysis was to obtain ...a precise and reliable estimate of the nature and magnitude of this association. We systematically searched Ovid-MEDLINE up to March 2021 for observational studies in which NAFLD was diagnosed in adults using blood-based panels, imaging techniques or liver biopsy and with a follow-up ≥1 year. Measures of association from individual studies were meta-analyzed using random-effects models. Of the 1108 titles initially scrutinized, we included 11 cohort studies with data on 390 348 participants (52% male) and a mean follow-up of 5.7 years. In the overall analysis, NAFLD was associated with a moderately increased risk of incident hypertension (hazard ratio 1.66; 95% confidence interval (CI), 1.38-2.01; test for overall effect z = 5.266; P < 0.001). There was significant heterogeneity among the studies (P < 0.001). Sensitivity analyses showed that estimates were not affected by geographical location, duration of follow-up and adjustment for baseline blood pressure values. On the other hand, the magnitude of the association was lower in studies that adjusted for baseline adiposity compared with those that did not, explaining part of the observed heterogeneity. No significant publication bias was detected by funnel plot analysis and Egger's and Begg's tests. This large meta-analysis indicates that NAFLD is associated with a ~1.6-fold increased risk of developing hypertension. Further studies are needed to investigate the role of NAFLD severity in terms of inflammation and fibrosis on incident hypertension.
Aims
Soluble Klotho (s-Klotho) is associated with chronic kidney disease (CKD) and aging, but little is known on its relationship with chronic micro- and macro-vascular complications of type 2 ...diabetes and glycemic control. Here, we evaluate the association between s-Klotho levels, glycemic control and renal function in patients with type 2 diabetes (T2D).
Methods
This is a cross-sectional study including 2989 patients with T2D and available s-Klotho measurements from the 2007–2016 cycles of the National Health and Nutrition Examination Survey (mean ± SE, age: 60.0 ± 0.2 years, BMI 33.3 ± 0.2 kg/m
2
, 46.7 ± 1.3% female). Determination of s-Klotho concentrations was performed with a sandwich ELISA test.
Results
Patients with higher s-Klotho levels were younger, more frequently female and had a lower prevalence of CKD and higher HbA1c levels. In multivariable linear regression models adjusting for age, race-ethnicity and BMI, both estimated glomerular filtration rate (B = 2.21, 95% CI 1.41–3.01,
p
< 0.001) and hemoglobin A1c (B = 37.38, 95% CI 28.91–45.86,
p
< 0.001) were positively associated with s-Klotho, while no significant association was found with cardiovascular disease. Results were confirmed when analyses were performed in men and women separately. No significant differences were identified between patients with an albuminuric or non-albuminuric CKD phenotype.
Conclusions
s-Klotho levels are dependent on kidney function and glycemic control in patients with T2D. Additional studies elucidating the mechanisms linking glycemic control and s-Klotho levels and exploring their predictive ability of clinically meaningful outcomes in patients with diabetes are needed.
An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, ...most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m
. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89-3.29; test for overall effect z = 6.475,
< 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29-3.05; test for overall effect z = 3.113,
= 0.002). Neither analysis showed significant heterogeneity (I
= 0% and I
= 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease.
It is still debated whether prolonged use of proton pump inhibitors (PPIs) might affect metabolic health.
To investigate the relationship between prolonged use of PPIs and the risk of developing ...diabetes.
We performed a case-control study nested into a cohort of 777 420 patients newly treated with PPIs between 2010 and 2015 in Lombardy, Italy. A total of 50 535 people diagnosed with diabetes until 2020 were matched with an equal number of controls that were randomly selected from the cohort members according to age, sex, and clinical status. Exposure to treatment with PPIs was assessed in case-control pairs based on time of therapy. A conditional logistic regression model was fitted to estimate the odds ratios and 95% CIs for the exposure-outcome association, after adjusting for several covariates. Sensitivity analyses were performed to evaluate the robustness of our findings.
Compared with patients who used PPIs for < 8 weeks, higher odds of diabetes of 19% (95% CI, 15-24), 43% (38-49), and 56% (49-64) were observed among those who used PPIs for between 8 weeks and 6 months, 6 months and 2 years, and > 2 years, respectively. The results were consistent when analyses were stratified according to age, sex, and clinical profile, with higher odds ratios being found in younger patients and those with worse clinical complexity. Sensitivity analyses revealed that the association was consistent and robust.
Regular and prolonged use of PPIs is associated with a higher risk of diabetes. Physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use.
Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events ...in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials.
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD) affects ~70% of patients with type 2 diabetes (T2D), with ~20% showing ...signs of advanced liver fibrosis. Patients with T2D are at an increased risk of developing cirrhosis, liver failure, and hepatocellular carcinoma and their liver-related mortality is doubled compared with non-diabetic individuals. Nonetheless, the condition is frequently overlooked and disease awareness is limited both among patients and among physicians. Given recent epidemiological evidence, clinical practice guidelines recommend screening for NAFLD/MASLD and advanced liver fibrosis in patients with T2D. While many drugs are currently being tested for the treatment of NAFLD/MASLD, none of them have yet received formal approval from regulatory agencies. However, several classes of antidiabetic drugs (namely pioglitazone, sodium-glucose transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and multi-agonists) have shown favorable effects in terms of liver enzymes, liver fat content and, in some occasions, on histologic features such as inflammation and fibrosis. Therefore, diabetologists have the opportunity to actively treat NAFLD/MASLD, with a concrete possibility of changing the natural history of the disease. In the present narrative review, we summarize evidence and clinical recommendations for NAFLD/MAFLD screening in the setting of T2D, as well as on the effect of currently available glucose-lowering drugs on hepatic endpoints.
Purpose
Obesity represents a well-known risk factor for metabolic-dysfunction associated fatty liver disease (MAFLD) and its progression towards cirrhosis. The aim of this study is to estimate the ...proportion of potential candidates to a bariatric surgery intervention that has an elevated liver stiffness on vibration-controlled transient elastography (VCTE).
Materials and Methods
This is a cross-sectional study performed using data obtained during the 2017–2018 cycle of the National Health and Nutrition Examination Survey. Potential candidates for a bariatric surgery intervention from the general US population were identified by applying criteria from international guidelines. All included participants were evaluated by VCTE. A controlled attenuation parameter (CAP) value ≥ 288 dB/m was considered indicative of steatosis while liver stiffness measurement (LSM) was considered elevated if ≥ 9.7 kPa. Multivariable logistic regression models were fitted to identify independent predictors of both outcomes.
Results
A total of 434 participants were included (mean age 42.9 ± 0.6 years; 54.4% women). Among them, 76.7% (95% CI 71.7–81.0) had steatosis, while 23.1% (95% CI 17.8–29.3) had an elevated LSM. Male sex, older age, γ-glutamyltranspeptidase levels, and body mass index (BMI) were independent predictors of steatosis, while BMI was the only independent predictor of elevated LSM. Non-Hispanic black participants were protected from both outcomes, while other ethnicities were not.
Conclusion
The prevalence of elevated LSM is high in potential candidates for a bariatric surgery intervention. Accurate screening for occult advanced liver disease might be indicated in this patient population.
Graphical abstract
Aims
Liver steatosis, a typical finding in patients with type 2 diabetes (T2D), can lead to cirrhosis and hepatocellular carcinoma. The aim of the present study is to estimate the awareness of liver ...disease among patients with T2D and whether it differs according to the degree of liver fibrosis estimated by transient elastography (TE).
Methods
This is a population-based cross-sectional study. We included all patients with T2D that participated in the 2017–2018 cycle of the National Health and Nutrition Examination Survey and underwent a TE examination. Presence of liver steatosis and fibrosis was assessed by the median values of controlled attenuation parameter and liver stiffness measurement, respectively.
Results
Among the 825 patients included in the analysis, 8.1% (95% CI 5.1%-12.7%) of patients with steatosis were aware of having a liver condition. Even if awareness increased proportionally with increasing severity of organ damage, it remained limited even among patients with advanced fibrosis (17.9%, 95% CI 8.8%-33.3%).
Conclusions
Despite increasing evidence of a frequent hepatic involvement associated with poor prognosis, awareness of suffering of advanced liver disease in patients with T2D is remarkably low, likely reflecting little recognition also among the team of health care professionals.
The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is uncertain. We conducted a ...systematic review and meta‐analysis of published prospective observational studies evaluating the associations of baseline levels of GGT and ALT with risk of overall (incidence and/or mortality) and site‐specific cancers. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, reference lists of relevant studies to April 2014 and email contact with investigators. Study specific relative risks (RRs) were meta‐analyzed using random effects models. Fourteen cohort studies with data on 1.79 million participants and 57,534 cancer outcomes were included. Comparing top versus bottom thirds of baseline circulating GGT levels, pooled RRs (95% confidence intervals) were 1.32 (1.15–1.52) for overall cancer, 1.09 (0.95–1.24) for cancers of the breast and female genital organs, 1.09 (1.02–1.16) for cancers of male genital organs, 1.94 (1.35–2.79) for cancers of digestive organs and 1.33 (0.94–1.89) for cancers of respiratory and intrathoracic organs. For ALT, corresponding RRs for overall cancer were 0.96 (0.94–0.99) and 1.65 (1.52–1.79) in European and Asian populations, respectively. There was an increased risk of cancers of the digestive organs 2.44 (1.23–4.84). The pooled RR for overall cancer per 5 U/L increment in GGT levels was 1.04 (1.03–1.05). Available observational data indicate a positive log‐linear association of GGT levels with overall cancer risk. The positive association was generally evident for site‐specific cancers. There are geographical variations in the association of ALT and overall cancer.
What's new?
Emerging evidence indicates that the level of gamma glutamyltransferase (GGT) and the level of alanine aminotransferase (ALT)–two markers of liver dysfunction–may each be linked to cancer risk. So far, the prospective evidence on their associations has been inconsistent. However, in the review presented here, GGT level was found to be positively and log‐linearly associated with overall cancer risk. The positive association was consistent for site‐specific cancers. As for ALT, there were geographical variations in its association with overall cancer, and ALT was also found to be associated with an increased risk of cancers of digestive organs.
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