Glycemic Measures and Development and Resolution of Nonalcoholic Fatty Liver Disease in Nondiabetic Individuals

2020 ◽  
Vol 105 (5) ◽  
pp. 1416-1426
Author(s):  
Bin Wang ◽  
Mian Li ◽  
Zhiyun Zhao ◽  
Shuangyuan Wang ◽  
Jieli Lu ◽  
...  

Abstract Context Type 2 diabetes (T2D) is closely associated with nonalcoholic fatty liver disease (NAFLD); however, evidence regarding the link between blood glucose, especially below the threshold for T2D, and NAFLD is scarce. Objective The objective of this work is to examine the associations of fasting glucose, oral glucose tolerance test (OGTT) 2-hour glucose, and hemoglobin A1c (HbA1c), and changes in these measures with development and resolution of NAFLD in nondiabetic individuals. Methods This longitudinal cohort study comprised 4273 Chinese adults age 40 years or older and free of baseline T2D from 2010 to 2015. Blood sampling was performed during the OGTT test. NAFLD was ascertained by hepatic ultrasonography. Risk ratios (RRs) were calculated using modified Poisson regression models. Results During a mean 4.4 years of follow-up, NAFLD occurred in 573 (17.9%) of the 3209 participants without baseline NAFLD and resolved in 304 (28.6%) of the 1064 participants with baseline NAFLD. OGTT 2-h glucose was positively associated with NAFLD incidence (RR per 1-SD increase: 1.16, 95% CI: 1.08-1.25), whereas fasting (RR: 0.86, 95% CI: 0.78-0.94) and 2-hour glucose (RR: 0.85, 95% CI: 0.77-0.93) were inversely associated with resolution of NAFLD. Glycemic deterioration conferred increased risk of developing NAFLD and decreased likelihood of resolution of NAFLD than maintaining normal glycemic regulation (NGR). The strongest associations were observed for individuals who developed T2D. Meanwhile, baseline or incident NAFLD significantly increased the risk of deterioration in glucose metabolism. Conclusions Increased glycemic levels within the nondiabetic range, as well as progression from NGR to T2D or prediabetes, were adversely associated with development and improvement of NAFLD.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
So-Ryoung Lee ◽  
Kyung-Do Han ◽  
Eue-Keun Choi ◽  
Seil Oh ◽  
Gregory Y. H. Lip

AbstractWe evaluated the association between nonalcoholic fatty liver disease (NAFLD) and incident atrial fibrillation (AF) and analyzed the impact of NAFLD on AF risk in relation to body mass index (BMI). A total of 8,048,055 subjects without significant liver disease who were available fatty liver index (FLI) values were included. Subjects were categorized into 3 groups based on FLI: < 30, 30 to < 60, and ≥ 60. During a median 8-year of follow-up, 534,442 subjects were newly diagnosed as AF (8.27 per 1000 person-years). Higher FLI was associated with an increased risk of AF (hazard ratio [HR] 1.053, 95% confidence interval [CI] 1.046–1.060 in 30 ≤ FLI < 60, and HR 1.115, 95% CI 1.106–1.125 in FLI ≥ 60). In underweight subjects (BMI < 18.5 kg/m2), higher FLI raised the risk of AF (by 1.6-fold in 30 ≤ FLI < 60 and by twofold in FLI ≥ 60). In normal- and overweight subjects, higher FLI was associated with an increased risk of AF, but the HRs were attenuated. In obese subjects, higher FLI was not associated with higher risk of AF. NAFLD as assessed by FLI was independently associated with an increased risk of AF in nonobese subjects with BMI < 25 kg/m2. The impact of NAFLD on AF risk was accentuated in lean subjects with underweight.


Author(s):  
Søren Møller ◽  
Nina Kimer ◽  
Thit Kronborg ◽  
Josephine Grandt ◽  
Jens Dahlgaard Hove ◽  
...  

AbstractNonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.


2020 ◽  
Author(s):  
Limin Wei ◽  
Xin Cheng ◽  
Yulong Luo ◽  
Rongxuan Yang ◽  
Zitong Lei ◽  
...  

Abstract Background: Although recent evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance and an increased risk of diabetes, the association between lean NAFLD and incident diabetes is unclear. This study aimed to investigate whether lean NAFLD and overweight/obese NAFLD have similar or dissimilar effects on the risk of new-onset diabetes.Methods: A longitudinal study was performed in 14,482 euglycemic adults who participated in a health check-up program. Fatty liver was diagnosed by abdominal ultrasonography. The outcome of interest was incident diabetes.Cox proportional hazards regression models were applied to calculate HRs with 95% CIs for future diabetes risk.Results: During the median 6.0 years of follow-up, 356 cases of diabetes occurred. Despite a low probability of hepatic fibrosis indicated by the BAAT score, lean NAFLD was positively associated with an increased risk of diabetes. Moreover, after adjusting for sociodemographic and potential confounders, the fullyadjusted HRs (95% CIs) for incident diabetes between lean NAFLD and overweight/obese NAFLD to the reference (lean without NAFLD) were 2.58 (95% CI 1.68 to 3.97) and 2.52 (95% CI 1.79 to 3.55), respectively. In post hoc analysis, the HR (95% CI) for diabetes comparing lean NAFLD to obese/overweight NAFLD was 1.02 (95% CI 0.68 to 1.54, p = 0.909). The results were robust to challenges in multiple subgroup analyses and appeared to be more pronounced for female participants (p for interaction = 0.005).Conclusions: In this cohort study, lean patients with NAFLD had a risk of incident type 2 diabetes similar to that of overweight/obese ones with NAFLD. These findings suggest that lean NAFLD is not a benign condition. Further investigations are needed to gain a better understanding of the pathogenesis and natural history of NAFLD in lean subjects.


2019 ◽  
Vol 17 ◽  
pp. 205873921983447
Author(s):  
Hongmei Zhang ◽  
Yixin Niu ◽  
Hongxia Gu ◽  
Shuai Lu ◽  
Weikang Su ◽  
...  

The association between white blood cell (WBC) and nonalcoholic fatty liver disease (NAFLD) has been studied before, but whether different WBC subtypes were related to NAFLD was not detailed. The aim of our study was to investigate the relationship between WBC subtypes and NAFLD cross-sectionally and prospectively. The detailed research design has been described previously. At baseline, there were 9930 participants who had complete information, in the end a total of 8079 participants (2588 men and 5491 women) were eventually included in this study. Hepatic ultrasound examination was performed on each participant at baseline and at the end of follow-up. Alcohol abuse and hepatitis were excluded. WBC subtypes and other serum indices were measured at baseline. We found that the total WBC, neutrophil, and lymphocyte counts were independently associated with the prevalence and incidence of NAFLD. After multiple adjustments for age, gender, body mass index (BMI), insulin, HOMA-IR, TG, TC, LDL, and HDL, increased odds ratios (ORs) for new onset NAFLD were observed from the 1st to the 4th quartiles of WBC, neutrophil, and lymphocyte (all P < 0.001 for trend). In conclusion, total WBC counts, neutrophils, and lymphocytes were all independent risk factors for NAFLD in the rural Chinese population. The association was independent of insulin resistance.


2020 ◽  
Vol 105 (10) ◽  
pp. e3575-e3585
Author(s):  
Ayesha Monga Kravetz ◽  
Todd Testerman ◽  
Brittany Galuppo ◽  
Joerg Graf ◽  
Bridget Pierpont ◽  
...  

Abstract Context Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, affecting approximately 3 in 10 obese children worldwide. Objective We aimed to investigate the potential relationship between gut microbiota and NAFLD in obese youth, while considering the role of PNPLA3 rs738409, a strong genetic contributor to NAFLD. Design In this cross-sectional study, participants completed an abdominal magnetic resonance imaging to measure hepatic fat fraction (HFF), oral glucose tolerance test, and PNPLA3 rs738409 genotyping. Fecal samples were collected to analyze the V4 region of the 16S rRNA gene for intestinal bacteria characterization. Setting Yale Pediatric Obesity Clinic. Participants Obese youth (body mass index &gt;95th percentile) with NAFLD (HFF ≥5.5%; n = 44) and without NAFLD (HFF &lt;5.5%; n = 29). Main Outcome Measure Shannon-Wiener diversity index values and proportional bacterial abundance by NAFLD status and PNPLA3 genotype. Results Subjects with NAFLD had decreased bacterial alpha-diversity compared with those without NAFLD (P = 0.013). Subjects with NAFLD showed a higher Firmicutes to Bacteroidetes (F/B) ratio (P = 0.019) and lower abundance of Bacteroidetes (P = 0.010), Prevotella (P = 0.019), Gemmiger (P = 0.003), and Oscillospira (P = 0.036). F/B ratio, Bacteroidetes, Gemmiger, and Oscillospira were associated with HFF when controlling for group variations. We also observed an additive effect on HFF by PNPLA3 rs738409 and Gemmiger, and PNPLA3 rs738409 and Oscillospira. Conclusions Obese youth with NAFLD have a different gut microbiota composition than those without NAFLD. These differences were still statistically significant when controlling for factors associated with NAFLD, including PNPLA3 rs738409.


2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P &lt; 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P &lt; 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Wei-Fan Hsu ◽  
Lee-Yan Sheen ◽  
Hung-Jen Lin ◽  
Hen-Hong Chang

Nonalcoholic fatty liver disease (NAFLD) is a disease of attention because of increase in prevalence from 20% to 41%. The clinical and pathological conditions in patients with NAFLD range from steatosis alone to nonalcoholic steatohepatitis (NASH) with or without fibrosis to hepatic cancer. In the United States, NAFLD was the second-leading indication for liver transplant between 2004 and 2013. Although imaging studies such as magnetic resonance elastography and the use of diagnostic panels and scoring systems can provide a fairly accurate diagnosis of NAFLD, there are few treatment options for patients with mild to moderate disease other than lifestyle modification. Many of the currently used medical treatments have been shown to cause severe side effects and some have been shown to be associated with increased risk for certain types of cancer. In recent years, a number of traditional Chinese herbal treatments have been examined for their potential uses as treatment for NAFLD. In this review, we provide a general overview of NAFLD and a survey of Western pharmacologic drugs currently used to treat the disease as well as the results of recent studies on the effectiveness of traditional Chinese herbal remedies for managing nonalcoholic fatty liver disease.


2016 ◽  
Vol 34 (Suppl. 1) ◽  
pp. 3-10 ◽  
Author(s):  
Arianna Mazzotti ◽  
Maria Turchese Caletti ◽  
Anna Simona Sasdelli ◽  
Lucia Brodosi ◽  
Giulio Marchesini

Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). Key Messages: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease. Conclusions: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies.


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