Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka

Niriella, Madunil Anuk; Kasturiratne, A.; Pathmeswaran, A.; Silva, S T De; Perera, K.R.; Subasinghe, S.; Kodisinghe, S.K.; Piyaratna, T.A.C.L.; Vithiya, K.; Dassanayaka, A.S.; Silva, A P De; Wickramasinghe, Anura; Takeuchi, Fumihiko; Kato, Norihiro; Silva, H J de

doi:10.1007/s12072-018-9916-4

Cited by 67 publications

(65 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PNPLA3 or adiponutrin is an adipose triglyceride lipase in which the rs738409 variant structurally prevents substrate binding [115]. The PNPLA3 rs738409 variant does not modify the disease through changes in insulin sensitivity, metabolic syndrome, body mass index, or dyslipidemia [116][117][118]. This subtype of NASH patients would theoretically not benefit from insulin-sensing PPAR agonists, yet they might do from PPAR agonists with strong β-oxidative capacity.…”

Section: Lean Nashmentioning

confidence: 99%

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Boeckmans

Natale

Rombaut

et al. 2019

Cells

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) affects one-third of the population worldwide, of which a substantial number of patients suffer from non-alcoholic steatohepatitis (NASH). NASH is a severe condition characterized by steatosis and concomitant liver inflammation and fibrosis, for which no drug is yet available. NAFLD is also generally conceived as the hepatic manifestation of the metabolic syndrome. Consequently, well-established drugs that are indicated for the treatment of type 2 diabetes and hyperlipidemia are thought to exert effects that alleviate the pathological features of NASH. One class of these drugs targets peroxisome proliferator-activated receptors (PPARs), which are nuclear receptors that play a regulatory role in lipid metabolism and inflammation. Therefore, PPARs are now also being investigated as potential anti-NASH druggable targets. In this paper, we review the mechanisms of action and physiological functions of PPARs and discuss the position of the different PPAR agonists in the therapeutic landscape of NASH. We particularly focus on the PPAR agonists currently under evaluation in clinical phase II and III trials. Preclinical strategies and how refinement and optimization may improve PPAR-targeted anti-NASH drug testing are also discussed. Finally, potential caveats related to PPAR agonism in anti-NASH therapy are stipulated.

show abstract

Section: Lean Nashmentioning

confidence: 99%

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Boeckmans

Natale

Rombaut

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…Based on the titles and abstracts of 2,627 citations, we initially identified 42 potentially relevant studies from three electronic databases prior to June 30, 2020 (date last searched). After examining the full text of these 42 publications, we excluded 9 studies[15][16][17][18][19][20][21][22][23], because of unsatisfactory inclusion criteria or unsatisfactory outcome measures as specified in the flow diagram. Therefore, 33 longitudinal studies were eligible for inclusion in the meta-analysis and were assessed for quality.The main characteristics of the included studies are summarized insupplementary Table S1.…”

mentioning

confidence: 99%

Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals

Mantovani

Petracca

Beatrice

et al. 2020

Gut

297

211

View full text Add to dashboard Cite

ObjectiveFollow-up studies have shown that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident diabetes, but currently, it is uncertain whether this risk changes with increasing severity of NAFLD. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.DesignWe systematically searched PubMed, Scopus and Web of Science databases from January 2000 to June 2020 using predefined keywords to identify observational studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by imaging techniques or biopsy. Meta-analysis was performed using random-effects modelling.Results33 studies with 501 022 individuals (30.8% with NAFLD) and 27 953 cases of incident diabetes over a median of 5 years (IQR: 4.0–19 years) were included. Patients with NAFLD had a higher risk of incident diabetes than those without NAFLD (n=26 studies; random-effects HR 2.19, 95% CI 1.93 to 2.48; I2=91.2%). Patients with more ‘severe’ NAFLD were also more likely to develop incident diabetes (n=9 studies; random-effects HR 2.69, 95% CI 2.08 to 3.49; I2=69%). This risk markedly increased across the severity of liver fibrosis (n=5 studies; random-effects HR 3.42, 95% CI 2.29 to 5.11; I2=44.6%). All risks were independent of age, sex, adiposity measures and other common metabolic risk factors. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.ConclusionThis updated meta-analysis shows that NAFLD is associated with a ~2.2-fold increased risk of incident diabetes. This risk parallels the underlying severity of NAFLD.

show abstract

“…NAFLD was de ned as the presence of fatty liver in the absence of excessive alcohol consumption. There is no standard de nition of lean NAFLD; however, numerous studies recommended a cut-off point of BMI 23 kg/m 2 for Asian populations, [23][24][25] and the following four groups were assessed: lean without NAFLD, lean with NAFLD, overweight/obese without NAFLD, and overweight/obese with NAFLD. For further NAFLD categorization, a representativenoninvasive score was used to assess the severity of brosis.…”

Section: Endpoint and De Nitionsmentioning

confidence: 99%

Lean Nonalcoholic Fatty Liver Disease and Risk of Incident Diabetes in a Euglycemic Population Receiving Health Checkups: A Cohort Study

Wei

Cheng

Luo

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka

Cited by 67 publications

References 28 publications

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Anti-NASH Drug Development Hitches a Lift on PPAR Agonism

Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals

Lean Nonalcoholic Fatty Liver Disease and Risk of Incident Diabetes in a Euglycemic Population Receiving Health Checkups: A Cohort Study

Contact Info

Product

Resources

About