Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety

Mills, Elizabeth; Brown, K Paige D; Smith, Jennifer D.; Vang, Phillip W; Trotta, K.

doi:10.1177/2042018817741852

Cited by 29 publications

(24 citation statements)

References 38 publications

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“…Even though the studied cohort exhibited a high burden of metabolic comorbidities at the time of liver biopsy, drug therapy according to current guidelines on the management of hyperlipidaemia was only administered in roughly 50% of patients . This could in parts be related to concerns of drug‐induced liver injury as has been described in this class, but considering the high cardiovascular mortality of patients with NAFLD, this class of drugs should not be withheld and the safety concerns are low . One‐third of the cohort was diabetic.…”

Section: Discussionmentioning

confidence: 99%

“…33 This could in parts be related to concerns of drug-induced liver injury as has been described in this class, 34 but considering the high cardiovascular mortality of patients with NAFLD, 25 this class of drugs should not be withheld and the safety concerns are low. 35 One-third of the cohort was diabetic. Interestingly, the use of insulin in this cohort was high: 30% of the patients with diabetes type 2 were on some form of injectable insulin, mostly a combination of short and longacting compounds.…”

Section: Discussionmentioning

confidence: 99%

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Predictors of advanced fibrosis in non‐cirrhotic non‐alcoholic fatty liver disease in Germany

Labenz

Huber

Kalliga

et al. 2018

Aliment Pharmacol Ther

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Summary Background Advanced fibrosis has been established as the most important predictor of overall mortality in patients with non‐alcoholic fatty liver disease (NAFLD). In contrast to cirrhosis, advanced, non‐cirrhotic NAFLD is difficult to identify and data from Germany are lacking. Aim To identify clinical factors associated with advanced, non‐cirrhotic fibrosis. Methods Patients were recruited in the prospectively enrolling European NAFLD Registry. Clinical characteristics and the performance of non‐invasive surrogate scores compared with vibration‐controlled transient elastography are reported. Results Two hundred and sixty‐one patients with non‐cirrhotic NAFLD on liver biopsy (mean age 51 years, equal sex distribution) were included. The prevalence of stage 3 fibrosis on liver biopsy was 15.7%. These patients were significantly older (57 vs 50 years, P < 0.01), had a higher body mass index (32.3 vs 30.5, P < 0.05), and more frequent arterial hypertension (78% vs 50%, P = 0.001) and type 2 diabetes (61% vs 24.1%, P < 0.001). On multivariate logistic regression, diabetes (OR = 4.68, 95% CI 2.17‐10.10) and hypertension (OR = 2.91, 95% CI 1.12‐7.18) were independent predictors of advanced fibrosis. Comedication included metformin in 50% and insulin in 33% of patients with diabetes. Despite the presence of cardiovascular risk factors, the use of statins was low. Liver stiffness measurement identified advanced fibrosis with an AUROC of 0.81 (95% CI 0.72‐0.91). The performance of NAFLD fibrosis score, Fibrosis‐4, and AST to platelet ratio index were lower with AUCs of 0.74, 0.71, and 0.67, respectively. Conclusions The prevalence of metabolic comorbidities in a German population with non‐cirrhotic biopsy‐proven NAFLD is high. While the examined scores exhibit an acceptable specificity, liver stiffness measurement appeared to be superior to blood‐based non‐invasive surrogate scores in ruling out advanced fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Predictors of advanced fibrosis in non‐cirrhotic non‐alcoholic fatty liver disease in Germany

Labenz

Huber

Kalliga

et al. 2018

Aliment Pharmacol Ther

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“…In our small cohort with repeat biopsies, NAS and steatosis were stable or improved. Prior studies have suggested that treatment with insulin sensitizers such as metformin, rosiglitazone, or pioglitazone may help to improve NAFLD in type 2 diabetes . The histologic stability or improvement demonstrated by our subjects provides further support to the previous suggestion that metformin may exert beneficial effects on NAFLD that are unrelated to its glycemic actions, and further study is warranted.…”

Section: Discussionmentioning

confidence: 99%

Non‐alcoholic fatty liver disease in pediatric type 2 diabetes: Metabolic and histologic characteristics in 38 subjects

et al. 2018

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Background Obesity and type 2 diabetes (T2D) is risk factors for non‐alcoholic fatty liver disease (NAFLD) and non‐alcoholic steatohepatitis (NASH). In children with T2D and liver biopsies, we investigated correlations between NAFLD/NASH and transaminase activity, A1c, lipids, and histologic changes in repeat biopsies. Methods Liver histology of children with T2D was evaluated using the NASH CRN scoring system and NAFLD Activity Score (NAS). We included results ≤6 months from biopsy and A1c nearest biopsy. Results Thirty‐eight subjects (21 females, 17 males, 63.2% Hispanic, 15.8% Caucasian) had T2D diagnosed at 13.4 ± 2.7 years, 78.9% using metformin and 50% on insulin. Histological diagnosis of NAFLD occurred at mean age 14.3 ± 2.3 years, notable for NASH in 61%. Steatosis grade was higher in children with NASH than those without (mean 2.6 ± 0.7 vs 2.1 ± 0.5 (P < 0.001). Stage 3 fibrosis was noted only in subjects with NASH (26%). ALT was higher in NASH vs those without (112 ± 56 vs 85 ± 112, P = 0.016). NAS correlated with A1c (r = 0.51, P < 0.01) and triglycerides (r = 0.5, P < 0.01), and inversely with high‐density lipoprotein (HDL) (r = −0.42, P = 0.04). Males had lower HDL and higher triglycerides (P < 0.04). In eight subjects with repeat biopsies, NAS was equal (37.5%) or improved (62.5%), and steatosis decreased (68.1% to 32.8%, P = 0.027). Conclusions In children with T2D and NAFLD, NASH is common. Having advanced fibrosis in 26% of NASH cases at this age is concerning. Better control of lipids, weight, and diabetes may help avoid worsening in NAS.

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“…Metformin, an indirect AMPK activator, is being considered a possible option, 36 current evidence however is insufficient to recommend metformin against NAFLD. 37 Metformin primarily acts by decreasing mitochondrial capacity (leading to AMP accumulation activating AMPK) and therefore may not be an ideal exercise mimetic, as evinced through blunted exercise effects in prediabetic patients on metformin. 38 AICAR, on the other hand, has been trialed particularly in myocardial ischemia, with some, but not all, studies documenting ischemic protection including a reduced mortality.…”

Section: Discussionmentioning

confidence: 99%

Exercise Improves Outcomes of Surgery on Fatty Liver in Mice

et al. 2020

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Exercise efficiently counteracts the metabolic, ischemic, and regenerative deficits of fatty liver. AICAR acts as an exercise mimetic in settings of fatty liver disease, an important finding given the compliance issues associated with exercise. Exercising, or its substitution through AICAR, may provide a feasible strategy to negate the hepatic consequences of energy-rich diet, and has the potential to extend the application of liver surgery if confirmed in humans.

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Treating nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a review of efficacy and safety

Abstract: All reviewed treatment options are safe for management of NAFLD in patients with T2DM but long-term histological improvements are minimal. TZDs are efficacious for resolution of NASH and improvements in fibrosis but long-term use is required to maintain these results.

Cited by 29 publications

References 38 publications

Predictors of advanced fibrosis in non‐cirrhotic non‐alcoholic fatty liver disease in Germany

Predictors of advanced fibrosis in non‐cirrhotic non‐alcoholic fatty liver disease in Germany

Non‐alcoholic fatty liver disease in pediatric type 2 diabetes: Metabolic and histologic characteristics in 38 subjects

Exercise Improves Outcomes of Surgery on Fatty Liver in Mice

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