Nonalcoholic fatty liver disease and type 2 diabetes: where do Diabetologists stand?
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ABSTRACT: Background
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The increasing prevalence of NAFLD mirrors that of obesity and type 2 diabetes over the last two decades.Main
In a two-way pathophysiologic relationship, NAFLD increases the risk of developing type 2 diabetes, while the latter promotes the progression of simple fatty liver to a more advanced form called nonalcoholic steatohepatitis (NASH). NASH increases the risk of cirrhosis and hepatocellular carcinoma (HCC), which may require liver transplantation. With the absence of FDA-approved medications for NAFLD treatment, lifestyle intervention remains the only therapy. Lately, extensive research efforts have been aimed at modifying NASH fibrosis and developing noninvasive screening methods.Conclusion
We highlight the pathophysiologic relationships between NAFLD and type 2 diabetes, discuss disease recognition, models of care, and current and emerging therapies for NASH treatment.
SUBMITTER: Tomah S
PROVIDER: S-EPMC7275502 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Nonalcoholic fatty liver disease and type 2 diabetes: where do Diabetologists stand?
Tomah Shaheen S Alkhouri Naim N Hamdy Osama O
Clinical diabetes and endocrinology 20200605
<h4>Background</h4>Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The increasing prevalence of NAFLD mirrors that of obesity and type 2 diabetes over the last two decades.<h4>Main</h4>In a two-way pathophysiologic relationship, NAFLD increases the risk of developing type 2 diabetes, while the latter promotes the progression of simple fatty liver to a more advanced form called nonalcoholic steatohepatitis (NASH). NASH increases the risk of cirrhosis a ...[more]
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Project description:Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of insulin resistance, which is the hallmark of type 2 diabetes (T2D). NAFLD is a known risk factor for developing T2D and has a very high prevalence in those with existing T2D. The diabetes spectrum includes several conditions from prediabetes to T2D to insulin-dependent diabetes leading to macrovascular and microvascular complications. Similarly, NAFLD has a histologic spectrum that ranges from the relatively benign nonalcoholic fatty liver to the aggressive form of nonalcoholic steatohepatitis with or without liver fibrosis to nonalcoholic steatohepatitis-cirrhosis leading to end-stage liver disease. The management of T2D has witnessed significant changes over the past few decades with multiple new drug classes entering the treatment algorithm. Unfortunately, there are no U.S. Food and Drug Administration-approved medications to treat NAFLD, and guidelines for the management of NAFLD are less established. However, the field of drug development in NAFLD has witnessed a revolution over the past 5 years with the establishment of a regulatory pathway for Food and Drug Administration approval; this has generated substantial interest from pharmaceutical companies. Several diabetes medications have been studied as potential treatments for NAFLD with promising results; moreover, drugs that target specific pathways that play a role in NAFLD development and progression are being developed at a rapid pace. Given the similarities between NAFLD and T2D in terms of pathogenesis, underlying risk factors, and disease spectrum, lessons learned from optimizing treatment for T2D can be extrapolated to the management of NAFLD. The aim of this review is to use the founding principles of the comprehensive type 2 diabetes management algorithm to optimize the management of NAFLD. (Hepatology Communications 2018;2:778-785).
| S-EPMC6049065 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide, the prevalence of which had progressively increased over the past 10 years where other liver diseases remained at the same prevalence rates or are expected to decrease as in the case of hepatitis C virus (HCV). The treatment of NAFLD is of prime concern to health care professionals and patients due to the significant mortality and morbidity it implies; the problem is further escalated by the fact that standard of care medications targeting NAFLD remain experimental and without evidence base. Treatment nowadays is focused on lifestyle modification and managing the comorbid associated diseases, with a possible role for some hepatic protective agents. This review presents all the medications that had been proposed and used for the treatment of NAFLD with or without scientific rationale and includes agents for weight loss, insulin sensitizers, drugs that reduce blood lipids, glucagon-mimetics, drugs that may reduce fibrosis, angiotensin receptor blockers, and medicines believed to reduce endoplasmic reticular stress such as vitamin E, ursodeoxycholic acid, and S-adenosyl methionine. A quick review of the newer agents that proved to be promising such as obeticholic acid and GFT505 and the medicines that are still in the pipeline is also presented.
| S-EPMC4817303 | biostudies-other
Project description:ImportanceNonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease in children in the United States and is associated with insulin resistance. In adults, NAFLD is also associated with type 2 diabetes. To our knowledge, the prevalence of type 2 diabetes in children with NAFLD is unknown.ObjectiveTo determine the prevalence of type 2 diabetes and prediabetes in children with NAFLD and assess type 2 diabetes and prediabetes as risk factors for nonalcoholic steatohepatitis (NASH).Design, setting, and participantsThis was a multicenter, cross-sectional study at 12 pediatric clinical centers across the United States participating in the National Institute of Diabetes and Digestive and Kidney Diseases NASH Clinical Research Network. Children younger than 18 years with biopsy-confirmed NAFLD enrolled in the NASH Clinical Research Network.Main outcomes and measuresThe presence of type 2 diabetes and prediabetes as determined by American Diabetes Association screening criteria using clinical history and fasting laboratory values.ResultsThere were 675 children with NAFLD included in the study with a mean age of 12.6 years and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 32.5. Most of the children were boys (480 of 675) and Hispanic (445 of 675).The estimated prevalence of prediabetes was 23.4% (95% CI, 20.2%-26.6%), and the estimated prevalence of type 2 diabetes was 6.5% (95% CI, 4.6%-8.4%). Girls with NAFLD had 1.6 (95% CI, 1.04-2.40) times greater odds of having prediabetes and 5.0 (95% CI, 2.49-9.98) times greater odds of having type 2 diabetes than boys with NAFLD. The prevalence of NASH was higher in those with type 2 diabetes (43.2%) compared with prediabetes (34.2%) or normal glucose (22%) (P < .001). The odds of having NASH were significantly higher in those with prediabetes (OR, 1.9; 95% CI, 1.21-2.9) or type 2 diabetes (OR, 3.1; 95% CI, 1.5-6.2) compared with those with normal glucose.Conclusions and relevanceIn this study, nearly 30% of children with NAFLD also had type 2 diabetes or prediabetes. These children had greater odds of having NASH and thus were at greater long-term risk for adverse hepatic outcomes.
| S-EPMC5479314 | biostudies-literature
Project description:Introduction Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are both chronic multisystem diseases that cause tremendous health burdens worldwide. Previous epidemiological studies have found a bidirectional relationship between these two diseases; however, their causality remains largely unknown. We aim to examine the causal relationship between NAFLD and T2DM. Methods The observational analysis included 2,099 participants from the SPECT-China study and 502,414 participants from the UK Biobank. Logistic regression and Cox regression models were used to examine the bidirectional association between NAFLD and T2DM. Two-sample Mendelian randomization (MR) analyses were conducted to investigate the causal effects of the two diseases using summary statistics of genome-wide association studies from the UK Biobank for T2DM and the FinnGen study for NAFLD. Results During the follow-up, 129 T2DM cases and 263 NAFLD cases were observed in the SPECT-China study, and 30,274 T2DM cases and 4,896 NAFLD cases occurred in the UK Biobank cohort. Baseline NAFLD was associated with an increased risk of incident T2DM in both studies (SPECT-China: OR: 1.74 (95% confidence interval (CI): 1.12–2.70); UK Biobank: HR: 2.16 (95% CI: 1.82–2.56)), while baseline T2DM was associated with incident NAFLD in the UK Biobank study only (HR: 1.58). Bidirectional MR analysis showed that genetically determined NAFLD was significantly associated with an increased risk of T2DM (OR: 1.003 (95% CI: 1.002–1.004, p< 0.001)); however, there was no evidence of an association between genetically determined T2DM and NAFLD (OR: 28.1 (95% CI: 0.7–1,143.0)). Conclusions Our study suggested the causal effect of NAFLD on T2DM development. The lack of a causal association between T2DM and NAFLD warrants further verification.
| S-EPMC10200946 | biostudies-literature
Project description:Purpose of reviewNonalcoholic fatty liver disease (NAFLD) is the most common chronic fatty liver disease worldwide. The incidence of NAFLD parallels the prevalence of obesity. Moreover, NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and primary hepatocellular cancer (HCC). As such, NAFLD has become a major public health concern. We discuss recent clinical trials and meta-analyses evaluating the efficacy of C20-22 ω3 polyunsaturated fatty acids (PUFA) to attenuate preexisting NAFLD in adults and children.Recent findingsHumans with NAFLD and NASH; and preclinical mouse models of NASH, have a high abundance of hepatic saturated (SFA) and monounsaturated (MUFA) fat, but a low abundance of hepatic C20-22 ω3 PUFA. This change in hepatic fat type and abundance is associated with hepatic lipotoxicity, inflammation, oxidative stress and fibrosis. Recent meta-analyses and clinical trials evaluated the capacity of C20-22 ω3 PUFA dietary supplementation to improve health outcomes in adults and children with preexisting NAFLD. Diets supplemented with docosahexaenoic acid (DHA, 22 : 6,ω3) alone or with eicosapentaenoic acid (EPA, 20 : 5,ω3) are tolerated and effective at lowering liver fat in NAFLD patients. However, outcomes are mixed with respect to C20-22 ω3 PUFA attenuation of more severe NAFLD markers, such as hepatic injury, inflammation and fibrosis.SummaryThese studies suggest that dietary supplementation with C20-22 ω3 PUFA should be considered as a viable and effective option to lower liver fat in obese adults and children with NAFLD.
| S-EPMC6355343 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) was first described in the 1980s, but in the 21st century, NAFLD has become a very common condition. The explanation for this relatively recent problem is in large part due to the recent epidemic of obesity and type 2 diabetes (T2DM) increasing the risk of NAFLD. NAFLD is a silent condition that may not become manifest until severe liver damage (fibrosis or cirrhosis) has occurred. Consequently, NAFLD and its complications often remain undiagnosed. Research evidence shows that NAFLD is extremely common and some estimates suggest that it occurs in up to 70% of people with T2DM. In the last 5 years, it has become evident that NAFLD not only increases the risk of cirrhosis, primary liver cancer and end-stage liver disease, but NAFLD is also an important multisystem disease that has major implications beyond the liver. NAFLD increases the risk of incident T2DM, cardiovascular disease, chronic kidney disease and certain extra-hepatic cancers, and NAFLD and T2DM form part of a vicious spiral of worsening diseases, where one condition affects the other and vice versa. Diabetes markedly increases the risk of liver fibrosis and liver fibrosis is the most important risk factor for hepatocellular carcinoma. It is now possible to diagnose liver fibrosis with non-invasive tools and therefore it is important to have clear care pathways for the management of NAFLD in patients with T2DM. This review summarises key recent research that was discussed as part of the Banting lecture at the annual scientific conference in 2022.
| S-EPMC9546361 | biostudies-literature
Project description:Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m2), metformin use, and basal metabolic rate (BMR) were obtained from participants' records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all p < 0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 (r = 0.221, p = 0.010), and negative correlations were noted between TSH and BMR (r = -0.618, p < 0.001) and between BMR and FT3 (r = -0.452, p < 0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 (t = 2.468, p = 0.0167) and TSH (t = 2.658, p = 0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals.
| S-EPMC7492895 | biostudies-literature
Project description:ImportancePrevious studies have indicated that liver cirrhosis is associated with hypoglycemia, but there have been no studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and hypoglycemia in noncirrhotic populations with type 2 diabetes.ObjectiveTo explore the association of NAFLD with severe hypoglycemia among patients with type 2 diabetes.Design, setting, and participantsThis nationwide population-based retrospective cohort study using the National Health Insurance System of South Korea included individuals aged 20 years or older who had undergone a medical health examination between January 1, 2009, and December 31, 2012, and were diagnosed with type 2 diabetes. Participants were followed up until December 31, 2015. Data analyses were performed between January 1, 2019, and February 2, 2021.ExposuresThe baseline fatty liver index (FLI) was used as a surrogate marker for NAFLD.Main outcomes and measuresThe outcome of interest, severe hypoglycemia, was measured using hospital admission and emergency department visit records with a primary diagnosis of hypoglycemia.ResultsAmong 1 946 581 individuals with type 2 diabetes, 1 125 187 (57.8%) were male. During a median (IQR) follow-up of 5.2 (4.1-6.1) years, 45 135 (2.3%) experienced 1 or more severe hypoglycemia events. Participants with severe hypoglycemia, vs those without severe hypoglycemia, were older (mean [SD] age, 67.9 [9.9] years vs 57.2 [12.3] years; P < .001) and had lower mean (SD) body mass index (24.2 [3.43] vs 25.1 [3.4]; P < .001). Patients with NAFLD tended to have less severe hypoglycemia without consideration of obesity status. However, after adjustment of multiple clinical covariates, including body mass index, there was a J-shaped association between FLI and severe hypoglycemia (5th decile: adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.90; 9th decile: aHR, 1.02; 95% CI, 0.96-1.08; 10th decile: aHR, 1.29; 95% CI, 1.22-1.37), and the estimated risk of hypoglycemia was higher in participants with NAFLD (aHR, 1.26; 95% CI, 1.22-1.30). The association was more prominent in female participants (aHR, 1.29; 95% CI, 1.23-1.36) and those with underweight (aHR, 1.71; 95% CI, 1.02-2.88).Conclusions and relevanceIn this study, NAFLD was associated with a higher risk of severe hypoglycemia in patients with type 2 diabetes independent of obesity status. Presence of NAFLD should be considered when evaluating vulnerability to hypoglycemia in patients with type 2 diabetes.
| S-EPMC8867244 | biostudies-literature
Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) showed significant association with PNPLA3 rs738409 polymorphism in unrelated individuals. However, it is still unknown whether the relationship of NAFLD with PNPLA3 variant exists or not among subjects with type 2 diabetes mellitus (T2DM). Therefore, the study aimed to evaluate sociodemographic and genetic determinants of NAFLD in type 2 diabetics.MethodsThe cross-sectional analytical study was conducted at the Department of Molecular Biology, Virtual University of Pakistan, Lahore, Pakistan, during 2019-2020. A total of 153 known cases of T2DM were enrolled using convenience sampling. After excluding patients (n = 24) with HCV, alcoholism, or missing information, data from 129 eligible diabetics with and without NAFLD were analyzed using SPSS. Odds ratios using crosstabs and adjusted odds ratios using binary and multinomial logistic regression were calculated to measure the risk of NAFLD.ResultsAdults 18-35 years were 7.0%, 36-55 years were 64.3%, ≥ 56 years were 28.7%, and females were 66.7%. A total of 41.1% of patients had obesity, 52.7% had NAFLD, and 29.05% carried mutant G allele of rs738409 polymorphism. Among overall diabetics, NAFLD showed association with female (OR = 2.998, p = 0.007), illiterate (OR = 3.067, p = 0.005), and obese (OR = 2.211, p = 0.046) but not with PNPLA3 genotype under any model (all p = > 0.05). Among obese diabetics, NAFLD showed association with female (AOR = 4.010, p = 0.029), illiterate (AOR = 3.506, p = 0.037), GG + CG/CC (AOR = 3.303, p = 0.033), and GG/CG + CC (AOR = 4.547, p = 0.034) using binary regression and with female (AOR = 3.411, p = 0.051), illiterate (AOR = 3.323, p = 0.048), GG + CG/CC (AOR = 3.270, p = 0.029), and GG/CG + CC (AOR = 4.534, p = 0.024) using multinomial regression.ConclusionsNAFLD and obesity were the most common comorbid diseases of T2DM. Gender female, being illiterate, and PNPLA3 rs738409 polymorphism were significant risk factors of NAFLD among obese diabetic patients.
| S-EPMC9054952 | biostudies-literature
Project description: Not available
| S-EPMC10446130 | biostudies-literature