Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity in individuals with obesity. Although multiple pharmacotherapeutics are in development, currently there are limited strategies ...specifically targeting NAFLD. This systematic review summarizes the existing literature on hepatic effects of medications used for weight loss. Glucagon-like peptide 1 (GLP-1) agonists are the best-studied in this regard, and evidence consistently demonstrates reduction in liver fat content, sometimes accompanied by improvements in histological features of steatohepatitis and reductions in serum markers of hepatic injury such as alanine aminotransferase (ALT). It remains unclear whether these benefits are independent of the weight loss caused by these agents. Literature is limited regarding effects of orlistat, but a small number of reports suggest that orlistat reduces liver fat content and improves histologic features of NASH, benefits which may also be driven primarily by weight loss. A sizeable body of literature on hepatic effects of metformin yields mixed results, with a probability of modest benefit, but no consistent signal for strong benefit. There are insufficient data on hepatic effects of topiramate, phentermine, naltrexone, bupropion, and lorcaserin. Finally, a few studies to date suggest that sodium-glucose co-transporter-2 (SGLT2) inhibitors may reduce liver fat content and cause modest reductions in ALT, but further study is needed to better characterize these effects. Based on available data, GLP-1 agonists have the strongest evidence base demonstrating beneficial effects on NAFLD, but it is not clear if any weight loss medication has effects on NAFLD superior to those of nutritional modification and exercise alone.
Abstract
Context
Growth hormone (GH) and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease ...(NAFLD).
Objective
To assess relationships between hepatic expression of IGF1 and IGF-binding proteins (IGFBPs) and measures of glycemia and liver disease in adults with NAFLD. Secondarily to assess effects of GH-releasing hormone (GHRH) on circulating IGFBPs.
Design
Analysis of data from a randomized clinical trial of GHRH.
Setting
Two US academic medical centers.
Participants
Participants were 61 men and women 18 to 70 years of age with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy.
Main Outcome Measures
Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis.
Results
Hepatic IGF1 mRNA was significantly lower in individuals with higher steatosis and NAFLD Activity Score (NAS) and was inversely related to glucose parameters, independent of circulating IGF-1. Among the IGFBPs, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) were higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA levels were positively associated with NAS. IGFBP7 mRNA increased with increasing fibrosis. Hepatic IGFBP1 mRNA was inversely associated with glycemia and insulin resistance, with opposite relationships present for IGFBP3 and IGFBP7. GHRH increased circulating IGFBP-1 and IGFBP-3, but decreased IGFBP-2 and IGFBP-6.
Conclusions
These data demonstrate novel relationships of IGF-1 and IGFBPs with NAFLD severity and glucose control, with divergent roles seen for different IGFBPs. Moreover, the data provide new information on the complex effects of GHRH on IGFBPs.
As antiretroviral therapy has decreased human immunodeficiency virus (HIV)—associated mortality, cardiometabolic abnormalities have become increasingly apparent in HIV-infected individuals. Many ...patients treated for HIV infection exhibit body composition changes, including peripheral fat atrophy and visceral lipohypertrophy. In addition, HIV-infected individuals demonstrate a higher prevalence of dyslipidemia, insulin resistance and diabetes, and cardiovascular risk, compared with the general population. Although antiretroviral therapy appears to contribute to some of the cardiometabolic abnormalities in HIV infection, HIV itself, immunologic factors, and lifestyle factors are also important mediators of cardiovascular risk. Treatment strategies for body composition changes and cardiometabolic abnormalities in HIV infection include lifestyle modification, lipid-lowering agents, insulin sensitizers, and treatments to reverse endocrine abnormalities in HIV, including growth hormone—releasing hormone. None of these strategies has comprehensively addressed the abnormalities experienced by this population, however, and further research is needed into combined strategies to improve body composition and ameliorate cardiovascular risk.
For any given body mass index (BMI), individuals vary substantially in fat distribution, and this variation may have important implications for cardiometabolic risk. Here, we study disease ...associations with BMI-independent variation in visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) fat depots in 40,032 individuals of the UK Biobank with body MRI. We apply deep learning models based on two-dimensional body MRI projections to enable near-perfect estimation of fat depot volumes (R
in heldout dataset = 0.978-0.991 for VAT, ASAT, and GFAT). Next, we derive BMI-adjusted metrics for each fat depot (e.g. VAT adjusted for BMI, VATadjBMI) to quantify local adiposity burden. VATadjBMI is associated with increased risk of type 2 diabetes and coronary artery disease, ASATadjBMI is largely neutral, and GFATadjBMI is associated with reduced risk. These results - describing three metabolically distinct fat depots at scale - clarify the cardiometabolic impact of BMI-independent differences in body fat distribution.
Williams syndrome is a multisystem disorder caused by a microdeletion on chromosome 7q. Throughout infancy, childhood, and adulthood, abnormalities in body composition and in multiple endocrine axes ...may arise for individuals with Williams syndrome. This review describes the current literature regarding growth, body composition, and endocrine issues in Williams syndrome with recommendations for surveillance and management by the endocrinologist, geneticist, or primary care physician.
In addition to known abnormalities in stature, calcium metabolism, and thyroid function, individuals with Williams syndrome are increasingly recognized to have low bone mineral density, increased body fat, and decreased muscle mass. Furthermore, recent literature identifies a high prevalence of diabetes and obesity starting in adolescence, and, less commonly, a lipedema phenotype in both male and female individuals. Understanding of the mechanisms by which haploinsufficiency of genes in the Williams syndrome-deleted region contributes to the multisystem phenotype of Williams syndrome continues to evolve.
Multiple abnormalities in growth, body composition, and endocrine axes may manifest in individuals with Williams syndrome. Individuals with Williams syndrome should have routine surveillance for these issues in either the primary care setting or by an endocrinologist or geneticist.
Context and Objective: Obesity is associated with activation of the TNF-α system, increased inflammatory markers, and insulin resistance. Although studies in rodents suggest that attenuation of TNF ...activity improves glucose homeostasis, the effect of prolonged inhibition of TNF-α with etanercept on inflammation and glucose homeostasis in a human model of obesity is not known.
Design and Participants: Forty obese subjects with features of metabolic syndrome were randomized to etanercept or placebo, 50 mg twice weekly for 3 months, followed by 50 mg once weekly for 3 months.
Outcome Measures: Subjects underwent oral glucose tolerance testing and measurement of serum inflammatory biomarkers and adipokines. Subcutaneous fat biopsy was performed in a subset for measurement of adipokine and TNF-α mRNA expression.
Results: Visceral adiposity was significantly associated with serum concentrations of TNF receptor 1 (TNFR1), TNFR2, and vascular cell adhesion molecule-1 and adipose tissue expression of TNF-α and SOCS-3 (all P < 0.05). Insulin resistance as assessed by homeostasis model assessment was significantly associated with TNFR1, C-reactive protein, IL-6, and soluble intracellular adhesion molecule-1 (sICAM-1) (all P < 0.05). Etanercept significantly improved fasting glucose (treatment effect vs. placebo over 6 months, −10.8 ± 4.4%, P = 0.02). Etanercept also increased the ratio of high molecular weight adiponectin to total adiponectin (+22.1 ± 9.2% vs. placebo, P = 0.02), and decreased levels of sICAM-1 (−11 ± 2% vs. placebo, P < 0.0001). In contrast, body composition, lipids, C-reactive protein, and IL-6 were unchanged after 6 months.
Conclusions: Prolonged therapy with etanercept improved fasting glucose, increased the ratio of high molecular weight to total adiponectin, and decreased sICAM-1 in obese subjects with abnormal glucose homeostasis and significant subclinical inflammation.
Etanercept treatment decreases fasting glucose and increases the ratio of HMW:total adiponectin in obesity, without any effect on body composition or lipids.
Many childhood-onset growth disorders (COGDs) require continued care into adulthood, and the time of transition between paediatric and adult providers carries a high risk for interruptions in medical ...care and consequent worsening of disease management.
Research into best practices for healthcare transition (HCT) describes three distinct stages. Stage 1, transition planning and preparation, begins in the paediatric setting during early adolescence and ensures that the patient has adequate medical knowledge, self-management skills, and readiness for transition. Stage 2, transfer to adult care, occurs with variable timing depending on transition readiness and is best facilitated by warm hand-offs and, when possible, joint visits with the paediatric and adult provider(s) and/or involvement of a care coordinator. Stage 3, intake and integration into adult care, entails retaining the patient in the adult setting, ideally through the involvement of a multidisciplinary approach.
This review covers general principles for ensuring smooth transition of adolescents and young adults (AYA) with COGD, disease-specific medical considerations for paediatric and adult endocrinologists during the transition process, and general and disease-specific resources to assess transition readiness and facilitate transition.
Women with HIV (WWH) face heightened risks of heart failure; however, insights on immune/inflammatory pathways potentially contributing to left ventricular (LV) systolic dysfunction among WWH remain ...limited.
Massachusetts General Hospital, Boston, Massachusetts.
Global longitudinal strain (GLS) is a sensitive measure of LV systolic function, with lower cardiac strain predicting incident heart failure and adverse heart failure outcomes. We analyzed relationships between GLS (cardiovascular magnetic resonance imaging) and monocyte activation (flow cytometry) among 20 WWH and 14 women without HIV.
WWH had lower GLS compared to women without HIV (WWH vs. women without HIV: 19.4±3.0 vs. 23.1±1.9%, P<0.0001). Among the whole group, HIV status was an independent predictor of lower GLS. Among WWH (but not among women without HIV), lower GLS related to a higher density of expression of HLA-DR on the surface of CD14+CD16+ monocytes (ρ = -0.45, P = 0.0475). Further, among WWH, inflammatory monocyte activation predicted lower GLS, even after controlling for CD4+ T-cell count and HIV viral load.
Additional studies among WWH are needed to examine the role of inflammatory monocyte activation in the pathogenesis of lower GLS and to determine whether targeting this immune pathway may mitigate risks of heart failure and/or adverse heart failure outcomes.
Clinical trials.gov registration: NCT02874703.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) are widely prescribed. Statins may have important metabolic effects on insulin sensitivity and liver fat, but limited studies ...have assessed these effects by using euglycemic hyperinsulinemic clamp, stable isotopes, and 1H magnetic resonance spectroscopy (MRS) for liver fat quantification.
To study the effects of pitavastatin on hepatic fat and insulin sensitivity.
Six-month, double-blind, randomized, placebo-controlled trial.
Academic clinical research center in Boston, Massachusetts.
Overweight, insulin-resistant men aged 40 to 65 years who had not received statin therapy for ≥1 year.
Pitavastatin 4 mg or placebo daily.
The primary endpoints were changes in insulin sensitivity measured by euglycemic hyperinsulinemic clamp and liver fat measured by 1H MRS.
Pitavastatin showed no effect on endogenous glucose production (ΔRa glucose 0.07 ± 0.07 vs 0.04 ± 0.07 mg/kg/min, pitavastatin vs placebo, P = 0.76) or insulin-stimulated glucose uptake during "low dose" (ΔM 0.1 ± 0.1 vs -0.3 ± 0.2 mg/kg/min, P = 0.11) and "high dose" (ΔM -0.5 ± 0.3 vs -0.7 ± 0.4 mg/kg/min, P = 0.70) euglycemic hyperinsulinemic clamps. There was also no effect of pitavastatin on fasting glucose, HbA1c, and 2-hour glucose after 75-g glucose challenge. There was also no change in liver fat fraction (-1 ± 1 vs -0 ± 1%, P = 0.56).
Compared with placebo, pitavastatin did not affect hepatic or whole-body insulin sensitivity, and it did not reduce liver fat.
Background
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in young adults with obesity. Obesity is associated with relative growth hormone (GH) deficiency, and data from animal studies ...and from humans with pituitary GH deficiency suggest a role for GH deficiency in the pathogenesis of NAFLD. The effects of GH on NAFLD in those with obesity are unknown, however, prompting this pilot study to assess effects of GH administration on measures of NAFLD in young adults.
Methods
Twenty‐four men and women aged 18–29 years with BMI ≥ 30 kg/m2, hepatic fat fraction (HFF) ≥ 5% on proton magnetic resonance spectroscopy (1H‐MRS) and insulin‐like growth factor 1 (IGF‐1) z‐score ≤ 0 were randomized to treatment with recombinant human GH (rhGH) versus no treatment for 24 weeks. The primary endpoint was change in HFF.
Results
Compared to no treatment, the effect size of rhGH on absolute HFF over 24 weeks was −3.3% (95% confidence interval: −7.8%, 1.2%; p = .14). At 24 weeks, HFF < 5% was achieved in 5 of 9 individuals receiving rhGH versus 1 of 9 individuals receiving no treatment (p = .04). rhGH did not significantly reduce ALT, AST or GGT. Serum IGF‐1 increased as expected with rhGH treatment, and there were no changes in fasting lipids, C‐reactive protein, fasting glucose or 2‐h glucose following an oral glucose tolerance test.
Conclusion
Data from this pilot study suggest that rhGH treatment in young adults with obesity and NAFLD may have benefits to reduce liver fat content, although larger studies are needed to confirm this effect.
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