Societal costs and survival of patients with biopsy-verified non-alcoholic steatohepatitis: Danish nationwide register-based study.

INTRODUCTION AND OBJECTIVES: Studies on the societal burden of patients with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) are sparse. This study examined this question, comparing NAFLD with matched reference groups. MATERIALS AND METHODS: Nationwide Danish healthcare registers were used to include all patients (≥18 years) diagnosed with biopsy-verified NAFLD (1997-2021). Patients were classified as having simple steatosis or non-alcoholic steatohepatitis (NASH) with or without cirrhosis, and all matched with liver-disease free reference groups. Healthcare costs and labour market outcomes were compared from 5 years before to 11 years after diagnosis. Patients were followed for 25 years to analyse risk of disability insurance and death. RESULTS: 3,712 patients with biopsy-verified NASH (n = 1,030), simple steatosis (n = 1,540) or cirrhosis (n = 1,142) were identified. The average total costs in the year leading up to diagnosis was 4.1-fold higher for NASH patients than the reference group (EUR 6,318), 6.2-fold higher for cirrhosis patients and 3.1-fold higher for simple steatosis patients. In NASH, outpatient hospital contacts were responsible for 49 % of the excess costs (EUR 3,121). NASH patients had statistically significantly lower income than their reference group as early as five years before diagnosis until nine years after diagnosis, and markedly higher risk of becoming disability insurance recipients (HR: 4.37; 95 % CI: 3.17-6.02) and of death (HR: 2.42; 95 % CI: 1.80-3.25). CONCLUSIONS: NASH, simple steatosis and cirrhosis are all associated with substantial costs for the individual and the society with excess healthcare costs and poorer labour market outcomes.

Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure, and appetite in overweight men.

Our aim was to examine the effects of GLP-1 and PYY3-36, separately and in combination, on energy intake, energy expenditure, appetite sensations, glucose and fat metabolism, ghrelin, and vital signs in healthy overweight men. Twenty-five healthy male subjects participated in this randomized, double-blinded, placebo-controlled, four-arm crossover study (BMI 29 ± 3 kg/m(2), age 33 ± 9 yr). On separate days they received a 150-min intravenous infusion of 1) 0.8 pmol·kg(-1)·min(-1) PYY3-36, 2) 1.0 pmol·kg(-1)·min(-1) GLP-1, 3) GLP-1 + PYY3-36, or 4) placebo. Ad libitum energy intake was assessed during the final 30 min. Measurements of appetite sensations, energy expenditure and fat oxidation, vital signs, and blood variables were collected throughout the infusion period. No effect on energy intake was found after monoinfusions of PYY3-36 (-4.2 ± 4.8%, P = 0.8) or GLP-1 (-3.0 ± 4.5%, P = 0.9). However, the coinfusion reduced energy intake compared with placebo (-30.4 ± 6.5%, P < 0.0001) and more than the sum of the monoinfusions (P < 0.001), demonstrating a synergistic effect. Coinfusion slightly increased sensation of nausea (P < 0.05), but this effect could not explain the effect on energy intake. A decrease in plasma ghrelin was found after all treatments compared with placebo (all P < 0.05); however, infusions of GLP-1 + PYY3-36 resulted in an additional decrease compared with the monoinfusions (both P < 0.01). We conclude that coinfusion of GLP-1 and PYY3-36 exerted a synergistic effect on energy intake. The satiating effect of the meal was enhanced by GLP-1 and PYY3-36 in combination compared with placebo. Coinfusion was accompanied by slightly increased nausea and a decrease in plasma ghrelin, but neither of these factors could explain the reduction in energy intake.

Thermic effect of a meal and appetite in adults: an individual participant data meta-analysis of meal-test trials.

BACKGROUND: Thermic effect of a meal (TEF) has previously been suggested to influence appetite. OBJECTIVE: The aim of this study was to assess whether there is an association between appetite and TEF. Second, to examine whether protein intake is associated with TEF or appetite. DESIGN: Individual participant data (IPD) meta-analysis on studies were performed at the Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. Five randomized meal-test studies, with 111 participants, were included. The included studies measured energy expenditure (EE) in respiration chambers and pre- and postprandial appetite sensations using Visual Analog Scales (VAS). The primary meta-analysis was based on a generic-inverse variance random-effects model, pooling individual study Spearman's correlation coefficients, resulting in a combined r-value with 95% confidence interval (95% CI). The I (2) value quantifies the proportion (%) of the variation in point estimates due to among-study differences. RESULTS: The IPD meta-analysis found no association between satiety and TEF expressed as the incremental area under the curve (TEFiAUC) (r=0.06 [95% CI -0.16 to 0.28], P=0.58; I (2)=15.8%). Similarly, Composite Appetite Score (CAS) was not associated with TEFiAUC (r=0.08 [95% CI -0.12 to 0.28], P=0.45; I (2)=0%). Posthoc analyses showed no association between satiety or CAS and TEF expressed as a percentage of energy intake (EI) (P>0.49) or TEF expressed as a percentage of baseline EE (P>0.17). When adjusting for covariates, TEFiAUC was associated with protein intake (P=0.0085). CONCLUSIONS: This IPD meta-analysis found no evidence supporting an association between satiety or CAS and TEF at protein intakes ∼15 E% (range 11-30 E%).

Energy expenditure and respiratory diseases: is there a link?

Recent studies have suggested that respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea syndrome (OSAS), influence energy expenditure (EE). This influence on energy balance may be responsible for the weight changes that are often seen in individuals suffering from OSAS and COPD. However, even though EE has been assessed in several studies, be it in OSAS or COPD, there are still controversies regarding these potential relationships. Thus, the objective of this review is to describe some of the potential mechanisms that may affect EE in respiratory diseases and, thereby discuss whether there seems to be an explanation for the aforementioned relationship. The primary focus is on the oxygen transport system, which may be an important determinant for the relationship between both of these respiratory diseases and EE.

Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects.

Peptide YY (PYY)(3-36) has been shown to produce dramatic reductions in energy intake (EI), but no human data exist regarding energy expenditure (EE), glucose and fat metabolism. Nothing is known regarding PYY1-36. To compare effects of PYY(1-36) and PYY(3-36) on appetite, EI, EE, insulin, glucose and free fatty acids (FFA) concentrations, 12 lean and 12 obese males participated in a blinded, randomized, crossover study with 90-min infusions of saline, 0.8 pmol x kg(-1) x min(-1) PYY(1-36) and PYY(3-36). Only four participants completed PYY(3-36) infusions because of nausea. Subsequently, six lean and eight obese participants completed 0.2 pmol x kg(-1) x min(-1) PYY(3-36) and 1.6 pmol x kg(-1) x min(-1) PYY(1-36) infusions. PYY(3-36) [corrected] produced [corrected] lower ratings of well-being and [corrected] increases in heart rate, [corrected] FFA, and [corrected] postprandial [corrected] insulin concentrations. Furthermore, high-dose [corrected] PYY(3-36) (0.8 [corrected] pmol x kg(-1) x min(-1)) produced decreased [corrected] EI and increased postprandial [corrected] glucose concentrations and tendency to reduced EE [corrected]