Diet-induced weight loss reduces postprandial dicarbonyl stress in abdominally obese men : Secondary analysis of a randomized controlled trial

Aims: Dicarbonyl compounds contribute to the formation of advanced glycation endproducts (AGEs) and the development of insulin resistance and vascular complications. Dicarbonyl stress may already be detrimental in obesity. We evaluated whether diet-induced weight loss can effectively reverse dicarbonyl stress in abdominally obese men. Materials and methods: Plasma samples were collected from lean (n = 25) and abdominally obese men (n = 52) in the fasting state, and during a mixed meal test (MMT). Abdominally obese men were randomized to 8 weeks of dietary weight loss or habitual diet, followed by a second MMT. The α-dicarbonyls methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG) and AGEs were measured by UPLC-MS/MS. Skin autofluorescence (SAF) was measured using the AGE reader. T-tests were used for the cross-sectional analysis and ANCOVA to assess the treatment effect. Results: Postprandial glucose, MGO and 3-DG concentrations were higher in obese men as compared to lean men (p < 0.05 for all). Fasting dicarbonyls, AGEs, and SAF were not different between lean and obese men. After the weight loss intervention, fasting MGO levels tended to decrease by 25 nmol/L (95%-CI: -51-0.5; p = 0.054). Postprandial dicarbonyls were decreased after weight loss as compared to the control group: iAUC of MGO decreased by 57% (5280 nmol/L∙min; 95%-CI: 33–10526; p = 0.049), of GO by 66% (11,329 nmol/L∙min; 95%-CI: 495–22162; p = 0.041), and of 3-DG by 45% (20,175 nmol/L∙min; 95%-CI: 5351–35000; p = 0.009). AGEs and SAF did not change significantly after weight loss. Conclusion: Abdominal obesity is characterized by increased postprandial dicarbonyl stress, which can be reduced by a weight loss intervention. Registered under ClinicalTrials.gov Identifier no. NCT01675401.</p

Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial

BACKGROUND: There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. OBJECTIVES: The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. METHODS: Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. RESULTS: Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: -57.0 g/d; 95% CI: -77.9, -39.5 g/d; and -38.8 μmol/d; 95% CI: -91.2, -10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P < 0.001 and P = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: -0.7% point, 95% CI: -2.0, -0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. CONCLUSIONS: Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group.This trial was registered at clinicaltrials.gov as NCT03067428