Effects of short-term high-fructose diets in humans: modulation by environmental factors

It is currently suspected that sugar overconsumption, and more specifically fructose, may promote the development of obesity and of several cardio-metabolic disorders. However, environmental factors, such as fish oil and dietary proteins, may prevent some deleterious effects of fructose. The aim of this thesis was to identify potential environmental factors that may modulate the metabolic effects of fructose. The first study was designed to evaluate the impact of endurance exercise in healthy young men fed a high-fructose, isocaloric diet. Fructose-induced effects on lipid profile were totally prevented by endurance exercise and may be explained by an enhanced clearance of TRL-TG and the inhibition of de novo lipogenesis. As energy intake was adjusted to energy requirement, we can conclude that exercise acts on fructose metabolism independently of energy imbalance. The second study aimed at determining whether coffee and more specifically chlorogenic acid consumption may prevent fructose-induced intrahepatic lipids accumulation, hypertriglyceridemia and hepatic insulin resistance, through a stimulation of lipid oxidation. Coffee did not prevent the fructose-induced increase in IHCL or plasma TG. Interestingly, the three coffees tested prevented the decrease in hepatic insulin sensitivity, independently of their content in caffeine or chlorogenic acid. Finally, in the third study, we evaluated the effect of essential amino acid supplementation on the increase of hepatic lipids induced by a high-fructose diet. This intervention slightly decreased IHCL concentration. The exact mechanisms remain unidentified but may involve an increased secretion of VLDL-TG. In conclusion, the environmental factors evaluated allow to prevent some of the deleterious effects of fructose and suggest that recommendations on fructose consumption should also take into account environmental factors.

The SYNTAX score predicts early mortality risk in the elderly with acute coronary syndrome having primary PCI.

BACKGROUND: The SYNTAX score (SXscore), an angiographic score reflecting coronary lesion complexity, predicts clinical outcomes in patients with left main or multivessel disease, and in patients with ST-segment elevation myocardial infarction undergoing primary PCI. The clinical SXscore (CSS) integrates the SXscore and clinical variables (age, ejection fraction, serum creatinine) into a single score. We analyzed these scores in elderly patients with acute coronary syndrome (ACS) undergoing primary PCI. The purpose of this analysis was not to decide which patients should undergo PCI, but to predict clinical outcomes in this population. METHODS: The SXscore was determined in a consecutive series of 114 elderly patients (mean age, 79.6 ± 4.1 years) undergoing primary PCI for ACS. Outcomes were stratified according to SXscore tertiles: SXLOW ≤15 (n = 39), 15< SXMID <23 (n = 40), and SXHIGH ≥23 (n = 35). The primary endpoint was all-cause mortality at 30 days. Secondary endpoints were nonfatal major adverse cardiac and cerebrovascular events (MACCE) at 30 days, and 1-year outcomes in patients discharged alive. RESULTS: Mortality at 30 days was higher in the SXHIGH group compared with the aggregate SXLOW+MID group (37.1% vs 5.1%; P<.0001), and in the CSSHIGH group compared with the aggregate CSSLOW+MID group (25.5% vs 1.4%; P=.0001). MACCE rates at 30 days were similar among SXscore tertiles. The CSS predicted 1-year MACCE rates (12.1% for CSSHIGH vs 3.1% for CSSLOW+MID; P=.03). CONCLUSIONS: The SXscore predicts 30-day mortality in elderly patients with ACS undergoing primary PCI. In patients discharged alive, the CSS predicts risk of MACCE at 1 year.

Intrauterine devices and endometrial cancer risk : a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes.

Discriminating irritable bowel syndrome from inflammatory bowel disease: what is the role of biomarkers in daily practice?

Background and Aims: Discriminating irritable bowel syndrome (IBS) from inflammatorybowel disease (IBD) can be a clinical challenge as symptoms can overlap. We and othershave recently shown that fecal calprotectin (FC) is more accurate for discriminating IBSfrom IBD compared to C-reactive protein (CRP) and blood leukocytes. Data on the biomarkersused in daily gastroenterological practice are lacking. We therefore aimed to assess whichbiomarkers are used by gastroenterologists in their daily practice for discriminating IBSfrom IBD.Methods: A questionnaire was sent to all board certified gastroenterologists inSwitzerland focusing on demographic informations, number of IBS patients treated in thetime period from May 2009 to April 2010, and the specific biomarkers evaluated fordiscriminating IBS from IBD.Results: Response rate was 57% (153/270). Mean physician'sage was 50±9years, mean duration of gastroenterologic practice 14±8years, 52% of themwere working in private practice and 48% in hospitals. Thirty-nine percent had taken careof more than 100 IBS patients in the last 12 months, 37% had seen 41-100 and 24% hadseen 1-40 IBS patients. Gastroenterologists in private practice more frequently took care ofat least 40 IBS patients in a year compared to hospital-based gastroenterologists (P<0.001).The following biomarkers were determined for discriminating IBS from IBD: CRP 100%,FC 79%, hematogram (red blood cells and leukocytes) 70%, iron status (ferritin, transferrinsaturation) 59%, erythrocyte sedimentation rate 2.7%, protein electrophoresis 0.7%, andalpha-1 antitrypsin clearance 0.7%. There was a trend for using FC more often in privatepractice than in hospital (P = 0.08). Twenty-four percent of gastroenterologists had usedFC in the workup of more than 70% of patients classified as IBS, 22% had used FC in 30-70% of IBS patients, 39% in less than 30%, and 15% had never used FC for the work-upof suspected IBS. Eighty-nine percent of gastroenterologists considered FC to be superiorto CRP for discriminating IBS from IBD, 87% thought that patient's compliance for fecalsampling is high, and 51% judged the fee of USD 60 for a FC test as appropriate.Conclusions:FC is widely used in clinical practice to discriminate IBS from IBD. In accordance with thescientific evidence, the majority of gastroenterologists consider FC to be more accurate thanCRP for discriminating IBS from IBD. Gastroenterologists in private practice take care ofsignificantly more IBS patients than colleagues in hospital.