Fructose use in clinical nutrition: metabolic effects and potential consequences.

PURPOSE OF REVIEW: The current article presents recent findings on the metabolic effects of fructose. RECENT FINDINGS: Fructose has always been considered as a simple 'caloric' hexose only metabolized by splanchnic tissues. Nevertheless, there is growing evidence that fructose acts as a second messenger and induces effects throughout the human body. SUMMARY: Recent discoveries made possible with the evolution of technology have highlighted that fructose induces pleiotropic effects on different tissues. The fact that all these tissues express the specific fructose carrier GLUT5 let us reconsider that fructose is not only a caloric hexose, but could also be a potential actor of some behaviors and metabolic pathways. The physiological relevance of fructose as a metabolic driver is pertinent regarding recent scientific literature.

Prognostication of Mortality in Critically Ill Patients With Severe Infections.

BACKGROUND: The purpose of this study was to confirm the prognostic value of pancreatic stone protein (PSP) in patients with severe infections requiring ICU management and to develop and validate a model to enhance mortality prediction by combining severity scores with biomarkers. METHODS: We enrolled prospectively patients with severe sepsis or septic shock in mixed tertiary ICUs in Switzerland (derivation cohort) and Brazil (validation cohort). Severity scores (APACHE [Acute Physiology and Chronic Health Evaluation] II or Simplified Acute Physiology Score [SAPS] II) were combined with biomarkers obtained at the time of diagnosis of sepsis, including C-reactive-protein, procalcitonin (PCT), and PSP. Logistic regression models with the lowest prediction errors were selected to predict in-hospital mortality. RESULTS: Mortality rates of patients with septic shock enrolled in the derivation cohort (103 out of 158) and the validation cohort (53 out of 91) were 37% and 57%, respectively. APACHE II and PSP were significantly higher in dying patients. In the derivation cohort, the models combining either APACHE II, PCT, and PSP (area under the receiver operating characteristic curve [AUC], 0.721; 95% CI, 0.632-0.812) or SAPS II, PCT, and PSP (AUC, 0.710; 95% CI, 0.617-0.802) performed better than each individual biomarker (AUC PCT, 0.534; 95% CI, 0.433-0.636; AUC PSP, 0.665; 95% CI, 0.572-0.758) or severity score (AUC APACHE II, 0.638; 95% CI, 0.543-0.733; AUC SAPS II, 0.598; 95% CI, 0.499-0.698). These models were externally confirmed in the independent validation cohort. CONCLUSIONS: We confirmed the prognostic value of PSP in patients with severe sepsis and septic shock requiring ICU management. A model combining severity scores with PCT and PSP improves mortality prediction in these patients.

Effect of nutritional support on glucose control.

PURPOSE OF REVIEW: There is evidence that maintaining a normal glycemia level in critically ill patients has beneficial effects on outcome. Strategies aimed at lowering glycemia are based on the understanding of mechanisms regulating glucose metabolism. RECENT FINDINGS: Activation of AMP protein kinase in skeletal muscle and in the liver leads to a reduction in glucose production, a stimulation of glucose uptake, and a lowering of glycemia. These mechanisms appear to be activated during exercise, or by the endogenous adipokine adiponectin. Alterations in adiponectin concentrations during critical illness may thus play a role in the metabolic stress responses. In addition, AMP-activated protein kinase is the target for drugs (metformin, thazolidinediones), which may be of interest in the intensive care unit. Besides insulin, plasma glucose concentrations may be lowered by hypocaloric feeding, or by feeding 'diabetic' formula with low glucose content and supplemented with fructose. Whether such approaches lead to beneficial effects comparable to those observed with insulin remains to be established. SUMMARY: Recent findings regarding the molecular mechanisms underlying glucose transport and metabolism are summarized, and potential strategies other than insulin are outlined which may contribute to lowering glycemia in critically ill patients.

Relationship between stress, inflammation and metabolism.

PURPOSE OF REVIEW: Various threatening stimuli, such as pain, low blood pressure, or infection, elicit a set of neuroendocrine responses that include an increased secretion of catecholamines and glucocorticoid from the adrenal gland and activation of the sympathetic nervous system. These hormonal secretions allow a "fight or flight" response by mobilizing endogenous substrate. They also exert anti-insulin actions, and may in the long term induce a state of insulin resistance. In addition, stress stimulates inflammatory mediators in mononuclear cells. Given the possible role of low-grade inflammation in chronic metabolic disorders, this suggests that stress may be a factor in the development of insulin resistance and the metabolic syndrome. RECENT FINDINGS: Studies reviewed in this article cover: (1) the metabolic and haemodynamic effects of stress in healthy and insulin-resistant individuals; (2) the relationship between stress and inflammation and the role of the autonomic nervous system; and (3) some factors known to modulate the neuroendocrine responses to stress. Future perspectives, together with some hints regarding the role of neurotrophins such as brain-derived neurotrophic factor, are delineated. SUMMARY: Recent work performed in the field has indicated that stress may be a significant factor in the pathogenesis of metabolic disorders. Nutritional intervention or pharmacological agents targeted at modulating stress should be investigated.

Metabolic effects of mental stress during over- and underfeeding in healthy women.

OBJECTIVE: To assess the short-term consequences of carbohydrate or fat overfeeding or of food restriction on the metabolic effects of mental stress in healthy lean women. RESEARCH METHODS AND PROCEDURES: The effects of a sympathetic activation elicited by mental stress were evaluated in a group of healthy women after standardized isocaloric feeding (ISO) or after a 3-day overfeeding with 40% excess calories as either carbohydrate overfeeding (CHO OF) or fat overfeeding (FAT OF). Oxygen consumption rate (VO(2)) was measured as an index of energy expenditure, and subcutaneous glycerol concentrations were monitored with microdialysis. The same measurements were performed in another group of healthy women after ISO and after a 3-day period of underfeeding with a protein sparing modified fast (UF). RESULTS: In all conditions, mental stress significantly increased heart rate, blood pressure, plasma norepinephrine and epinephrine concentrations, and VO(2), and produced a nonsignificant increase in subcutaneous glycerol concentrations. CHO OF and FAT OF did not alter the effects of mental stress on VO(2) and subcutaneous glycerol concentrations. In contrast, UF increased basal VO(2) but significantly reduced its stimulation by mental stress. UF also enhanced the increase in subcutaneous glycerol concentrations during mental stress. DISCUSSION: UF reduces the stimulation of energy expenditure and enhances lipolysis during sympathetic activation. These adaptations may be involved in mobilization of endogenous fat while limiting weight loss. In contrast, short-term overfeeding fails to alter the sympathetic control of energy expenditure and lipolysis.