Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders.

BACKGROUND AND AIMS: Though low levels of insulin-like growth factor-1 (IGF-1) have been repeatedly reported in patients with eating disorders, the nutritional significance of IGF-1 has not been evaluated. The study aimed to assess the utility of IGF-1 for screening malnutrition and for monitoring nutrition intervention in patients with eating disorders. METHODS: IGF-1 and nutritional status were evaluated in 82 patients, 59 with anorexia nervosa (AN), and 23 with bulimia nervosa (BN). Nutritional assessment included the evaluation of body mass index (BMI), body fat (FAT) and muscle mass (MM), assessed by skinfold anthropometry, serum albumin, transthyretin and retinol-binding protein, energy and protein intake. IGF-1 and nutritional parameters were reevaluated in the early phase of refeeding (2-4 weeks) in 20 AN patients who entered a refeeding program. RESULTS: Mean IGF-1 z-score was -1.74+/-0.74 in AN, and -0.74+/-0.91 in BN. Serum proteins were reduced in only a minority of patients. IGF-1 correlated with BMI (r=0.64), FAT (r=0.57), MAMC (mid-arm muscle circumference) (r=0.58) and MM (r=0.66) (P<0.001), while it did not correlate with serum proteins. In the early phase of nutritional repletion serum proteins and anthropometric parameters did not vary significantly, while a prompt and marked increase (73.9%) of IGF-1 was observed. CONCLUSIONS: IGF-1 represents a biochemical marker of malnutrition and a sensitive index of nutritional repletion in patients with eating disorders.

Nutrition and survival in patients with liver cirrhosis.

Although the effect of malnutrition on survival has been demonstrated by a number of studies, it is not clear whether malnutrition represents an independent risk factor in patients with liver disease. We studied 212 hospitalized patients with liver cirrhosis who were followed clinically for 2 y or until death. Body fat and muscle mass were evaluated by triceps skinfold thickness (TSF) and midarm muscle circumference (MAMC), respectively. Multivariate analysis according to Cox's model assessed the predictive power of nutritional parameters on survival. Thirty-four percent of patients had severe malnutrition as determined by MAMC and/or TSF below the 5th percentile and 20% had moderate malnutrition (MAMC and/or TSF < 10th percentile). Twenty-six percent of patients were overnourished (MAMC and/or TSF > 75th percentile). Severely and moderately malnourished patients had lower survival rates than normal and overnourished patients. When analyzed with Cox's regression analysis, severe depletion of muscle mass and body fat were found to be independent predictors of survival. The inclusion of MAMC and TSF in the Child-Pugh score, the prognostic score used most with liver disease, improved its prognostic accuracy. The prognostic power of MAMC was higher than that of TSF. These data demonstrate that malnutrition is an independent predictor of survival in patients with liver cirrhosis. The inclusion of anthropometric measures in the assessment of these patients might provide better prognostic information.

Nutritional and prognostic significance of serum hypothyroxinemia in hospitalized patients with liver cirrhosis.

BACKGROUND/AIMS: A variety of severe illnesses can induce changes in thyroid hormone metabolism, leading to findings referred to as "sick euthyroid syndrome". In several groups of patients the reduction of serum thyroxine concentration (T4), characteristic of the low-T4 variant of sick euthyroid syndrome, has been found to be a good predictor of survival. Although the pathophysiology of hormonal alterations has not yet been defined, nutritional deficits have been suggested to play a role. The study aimed to define the prognostic and nutritional significance of serum thyroxine in liver cirrhosis. METHODS: Thyroid hormones and nutritional status were evaluated in a group of 75 consecutive hospitalized patients with cirrhosis, followed-up clinically for 12 months. RESULTS: A low-T4 variant of sick euthyroid syndrome was found in 23 of the 75 enrolled patients with cirrhosis (30.6%). Serum T4, but not serum T3, correlated with mid-arm muscle circumference (p < 0.01), an indicator of muscle protein compartment. While both serum T3 and T4 correlated directly with serum proteins and inversely with Child-Pugh score, only T4 was predictive of outcome. Patients with the low-T4 variant of sick euthyroid syndrome showed significantly lower short- and long-term survival rates compared to those with normal serum T4 concentrations (p < 0.008 at 3 months, p < 0.001 at 6 months and 1 year). A multivariate analysis using the proportional hazards Cox's regression procedure showed that serum T4, but not serum T3 or nutritional parameters, improves the prognostic capacity of Child-Pugh score (p < 0.01). CONCLUSIONS: These data indicate that the low T4-variant of sick euthyroid syndrome distinguishes a subgroup of patients with cirrhosis at risk for decreased survival. The inclusion of T4 in the Child-Pugh score, by improving its prognostic power, may optimize the selection of patients with advanced cirrhosis to receive specific therapy such as transplantation.

Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis.

Most of the traditional parameters for nutrition assessment have important limitations in patients with chronic liver disease. Insulin-like growth factor 1 (IGF-1) has been found to be regulated by nutrition and proposed as a nutritional marker. Its nutritional significance in patients with liver cirrhosis, however, has not been investigated. Serum IGF-1 as well as traditional anthropometric, visceral, and immunologic parameters were evaluated in 64 hospitalized cirrhotics, followed up clinically for 2 y. IGF-1Z-score averaged -2.16 +/- 1.08 and inversely correlated with Child-Pugh score (P < 0.01), the most reliable composite score reflecting the severity of liver disease. IGF-1Z-score was not different in patients with or without signs of energy malnutrition, as defined by values of midarm muscle circumference (MAMC) and/or triceps skinfold (TSF) < 5th percentile. Moreover, IGF-1Z-score did not correlate with MAMC or TSF. Despite its correlation with all visceral proteins, the reduction of IGF-1 was much greater and more frequent than that of visceral proteins. Patients with IGF-1Z-score < median values (-2.5) showed lower long-term survival rates compared with patients with IGF-1Z-score > -2.5 (P < 0.01). These data indicate that serum IGF-1 is not related to energy malnutrition in cirrhotic patients, while it appears to be a good predictor of survival and an early marker of liver dysfunction. Multiple factors, most of which are related to the severity of the liver disease, may contribute to the reduction of IGF-1. This multifactorial pathogenesis probably accounts for its prognostic significance.

Malnutrition in alcoholic and virus-related cirrhosis.

The study aimed to define the prevalence, characteristics, and clinical importance of nutritional disorders in patients with liver cirrhosis. Nutritional status was evaluated in 120 hospitalized patients--77 with alcoholic and 43 with virus-related cirrhosis--by anthropometric, visceral, and immunologic measurements. Energy malnutrition, defined as triceps skinfold thickness (TSF) and/or midarm muscle circumference (MAMC) below the 5th percentile of standard values, was found in 34% of the study population. Patients below the 5th percentile for MAMC and/or TSF showed significantly lower survival rates at e, 6, 12, and 24 mo compared with patients above the 5th percentile. Protein malnutrition (low albumin, transthyretin, transferrin, and retinol-binding-protein concentrations) and immunoincompetence (abnormal response to skin tests) were much more frequent (81% and 59%) than energy malnutrition (34%). Serum proteins correlated with the degree of liver function impairment, but not with immunologic tests. The prevalence, characteristics, and severity of protein-energy malnutrition were comparable in alcoholic and viral cirrhosis. Malnutrition was correlated with the clinical severity of the liver disease. The study shows that protein-energy malnutrition is a common complication of liver cirrhosis. Nutritional disorders appear to be related to the degree of liver injury rather than to its etiology. Compared with other methods, which have important limitations in liver disease, anthropometry is currently the most reliable method for nutritional assessment in clinical practice and may be valuable for predicting survival in cirrhotic patients.

Limitations of serum creatinine level and creatinine clearance as filtration markers in cirrhosis.

BACKGROUND: Several studies carried out in a limited number of patients demonstrated a wide range of overestimation of glomerular filtration rate (GFR) by serum creatinine level and creatinine clearance (Ccr) in liver disease. METHODS: We simultaneously evaluated Ccr, inulin clearance, and predicted GFR calculated from serum creatinine level in 56 cirrhotic patients. Inulin clearance was considered the gold standard for GFR evaluation. RESULTS: The sensitivity of serum creatinine level, predicted GFR, and Ccr in detecting renal failure was 18.5%, 51%, and 74%, respectively. On the basis of inulin clearance, patients were divided into two groups: those with normal GFR (mean, 106 +/- 34 mL/min per 1.73 m2) (group 1, 29 patients) and those with reduced GFR (mean, 56 +/- 19 mL/min per 1.73 m2) (group 2, 27 patients). Predicted GFR and Ccr were accurate markers of GFR in group 1 patients, while both overestimated GFR by about 50% in group 2 patients. An increased tubular secretion of creatinine accounted for the disparity between Ccr and inulin clearance in these patients. CONCLUSIONS: Our results indicate that renal failure is greatly underestimated on the basis of serum creatinine level and Ccr in cirrhotic patients. Clinical implications of this observation include excessive dosage of potentially nephrotoxic drugs and failure to recognize renal impairment induced by such medical treatments as diuretic therapy or paracentesis.