Addition of Insulin to Parenteral Nutrition for Control of Hyperglycemia.

Administration of parenteral nutrition (PN) may result in hyperglycemia in patients with preexisting diabetes or disease-related insulin resistance, and it can be associated with increased rates of complications. Treatment requires insulin therapy. Insulin can be administered subcutaneously, intravenously via a variable rate sliding scale, or by adding it directly to the PN. The last method is a potentially attractive technique for a number of reasons-it could deliver the insulin intravenously at a steady rate alongside carbohydrates, and in malnourished patients with little subcutaneous tissue, it may prevent the need for frequent insulin injections. Despite such potential advantages, the addition of insulin to PN remains controversial, largely with respect to the bioavailability of insulin in PN and resultant concerns of the risk of hypoglycemia. There is a paucity of long-term quality controlled studies to address this question. The available literature suggests that, at least in the short term, insulin addition to PN can achieve reasonable glycemic control with low rates of hypoglycemia, and the technique compares favorably with the use of long-acting insulin preparations. This literature review finds a wide range of values reported for insulin availability via PN, ranging from 44% to 95% depending on the type of PN container material used and the presence of added vitamins and trace elements. Few studies looking at glycemic control among patients receiving home PN were found, and larger prospective trials are needed to assess the efficacy and safety of this technique in this patient group.

Endoplasmic Reticulum Stress Is Implicated in Intestinal Failure-Associated Liver Disease.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) is the most serious consequence of long-term parenteral nutrition for intestinal failure. Little is known about the pathogenesis of IFALD, although many of the risk factors are also linked to endoplasmic reticulum stress (ERS). We propose that ERS may have a role in the development of IFALD. METHODS: Archived liver tissue from patients with early and late IFALD, as well as from normal controls, was used for RNA extraction and immunohistochemistry to demonstrate the presence of ERS markers. RESULTS: Mean relative RNA levels of glucose regulatory protein 78 in normal liver (n = 3), early IFALD (n = 15), and late IFALD (n = 5) were 0.5, 37.86, and 212.11, respectively. Mean relative expression of ERDj4 (ER DnaJ homologue 4, a downstream ERS effector) in normal liver, early IFALD, and late IFALD was 5.51, 216.68, and 213.22, respectively. The degree of splicing of X-box binding protein 1 in IFALD compared with normal liver was significantly higher (mean, 0.0779 normal, 0.102 early IFALD, 0.2063 late IFALD). CONCLUSIONS: This is the first description of ERS in IFALD. This information may open up new therapeutic possibilities in the form of chemical chaperones known to ameliorate ERS.

The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency.

OBJECTIVES: A severe enteropathy of unknown etiology can be associated with common variable immunodeficiency (CVID). METHODS: S tool and archived small intestinal mucosal biopsies from patients with CVID enteropathy were analyzed by PCR for the presence of Norovirus RNA. The PCR products were sequenced to determine the relationship of viral isolates. Stool samples from 10 patients with CVID but no enteropathy served as controls. RESULTS: All eight patients in our CVID cohort with enteropathy showed persistent fecal excretion of Norovirus. Analysis of archived duodenal biopsies revealed a strong association between the presence of Norovirus and villous atrophy over a period of up to 8 years. Analysis of the viral isolates from each patient revealed distinct strains of genogroup II.4. Sequence analysis from consecutive biopsy specimens of one patient demonstrated persistence of the same viral strain over a 6-year period. CVID patients without enteropathy showed no evidence of Norovirus carriage. Viral clearance occurred spontaneously in one patient and followed oral Ribavirin therapy in two further patients, and resulted in complete symptomatic and histological recovery. However, Ribavirin treatment in two further patients was unsuccessful. CONCLUSIONS: Norovirus is an important pathogen for patients with CVID and a cause of CVID enteropathy, as viral clearance, symptom resolution, and histological recovery coincide. Ribavirin requires further evaluation as a potential therapy.

The skinny on cocaine: insights into eating behavior and body weight in cocaine-dependent men.

There is a general assumption that weight loss associated with cocaine use reflects its appetite suppressing properties. We sought to determine whether this was justified by characterizing, in detail, alterations in dietary food intake and body composition in actively using cocaine-dependent individuals. We conducted a cross-sectional case-control comparison of 65 male volunteers from the local community, half of whom satisfied the DSM-IV-TR criteria for cocaine dependence (n=35) while the other half had no personal or family history of a psychiatric disorder, including substance abuse (n=30). Assessments were made of eating behavior and dietary food intake, estimation of body composition, and measurement of plasma leptin. Although cocaine users reported significantly higher levels of dietary fat and carbohydrates as well as patterns of uncontrolled eating, their fat mass was significantly reduced compared with their non-drug using peers. Levels of leptin were associated with fat mass, and with the duration of stimulant use. Tobacco smoking status or concomitant use of medication did not affect the significance of the results. Weight changes in cocaine users reflect fundamental perturbations in fat regulation. These are likely to be overlooked in clinical practice but may produce significant health problems when cocaine use is discontinued during recovery.

Clinical application of magnetic resonance spectroscopy of the liver in patients receiving long-term parenteral nutrition.

BACKGROUND: Intestinal failure-associated liver disease (IFALD) may have progressed to an advanced stage by the time it becomes evident via laboratory or physical signs. A safe, noninvasive technique for assessing the liver could significantly aid in monitoring the effects of therapeutic intervention, improve the timing of liver and small intestinal transplantation, and increase our understanding of the causes of IFALD. METHODS: Six female patients fed intravenously for >1 year and 6 controls matched for body mass index (BMI) underwent liver magnetic resonance scanning with acquisition of (1)H and (31)P resonance spectra. Areas under the curve for lipid (the sum of CH, CH(2), and CH(3)), water, and choline peaks were calculated and expressed semi-quantitatively as ratios of lipid:water and choline:lipid. Phosphomonoester (PME) and phosphodiester (PDE) peak areas were similarly expressed as a ratio. Controls and cases were compared using Mann-Whitney U test; least squares regression analysis was used to compare the effect of measured variables on the lipid:water peak area ratio. RESULTS: Patients and controls were well matched for BMI. Parenteral feeding was associated with a highly significant increase in lipid:water peak ratio (P < .005). Choline:lipid (P < .05) and choline:water (not significant) ratios were reduced in patients compared with controls. The increase in lipid:water ratios in patients was independent of BMI and choline:water ratios. A ratio of PME:PDE of >0.3 (and >3 SD from the control mean) predicted the 2 patients at most risk of advanced liver disease. CONCLUSIONS: This pilot study confirms the potential of magnetic resonance spectroscopic techniques in evaluating IFALD and could contribute significantly to our understanding and management of this condition.

Recent advances in the management of intestinal failure-associated liver disease.

PURPOSE OF REVIEW: To summarize the current management of intestinal failure-associated liver disease (IFALD) by reviewing recent advances in our understanding of the condition and the effects of different therapeutic approaches. RECENT FINDINGS: The importance of gastrointestinal length and continuity in the aetiology and treatment of IFALD has been demonstrated in both retrospective and interventional cohorts. A mechanism for the cholestatic effect of soy-based lipid has been described, and the clinical use of alternative lipid sources has demonstrated benefit. Prevention of IFALD has been shown with the use of erythromycin in neonates, and reversal of established IFALD has been demonstrated with isolated intestinal transplantation. SUMMARY: A greater understanding of the mechanisms of IFALD has led to promising interventions to prevent and treat the condition. Other possible therapeutic targets require more formal evaluation, and further work is required to develop noninvasive tools for the assessment and prognosis of IFALD that will guide treatment and help in the selection of patients and timing of transplantation.