Should we measure routinely oxidised and atherogenic dense low-density lipoproteins in subjects with type 2 diabetes?

Beyond low-density lipoprotein (LDL)-cholesterol concentrations, in recent years, several clinical studies have shown that both oxidised and small, dense LDL have a strong predictive role for the presence of vascular atherosclerosis. These two lipid parameters seem to have a synergistic impact on cardiovascular risk, with a greater importance in patients at higher-risk, such as those with type-2 diabetes. Increased levels of oxidised and small, dense LDL levels are a feature of diabetic dyslipidaemia, and small, dense LDL have been shown to be a good predictor of future cardiovascular events, at both univariate and multivariate analyses. On the other hand, although the association of oxidised LDL with surrogate markers of atherosclerosis is consistent, the correlation with hard clinical end points seems to be smaller. Yet, measurement of these two lipid parameters has not been widely used in daily practice because of the limited availability of clinical data and methodological problems: lack of availability of easy, cheap and reproducible essays for measurement of oxidised and, particularly, small, dense LDL has reduced their assessment in large clinical end-points trials. However, on the basis of available data, the therapeutic modulation of small, dense LDL is significantly associated with reduced cardiovascular risk, even after adjustment for confounding factors. In conclusion, the routine measurement of oxidised and small, dense LDL in patients with type-2 diabetes cannot be recommended in daily clinical practice so far; yet, their measurement is strongly encouraged to better understand their role on the cardiovascular risk of patients with type-2 diabetes.

Interleukin-18 levels are associated with low-density lipoproteins size.

INTRODUCTION: Both low-density lipoproteins (LDL) size and serum interleukin (IL)-18 levels have been shown to be predictors of cardiovascular morbidity and mortality. However, it is still unknown whether IL-18 levels are independently associated with LDL size. METHODS: In this cross-sectional study including 53 premenopausal women (18-45 years), LDL size (by gradient gel electrophoresis), serum IL-18, high-sensitivity C-reactive protein (hs-CRP), serum lipids, insulin sensitivity (S(I), by frequently sampled intravenous glucose tolerance test) were measured. RESULTS: LDL size correlated with IL-18 (r = -0.38, P = 0.006), hs-CRP (r = -0.40, P = 0.003), S(I) (r = 0.36, P = 0.011), serum triglycerides (r = -0.32, P = 0.018) and high-density lipoproteins (HDL)-cholesterol (r = 0.40, P = 0.003). When these variables were entered into a regression model, serum IL-18 (beta = -0.26, P = 0.04), triglycerides (beta = -0.29, P = 0.02) and HDL-cholesterol (beta = 0.34, P = 0.01) levels were independently associated with LDL size, accounting for 42% of the variance (P < 0.001). Serum hs-CRP levels and S(I) were not significant independent predictors of LDL size in this model. CONCLUSIONS: This is the first report showing that elevated IL-18 levels are associated with reduced LDL size, independent of other inflammatory and metabolic risk factors. Future prospective studies are needed to evaluate the predictive role of IL-18 as an inflammatory marker of LDL size and the development of subclinical and/or clinical atherosclerosis.

Quantitative and qualitative effects of rosuvastatin on LDL-cholesterol: what is the clinical significance?

BACKGROUND: Statins have emerged as the global leader in pharmacologic therapy for dyslipidaemia, and rosuvastatin has demonstrated clinical efficacy as well as safety in several clinical trials and postmarketing analyses. AIM: The present article reviewed the effects of rosuvastatin on the quantity and the quality of low-density lipoproteins (LDL). METHODS: We searched for and reviewed all the available evidence in a systematic way. A literature search (by Medline and Scopus) was performed using the following headings: 'LDL-cholesterol', 'LDL size', 'LDL subclasses', 'small dense LDL', 'apolipoprotein B, apo B' and 'rosuvastatin' up to 11 November 2008. The authors also manually reviewed the references of selected articles for any pertinent material. RESULTS: Rosuvastatin reduces LDL-cholesterol levels to a greater extent than other statins and is able to modulate significantly LDL size and subclasses towards less atherogenic particles as well as the LDL particle number, as indirectly measured by the levels of apo B. DISCUSSION AND CONCLUSIONS: The recent Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin study provides more evidence about the effectiveness of rosuvastatin therapy in reducing cardiovascular risk, even among persons who would not currently be considered for pharmacotherapy. Further insights on cardiovascular outcomes will be available by the on-going trials included in the GALAXY program that includes subjects with type-2 diabetes, haemodialysis recipients, patients with congestive heart failure and specific ethnic groups, such as African American, Hispanic and South Asian populations.

Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome.

OBJECTIVE: Dyslipidaemia is very common in patients with polycystic ovary syndrome (PCOS) but, beyond plasma lipids, atherogenic lipoprotein (Lp) and apolipoprotein (apo) alterations are still ill defined. DESIGN: We measured concentrations of apoB, Lp(a) and small, dense low-density lipoprotein (LDL) in 42 patients with PCOS [age: 28 +/- 7 years, body mass index (BMI): 27 +/- 5 kg/m(2)] vs. 37 age- and BMI-matched healthy controls. METHODS: Elevated Lp(a) levels considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l. RESULTS: Polycystic ovary syndrome showed increased triglycerides levels (p = 0.0011) and lower high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.0131) while total- and LDL cholesterol were similar. PCOS also showed smaller LDL size (p = 0.0005), higher levels of total small, dense LDL (p < 0.0001), higher concentrations of Lp(a), as considered as absolute values (p = 0.0143) and log-transformed (p = 0.0014), while no differences were found in apoB levels. Elevated Lp(a) concentrations were found in 24% of PCOS, while elevated apoB levels were relatively uncommon (14%). Spearman correlation analysis revealed that Lp(a) concentrations were weakly correlated only with HDL-cholesterol levels (r = -0.378, p = 0.0431). In addition, 36% of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a), apoB or small, dense LDL. CONCLUSIONS: Atherogenic Lp abnormalities may be found in one-third of women with PCOS who have a normal lipid pattern. Future prospective studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS.

Atherogenic lipoprotein phenotype and LDL size and subclasses in women with gestational diabetes.

AIMS: Women with gestational diabetes are more likely to develop Type 2 diabetes and cardiovascular disease after pregnancy; however, the exact nature of the lipid alterations present is not clear. In Mediterranean women with gestational diabetes, we measured low-density lipoprotein (LDL) size and all seven subclasses, as well as the 'atherogenic-lipoprotein phenotype'[ALP, e.g. concomitant presence of elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol and increased small, dense LDL]. METHODS: In 27 women with gestational diabetes and 23 healthy pregnant women matched for age, weeks of gestation and body mass index, we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis between 24 and 28 weeks of gestation. RESULTS: Although no significant differences were found in the concentrations of any of the plasma lipids, compared with control subjects women with gestational diabetes had lower LDL size (P = 0.0007) due to reduced LDL-I (P = 0.0074) and increased LDL-IVA (P = 0.0146) and -IVB (P < 0.0001) subclasses. Correlation analysis revealed that fasting glucose, homeostasis model assessment and glycated haemoglobin were inversely correlated with LDL-I and positively with LDL-IVA and -IVB (all P < 0.05). ALP due to high HDL-cholesterol levels was not seen in either group, whereas elevated small, dense LDL were more common in women with gestational diabetes than control subjects (33% vs. 4%, P = 0.0107). CONCLUSIONS: Increased levels of small, dense LDL are common in Mediterranean women with gestational diabetes. Whether these findings affect the atherogenic process and clinical end-points in these women remains to be determined by future prospective studies.

Who needs to care about small, dense low-density lipoproteins?

BACKGROUND: Increasing evidence suggest that the 'quality' rather than only the 'quantity' of low-density lipoprotein (LDL) exerts a great influence on the cardiovascular risk. Small, dense LDL seem to be an important predictor of cardiovascular events and progression of coronary artery disease (CAD) and their predominance has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. DISCUSSION: Some studies showed in past years that small, dense LDL are usually elevated in patients at very high cardiovascular risk, such as those with CAD and type 2 diabetes. More recently elevated levels of these particles have been found in other categories of patients at high cardiovascular risk, such as those with non-coronary forms of atherosclerosis (e.g. with carotid artery disease, aortic abdominal aneurysm and peripheral arterial disease) and metabolic diseases (with polycystic ovary syndrome and growth hormone deficiency); notably, in most of them, the predominance of small, dense LDL characterised their type of dyslipidaemia, alone or in combination with elevated triglycerides and reduced high-density lipoproteins cholesterol concentrations. CONCLUSIONS: The therapeutical modulation of small, dense LDL have been shown to significantly reduce cardiovascular risk and weight reduction and increased physical activity may constitute first-line therapy. In addition, lipid-lowering drugs are able to favourably alter these particles and fibrates and nicotinic acid seem to be the most effective agents. Promising data are also available with the use of rosuvastatin, the latest statin introduced in the market, and ezetimibe, a cholesterol absorption inhibitor.

The clinical relevance of LDL size and subclasses modulation in patients with type-2 diabetes.

Increasing evidence suggest that the "quality" rather than only the "quantity" of low density lipoproteins (LDL) exerts a great influence on the cardiovascular risk. Hypertriglyceridemia, low HDL-cholesterol and increased levels of small dense LDL characterise diabetic dyslipidemia. In subjects with type-2 diabetes LDL size seems also to represent a good marker of clinical apparent and non-apparent atherosclerosis. Recently, the Coordinating Committee of the National Cholesterol Education Program stated that high-risk patients may benefit of stronger therapeutical approaches, a category of subjects that include those with type-2 diabetes. Screening for the presence of small, dense LDL may potentially identify those with even higher risk and may contribute in directing specific treatments in order to prevent new cardiovascular events. Hypolipidemic treatments are able to favourably modulate LDL size and subclasses in patients at higher cardiovascular risk. Regarding subjects with type-2 diabetes this seems particularly true for fibrates and less for statins. Analysis of all published studies revealed that atorvastatin represents the most effective agent among statins, while fenofibrate, bezafibrate and gemfibrozil are all very beneficial in modifying LDL size and subclasses towards less atherogenic particles. Nicotinic acid has been found also effective but the extended-release form should be preferred for the reduced intolerance, while fish oils have been shown to be less beneficial. Promising data are also available with the use of ezetimibe, a cholesterol absorption inhibitor.

Effects of infectious disease on plasma lipids and their diagnostic significance in critical illness.

BACKGROUND: Plasma lipids can be affected by acute illnesses. The present study attempts to characterize the impact of infectious disease on plasma lipids in critical illness. It also aims to determine the value of plasma lipid routine measurements in the diagnosis of infection in critical illness in comparison to markers of infection and acute phase reactants. MATERIALS AND METHODS: An observational study was carried out in 101 critically ill patients admitted consecutively to a medical intensive care unit in a university medical centre. Levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and additional variables were measured in blood samples taken on the day of admission. RESULTS: In critically ill patients significantly lower levels of HDL-C and TC were found in infectious disease patients compared to non-infectious disease patients (P < 0.001). No significant differences in levels of TG were found between infectious and non-infectious disease patients. Using receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) value for HDL-C and TC in the diagnosis of infection was 0.791 (P < 0.001) and 0.730 (P < 0.001), respectively. At a cutoff value for HDL-C of

The significance of low-density-lipoproteins size in vascular diseases.

Low density lipoproteins (LDL) comprise in humans two different main fractions: large, buoyant and small, dense particles. Small, dense LDL particles correlate negatively with plasma HDL levels and positively with plasma triglyceride concentrations and are associated with the metabolic syndrome and increased risk for cardiovascular disease. LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease (CHD). In addition, several studies have suggested that therapeutic modulation of specific LDL subclasses may be of great benefit in reducing the atherosclerotic risk. Therefore, LDL size measurement may be of potential value in the clinical assessment and management of patients at high risk of CHD, a category that comprises individuals with non-coronary forms of atherosclerosis: peripheral arterial disease, carotid artery disease, abdominal aortic aneurysm. Potentially, screening for the presence of small, dense LDL in patients with those clinical forms of atherosclerosis may identify those with even higher vascular risk and may contribute in directing specific anti-atherosclerotic treatments in order to prevent new vascular events in the same or another district. However, to-date, not so many studies have investigated the LDL size in patients with non-coronary forms of atherosclerosis and we need to wait for further contributions with larger number of patients, even if available data seem to suggest an association between small, dense LDL and such diseases. The predominance of small dense LDL particles has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III but screening for the presence of small, dense LDL particles in patients with non-coronary forms of atherosclerosis has not been so far recommended.

Low-density lipoprotein size and cardiovascular risk assessment.

A predominance of small, dense low-density lipoproteins (LDL) has been accepted as an emerging cardiovascular risk factor by the National Cholesterol Education Program Adult Treatment Panel III. LDL size seems to be an important predictor of cardiovascular events and progression of coronary heart disease and evidences suggests that both quality (particularly small, dense LDL) and quantity may increase cardiovascular risk. However, other authors have suggested that LDL size measurement does not add information beyond that obtained by measuring LDL concentration, triglyceride levels and HDL concentrations. Therefore, it remains debatable whether to measure LDL particle size in cardiovascular risk assessment and, if so, in which categories of patient. Therapeutic modulation of LDL particle size or number appears beneficial in reducing the risk of cardiovascular events, but no clear causal relationship has been shown, because of confounding factors, including lipid and non-lipid variables. Studies are needed to investigate the clinical significance of LDL size measurements in patients with coronary and non-coronary forms of atherosclerosis; in particular, to test whether LDL size is associated with even higher vascular risk, and whether LDL size modification may contribute to secondary prevention in such patients.

LDL size: does it matter?

The atherogenic lipoprotein phenotype is characterised by a moderate increase in plasma triglycerides, a decrease in high density lipoprotein cholesterol and the prevalence of smaller denser low density lipoprotein particles. The prevalence of this partially inheritable phenotype is approximately 30% and is a feature of the metabolic syndrome associated with an increased risk for cardiovascular events. The predominance of small dense LDL has been accepted as an emerging cardiovascular risk factor by the adult treatment panel (ATP) III.

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health.

Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 285+/-1 to 296+/-1 mosm/kg (P<0.001 during hyperosmolality, and decreased from 286+/-1 to 265+/-1 mosm/kg during hypo-osmolality (P<0.001). Total body leucine flux ([1-(13)C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[(13)C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.

Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function.

The metyrapone test is used to test the hypothalamic-pituitary-adrenocortical axis. The present study aims to assess the diagnostic accuracy of combined stimulation of ACTH and compound-S (CMP-S). In addition, we analyzed the safety and practicability of this test as an outpatient procedure. A total of 327 metyrapone tests were analyzed retrospectively in 185 patients (mean age, 50.3 +/- 15.2 yr). One hundred thirteen patients had one test, and 72 patients had between 2 and 6 tests over 1-3 yr. Most patients suffered from pituitary adenomas (60 macroadenomas, 63 microadenomas) or other pituitary lesions (n = 29). Metyrapone (2 g) was given at 2400 h as an outpatient procedure. Blood samples for analysis of ACTH, CMP-S, and cortisol were taken at 0730 h. Stimulation of adrenal CMP-S and cortisol by pituitary ACTH demonstrated a dose-response curve with the shape of half a geometric parabola. CMP-S reached a plateau when ACTH rose above 175 ng/liter [r = 0.661, P < 0.0001 for ACTH <175 ng/liter; r = 0.083, P = not significant (NS) for ACTH >175 ng/liter], cortisol flattened at ACTH levels above 230 ng/liter (r = 0.633; P < 0.0001 for ACTH < 230 ng/liter; P = NS for ACTH >230 ng/liter). Alternatively, the sum of CMP-S plus cortisol also flattened when ACTH rose above 230 ng/liter (r = 0.696; P < 0.0001 for ACTH <230; P = NS for ACTH > 230 ng/liter). Receiver operating curve analysis defining a cut-off for ACTH at 150 ng/liter demonstrated a sensitivity of 47% and 67% at a cut-off level for CMP-S at 200 or 260 nmol/liter, respectively. The respective specificity was 82% and 68% for CMP-S. This compared with a sensitivity of 71% and specificity of 69% if the sum of CMP-S plus cortisol of 450 nmol/liter were used as cut-off. The response curve between CMP-S and ACTH implies a maximally stimulated adrenal cortex at circulating ACTH levels above 175 ng/liter. Single measurement of CMP-S using the cut-off at 200 nmol/liter, as suggested in the literature, yields a poor sensitivity of only 47% compared with ACTH. Despite the relatively high cross-reactivity of CMP-S in the cortisol assay, the sum of CMP-S and cortisol levels with a cut-off value of 450 nmol/liter yields a better diagnostic accuracy compared with CMP-S alone.

Bioelectrical impedance analysis during acute changes of extracellular osmolality in man.

BACKGROUND & AIMS: Bioelectrical impedance analysis (BIA) is widely used as an inexpensive and noninvasive method to provide estimates of body compartments such as total body water, lean body mass and fat mass. The present study was performed to test the reliability of this method during acute changes of extracellular osmolality in eight young health men. METHODS: Hyperosmolal isohydration was achieved by overnight infusions of hypertonic saline solutions (2 and 5% NaCl) and thirsting, and hypoosmolal hyperhydration by drinking of free water and overnight application of desmopressin. The control study (isoosmolality) consisted of oral water ad libitum. RESULTS: When plasma osmolality and sodium concentrations increased (from 285 +/- 1 to 296 +/- 1 mmol/kg (P<0.001) and from 141.9 +/- 0.7 to 148.3 +/- 0.6 mmol/l (P<0.0001)) and total body water remained unchanged, body impedance decreased and calculated total body water increased from 42.7 +/- 2.7 to 45.6 +/- 2.3 liters (P<0.03). In contrast, during hypoosmolal hyperhydration total body water increased by 1.56 +/- 0.17 kg and plasma osmolality decreased from 285 +/- 1 to 272 +/- 1 mmol/kg (P<0.001) and plasma sodium concentrations from 142 +/- 0.5 to 134.8 +/- 0.4 mmol/l (P<0.0001). In spite of these changes of body water, impedance measurements and calculated total body water remained unchanged. During conditions of isoosmolal isohydration (as demonstrated by unchanged plasma sodium concentrations and osmolality) the measurements by BIA also remained unchanged. CONCLUSIONS: Measurements of total body water using BIA under conditions of unknown hydration status (hyper-, hypo- or isohydration) and unknown osmolality (hyper-, hypo- or isoosmolality) may not be reliable. Therefore bioelectrical impedance analysis is not a suitable bedside method to assess changes of body compartments under unstable hydration status.

Nutritional supplements combined with dietary counselling diminish whole body protein catabolism in HIV-infected patients.

BACKGROUND: Weight loss and protein malnutrition are frequent complications in HIV-infected patients. The effect of an oral nutritional supplement combined with nutritional counselling on whole body protein metabolism was assessed. MATERIALS AND METHODS: HIV-infected individuals with a body mass index < 21 kg m-2 or CD4-T cells < 500 micro L-1 in stable clinical condition were randomly allocated to [1] receive either oral nutritional supplements (containing 2510 kJ, complete macro- and micronutrients) and dietary counselling (n = 8), or [2] identical monitoring but no supplements or specific nutritional advice (controls, n = 7). Whole body leucine kinetics and leucine oxidation rate were determined by [1-13C]-leucine infusions and lean and fat mass were measured before and 12 weeks after intervention. RESULTS: Leucine oxidation (protein catabolism) decreased in the group receiving nutritional intervention from 0.33 +/- 0.02 to 0.26 +/- 0.02 micromol kg-1 min-1 after 12 weeks (P < 0.05; P < 0.05 vs. control group) but remained unchanged in the control group. Whole body leucine flux showed a tendency to decrease in the intervention group from 1.92 +/- 0.19 to 1.73 +/- 0.14 micromol kg-1 min-1 (P = 0.07) and remained unchanged in the control group (2.21 +/- 0.16 and 2.27 +/- 0.14 micromol kg-1 min-1, respectively). Lean body mass determined by bioelectrical impedance analysis increased in the nutritional intervention group from 84 +/- 2 to 86 +/- 2 per cent (P < 0.05) and fat mass decreased from 17 +/- 2 to 14 +/- 2 per cent (P < 0.05) of total body weight whereas neither mass changed in the control group. Nutritional intervention had no significant effect on lymphocyte CD4 counts, on plasma TNFR 55, TNFR 75 and ILR 2 concentrations and on quality of life. CONCLUSIONS: The data demonstrate an anticatabolic effect of nutritional supplements combined with dietary counselling in HIV-infected subjects. They suggest that diminished whole body protein catabolism resulted in a change of body composition (increased lean mass, decreased fat mass).

Effects of intradialytic parenteral nutrition in chronic haemodialysis patients with malnutrition: a pilot study.

BACKGROUND AND AIMS: Protein and calorie malnutrition is frequently observed in chronic haemodialysis (HD) patients. Recently it has been suggested that intradialytic nutritional support with amino acids may improve nutritional status and increase immunocompetence. The aim of this study was to evaluate the effects of intradialytic infusion of amino acids, lipids and glucose on body composition and other parameters of nutritional status in patients undergoing HD. METHODS: Seven patients with a mean age of 77 +/- 6 years (range, 60-86 years), a mean BMI of 20.1 +/- 2.8 (range, 16.1-24.4) and clinical signs of malnutrition participated in the study (mean time on HD, 51 +/- 36 months). HD was performed 12 hours per week with bicarbonate as a buffer and a polysulfon capillary dialyzer (F-60). During the 3-month period of intervention the patients received an intradialytic parenteral solution during the regular scheduled dialysis treatment, containing amino acids (12 g s/h), a glucose 15% solution (37.5 g/h) and a fat emulsion (12.5 g/h). RESULTS: (mean +/- SEM) Total calorie intake increased from 1550 +/- 63 to 2255 +/- 114 (kcal/24 h) p < 0.01, during the intervention period and body weight increased from 49.9 +/- 5.9 to 51.9 +/- 5.7 kg (p < 0.005). Fat mass and lean body mass (bioelectrical impedance analysis, BIA) increased from 13.2 +/- 2.6 to 14.2 +/- 2.6 (p < 0.02) and from 36.9 +/- 3.2 to 37.9 +/- 3.2 kg (p < 0.003), respectively. Plasma concentrations of albumin, total protein, transferrin, leptin IGF-I, IGFBP-3 and the protein catabolic rate remained unchanged. CONCLUSIONS: Supplementary intravenous intradialytic nutrition in chronic HD patients with malnutrition increased total body weight by effecting equivalent increases in lean body and fat masses.

Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man.

Chronic glucocorticoid therapy results in negative bone and connective tissue balance. To assess the effects of GH and a combination of IGF-I and GH, 24 healthy male volunteers received in a double blind fashion either recombinant human GH (0.3 IU/kg per day s.c.), or a combination of GH (0.3 IU/kg per day s.c.) and IGF-I (80 microgram/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0.5 mg/kg per day) treatment. Methylprednisolone decreased serum osteocalcin concentrations during placebo treatment from 32.9+/-2.1 to 9.0+/-1.4 microgram/l (P<0.0001), indicating diminished osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0.005), indicating diminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased during treatment with methylprednisolone alone, indicating increased bone resorption (P<0.05 or less). The combination of GH and IGF-I resulted in a significant blunting of the methylprednisolone effect on serum PICP and PIIINP concentrations (P<0.005 or less vs placebo); this effect was in part due to IGF-I, since serum PICP concentrations decreased less in the combination group than during GH treatment alone (P<0.05). In the groups receiving GH and GH combined with IGF-I, urinary hydroxyproline excretion increased more when compared with methylprednisolone alone (P<0.05 or less). These findings demonstrate that only the combination of GH and IGF-I, but not GH alone, markedly counteracts diminished bone and body collagen synthesis caused by glucocorticoids, whereas connective tissue resorption is enhanced during treatment with GH alone and in combination with IGF-I.

Effects of hyper- and hypoosmolality on whole body protein and glucose kinetics in humans.

To investigate the effect of acute changes of extracellular osmolality on whole body protein and glucose metabolism, we studied 10 male subjects during three conditions: hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl [2-5%; (wt/vol)] during 17 h; hypoosmolality was produced by intravenous administration of desmopressin, liberal water drinking, and infusion of hypotonic saline (0.4%); and the isoosmolality study consisted of ad libitum oral water intake by the subjects. Leucine flux ([1-13C]leucine infusion technique), a parameter of whole body protein breakdown, decreased during the hypoosmolality study (P < 0. 02 vs. isoosmolality). The leucine oxidation rate decreased during the hypoosmolality study (P < 0.005 vs. isoosmolality). Metabolic clearance rate of glucose during hyperinsulinemic-euglycemic clamping increased less during the hypoosmolality study than during the isoosmolality study (P < 0.04). Plasma insulin decreased, and plasma nonesterified fatty acids, glycerol, and ketone body concentrations and lipid oxidation increased during the hypoosmolality study. It is concluded that acute alterations of plasma osmolality influence whole body protein, glucose, and lipid metabolism; hypoosmolality results in protein sparing associated with increased lipolysis and lipid oxidation and impaired insulin sensitivity.