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Objective: The surgical option could represent a valid alternative to medical therapy in some diabetic patients. However, no data are available on long-term effects of metabolic surgery on diabetic complications. We aimed to determine whether patients with newly diagnosed type 2 diabetes who underwent bilio-pancreatic diversion (BPD) had less micro- and macrovascular complications than those who received conventional therapy.Research Design and Methods: This was an unblinded, case-controlled trial with 10-years' follow-up, conducted from July 1998 through October 2009 at the Day Hospital of Metabolic Diseases, Catholic University, Rome, Italy. A consecutive sample of 110 obese patients (BMI >35 kg/m(2)) with newly diagnosed type 2 diabetes was enrolled. The study was completed by 50 subjects. The main outcome measure was long-term effects (10 years) of BPD versus those associated with conventional therapy on microvascular outcome, micro- and macroalbuminuria, and glomerular filtration rate (GFR). Secondary measures included macrovascular outcomes, type 2 diabetes remission, glycated hemoglobin, and hyperlipidemia.Results: Ten-year GFR variation was -45.7 ± 18.8% in the medical arm and 13.6 ± 24.5% in the surgical arm (P < 0.001). Ten-year hypercreatininemia prevalence was 39.3% in control subjects and 9% in BPD subjects (P = 0.001). After 10 years, all BPD subjects recovered from microalbuminuria, whereas microalbuminuria appeared or progressed to macroalbuminuria in control subjects. Three myocardial infarctions, determined by electrocardiogram, and one stroke occurred in control subjects. After the 10-year follow-up, coronary heart disease (CHD) probability was 0.22 ± 0.10 and 0.05 ± 0.04 in the medical and surgical groups, respectively (P < 0.001). Remission from type 2 diabetes was observed in all patients within 1 year of surgery. Surgical and medical subjects had lost 34.60 ± 10.25 and 0.38 ± 6.10% of initial weight at the 10-year follow-up (P < 0.001).Conclusions: Renal and cardiovascular complications were dramatically reduced in the surgical arm, indicating long-term benefits of BPD on diabetic complications, at least in the case of morbid obesity with decompensated type 2 diabetes. [ABSTRACT FROM AUTHOR]

ims/hypothesis: Incretins are hormones released by enteroendocrine cells in response to meals, depending upon absorption of nutrients. The present study aimed to elucidate the mechanisms through which a high-fat diet (HFD) induces insulin resistance and insulin hypersecretion by focusing on the effects on enteroendocrine cells, especially those secreting glucose-dependent insulinotropic polypeptide (GIP). Methods: Forty male Wistar rats, 4 months old, were randomised into two groups; one group received a chow diet and the other one received a purified tripalmitin-based HFD ad libitum. An OGTT was performed every 10 days and histological and immunofluorescence evaluations of the duodenum were obtained at 60 days from the beginning of the diets. Plasma glucose, insulin, GIP and glucagon-like peptide-1 (GLP-1) levels were measured. Immunofluorescence analysis of duodenal sections for pancreatic duodenal homeobox-1 (PDX-1), KI67, GLP-1, GIP and insulin were performed. Results: Compared with chow diet, HFD induced a progressive significant increase of the glucose, insulin and GIP responses to OGTT, whereas GLP-1 circulating levels were reduced over time. After 60 days of HFD, cellular agglomerates of KI67 and PDX-1 positive cells, negative for insulin and GLP-1 but positive for GIP staining, were found inside the duodenal mucosa, and apoptosis was significantly increased. Conclusions/interpretation: With the limitation that we could not establish a causal relationship between events, our study shows that HFD stimulates duodenal proliferation of endocrine cells differentiating towards K cells and oversecreting GIP. The progressive increment of GIP levels might represent the stimulus for insulin hypersecretion and insulin resistance. [ABSTRACT FROM AUTHOR]

Bariatric surgery is the most effective therapy for severe obesity in terms of reduction of morbidity and mortality and quality of life improvement. Different bariatric procedures distinctly differ with regard to their effectiveness to reduce body weight and to improve morbidities, such as type 2 diabetes. In this regard, the most effective procedures are bilio-pancreatic diversion (BPD) and duodenal switch procedure curing 98.9% of the diabetes patients, followed by Roux-en-Y gastric bypass (RYGB) with 83.7% success rate, by gastroplasty with 71.6% and by gastric banding with 47.9%. Interestingly, a net improvement up to resolution of type 2 diabetes has been consistently reported few days after RYGB and BPD. RYGB promotes incretin secretion which, in turn, stimulates insulin secretion while insulin sensitivity is slightly improved. Rarely, the long-term effect of incretin hypersecretion might result in hypertrophy and hyperplasia of the islets of Langerhans, otherwise known as nesidioblastosis, associated with hyperinsulinaemia and severe postprandial hypoglycaemia. In contrast, BDP improves insulin resistance to a greater extent and results, in the long run, in supra-normal values of insulin sensitivity with subsequent reduction of insulin secretion. The mechanism allowing diabetes resolution after surgical intestinal manipulation is extremely interesting but only partially understood. [ABSTRACT FROM AUTHOR]

To aim of the study was to investigate the effect of bilio-pancreatic diversion (BPD) on type 2 diabetes in patients with BMI <35 kg/m2. OGTTs were performed and anthropometric data were compared between five diabetes patients (BMI 27–33 kg/m2) following BPD and seven diabetes patients after a low-energy diet. Insulin secretion was computed by C-peptide deconvolution. A euglycaemic–hyperinsulinaemic clamp was performed only in the BPD group and the M value measured. One month after BPD, fasting and 2 h post-OGTT glycaemia decreased from 15.22 ± 3.22 to 6.22 ± 0.51 mmol/l ( p = 0.043), while insulin sensitivity increased significantly. No significant changes were observed in the low-energy diet group. Insulin secretion did not differ significantly after either intervention. Diabetes amelioration (change in HbA1c level) was observed up to 18 months after BPD without pharmacological therapy. BPD can achieve adequate control of type 2 diabetes also in patients with BMI <35 kg/m2. The rapid postoperative remission of diabetes is primarily related to an improvement in insulin sensitivity. [ABSTRACT FROM AUTHOR]

Lipoapoptosis has been described in many organs and tissues, but never in enterocytes. We hypothesized that a high saturated-fat diet can induce duodenal enterocyte apoptosis and impair gastric inhibitory polypeptide (GIP) secretion. Forty male Wistar rats, ∼4 months old, were randomized on standard laboratory or purified tripalmitin-based high-fat diet (59% calories). An oral-glucose tolerance test was performed after 30 and 90 days of diet to measure plasma glucose, insulin and GIP. Duodena were processed for histology and immunohistochemistry by transferase-mediated dUTP nick end-labeling (TUNEL) method. Apoptosis was confirmed by enzyme-linked immunosorbent assay. Glycemic response was significantly higher (P<0.01 vs controls) in rats after 90 days. Insulin curve was markedly increased at 30 days, while it was blunted at 90 days. GIP area under the curve was 425.6±67.6 ng ml−1 at 30 days vs 150.2±33.4 ng ml−1 in controls (P<0.001) and dropped to 53.8±25.8 ng ml−1 at 90 days (P<0.0001). TUNEL-positive nuclei were 66.08±26.19 at 30 days 57 (34.58±17 in controls, P<0.05) and 216.99±129.42 nuclei per mm3 at 90 days (38.75±18.36 in controls, P<0.0001). A high saturated-fat diet stimulates GIP secretion but with time induces apoptosis of duodenal villi epithelium, showing for the first time that enterocytes are also prone to lipoapoptosis. The reduction of circulating GIP levels might contribute to hypoinsulinemia and hyperglycemia.International Journal of Obesity (2008) 32, 871–874; doi:10.1038/ijo.2008.9; published online 19 February 2008 [ABSTRACT FROM AUTHOR]

Objective:Insulin resistance is a strong biological marker of both obesity and type 2 diabetes. Abnormal fat deposition within skeletal muscle has been identified as a mechanism of obesity-associated insulin resistance. Biliopancreatic diversion (BPD), inducing a massive lipid malabsorption, leads to a reversion of type 2 diabetes. To elucidate the mechanisms of diabetes reversibility, the expression of genes involved in glucose and free fatty acids (FFAs) metabolism was investigated in skeletal muscle biopsies from obese, type 2 diabetic subjects. Peripheral insulin sensitivity and insulin secretion was also measured.Subjects:Eight Caucasian obese diabetic patients (BMI 52.1±1.85 kg/m2) were studied before and 3 years after BPD.Measurements:The mRNA levels were estimated by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), insulin sensitivity by the euglycemic–hyperinsulinemic clamp and insulin secretion using a model describing the relationship between insulin secretion and glucose concentration.Results:Whole-body glucose uptake (M), normalized by fat-free mass, significantly increased in post-obese subjects (P<0.0001). Total insulin output decreased (P<0.05) in association with a significant improvement of β-cells glucose sensitivity (P<0.05). mRNA levels of FABP3 (P<0.05), FACL (P<0.05), ACC2 (P<0.05), HKII (P<0.05) and PDK4 (P<0.05) were significantly decreased, while SREBP1c mRNA increased (P<0.05) after BPD.Conclusion:Reversibility of type 2 diabetes after BPD is dependent on the improvement of skeletal muscle insulin sensitivity, mediated by changes in the expression of genes regulating glucose and fatty acid metabolism in response to nutrient availability.International Journal of Obesity (2007) 31, 1429–1436; doi:10.1038/sj.ijo.0803630; published online 22 May 2007 [ABSTRACT FROM AUTHOR]

Aims/hypothesis The aim of this study was to analyse the mechanisms underlying the improvement in glucose tolerance seen in morbidly obese patients undergoing biliopancreatic diversion (BPD). Subjects and methods We evaluated glucose tolerance (by OGTT), insulin sensitivity (euglycaemic-hyperinsulinaemic clamp and the OGTT index OGIS) and beta cell function (OGTT modelling analysis) in 32 morbidly obese (BMI=52± 7 kg/m², mean±SD) patients (12 with NGT, 9 with IGT and 11 with type 2 diabetes), before and after BPD, and in 22 lean control subjects. Patients were studied before and from 7 days to 60 months after surgery. Results BPD improved glucose tolerance in all subjects, who after surgery all had normal glucose tolerance. Insulin sensitivity was restored to normal levels in all subjects (pre-BPD 341±79 ml min-1 m-2, post-BPD 511±57 ml min-1 m-2, lean 478±49 ml min-1 m-2). The insulin sensitivity change was detectable within 10 days of BPD. At baseline, beta cell sensitivity to glucose was impaired in diabetic subjects (25 [18] pmol min-1 m-2 l mmol-1, median [interquartile range]) compared with lean subjects (82 [98]; p≤0.05). After BPD, beta cell glucose sensitivity showed a tendency towards improvement but remained impaired in diabetic subjects (30 [62]; p<0.01 vs lean). Total insulin output decreased in parallel with the insulin sensitivity increase in all groups. In the whole patient group, mean OGTT glucose levels were inversely related to both insulin sensitivity and beta cell glucose sensitivity (r²=0.67, partial r=-0.76 and -0.41, respectively). NEFAs, leptin and adiponectin were related to insulin sensitivity but could not explain the early improvement. Conclusions/interpretation Following BPD, glucose tolerance was restored mainly as a result of a rapid and large improvement in insulin sensitivity. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: In obesity the cellular capacity to switch from using lipid to carbohydrate and vice versa as the energy substrate, known as ‘metabolic flexibility’, is impaired. Mitofusin 2 (MFN2), a mitochondrial membrane protein, seems to contribute to the maintenance and operation of the mitochondrial network, and its expression is reduced in obesity. The aim of this study was to verify whether MFN2 might be implicated in the metabolic inflexibility of obesity. Materials and methods: Insulin sensitivity was measured in six morbidly obese women before and 2 years after malabsorptive bariatric surgery (BMI 53.3±10.5 vs 30.3±4.0 kg/m²). Skeletal muscle MPN2, SLC2A4 (formerly known as GLUT4), COX3 (encoding cytochrome c oxidase subunit III) and CS (encoding citrate synthase) mRNA levels were measured by real-time PCR. Results: Following bilio-pancreatic surgery, significant increases in MPN2 mRNA (from 0.4±0.2 to 1.7±1.1 arbitrary units [AU], p=.019) and SLC2A4 mRNA (0.38ଐ.12 to 0.76±0.24 AU, p=0.04) were observed, while increases in COX3 mRNA (from 14.2±6.4 to 20.2±12.5 AU) and CS mRNA (from 0.4±0.1 to 0.7±0.3 AU) failed to reach statistical significance. Insulin-mediated whole-body glucose uptake significantly (p<0.0001) increased from 21.2±4.1 to 52.8±5.9 µmol kg fat-free mass-1 min-1 and glucose oxidation rose from 11.1±2.1 to 37.7±4.7 µmol kg fat-free mass-1 min-1 (p<0.0001). Levels of MFN2 mRNA were strongly correlated with the absolute values for the glucose oxidation rate, both during fasting (glucose oxidation =3.55 MFN2 mRNA + 3.93; R²=0.92, p<0.0001) and during the clamp (glucose oxidation=18.8 MFN2 mRNA+34.7; R²=0.80, p<0.0001). The percentage changes in MFN2 mRNA were positively correlated with the percentage change in glucose oxidation during the clamp (glucose oxidation percent (%) change=0.3 MFN2 mRNA percent (%) change +153.2; R²=0.6 1, p<0.001). Conclusions/interpretation: We propose that the significant increase in MFN2 mRNA levels may explain the increase in glucose oxidation observed in morbid obesity following bariatric surgery. [ABSTRACT FROM AUTHOR]

AIMS/HYPOTHESIS: The aim of the present study was to investigate the relationship between intramyocytic triglycerides levels, muscle TNF-α and GLUT4 expression and insulin resistance. METHODS: Insulin sensitivity was studied in 14 severely obese women (BMI > 40 kg/m²), before and 6 months after low-dietary intake or bariatric malabsorptive surgery (bilio-pancreatic diversion, BPD), by the euglycaemic hyperinsulinaemic clamp technique, while the amount of intramyocytic triglycerides was chemically measured in needle muscle biopsies. Using reverse transcriptase-polymerase chain reaction analysis, the muscle mRNA expression of TNF-α and GLUT4 was also investigated. RESULTS: The weight loss after surgery was 25.98 ± 5.81 kg (P < 0.001), while that obtained with the diet was 5.07 ± 5.99 kg (P = NS). Marked decrease in TNF-α mRNA levels (76.67 ± 12.59 to 14.01 ± 5.21 AU, P <0.001) were observed in comparison with pre-treatment, whereas GLUT4 was significantly increased (62.25 ± 11.77 ± 124.25 ± 21.01 AU, P< 0.001) only in BPD patients. Increased glucose uptake (M) was accompanied by a significant decrease of TNF-α mRNA (76.67 ± 12.59 14.01 ± 5.21 AU, P < 0.01) and an increase of GLUT4. The amounts of TNF-α mRNAs in skeletal muscle correlated inversely with GLUT4 mRNAs and directly with intramyocytic triglycerides levels, in a step-down regression analysis (r² = 0.95) TNFα mRNA (P=0.0014), muscular TG levels (P=0.018), and GLUT4 mRNA (P=0.028) resulted to be the most powerful independent variables for predicting M values. CONCLUSION/INTERPRETATION: These findings suggest that insulin resistance in morbidly obese patients is positively associated to the intramyocytic triglycerides content and to TNF-α gene expression and inversely correlated to GLUT4 expression. [ABSTRACT FROM AUTHOR]

Sex mismatch is a well-known risk factor for chronic rejection of liver allografts, but the mechanisms involved remain unclear. Since experimental observations suggest that female liver is more sensitive to reperfusion injury than male liver, we assessed the influence of gender on oxidative stress. Livers from male and female rats were exposed to warm ischemia and reperfused by an oxygenated buffer. Chemiluminescence was continuously recorded. Reduced and oxidized glutathione and malondialdehyde lactic dehydrogenase values were also determined. Chemiluminescence increased during reperfusion in both groups, but was significantly greater in livers from female rats. Malondyaldehyde and lactic dehydrogenase progressively increased in all animals, reaching significantly greater values in female rats. Livers from female rats showed an increase in all the parameters of oxidative stress compared to male animals. A greater susceptibility to reperfusion injury may be evoked as an alternative mechanism to explain the poor outcome of female organ after liver transplantation. [ABSTRACT FROM AUTHOR]

Although reports of decreased plasma taurine in trauma, sepsis and critical illness are available, very little is known about the relationships among changes in plasma taurine, other amino acid levels and metabolic variables. We analyzed a large series of plasma amino acid profiles obtained in trauma patients with sepsis who were undergoing total parenteral nutrition. The correlations between plasma taurine, other amino acid levels, parenteral substrate doses and metabolic and cardiorespiratory variables were assessed by regression analysis. Post-traumatic hypotaurinemia was followed by partial recovery toward less abnormal values when sepsis developed. Levels of taurine were directly and significantly related to levels of glutamate, aspartate, beta-alanine and phosphoethanolamine (and unrelated to other amino acids). Levels of these amino acids increased simultaneously with increasing doses of leucine, isoleucine and valine in total parenteral nutrition. Decreasing taurine was associated with increasing lactate, arteriovenous O(2) concentration difference and respiratory index, and with decreasing cholesterol and cardiac index. These results characterize the relationships between plasma taurine and other amino acid levels in sepsis, provide evidence of amino acid interactions that may support taurine availability and show more severe decreases in plasma taurine with the worsening of metabolic and cardiorespiratory patterns. [ABSTRACT FROM AUTHOR]

This study has been performed to characterize the relationship between changes in plasma taurine (TAU) and hemodynamic patterns in sepsis. Analysis of 249 plasma aminoacidograms (AA-grams) and associated measurements in a group of critically ill, mechanically ventilated septic patients, showed that decreases in TAU were significantly correlated with increases in pulmonary artery pressure and pulmonary vascular resistance, and with worsening of pulmonary dysfunction. All cases requiring posi-tive end-expiratory pressure greater than 10 cmH2O had TAU lower than 50 μM/L. Low TAU was paralleled by decreases in other sulfur-containing AA, phosphoethanolamine, β-alanine, glutamate and aspartate, within a pattern of greater metabolic dysregulation. These data provide evidence of a link between severity of pulmonary dysfunction and reduced TAU availability in clinical sepsis. The implications relate also to the need for specific investigations of the clinical effect of exogenous TAU on proinflammatory mediator-induced pulmonary dysfunction. [ABSTRACT FROM AUTHOR]

Raised plasma triglycerides (TGs) and nonesterified fatty acid (NEFA) concentrations are thought to play a role in the pathogenesis of insulin-resistant diabetes. We report on two sisters with extreme hypertriglyceridemia and overt diabetes, in whom surgical normalization of TGs cured the diabetes. In all of the family members (parents, two affected sisters, ages 18 and 15 years, and an 11-year-old unaffected sister), we measured oral glucose tolerance, insulin sensitivity (by the euglycemic-hyperinsulinemic clamp technique), substrate oxidation (indirect calorimetry), endogenous glucose production (by the [6,6-2H2]glucose technique), and postheparin plasma lipoprotein lipase (LPL) activity. In addition, GC-clamped polymerase chain reaction-amplified DNA from the promoter region and the 10 coding LPL gene exons were screened for nucleotide substitution. Two silent mutations were found in the father's exon 4 (Glu118 Glu) and in the mother's exon 8 (Thr361 Thr), while a nonsense mutation (Ser447 Ter) was detected in the mother's exon 9. Mutations in exons 4 and 8 were inherited by the two affected girls. At 1-2 years after the appearance of hyperchylomicronemia, both sisters developed hyperglycemia with severe insulin resistance. Because medical therapy (including high-dose insulin) failed to reduce plasma TGs or control glycemia, lipid malabsorption was surgically induced by a modified biliopancreatic diversion. Within 3 weeks of surgery, plasma TGs and NEFA and cholesterol levels were drastically lowered. Concurrently, fasting plasma glucose levels fell from 17 to 5 mmol/l (with no therapy), while insulin-stimulated glucose uptake, oxidation, and storage were all markedly improved. Throughout the observation period, plasma TG levels were closely correlated with both plasma glucose and insulin concentrations, as measured during the oral glucose tolerance test. These cases provide evidence that insulin-resistant diabetes can be caused by extremely high levels of TGs. [ABSTRACT FROM AUTHOR]

Increased airway reactivity has been found in family members of school age children and adults with asthma. As the relation between recurrent wheeze in infancy and bronchial reactivity is not yet clear, it was decided to test bronchial reactivity to methacholine in both parents of 50 preschool age children with recurrent wheeze and in 200 population based controls matched for sex, age, smoking habits, and atopy. Wheezy children fulfilled the following criteria: first attack of wheezing before the age of 2 years, at least four wheezing episodes triggered by a respiratory infection, negative skin prick tests, and no symptoms related to allergy. Four parents and five controls did not undergo the methacholine challenge because their forced expiratory volume in one second was < 80% of the predicted value. Methacholine reactivity was not significantly different in parents and controls. In summary, an increased bronchial responsiveness was not found in parents of infants and young children with recurrent wheeze triggered by infection. [ABSTRACT FROM AUTHOR]

BACKGROUND: Obesity is characterised by growth hormone (GH) abnormalities, including a blunted response to stimulation and a ‘paradoxical’ increase after meals. The blunted GH release is reversed by a surgical intestinal bypass procedure. However, this does not mean that normal GH dynamics have been restored. The present study assessed whether post-surgical weight reduction in obese patients normalised the modulation of GH release produced by metabolic fuels. SUBJECTS: Ten obese female subjects, aged 23–54 y, were studied before and after biliopancreatic diversion (BPD). All patients, after surgery, had experienced a significant reduction in body weight (mean body mass index (BMI) 25.78±1.01 kg/m2 vs 44.68±1.73 kg/m2). Two groups were also studied as controls: Ten normal body weight female subjects and ten patients suffering from anorexia nervosa (AN, mean BMI 17.46±1.12 kg/m2). MEASUREMENTS: We have studied the GH response to a GH releasing hormone (GHRH) bolus (1 μg/kg iv, at 13.00 h) before and after a standard meal. RESULTS: In post-BPD subjects, the GH response to GHRH in the fasting state, was clearly augmented in comparison with the pre-BPD values (peak values 18.06±4.56 vs 3.24±0.68 μg/L). In post-BPD subjects the postprandial GH response was further augmented in comparison with the fasting test (peak 30.12±4.99 μg/L, P<0.05). This pattern was similar to that observed in anorexic patients. CONCLUSION: The surgical procedure restores a normal GH response to GHRH in the fasting state, but the ‘paradoxical’ GH response after meals remains present, suggesting a persistent GH derangement in such patients, which is not related to body weight per se. The surgical procedure makes obese patients similar to anorexics, in the relationships between metabolic fuels and GH secretion. The persistence of the GH postprandial response to GHRH in post-BPD... [ABSTRACT FROM AUTHOR]

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery (POI); and after reaching stable body weight, at least 2 years after surgery (POII). A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 ± 8.57 vs 18.14 ± 8.57 μmol · kg−1· min−1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 ± 7.23 vs 9.42 ± 3.91 μmol · kg−1· min−1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 ± 223.9 vs 1039.6 ± 283.4 vs 616.0 ± 77.6 μmol · l−1). The same applied to basal plasma triglycerides (2.07 ± 0.77 vs 1.36 ± 0.49 vs 0.80 ± 0.19 g · l−1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 ± 11.22 to 69.71 ± 11.78, 83 % of total decrement), rather than in the early postoperative period (Ob to POI 135.25 ± 14.99 to 124.28 ± 11.22 kg, 17 % of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance. [Diabetologia (1997) 40: 599–605] [ABSTRACT FROM AUTHOR]

Even-numbered dicarboxylic acids (DA) have been proposed as an alternative fuel substrate in parenteral nutrition. In particular, dodecanedioic acid (C12) shows a rapid plasma clearance from tissues, a very low urinary excretion compared with other DA and a high oxidation rate. The aim of the present study was to investigate the effect of C12 infusion on insulin-stimulated glucose uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM) compared with healthy volunteers. A primed-constant infusion of C12 (0·39 mmol/min) was administered over 240 min, and at 120 min a 2 h euglycaemic hyperinsulinaemic clamp was performed. Blood specimens were sampled every 30 min and fractioned urines were collected over 24 h. The levels of C12 were measured by HPLC. Indirect calorimetry was performed continuously during the entire session. Body composition was assessed in all subjects studied to obtain fat-free mass (FFM) values. Whole-body glucose uptake decreased significantly during C12 infusion in both groups, although this effect was much more evident (P < 0·01) in NIDDM patients (52·4 (sd 15·8) % decrease compared with saline) than in controls (25·9 (sd 12·1) % decrease). The M value (μmol/kgffm per min) was reduced by C12 to lower levels in NIDDM patients than in normal controls (12·6 (sd 3·9) ν. 25·9 (sd 4·5), P < 0·01). Urinary excretion of C12 over 24 h was significantly lower in NIDDM patients than in controls (4·26 (sd 0·30) mmol ν. 5·43 (sd 0·48), P < 0·01), corresponding to less than 3 % of the administered dose. The infusion of C12 decreased non-protein RQ significantly in both groups of patients. In conclusion, this study shows, for the first time, that C12 significantly reduces glucose uptake in both normal controls and NIDDM patients, although this sparing effect on glucose uptake is much more pronounced in diabetic patients. These data suggest that C12 decreases glucose uptake and oxidation, mainly through a mechanism of substrate competition. Thus, it might be a useful alternative substrate in enteral or parenteral nutrition, sparing glucose utilization and increasing glycogen stores, in those clinical conditions, like NIDDM, where reduced insulin-induced glucose uptake and oxidation are observed. [ABSTRACT FROM PUBLISHER]

Hemodynamic variables were used to evaluate the effectiveness of lumbar chemical sympathectomy in 20 patients with ischemic foot lesions. Early clinical improvement was obtained in 68% of the cases. The two-year cumulative limb salvage rate was 52%. Results indicate that lumbar chemical sympathectomy offers the same benefits as surgical sympathectomy and represents a useful alternative in patients with advanced ischemic disease of the lower limb, decreasing the rate and the level of amputations. [ABSTRACT FROM AUTHOR]

A four-year prospective study of distal revascularization in diabetics with trophic damage of the limbs is presented. Thirty-two infrapopliteal bypasses in 32 limbs of 31 diabetic patients were performed. One-year and three-year graft patency rates were 68% and 59% respectively. Limb salvage was obtained in every case of surgical success. [ABSTRACT FROM PUBLISHER]

Hemodynamic, metabolic, and respiratory parameters were measured be fore aortic cross-clamping and after declamping in 14 pigs undergoing experi mental aorto-aortic bypass procedures.The changes observed at declamping provided cumulative evidences of a loss of myocardial competence and of peculiar metabolic alterations, which were more pronounced in the cases with a lethal outcome.These findings emphasize the need for perioperative support of physiologic functions and for the use of protective measures during aortic cross-clamping and ischemia. They also imply the possibility of using new parameters as indica tors of the severity of the alterations induced by ischemia and as prognostic indicators. [ABSTRACT FROM PUBLISHER]

Sepsis is characterized by an abnormal increase in plasma proline (PRO) level, which tends to be related to the severity of disease. This study has been performed to assess the relationship between changes in plasma PRO and levels and doses of other amino acids (AA) in critically ill septic patients undergoing total parenteral nutrition (TPN). Sixteen septic patients receiving TPN were randomly divided into two groups: 8 patients (Group A) received TPN with a standard AA solution, and 8 patients (Group B) with a modified AA solution (isonitrogenous, branchedchain AA enriched, with unchanged PRO concentration). Serial determinations of plasma AA profiles and of other variables were performed in each patient for a total of 396 measurements. In Group A mean plasma PRO level was 372 μM/L; changes in PRO were tightly correlated with changes in the levels of most of the other AA, and the highest PRO levels characterized the more severely unbalanced septic metabolic profiles. In Group B, plasma levels of PRO and of the other AA (except glutamate, aspartate, taurine and the three branched-chain AA) decreased. The decrease in PRO level was well correlated with the increased branched-chain AA dose and with simultaneous decreases in plasma lactate and respiratory quotient. These changes could be related to a specific effect of branched-chain AA on septic metabolic derangement and on PRO metabolism, and to an improved balance between protein synthesis and catabolism. [ABSTRACT FROM AUTHOR]

A four-year prospective study of distal revascularization in diabetics with trophic damage of the limbs is presented. Thirty-two infrapopliteal bypasses in 32 limbs of 31 diabetic patients were performed. One-year and three-year graft patency rates were 68% and 59% respectively. Limb salvage was obtained in every case of surgical success. [ABSTRACT FROM AUTHOR]

Hemodynamic, metabolic, and respiratory parameters were measured before aortic cross-clamping and after declamping in 14 pigs undergoing experimental aorto-aortic bypass procedures. The changes observed at declamping provided cumulative evidences of a loss of myocardial competence and of peculiar metabolic alterations, which were more pronounced in the cases with a lethal outcome. These findings emphasize the need for perioperative support of physiologic functions and for the use of protective measures during aortic cross-damping and ischemia. They also imply the possibility of using new parameters as indicators of the severity of the alterations induced by ischemia and as prognostic indicators. [ABSTRACT FROM AUTHOR]

The inhibitory effect of glucocorticoids on the in vitro response to phytohaemagglutinin of the residual circulating T lymphocytes in renal transplant patients during maintenance immunosuppressive therapy with glucocorlicostcroids and azathioprine has been investigated. As in normal subjects, the steroid-induced inhibition of transplanted patients' lymphocyte response was inversely correlated with the mitogen concentration used. On the other hand, the response of the various lymphocyte preparations from transplanted patients appeared less inhibited by steroids than the corresponding preparations from normal subjects. The addition lo the culture of the adherent cell product interleukin I was effective in removing to a similar extent the steroid inhibitory effect on lymphocytes from normal and transplanted subjects. Thus, the lesser inhibitory effect of glucocorticoids on transplanted patient lymphocytes could be explained by the higher percentages of monocytes present in all peripheral blood mononuclear cell preparations. These results suggest that during immunosuppressive therapy with glucocorticoids and azathioprine the residual circulating lymphocytes have a responsiveness to in vitro dexamethasone suppression similar to that of normal peripheral blood lymphocytes. [ABSTRACT FROM AUTHOR]

The distribution of T-lymphocyte subpopulations bearing receptors for the Fc portion of IgG (TG) or IgM (TM) was monitored in 22 renal allograft recipients treated with immunosuppressive therapy and in 10 uraemic patients on haemodialysis. No significant difference in the distribution of T cells and T-cell subsets was found between normal controls and haemodialysed patients. In transplanted patients, however, a significant reduction of the total T-cell percentage (P < 0.005), of TM subset percentage (P < 0.025) and absolute number (P < 0.005) and of TG absolute number (P < 0.05) was observed. Considering patients with allografts functioning for more than 1 year only, the reduction in TM cells in terms of percentage (P < 0.0005) and absolute number (P < 0.025) was significant, while TG subset levels did not change significantly. In patients transplanted less than 1 year previous to our study, total T cells and T-cell subsets were reduced significantly only as absolute numbers. During the 1st year we observed several increments of TM values towards normal levels, especially in the first 2 months after transplantation. During this period, TM subset levels sharply increased at acute rejection crisis and returned to previous values with rejection reversal. Our results suggest that the TM subset plays a prominent role in the mechanisms involved in the immunological response to allografts, and therefore repeated TM cell monitoring could be useful in the follow-up of renal transplant patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on livedo reticularis as a side effect of amantadine during the treatment of chronic hepatitis C.

Background: About 50% of kidney-transplant patients undergo organ rejection within 10 years. Chronic allograft nephropathy (CAN) represents the dominant cause of kidney transplant failure and accounts for 50-80% of graft loss in long-term surviving patients. CAN pathogenesis is multifactorial and not-completely elucidated; several reports indicate TGF-beta1 and platelet-derived growth factor (PDGF)-BB expression in CAN suggesting a possible role of these factors in the allograft arteriosclerosis and graft failure.Methods: We investigated the plasma expression concentrations of human growth factors with enzyme-linked immunosorbent assays and appropriate statistical analysis.Results: We present evidences showing statistically significant association of CAN with a specific balance between TGF Beat1 and PDGF-BB plasma concentrations, in 129 kidney-transplant patients and 15 healthy controls. Odds ratios were computed to correlate expression-levels with CAN occurrence.Conclusion: We believe these data may suggest a novel non-invasive method to identify early molecular markers of graft deterioration. [ABSTRACT FROM AUTHOR]