Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).     

A potential role for muscle in glucose homeostasis: in vivo kinetic studies in glycogen storage disease type 1a and fructose-1,6-bisphosphatase deficiency

Background  

A potential role for muscle in glucose homeostasis was recently suggested based on characterization of extrahepatic and extrarenal glucose-6-phosphatase (glucose-6-phosphatase-β). To study the role of extrahepatic tissue in glucose homeostasis during fasting glucose kinetics were studied in two patients with a deficient hepatic and renal glycogenolysis and/or gluconeogenesis.     

Extended metabolic evaluation of suspected symptomatic hypoglycemia: the prolonged fast and beyond

The diagnostic evaluation of spontaneous hypoglycemia in adults is mainly directed at detecting an insulinoma. Its interpretation is troublesome in those patients who develop low venous plasma glucose levels with appropriate hypoinsulinemia during a prolonged supervised fast. In this study, we investigated in this group of patients whether abnormalities in intermediary metabolism (fatty acid oxidation and amino/organic acids) could be detected that might explain the hypoinsulinemic hypoglycemia. Ten patients with otherwise unexplained low venous plasma glucose levels (<3 mmol/L) during prolonged fasting were included in the study. The patients participated in an extended metabolic protocol based on stable isotope techniques after an overnight fast to explore abnormalities in endogenous glucose production and intermediary metabolism. Endogenous glucose production, glucoregulatory hormones, plasma acylcarnitines, gluconeogenic amino acids, and rates of fatty acid and carbohydrate oxidation after 16 and 22 hours of fasting were measured. Although during the prolonged fast all patients had low venous plasma glucose level, there were no hypoglycemic events during the extended metabolic protocol. No abnormalities in endogenous glucose production (compared with reference values obtained in young healthy volunteers), fatty acid oxidation, or amino acid/organic acids were found in this patient group. In a group of patients exhibiting low venous plasma glucose levels during prolonged fasting in whom insulinoma was excluded, we found no signs of metabolic disorders. Therefore, the observation of low plasma glucose values in this subgroup of patients probably does not warrant extensive metabolic evaluation.     

Short-term exogenous galactose supplementation does not influence rate of appearance of galactose in patients with classical galactosemia

INTRODUCTION: Recently, evidence has been presented that adult patients with classical galactosemia have higher than expected galactose tolerance. This may be caused by a decrease of endogenous galactose production with ageing. Alternatively, suppression of endogenous galactose production by exogenous galactose might be implicated. The aim of this study was to determine if the rate of appearance of galactose is suppressed by exogenous galactose. MATERIALS AND METHODS: Two adult patients with classical galactosemia and three healthy control subjects were given a primed continuous infusion of D-[1-13C]galactose to determine the rate of appearance of galactose (GAR, expressed as micromol/kg/h) before and during additional galactose supplementation. After initial assessment of GAR (GAR1), GAR was determined during doubled (GAR2) or quadrupled (GAR4) galactose infusion. RESULTS: GAR1 was 2.48 and 2.44 in patients 1 and 2, and 0.46, 0.34, and 0.39 in control subjects 1, 2, and 3, respectively. GAR(2) was 2.43 and 2.13 in patients 1 and 2, and 0.57, 0.38, and 0.47 in control subjects 1, 2, and 3, respectively. In patient 1 the experiment was repeated during quadrupled galactose infusion. Here GAR1 was 3.01 and GAR4 was 3.26. CONCLUSIONS: No significant differences between GAR before and during additional galactose infusion were found in patients and in control subjects. GAR1 was significantly higher in patients than in control subjects. We conclude that the rate of appearance of galactose is not influenced by exogenous galactose, at least under short-term conditions, in patients with classical galactosemia and in control subjects.     

Management of hardware infections following deep brain stimulation

Summary Objective. To report our experience on hardware-related infections following deep brain stimulation (DBS).Methods. The present article presents the retrospective clinical notes review of gained in a two-centre, single-surgeon study experience of 108 consecutive DBS cases between 1996 and 2002. In all patients the minimum follow-up was six months. One hundred and eight patients received an intracerebral electrode implantation and 106 underwent internalization.Results. In total 178 electrodes were implanted with a mean follow-up of 42.6 months and a cumulative follow-up of 367.7 patient-years. Four patients (3.8%) developed an infection related to the DBS-hardware and all were initially treated with antibiotics. Two patients eventually required additional surgical treatment.Conclusion. Infections due to DBS-hardware can result in considerable levels of morbidity. In certain cases antibiotic therapy may be adequate. In others, surgical intervention to externalise the electrodes may be necessary. In our experience, there was never a need to remove the electrodes.     

Dietary fat content alters insulin-mediated glucose metabolism in healthy men

BACKGROUND: A high dietary fat intake is involved in the pathogenesis of insulin resistance. OBJECTIVE: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. DESIGN: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: approximately 190 pmol/L). RESULTS: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4 micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to 20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/- 2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and 0.05 +/- 0.01 mmol/L, respectively (P < 0.05). CONCLUSION: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.     

Gender-related differences in the metabolic response to fasting

CONTEXT: Free fatty acids (FFA) may induce insulin resistance via synthesis of intramyocellular ceramide. During fasting, women have lower plasma glucose levels than men despite higher plasma FFA, suggesting protection from FFA-induced insulin resistance. OBJECTIVE: We studied whether the relative protection from FFA-induced insulin resistance during fasting in women is associated with lower muscle ceramide concentrations compared with men. MAIN OUTCOME MEASURES AND DESIGN: After a 38-h fast, measurements of glucose and lipid fluxes and muscle ceramide and fatty acid translocase/CD36 were performed before and after a hyperinsulinemic euglycemic clamp. RESULTS: Plasma glucose levels were significantly lower in women than men with a trend for a lower endogenous glucose production in women, whereas FFA and lipolysis were significantly higher. Insulin-mediated peripheral glucose uptake was not different between sexes. There was no gender difference in muscle ceramide in the basal state, and ceramide did not correlate with peripheral glucose uptake. Muscle fatty acid translocase/CD36 was not different between sexes in the basal state and during the clamp. CONCLUSION: After 38 h of fasting, plasma FFA were higher and plasma glucose was lower in women compared with men. The higher plasma FFA did not result in differences in peripheral insulin sensitivity, possibly because of similar muscle ceramide and fatty acid translocase/CD36 levels in men and women. We suggest that during fasting, women are relatively protected from FFA-induced insulin resistance by preventing myocellular accumulation of ceramide.     

A modified ECG-triggered cinefilm-mark unit for DSA studies of the heart and great vessels

The authors developed an inexpensive, reliable, and easy-to-install, ECG-triggered cinefilm-mark device that permits performance of high-quality subtraction studies of the coronary circulation.     

Between‐hospital variation in rates of complications and decline of patient performance after glioblastoma surgery in the dutch Quality Registry Neuro Surgery

Journal of Neuro-Oncology - For decisions on glioblastoma surgery, the risk of complications and decline in performance is decisive. In this study, we determine the rate of complications and...