Postprandial glucose variability in type 1 diabetes: The individual matters beyond the meal.

AIM: To explore intraindividual (between-meals) and interindividual (between-subjects) variability of postprandial glucose response (PGR) in type 1 diabetes (T1DM). METHODS: Data were taken from five cross-over trials in 61 subjects with T1DM on insulin pump wherein the effects of different dietary components or the intraindividual-variability of PGR to the same meal were evaluated by CGM. Predictors (type of meal or nutrient composition) of early (iAUC0-3h), late (iAUC3-6h), total (iAUC0-6h), and time-course of postprandial blood glucose changes (iAUC3-6hminus0-3h) were evaluated using two mixed-effect linear regression models considering the patient's identification number as random-effect. RESULTS: High-glycemic-index (HGI) and low-glycemic-index meals were the best positive and negative predictors of glucose iAUC0-3h, respectively. A Low-Fat-HGI meal significantly predicted iAUC3-6hminus0-3h (Estimate 3268; p = 0.017). Among nutrients, dietary fiber was the only significant negative predictor of iAUC0-3h (Estimate -550; p < 0.001) and iAUC0-6h (Estimate -742; p = 0.01) and positive predictor of iAUC3-6hminus0-3h (Estimate 336; p = 0.043). For all models, the random-effect patient was statistically significant (p < 0.001 by ANOVA). CONCLUSION: Beyond the meal characteristics (including glycemic index, fat and fiber content), individual traits significantly influence PGR. Specific interindividual factors should be further identified to properly predict glucose response to meals with different composition in individuals with T1DM.

Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study.

BACKGROUND & AIMS: Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. METHODS: Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. RESULTS: Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). CONCLUSIONS: RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS. GOV IDENTIFIER: NCT02865278.

Diabetes remission after bariatric surgery is characterized by high glycemic variability and high oxidative stress.

BACKGROUND AND AIM: To evaluate glycemic variability (GV) and oxidative stress in patients who achieved type 2 diabetes (T2DM) remission after bariatric surgery (BS). METHODS AND RESULTS: Twenty-two patients (M/F10/12, age 50 ± 9 years, BMI 31 ± 6 kg/m2) who were in remission of T2DM (T2DM remitters) after BS since at least 1 year and 22 age-, sex- and BMI-matched control subjects were studied. Of the BS group, eleven subjects had undergone Roux-en-Y gastric bypass (RYGB) and eleven subjects sleeve gastrectomy (SG). Oral glucose tolerance test (OGTT), 7 days-continuous glucose monitoring, 24-h urinary excretion of 8-isoprostaglandin F2α (8-isoPGF2α) and dietary intake evaluation were performed. According to general linear model for repeated measures, glucose and insulin response during OGTT were significantly different in T2DM remitter than in control subjects (p < 0.001, for both). All measures of GV (standard deviation, coefficient of variation and mean amplitude of glucose excursions) were significantly higher in T2DM remitters than in controls, (p < 0.001 for all). These indexes were higher among RYGB than SG patients (p < 0.05). The time spent out of the 60-160 mg/dl range was significantly longer in T2DM remitters undergoing RYGB than in controls (p < 0.02). Mean 24-h urinary 8-isoPGF2α excretion was significantly higher in T2DM remitters than that of control subjects (p = 0.04). All GV indexes were directly correlated with blood glucose levels at 30 and 60 min during OGTT (p < 0.05-0.001). CONCLUSION: Remission of T2DM after BS is characterized by high GV and high oxidative stress in the face of fasting blood glucose and HbA1c within the normal range.

Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3, a 6-fold higher dose of 5-FC should be administered intravenously. Taken together, our data demonstrate the feasibility to deliver 5-FC by the pulmonary route likely avoiding/reducing the well-known side effects associated to the high systemic 5-FC doses currently used in humans. Furthermore, our results highlight that an appropriate formulation design can improve the persistence of the drug at lungs, where microorganisms causing severe infections are located.

A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome.

BACKGROUND AND AIM: Until recently, very few intervention studies have investigated the effects of whole-grain cereals on postprandial glucose, insulin and lipid metabolism, and the existing studies have provided mixed results. The objective of this study was to evaluate the effects of a 12-week intervention with either a whole-grain-based or a refined cereal-based diet on postprandial glucose, insulin and lipid metabolism in individuals with metabolic syndrome. METHODS AND RESULTS: Sixty-one men and women age range 40-65 years, with the metabolic syndrome were recruited to participate in this study using a parallel group design. After a 4-week run-in period, participants were randomly assigned to a 12-week diet based on whole-grain products (whole-grain group) or refined cereal products (control group). Blood samples were taken at the beginning and end of the intervention, both fasting and 3 h after a lunch, to measure biochemical parameters. Generalized linear model (GLM) was used for between-group comparisons. Overall, 26 participants in the control group and 28 in the whole-grain group completed the dietary intervention. Drop-outs (five in the control and two in the whole-grain group) did not affect randomization. After 12 weeks, postprandial insulin and triglyceride responses (evaluated as average change 2 and 3 h after the meal, respectively) decreased by 29% and 43%, respectively, in the whole-grain group compared to the run-in period. Postprandial insulin and triglyceride responses were significantly lower at the end of the intervention in the whole-grain group compared to the control group (p = 0.04 and p = 0.05; respectively) whereas there was no change in postprandial response of glucose and other parameters evaluated. CONCLUSIONS: A twelve week whole-grain cereal-based diet, compared to refined cereals, reduced postprandial insulin and triglycerides responses. This finding may have implications for type 2 diabetes risk and cardiovascular disease.

A CHO/fibre diet reduces and a MUFA diet increases postprandial lipaemia in type 2 diabetes: no supplementary effects of low-volume physical training.

The aim of the study was to evaluate the effects of a supervised physical training added to a healthy diet-rich in either carbohydrate and fibre (CHO/fibre) or monounsaturated fatty acids (MUFA)-on postprandial dyslipidaemia, an independent cardiovascular risk factor particularly relevant in type 2 diabetes (T2D). Participants were forty-five overweight/obese subjects with T2D, of both genders, in good blood glucose control with diet or diet+metformin, with normal fasting plasma lipids. According to a parallel groups 2 × 2 factorial design, participants were randomized to an 8-week isoenergetic intervention with a CHO/fibre or a MUFA diet, with or without a supervised low-volume aerobic training programme. The main outcome of the study was the incremental area under the curve (iAUC) of lipid concentrations in the plasma chylomicron+VLDL lipoprotein fraction, isolated by preparative ultracentrifugation (NCT01025856). Body weight remained stable during the trial in all groups. Physical fitness slightly improved with training (VO2 peak, 16 ± 4 vs. 15 ± 3 ml/kg/min, M ± SD, p < 0.05). Postprandial triglyceride and cholesterol iAUCs in plasma and chylomicron+VLDL fraction decreased after the CHO/fibre diet, but increased after the MUFA diet with a significant effect for diet by two-way ANOVA (p < 0.05). The addition of exercise training to either dietary intervention did not significantly influence postprandial lipid response. A diet rich in carbohydrates and fibre reduced postprandial triglyceride-rich lipoproteins compared with a diet rich in MUFA in patients with T2D. A supervised low-volume physical training did not significantly influence these dietary effects.

Nutrition and oxidative stress: a systematic review of human studies.

Oxidative stress (OS) - defined as the imbalance between free radical production and antioxidant defences - is a condition associated with chronic-degenerative disease, such as cancer, metabolic and disease cardiovascular diseases (CVDs). Several studies have shown that diet and some of its components could influence the intensity of OS damage. The aim of this review was to critically examine some pieces of evidence from observational and intervention study in human beings to assess whether diet and its components can really modify OS in vivo. Furthermore, we tried to find out the possible mechanism behind this association. We considered all studies in MEDLINE which fitted with the following criteria: (1) adult subjects who were healthy or affected by metabolic disease and CVDs; (2) no food supplements, pillows, powder but only common foods and beverages and (3) OS assessment with well-known and validated in vivo biomarkers.

A single Abrikosov vortex trapped in a mesoscopic superconducting cylindrical surface.

We investigate the behaviour of a single Abrikosov vortex trapped in a mesoscopic superconducting cylindrical surface with a magnetic field applied transverse to its axis. In the framework of the time-dependent Ginzburg-Landau formalism we show that, provided the transport current and the magnetic field are not large, the vortex behaves as an overdamped quasi-particle in a tilted washboard potential. The cylindrical thin strip with the trapped vortex exhibits E(J) curves and time-dependent electric fields very similar to the ones exhibited by a resistively shunted Josephson weak link.

Fasting and post-prandial adipose tissue lipoprotein lipase and hormone-sensitive lipase in obesity and type 2 diabetes.

BACKGROUND: Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. AIM: The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups - obese with Type 2 diabetes and obese without diabetes - and in non-diabetic normal-weight controls. MATERIAL/SUBJECTS AND METHODS: Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. RESULTS: The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p<0.05) as well as lower mRNA LPL levels. HSL activity was significantly reduced in the 2 groups of obese subjects compared to controls in both fasting condition and 6 h after the meal (p<0.05), while HSL mRNA levels were not different. There were no significant changes between fasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. CONCLUSIONS: Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.

Ratchet effect: demonstration of a relativistic fluxon diode.

We report the observation of the ratchet effect for a relativistic flux quantum trapped in an annular Josephson junction embedded in an inhomogeneous magnetic field. In such a solid state system, mechanical quantities are proportional to electrical quantities, so that the ratchet effect represents the realization of a relativistic-flux-quantum-based diode. Mean static voltage response, equivalent to directed fluxon motion, is experimentally demonstrated in such a diode for deterministic as well as stochastic oscillating current forcing.

New nerve root holders during spinal decompression.

New nerve root holders have been developed to protect nerve roots and dural sac during spinal bony decompression, especially if it takes place in the region of the lateral recess by means of a high speed air drill. Their design derives from the adaptation of common brain spatulas to the anatomy of the lumbar nerve roots. Their use, together with the contralateral approach (the operative microscopical visualization of the lesion from the side of the patient opposite to it), represents an available method to protect nervous structures from operative injuries without superfluous retraction of them. The contralateral approach permits the visualization of the deepest angles of the lateral recess without withdrawal of lateral parts of the articular facets, important for vertebral stability. In order to achieve satisfactory results without vertebral instrumental stabilization, the holder assists in the drilling procedure to enlarge the periradicular space covering the nerve root and helps avoid undue dural tearing or radicular damage.

Anterior cervical discectomy without fusion: a comparison with Cloward's procedure.

The antero-medial microsurgical disc or osteophyte removal without formal interbody fusion is a surgical alternative in the treatment of cervical discs causing radicular compression or cervical myelopathy. In the past 20 years 379 patients underwent anterior surgery, including 240 microdiscectomies without graft and 139 Cloward's dowel procedures. The long-term results of both procedures are compared in patients suffering from radicular compression, dominant myelopathy and radiculo-myelopathy. We found no statistically significant differences between the two methods treating three different conditions. The improvement rate in patients with soft and sequestrated discs is generally better compared to those with hard discs and spondylotic changes. Functional stability of the cervical spine is present in 92% of cases treated without interbody fusion immediately after surgery. A complete osseous fusion after a period of 6-12 months was found in 90% of Cloward procedures and in 81% of discectomy without graft. No definite correlation was found between the clinical improvement and the radiological results. According to our experience the Cloward's fusion procedure has no long-term advantages over discectomy without graft except in cases of severe myelopathy caused by multilevel ventral compression due to osteophytes. No permanent postoperative complication was encountered. Most of the treated patients returned to their previous activities.

[Usefulness of somatosensory evoked potentials in the diagnosis of low-pressure hydrocephalus]. / Przydatnosc somatosensorycznych potencjalów wywolanych dla rozpoznania wodoglowia niskocisnieniowego.

The study group comprised 35 patients in whom previous computed tomography had demonstrated significant dilatation of the ventricular system. On the basis of analysis of clinical manifestations and tomograms the patients were divided into two groups: 24 cases (group I) low-pressure hydrocephalus, 11 cases (group II) brain atrophy. For establishing of final diagnosis in both groups the resistance of cerebrospinal fluid outflow was determined (using continuous infusion at a rate of 2 ml/min) and somatosensory evoked potentials were produced by stimulation of median nerve. In patients with increased resistance to CSF resorption (low-pressure hydrocephalus) the conduction time in the N14-P15 segment involving brain stem structures was prolonged (in 17 out of 19 cases). In cases with not increased resistance no changes of evoked potentials were noted. It is thought that the so called posterior cranial fossa conduction time (N14-P15) may be a useful indicator for differential diagnosis of low-pressure hydrocephalus from brain atrophy.

Intrathecal infusion test and decrease in shunt revisions and infections.

The intrathecal infusion test leads to a more accurate diagnosis of communicating hydrocephalus, and is useful in identifying those patients with insufficient cerebrospinal fluid (CSF) absorption who are most likely to improve after a shunt operation. Furthermore, shunt function can be evaluated by assessing the CSF absorption of shunt-operated patients in the same way. Some patients do not improve after surgery because of irreversible or shunt-independent neurological and radiological signs, while the postoperative infusion test demonstrates a normal shunt function. The clinical condition and neuroradiological picture of such patients cannot be improved by shunt revision if the implanted shunt already allows a normal CSF outflow. By means of infusion tests the number of patients who need a further operation can be reduced, with a consequent drop in shunt infections, a very welcome aspect especially in pediatric neurosurgery. In our department 298 infusion tests were carried out over a seven-year period, and a decrease in shunt revisions and infections could be observed.

[Treatment of local infections, cranial and spinal, with suction irrigation drainage. Experiences in 60 patients]. / Die Behandlung lokaler Infekte, kranial und spinal, mit Saugspüldrainagen. Erfahrungen bei 60 Patienten.

In 60 cases with postoperative infection we used local suction/irrigation drainage with primary wound closure. This method has some advantages 1. Healing needs much less time, especially in spinal localisations and 2. in one third of cranial infections removal of the bone flap was not necessary.

Spinal epidural hematoma.

Three cases of spinal epidural hematoma are reported, one lumbar, another cervical, and the third thoracic. All were dorsolaterally localized, the first and the third were dependent on anticoagulant therapy, and the second was spontaneous. In addition to the symptoms of sudden onset, acute spinal pain, flaccid paralysis, and loss of sphincter control, the second case had the exceptional picture of a cervical anterior spinal cord syndrome with preoperative transient improvement, followed by the development of Brown--Séquard syndrome with subsequent deterioration. This case was diagnosed by means of computed tomography. The postoperative course has been satisfactory in all patients, with complete recovery in two.

Persistent hydrocephalus following removal of choroid plexus papilloma of the lateral ventricle.

We report a case of choroid plexus papilloma of the left lateral ventricle, which illustrates the difficulties of diagnosis of these tumours with air studies in advanced hydrocephalus. The hydrocephalus was apparent at the age of three months, but ventriculography failed to reveal the true nature of the communicating hydrocephalus. A ventriculocaval shunt was inserted, but the hydrocephalus progressed, in spite of the fact that the shunt was functioning well. The diagnosis of a papilloma of the choroid plexus was made after performing a CT examination at the age of 3 1/2 years. In spite of radical tumour removal, three years after the operation the axial computer tomography revealed a persistent hydrocephalus, but no recurrence of tumour. To control the hydrocephalus, a bilateral shunt with low pressure valve was necessary. With reference to the literature we discuss the possible causes of persistent hydrocephalus after surgical removal of these tumours. The majority of authors concluded, that because of repeated subarachnoid bleeding by these tumours, it must be a form of aresorptive hydrocephalus. The persisting hydrocephalus is probably caused by an increase of the CSF outflow resistance because of a distal CSF-pathway obstruction.