Patterns of adaptation to children's food allergies.

BACKGROUND: Families with food allergy (FA) are at risk of reduced quality of life and elevated anxiety. A moderate level of anxiety may be beneficial to sustain vigilance for food avoidance; however, excessive anxiety may increase risk for burden and maladjustment. The current study presents a framework for understanding the patterns of adaptation to FA across families and to identify typologies of families that would benefit from intervention. METHODS: Participants included 57 children, 6-12 years old with documented FA, and their mothers. Families were assessed using the Food Allergy Management and Adaptation Scale. Families also completed measures of quality of life, anxiety, FA management, and psychosocial impairment. RESULTS: A hierarchical cluster analysis revealed that 56 of the 57 families of food-allergic children were categorized into four groups that differed on their adequacy of family FA management, levels of anxiety, and balanced psychosocial functioning: balanced responders (n = 23; 41%), high responders (n = 25; 45%), and low responders (n = 3; 5%). The fourth group, anxious high responders (n = 5; 9%), was characterized by extremely high maternal FA anxiety scores and low scores for balanced integration of FA management and psychosocial functioning. Families in clusters differed across illness and psychosocial outcome variables. CONCLUSION: Families with FA were characterized by patterns of FA management, anxiety, and ability to integrate FA demands into daily life. Identified adaptation patterns correspond with clinical impressions and provide a framework for identifying families in need of intervention.

Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study.

BACKGROUND/OBJECTIVES: Food-induced thermogenesis is generally reported to be higher in the morning, although contrasting results exist because of differences in experimental settings related to the preceding fasting, exercise, sleeping and dieting. To definitively answer to this issue, we compared the calorimetric and metabolic responses to identical meals consumed at 0800 hours and at 2000 hours by healthy volunteers, after standardized diet, physical activity, duration of fast and resting. SUBJECTS/METHODS: Twenty subjects (age range 20-35 years, body mass index=19-26 kg m(-)(2)) were enrolled to a randomized cross-over trial. They randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal calorimetry was performed; a further 60-min calorimetry was done 120-min after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the 'morning effect', that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. RESULTS: Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P<0.001). RMR was significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal; P<0.001), whereas differences in areas-under-the-curve for glucose (-1800; -2564,-1036 mg dl(-1) × h, P<0.001), log-insulin (-0.19; -0.30,-0.07 µU ml(-1) × h; P=0.001) and fatty free acid concentrations (-16.1;-30.0,-2.09 mmol l(-1) × h; P=0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. CONCLUSIONS: The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. The timing of meals should probably be considered when nutritional recommendations are given.

New International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosing gestational diabetes compared with former criteria: a retrospective study on pregnancy outcome.

AIMS: The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommends new criteria for diagnosing gestational diabetes. We evaluated the clinical and metabolic characteristics, and pregnancy outcome, in women previously classifiable as 'normal' according to the 4th International Workshop Conference on gestational diabetes criteria, but reclassified as 'abnormal' according to the new recommendations. METHODS: Using the new IADPSG criteria, 3953 pregnancies were retrospectively reclassified as 1815 women with normal glucose tolerance and 2138 with gestational diabetes, 112 (2.8%) of whom would have been classified as normal according to the older criteria. RESULTS: Of the 2138 women classified as abnormal by the new criteria, the 112 women now reclassified as abnormal were younger and had a lower pre-pregnancy BMI than the 2026 women who had also been classified as abnormal by the previous criteria. The 100-g oral glucose tolerance test showed significantly higher glucose levels in these 112 women than in the 1815 women reclassified as normal (P < 0.0001). Caesarean section was significantly more frequent (P < 0.01) and the ponderal index for the newborn significantly higher in these reclassified women than in those classified as normal (P < 0.0001), and their basal glucose levels correlated significantly with the ponderal index (P < 0.05). CONCLUSION: The new criteria for diagnosing gestational diabetes identified a group of women previously classifiable as normal according to the 4th International Workshop Conference criteria, but revealing metabolic characteristics and pregnancy outcomes resembling those of women who would have been considered to have gestational diabetes by the previous criteria.

The general use of glycated haemoglobin for the diagnosis of diabetes and other categories of glucose intolerance: still a long way to go.

Glycated haemoglobin (HbA(1c)) is considered the 'gold standard' for monitoring metabolic control in diabetes. An International Expert Committee recently recommended HbA(1c) as a better method than measurement of glucose to use in the diagnosis of diabetes, based on its strong association with microvascular complications, a lower day-to-day variability and ease of use, not necessarily in the fasting state. These recommendations have been embraced by the American Diabetes Association (ADA), which stated in its Standards of Medical Care in Diabetes 2010 that "A(1c), fasting plasma glucose or the 2 h 75 g oral glucose tolerance test (OGTT) are appropriate for testing diabetes and assessing the risk of future diabetes," and that "a confirmed A(1c) ≥ 6.5% is diagnostic for diabetes." Measuring HbA(1c) has several advantages over glucose measurements, but its exclusive use should only be considered if the test is conducted under standardised conditions and its limitations are taken into due account. The impact of its use on the epidemiology of diabetes and other categories of glucose intolerance, as seen from recent reports, is also discussed.

Relationship between glyco-oxidation, antioxidant status and microalbuminuria in type 2 diabetic patients.

AIMS/HYPOTHESIS: This study examined the relationship, if any, between glucose-induced oxidative stress, antioxidant status and microalbuminuria in patients with type 2 diabetes. METHODS: The study involved 99 consecutive type 2 diabetic patients (57 men, 42 women). Patients with persistent microalbuminuria were identified and the following variables evaluated: fasting plasma glucose, HbA(1c), malonyldialdehyde (MDA), pentosidine, AGE, the total radical-trapping antioxidant parameter (TRAP), vitamin E, creatinine, estimated GFR and lipid profile. RESULTS: Patients were divided into two groups, i.e. 37 individuals without microalbuminuria (AER <20 microg/min) and 62 with microalbuminuria (AER > or =20 microg/min). The following variables were significantly higher in patients with microalbuminuria than in those without microalbuminuria (mean +/- SD): fasting plasma glucose 9.41 +/- 2.88 vs 8.19 +/- 1.93 mmol/l, p < 0.05; HbA(1c) 7.97 +/- 1.51 vs 7.39 +/- 1.03%, p < 0.05; MDA 1.18 +/- 0.35 vs 1.02 +/- 0.29 micromol/l, p < 0.05; pentosidine 98.5 +/- 24.6 vs 82.9 +/- 20.9 pmol/ml, p < 0.005; and AGE 13.2 +/- 4.8 vs 10.6 +/- 3.8 microg/mg protein, p < 0.01. However, vitamin E and TRAP did not differ between the two groups. Serum creatinine values and estimated GFR were similar in the two groups. Only in patients with microalbuminuria were significant linear correlations seen between AER and both oxidation (HbA(1c) r = 0.33, p < 0.01; MDA r = 0.59, p < 0.001; pentosidine r = 0.48, p < 0.001; and AGE r = 0.44, p < 0.001) and antioxidation variables (vitamin E r = -0.55, p < 0.001; TRAP r = -0.49, p < 0.001). Considering all variables together, multiple regression revealed a correlation between microalbuminuria and vitamin E, TRAP, HbA(1c) and MDA, but not pentosidine or AGE. CONCLUSIONS/INTERPRETATION: Our data suggest that microalbuminuria in type 2 diabetic patients might be promoted by an insufficient counter-regulation of the antioxidant system in the event of increased glyco-oxidation/glycation.

Health-related quality of life in college students with and without childhood-onset asthma.

OBJECTIVE: The current study investigated whether differences existed in health-related quality of life between individuals who self-identified as having childhood-onset asthma and individuals without a chronic illness. Additionally, the relationship between perceived illness intrusiveness and illness uncertainty to health-related quality of life was explored. METHODS: College undergraduates at least 18 years of age who self-identified as having childhood asthma were randomly matched by age and gender to healthy control participants. Participants completed a demographic form, the Mishel Uncertainty in Illness Scale-Community Form, the Illness Intrusiveness Scale, and the SF-36 Health Survey, a measure of health-related quality of life. RESULTS: Participants with asthma had significantly lower scores on the total and mental health-related quality of life scales than did healthy control subjects. There were no significant differences between self-identified participants with asthma and matched healthy control subjects on physical health-related quality of life scales. Illness intrusiveness was not related to either the physical (e.g., physical functioning, general health) or mental health-related quality of life. Higher levels of illness uncertainty were significantly related to higher levels of mental health-related quality of life (e.g., vitality, mental health). In addition, participants with asthma scored significantly lower than healthy controls on the social functioning and role-emotional subscales. CONCLUSION: The current study adds to the extant literature by examining the relationships between illness intrusiveness, illness uncertainty, and health-related quality of life among a young adult population. College students with asthma appear to be at risk for diminished quality of life compared to a healthy comparison group. Further examination of various domains of health-related quality of life among older adolescents and young adults with childhood asthma is needed.

Diabetes related autoimmunity in gestational diabetes mellitus: is it important?

Some GDM women show autoantibody positivity during and after pregnancy and pancreatic autoantibodies can appear for the first time in some patients after delivery. Autoantibody positivity is often accompanied by a high frequency of DR3 and DR4 alleles, which are classically related to the development of type 1 diabetes and, although not all studies agree on this point, by an immunological imbalance expressed by the behaviour of the lymphocyte subpopulation, which can be seen as diabetic anomalies overlapping with the immunological changes that occur during pregnancy. It is worth emphasizing that such patients may develop classical type 1 diabetes during and/or after their pregnancy or they may evolve, often some years after their pregnancy, into cases of latent autoimmune diabetes of adulthood (LADA). Autoimmune GDM accounts for a relatively small number of cases (about 10% of all GDM) but the risk of these women developing type 1 diabetes or LADA is very high, so these patients must be identified in order to prevent the severe maternal and fetal complications of type 1 diabetes developing in pregnancy, or its acute onset afterwards. Since women with autoimmune GDM must be considered at high risk of developing type 1 diabetes in any of its clinical forms, these women should be regarded as future candidates for the immunomodulatory strategies used in type 1 diabetes.

Early detection of insulin sensitivity and beta-cell function with simple tests indicates future derangements in late pregnancy.

OBJECTIVE: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The oral glucose tolerance test (OGTT) was performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and beta-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. RESULTS: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell function than ND. During the late visit, GDM2 also showed impaired beta-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. CONCLUSIONS: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. beta-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

Normal sleep homeostasis and lack of epilepsy phenotype in GABA A receptor alpha3 subunit-knockout mice.

Thalamo-cortical networks generate specific patterns of oscillations during distinct vigilance states and epilepsy, well characterized by electroencephalography (EEG). Oscillations depend on recurrent synaptic loops, which are controlled by GABAergic transmission. In particular, GABA A receptors containing the alpha3 subunit are expressed predominantly in cortical layer VI and thalamic reticular nucleus (nRT) and regulate the activity and firing pattern of neurons in relay nuclei. Therefore, ablation of these receptors by gene targeting might profoundly affect thalamo-cortical oscillations. Here, we investigated the role of alpha3-GABA A receptors in regulating vigilance states and seizure activity by analyzing chronic EEG recordings in alpha3 subunit-knockout (alpha3-KO) mice. The presence of postsynaptic alpha3-GABA A receptors/gephyrin clusters in the nRT and GABA A-mediated synaptic currents in acute thalamic slices was also examined. EEG spectral analysis showed no difference between genotypes during non rapid-eye movement (NREM) sleep or at waking-NREM sleep transitions. EEG power in the spindle frequency range (10-15 Hz) was significantly lower at NREM-REM sleep transitions in mutant compared with wild-type mice. Enhancement of sleep pressure by 6 h sleep deprivation did not reveal any differences in the regulation of EEG activities between genotypes. Finally, the waking EEG showed a slightly larger power in the 11-13-Hz band in alpha3-KO mice. However, neither behavior nor the waking EEG showed alterations suggestive of absence seizures. Furthermore, alpha3-KO mice did not differ in seizure susceptibility in a model of temporal lobe epilepsy. Strikingly, despite the disruption of postsynaptic gephyrin clusters, whole-cell patch clamp recordings revealed intact inhibitory synaptic transmission in the nRT of alpha3-KO mice. These findings show that the lack of alpha3-GABA(A) receptors is extensively compensated for to preserve the integrity of thalamo-cortical function in physiological and pathophysiological situations.

Desaturase activities and metabolic control in type 2 diabetes.

The aim of this study was to elucidate the effects of a poor glycemic control on fatty acid composition and desaturase activities in type 2 diabetic patients. Plasma phospholipid fatty acid composition and desaturase activities (estimated from fatty acid product to precursor ratios) were measured in 30 type 2 diabetic patients during poor metabolic control and after achieving a good metabolic control. Significant changes were recorded in the percentages of palmitic, stearic, dihomo-gamma-linolenic, docosatetraenoic and docosapentaenoic acid. The delta-5 desaturase activity was significantly higher with poor than with good metabolic control. The changes identified in plasma phospholipid fatty acid composition and the desaturase activity in type 2 diabetic patients go in the opposite direction to those described in similar conditions in type 1 diabetic patients and may be relevant to a better understanding of the role of metabolic control in the progression of chronic complications in type 2 diabetic patients.

Shift of adenosine kinase expression from neurons to astrocytes during postnatal development suggests dual functionality of the enzyme.

Adenosine is a potent modulator of excitatory neurotransmission, especially in seizure-prone regions such as the hippocampal formation. In adult brain ambient levels of adenosine are controlled by adenosine kinase (ADK), the major adenosine-metabolizing enzyme, expressed most strongly in astrocytes. Since ontogeny of the adenosine system is largely unknown, we investigated ADK expression and cellular localization during postnatal development of the mouse brain, using immunofluorescence staining with cell-type specific markers. At early postnatal stages ADK immunoreactivity was prominent in neurons, notably in cerebral cortex and hippocampus. Thereafter, as seen best in hippocampus, ADK gradually disappeared from neurons and appeared in newly developed nestin- and glial fibrillary acidic protein (GFAP)-positive astrocytes. Furthermore, the region-specific downregulation of neuronal ADK coincided with the onset of myelination, as visualized by myelin basic protein staining. After postnatal day 14 (P14), the transition from neuronal to astrocytic ADK expression was complete, except in a subset of neurons that retained ADK until adulthood in specific regions, such as striatum. Moreover, neuronal progenitors in the adult dentate gyrus lacked ADK. Finally, recordings of excitatory field potentials in acute slice preparations revealed a reduced adenosinergic inhibition in P14 hippocampus compared with adult. These findings suggest distinct roles for adenosine in the developing and adult brain. First, ADK expression in young neurons may provide a salvage pathway to utilize adenosine in nucleic acid synthesis, thus supporting differentiation and plasticity and influencing myelination; and second, adult ADK expression in astrocytes may offer a mechanism to regulate adenosine levels as a function of metabolic needs and synaptic activity, thus contributing to the differential resistance of young and adult animals to seizures.

A study on in vitro glycation processes by matrix-assisted laser desorption ionization mass spectrometry.

The number of glucose molecules condensed on glycated bovine serum albumin have been easily determined by means of matrix-assisted laser desorption/ionization mass spectrometry. Measurements were carried out on samples from incubation of the protein with glucose at different concentrations (0.02 M, 0.2 M, 2 M and 5 M). A clear increase in molecular mass of BSA with respect to incubation time is detected. In contrast to what is observed with fluorescence, the plots of molecular mass increase vs. incubation time show the occurrence of a steady state, corresponding to the complete saturation of all the protein sites reactive against glucose. Comparison of fluorescence and molecular mass data reveals that some further reactions, different from condensation, must take place, which could be in principle either intramolecular or originated by reactivity of modified condensed glucose moieties vs. free glucose.

Identification of furoyl-containing advanced glycation products in collagen samples from diabetic and healthy rats.

The compounds resulting from the reaction of glucose with proteins (advanced glycation products) can be important markers of chronic diabetic complications. To test the possible diagnostic value of advanced glycation products containing the furoyl moiety, collagen samples from diabetic and healthy rats were analyzed by parent ion spectroscopy. In our study, we compared normal collagen, diabetic collagen and normal collagen incubated with different glucose concentrations and we employed different hydrolysis procedures (HCl and proteinase). Mass spectroscopic measurements performed on hydrolyzed samples showed that either different samples or different hydrolysis procedures produce a similar set of furoyl-containing compounds. 2-(2-Furoyl)-4(5)-(2-furanyl)-1H-imidazole (FFI) which has been reported to be one of the advanced glycation products, was never found in any of the samples examined. Hence neither FFI nor furoyl-containing molecules can be considered markers of advanced glycation processes.

Suppression and stimulation mechanisms controlling glucagon secretion in a case of islet-cell tumor producing glucagon, insulin, and gastrin.

The mechanisms controlling secretion of glucagon and other pancreatic hormones were studied in a patient affected with multihormone-secreting islet-cell tumor. Fasting glucagon levels (3,000 pg./ml.) rose to 10 ng./ml. following arginine stimulation. While oral glucose load and intravenous glucose infusion did not suppress glucagon secretion, insulin administration induced a prompt depression in glucagon levels. Glucagon, insulin, and gastrin levels were suppressed by somatostatin while calcium infusion caused a paradoxical increase. It is suggested that only some of the stimulation-inhibition mechanisms were conserved in this case of glucagon-secreting pancreatic tumor.

Reduced in vivo biological activity of in vitro glycosylated insulin.

We evaluated the in vivo biological activity of in vitro extensively glycosylated insulin (GI) with the euglycemic-hyperinsulinemic glucose-clamp technique in postabsorptive nondiabetic subjects. Insulin-mediated glucose disposal was approximately 30% lower (P less than .03) with GI (9.2 +/- 1.2 mg.kg-1.min-1, mean +/- SE) than with the nonglycosylated hormone (12.6 +/- 0.7 mg.kg-1.min-1) at comparable plasma insulin concentrations (approximately 90 microU/ml). Binding of GI to a specific receptor on circulating cells (erythrocytes and monocytes) was normal. We conclude that in vitro extensive glycosylation of insulin reduces its biological activity in vivo, as reflected by insulin-mediated glucose disposal, probably at a postreceptor level.

Impaired auditory brainstem-evoked responses in insulin-dependent diabetic subjects.

Auditory brainstem-evoked responses (ABR) were recorded from the scalp of 30 normoacoustic insulin-dependent diabetic subjects, aged between 15 and 41 yr (29 +/- 7 yr). Three different stimulus repetition rates (11, 37, and 87 cps) were used. The results were compared with those obtained from 20 age- and sex-matched, normoacoustic control subjects. In diabetic patients, metabolic control (mean daily plasma glucose, glycosylated hemoglobin) and the presence of retinopathy, nephropathy, and somatic neuropathy were also investigated. The latencies (ms) of ABR waves were significantly impaired in diabetic subjects as compared with normals. Peripheral transmission time (wave I) and central transmission time (waves I-V) were also significantly delayed in diabetic subjects. Moreover, by increasing stimulus repetition rates, a significant increase in waves I-V shift was observed in diabetic patients. ABR impairment was not related to glucose balance, to the duration of diabetes, or to the presence of the diabetic retinopathy, nephropathy, and somatic neuropathy. In conclusion, diabetic neuropathy is characterized not only by somatic and autonomic nerve dysfunctions, but also by the early involvement of the central nervous system (CNS). ABR recording can represent a useful, noninvasive, simple procedure to detect both acoustic nerve and CNS damage.

Absence of brown product FFI in nondiabetic and diabetic rat collagen.

Accumulation of brown products in long-lived proteins might be an important factor in determining long-term diabetic complications. Fluorescent chromophore 2-(2-furoyl)-4-(5)-(2-furanyl)-1H-imidazole (FFI), isolated from hydrolyzed brown products synthesized in vitro, was proposed as a specific brown product responsible for functional and structural changes in long-lived proteins. In this study, an attempt was made to demonstrate by means of collision spectroscopy the presence of FFI in collagen samples taken from diabetic rats. Diabetic rat collagen samples showed mean values of absorbance per milligram of 4-hydroxy-L-proline significantly higher than those observed in nondiabetic rats, suggesting higher FFI levels. Surprisingly, all collagen samples from diabetic and nondiabetic rats gave collision spectra in which no peak diagnostic of FFI presence was observed. These data suggest that the absorbance level observed in diabetic rats is not due to the presence of FFI but to structurally related compounds, which are being investigated by means of mass spectrometry.

Advanced glycation end products/peptides: an in vivo investigation.

Advanced glycation end products/peptides (AGE/peptides) originate by in vivo enzymatic digestion of nonenzymatically glycated proteins, which are produced by reaction of glucose with primary amino groups present in the protein chain following the Maillard pattern. AGE/peptides are highly reactive species and can interact with tissue and circulating proteins, leading to tissue modification and impaired protein functionality. Serum levels of AGE/peptides are reported to be particularly high in diabetes (in terms of higher production) or in end-stage renal disease (in terms of accumulation). For these reasons, their structural identification is of high interest, giving information on their relationship with the pathological state and allowing the design of possible therapeutic interventions. We report here some preliminary results obtained by liquid chromatography/electrospray ionization/mass spectrometry (LC/ESI/MS) and matrix-assisted laser desorption ionization MS (MALDI-MS) investigations carried out on the low-molecular-weight serum peptide fraction from 10 healthy subjects, 10 patients with poorly controlled diabetes, and 10 patients with end-stage nephropathy.

Altered control of growth hormone secretion in patients with cirrhosis of the liver.

Ten male patients with cirrhosis of the liver (three with portacaval anastomosis [PCA]) and eight sex- and age-matched controls underwent an arginine infusion test followed by an intravenous glucose tolerance test. Plasma glucose and growth hormone (GH) levels were measured during a period of three hours. In the normal subjects, the peak GH response to arginine occurred 60 minutes after the start of the infusion and was followed by a progressive decline in GH concentration; dextrose injection resulted in a further rapid fall in GH concentration. In cirrhotic patients, both fasting and postarginine GH concentrations were significantly higher than in controls; in addition, the dextrose injection, after causing a transitory drop in plasma GH levels, resulted in a marked increase in plasma GH concentration. In the patients with PCA, the plasma GH increase after arginine and after dextrous was more marked. In these cirrhotic patients, the plasma GH levels correlated directly with the magnitude of the portal hypertension and inversely with the serum albumin concentration, suggesting that the abnormality of GH secretion was a reflection of the derangement in liver function.