Long-term abstinent alcoholics have a blunted blood glucose response to 2-Deoxy-d-glucose

- AIMS: In this study we explored the relationship between alcohol and carbohydrate consumption in long-term abstinent alcoholics. METHODS: We employed an established laboratory paradigm which allowed us to stimulate and measure dietary intake. 2-Deoxy-d-glucose (2-DG) is a glucose analogue that causes an intracellular energy deprivation resulting in exaggerated food consumption and a compensatory metabolic response to raise blood glucose. Using a double-blind design, we gave an infusion of 25 mg/kg 2-DG or placebo to 20 long-term abstinent alcoholics and 19 healthy volunteers. RESULTS: There were no baseline differences in any dietary, behavioural or biochemical variables. As expected, 2-DG increased caloric consumption and blood glucose levels in a time-dependent fashion. There were no differences in food consumption between the alcoholics and the healthy volunteers following the 2-DG stimulus. However, the alcoholic group had a significantly blunted response in blood glucose. CONCLUSIONS: The origin of this atypical blood glucose response may antedate the onset of alcoholism, or it may be secondary to alcohol-related damage that persists beyond 6 months. Previous accounts of increased sweet consumption in alcoholics were not substantiated, although they may be present in the peri-withdrawal period.     

Cortisol response to buspirone in extended abstinent alcoholics

We evaluated cortisol response to buspirone in extended abstinent alcoholic patients to determine 5-HT1A receptor sensitivity in alcoholism. Alcoholic patients were inpatients with an extended abstinent period of at least 3 months. Alcoholics had a significantly lower cortisol level than did the normal controls from 60 min through to 150 min after administration of 30 mg buspirone. Our results show that cortisol response to buspirone was significantly decreased in alcoholic patients compared to normal controls, reflecting decreased 5-HT1A receptor sensitivity.     

Growth hormone response to the GABA-B agonist baclofen in 3-week abstinent alcoholics.

Gamma-aminobutyric acid (GABA) dysfunction is a known feature of alcoholism. We investigated GABA-B receptor activity in 3-week abstinent alcoholics using the growth hormone (GH) response to baclofen, a GABA-B receptor agonist. The study aimed to investigate the relationship between GABA-B receptor activity and alcohol withdrawal. GH response to baclofen was measured in alcohol-dependent males without depression (n = 22) who were on day 21 of alcohol abstinence and in healthy control male subjects (n = 23). After 20mg baclofen was given orally to the subjects, blood samples for GH assay were obtained every 30 min for the subsequent 150 min. The patients were divided into two subgroups (continuing withdrawal and recovered withdrawal subgroups) according to their withdrawal symptom severity scores on day 21 of alcohol cessation. Baclofen administration significantly altered GH secretion in the controls, but not in the patients. When GH response to baclofen was assessed as DeltaGH, it was lower in the patients with continuing withdrawal symptoms than in the controls and in the recovered withdrawal group. Impaired GH response to baclofen in all patients mainly pertained to the patients whose withdrawal symptoms partly continued. Our results suggest that reduced GABA-B receptor activity might be associated with longer-term alcohol withdrawal symptoms in alcoholic patients.     

Event-related brain potentials to high incentive stimuli in abstinent alcoholics

We have previously found that the P3 component of the event-related potential (ERP) is reduced in alcoholics in visual target-selection paradigms. P3 voltage depends on the "subjective significance" of the stimulus (e.g., task relevance, probability of occurrence, motivational factors). We were interested in assessing P3s in alcoholics to motivationally significant stimuli that did not differ with respect to other aspects of significance. Equiprobable, task-relevant visual stimuli with different acquired incentive values were presented to alcoholics under baseline and two incentive conditions. Alcoholics manifested similar lower P3 voltages without P3 latency delays to all stimuli, regardless of incentive values. Latency Corrected Averages indicated that these results were not due to latency jitter in the averages. These results suggest multiple system deficits in alcoholics, perhaps in involving frontal and/or medial temporal lobe, the brain sources implicated in the generation of P3. Our results perhaps reflect a deficit in motivational-cognitive systems in alcoholics, possibly affecting their ability to actively sustain information processing.     

Rapid recovery from cognitive deficits in abstinent alcoholics: a controlled test-retest study.

The pattern of cognitive deficits and their time-dependent recovery were investigated in a cohort of 49 male alcohol-dependent patients using a repeated measurement design with 49 healthy male controls matched for age, education, and marital status. We combined parts of the Halstead Reitan Battery and the Wechsler Memory Scale with tests that are widely used in German-speaking countries. Patients were tested in the first week (T1) and 5 weeks later (T2) at the end of the in-patient treatment programme. Matched controls were tested also at T1 and T2, which enabled us to take learning effects into account. At T1, the patients showed distinct cognitive deficits on 5 of 12 neuropsychological parameters (perceptual-motor speed, verbal short-term memory, verbal knowledge, non-verbal reasoning, spatial imagination). At T2, significant improvements had occurred in four of the five dysfunctional domains with a significant difference remaining in verbal short-term memory. Duration of dependency and length of abstinence prior to testing had no essential effects on neuropsychological functions. Our results provide evidence for the well-established fact that chronic alcoholism has detrimental effects on cognitive performance, but that performance improves with neuropsychological recovery which occurs rapidly within weeks when abstinence is maintained. Cognitive deficits seem to be similar across different studies and cultures.     

Pre-irradiation at a low dose-rate blunted p53 response

We investigated whether chronic irradiation at a low dose-rate interferes with the p53-centered signal transduction pathway induced by radiation in human cultured cells and C57BL/6N mice. In in vitro experiments, we found that a challenge with X-ray irradiation immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge alone in glioblastoma cells (A-172). In addition, the levels of p53-centered apoptosis and its related proteins after the challenge were strongly correlated with the above-mentioned phenomena in squamous cell carcinoma cells (SAS/neo). In in vivo experiments, the accumulation of p53 and Bax, and the induction of apoptosis were observed dose-dependently in mouse spleen at 12 h after a challenge with X-rays (3.0 Gy). However, we found significant suppression of p53 and Bax accumulation and the induction of apoptosis 12 h after challenge irradiation at 3.0 Gy with a high dose-rate following chronic pre-irradiation (1.5 Gy, 0.001 Gy/min). These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced signaling and/or p53 stability.     

餐后血糖应答反应的影响因素及其调控

血糖水平异常,是许多慢性病的常见特点和危险因素。血糖生成指数(GI)是反映碳水化合物餐后血糖应答水平的特征性指数。测定各类碳水化合物的血糖生成指数之后,用来指导人们的日常膳食,改善糖尿病人、心脑血管病病人和肥胖者等的健康状况,具有重要的意义。现有的证据表明,影响食物血糖应答的因素很多,包括食物本身所具有的各种特征和机体自身的状态等。对这些因素的认识,有助于更有效的推广和应用GI来指导人们的膳食,维护和改善人们,尤其是糖尿病和肥胖等慢性疾病患者的健康。本文综述了碳水化合物的消化吸收和利用过程中影响血糖应答的各种因素及其机理。     

Postprandial blood glucose response in relation to gastric emptying and satiety in healthy subjects

Glucostatic appetite regulation has numerous determinants, among others: cephalic phase digestion, gastric emptying and absorption, together influencing postprandial blood glucose responses and satiety. This short communication presents and reviews studies of gastric emptying, antral distension and postprandial glucose response and their relation to reports of satiety in healthy non-obese over night fasting subjects.     

Long-term response to rituximab in a patient with acquired hemophilia

A 28 year-old female without history of previous disease. In the seventh month of her first pregnancy she developed hemorrhagic tendency that worsened in the early postpartum period. Activated partial thromboplastin time was 110 sec (control=35.8 sec) with negative tests for lupus anticoagulant. Factor VIII was <1% and a factor VIII inhibitor titer was 84 Bethesda Units/mL (BU). Initial therapy included methylprednisolone, prednisone, and cyclophosphamide. After two weeks of treatment, clinical conditions of the patient improved slightly and she was discharged. Outpatient therapy included azathioprine, and prednisone for a period of 22 months but in-hospital management was several times required. We initiated rituximab 375 mg/m2/week/4 weeks. A clinical improvement and increased levels of factors VIII and XI were observed 10 weeks later and factor VIII inhibitor decreased to undetectable levels. After a 82-month follow-up period (since the first rituximab infusion), she is asymptomatic and factor VIII and factor XI plasma levels are 70% and 94%, respectively FVIII inhibitor level is still undetectable. Rituximab seems an alternative for the treatment of acquired hemophilia refractory to standard treatment.     

Preprandial blood glucose values: influence on glycemic response studies

Through regressional analyses on data from two glycemic response studies, the influence of various preprandial blood glucose (PPBG) values upon glycemic response is highlighted. Repeated calculations on different subsamples of meals where the PPBG was below a given value showed that the influence of PPBG upon net glycemic response not was linear in the whole PPBG range. It was found that a PPBG less than 13 mmol/L had no influence upon net glycemic response whereas PPBGs greater than 13 mmol/L were significantly negatively correlated to the net glycemic response. To obtain more valid glycemic index figures we recommend that participants with PPBG greater than 13 mmol/L are excluded from glycemic response studies and that the number of participants are increased substantially.     

Consumption of the slow-digesting waxy maize starch leads to blunted plasma glucose and insulin response but does not influence energy expenditure or appetite in humans

Limited research in humans suggests that slowly digestible starch may blunt the postprandial increase and subsequent decline of plasma glucose and insulin concentrations, leading to prolonged energy availability and satiety, compared to more rapidly digestible starch. This study examined the postprandial metabolic and appetitive responses of waxy maize starch (WM), a slow-digestible starch. It was hypothesized that the waxy maize treatment would result in a blunted and more sustained glucose and insulin response, as well as energy expenditure and appetitive responses. Twelve subjects (6 men and 6 women) (age, 23 ± 1 years; body mass index, 22.2 ± 0.7 kg/m²; insulin sensitivity [homeostatic model assessment], 16% ± 2%; physical activity, 556 ± 120 min/wk) consumed, on separate days, 50 g of available carbohydrate as WM, a maltodextrin-sucrose mixture (MS), or white bread (control). Postprandial plasma glucose and insulin, energy expenditure, and appetite (hunger, fullness, desire to eat) were measured over 4 hours. Compared to control, the 4-hour glucose response was not different for MS and WM, and the 4-hour insulin response was higher for MS (P < .005) and lower for WM (P < .05). Compared to MS, WM led to lower 4-hour glucose and insulin responses (P < .001). These differences were driven by blunted glucose and insulin responses during the first hour for WM. Postprandial energy expenditure and appetite were not different among treatments. These results support that WM provides sustained glucose availability in young, insulin-sensitive adults.     

An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes

BACKGROUND: In single-meal studies, dietary protein does not result in an increase in glucose concentrations in persons with or without type 2 diabetes, even though the resulting amino acids can be used for gluconeogenesis. OBJECTIVE: The metabolic effects of a high-protein diet were compared with those of the prototypical healthy (control) diet, which is currently recommended by several scientific organizations. DESIGN: The metabolic effects of both diets, consumed for 5 wk each (separated by a 2-5-wk washout period), were studied in 12 subjects with untreated type 2 diabetes. The ratio of protein to carbohydrate to fat was 30:40:30 in the high-protein diet and 15:55:30 in the control diet. The subjects remained weight-stable during the study. RESULTS: With the fasting glucose concentration used as a baseline from which to determine the area under the curve, the high-protein diet resulted in a 40% decrease in the mean 24-h integrated glucose area response. Glycated hemoglobin decreased 0.8% and 0.3% after 5 wk of the high-protein and control diets, respectively; the difference was significant (P < 0.05). The rate of change over time was also significantly greater after the high-protein diet than after the control diet (P < 0.001). Fasting triacylglycerol was significantly lower after the high-protein diet than after the control diet. Insulin, C-peptide, and free fatty acid concentrations were not significantly different after the 2 diets. CONCLUSION: A high-protein diet lowers blood glucose postprandially in persons with type 2 diabetes and improves overall glucose control. However, longer-term studies are necessary to determine the total magnitude of response, possible adverse effects, and the long-term acceptability of the diet.     

Postprandial glucose response to Chinese foods in patients with type 2 diabetes

The objective of this study is to examine the glycemic response to common Chinese foods in patients with type 2 diabetes. Twenty-four Chinese adults with type 2 diabetes participated. Subjects were allocated to eat a pair of test meals in random order. Test meals included plain porridge with lean pork (meal 1A), plain porridge and Shrimp Shao Mai (Doll Brand, Winner Food Products Limited, Hong Kong) (meal 1B), boiled rice with boiled egg white (meal 2A), fried rice with whole egg (meal 2B), plain noodles in clear soup (meal 3A), and Pickled Vegetable and Pork-flavored Instant Bowl Noodles (Doll Brand, Winner Food Products Limited) (meal 3B). Nutritional content of the meals was calculated from the nutritional label on the food package and the food composition table. Plasma glucose was checked before the meal and in 30-minute intervals for up to 4 hours after the meal. Significant differences in the area under the curve of glucose up to 2 hours after the meal were detected between meal 1A and 2A (P=.044), 1A and 3A (P=.001), and 3A and 3B (P=.017). The results suggest that fat alone does not alter the glycemic response to rice or porridge. Porridge produces a higher glycemic response than rice and noodles despite similar carbohydrate contents, and different noodles lead to differences in glycemic excursion, suggesting that the glycemic index of common Chinese foods is affected by cooking methods and food processing.     

Variability in measurements of blood glucose response to foods in human subjects is not reduced after a standard breakfast

Measurements of blood glucose response to food are highly variable. We determined whether within-individual variability in data for blood glucose responses were reduced if individuals consumed a standard meal 2 hours before testing and investigated the effect of serving size. Blood glucose responses to muesli and macaroni cheese were determined in 13 individuals by taking 2 fasting capillary blood samples. Food was then consumed, and capillary blood samples were taken every 15 minutes for the first hour and every 30 minutes for the second hour. The incremental area under the blood glucose response curve was determined, and glycemic glucose equivalents (GGEs) were calculated. The GGE values were not significantly different whether the muesli and macaroni cheese were fed fasting or after a standard breakfast (29.2 vs 34.5 g for muesli and 11.0 vs 14.6 g for macaroni cheese). Within-individual coefficients of variation were not significantly different whether the food was consumed fasting or after a standard breakfast (24.9% and 32.5% for muesli and 38.1% and 59.4% for macaroni cheese). Differences in GGE between measured and estimated half serving size for macaroni cheese were 0.8 g (P = .6) and for muesli, 3 g (P = .2); for the double serving size for macaroni cheese, 1.7 g (P = .7); and for muesli, 6.7 g (P = .06). The GGE values for foods and variability in blood glucose response within individuals were not significantly different whether individuals fasted or consumed a standard breakfast before testing. However, blood glucose levels tended to differ significantly after consumption of the double serving size of muesli compared with other serving sizes.     

The use of the glycemic index in predicting the blood glucose response to mixed meals

There has been much interest in the use of the glycemic index (GI). A recent study reporting plasma glucose responses to mixed meals containing fat and protein concluded that the results were totally disparate from what would have been expected from published GI values of the foods fed. However, this conclusion was based upon an inappropriate assessment of the data using absolute rather than incremental blood glucose response areas. The present report demonstrates how data may be analyzed to make use of the GI values of individual foods to predict the GI of mixed meals (r = 0.987; p less than 0.02). It is concluded that the GI concept applies well to mixed meals containing fat and protein.     

Effect of processing on digestibility and the blood glucose response: a study of lentils

To test the effect of processing on digestibility and the glycemic response to a leguminous seed, a group of eight healthy volunteers took a series of breakfast test meals containing either lentils which had been processed in four different ways or the same amount of carbohydrate as white bread. Lentils, boiled for 20 min, resulted in a flattened blood glucose response by comparison with bread. This was unaltered by blending the lentils to a paste or boiling them for an additional 40 minutes. However the blood glucose response was significantly enhanced by drying the boiled blended lentils for 12 h at 250 degrees F. In vitro digestion with human saliva showed the rate of sugars released from the food related positively to the blood glucose rise. Breath hydrogen studies indicated that carbohydrate malabsorption was too small to account for differences in the blood glucose response. These results emphasize the importance of processing in determining digestibility and hence the glycemic response to a food.