Glycemic Carbohydrate: An International Perspective

Attention to the different types of carbohydrates and their role in health and disease is relatively recent. FAO and WHO jointly published a report on carbohydrates in human nutrition in 1998, with a number of recommendations about increasing carbohydrate intake as a sound approach to the prevention of obesity. The glycemic index (GI) was recommended as a means of classifying foods on the basis of their potential for raising blood glucose; this concept was based on the understanding that the state of hyperglycemia that is observed following the intake of certain high-GI carbohydrate foods could constitute a risk factor for diseases of lifestyle.     

Induction of Donor-Specific Allograft Tolerance by Short-Term Treatment with LF15-0195 After Transplantation. Evidence for a Direct Effect on T-Cell Differentiation

A 20-day treatment with LF15-0195, a deoxyspergualine analog, induced long-term heart allograft survival in the rat without signs of chronic rejection. LF15-0195-treated recipients did not develop an anti-donor alloantibody response. Analysis of graft-infiltrating cells, IL10, TNFalpha, IFNgamma mRNA and iNOS protein expression in allografts, 5 days after transplantation, showed that they were markedly decreased in allografts from LF15-0195-treated recipients compared with allografts from untreated recipients. Surprisingly, spleen T cells from LF15-0195 recipients, 5days after grafting, were able to proliferate strongly in vitro, when stimulated with donor cells, but had reduced mRNA expression for IFNy compared with spleen T cells from untreated graft recipients. Furthermore, when T cells from naive animals were stimulated in vitro, using anti-CD3 and anti-CD28, LF15-0195 also increased T-cell proliferation in a dose-dependent fashion: however, these cells expressed less of the Th1 -related cytokines, IFNgamma and IL2, compared with untreated cells, suggesting that LF15-0195 could act on T-cell differentiation. In conclusion, we show here that a short-term treatment with LF15-0195 induced long-term allograft tolerance, decreasing the in situ anti-donor response, and we illustrate evidence for the development of regulatory mechanisms.     

Biocompatibility pattern of a bicarbonate/lactate-buffered peritoneal dialysis fluid in APD: a prospective, randomized study.

BACKGROUND: In chronic ambulatory peritoneal dialysis, bicarbonate-buffered fluids, with their neutral pH and less advanced glycosylation end-products (AGE) and glucose degradation products (GDP), have better biocompatibility than conventional peritoneal dialysis (PD) solutions. That difference may be more beneficial in automated peritoneal dialysis (APD), due to its more frequent exchanges and longer contact times with fresh dialysate. We performed a prospective, randomized study in APD patients to compare the biocompatibility of conventional and bicarbonate/lactate-buffered PD fluids. METHODS: We randomized 14 APD patients to have APD with either conventional or bicarbonate/lactate-based fluids. After 6 months, both groups changed to the other solution. The overall observation period was 12 months. After 1 and 5 months and again after 7 and 11 months, phagocytotic and respiratory burst capacities of effluent peritoneal macrophages were determined. Plasma interleukin (IL)-6 and C-reactive protein (CRP) as well as effluent IL-6, CRP, transforming growth factor (TGF)-beta 1, AGE and CA125 concentrations were measured. Inflow pain was quantified using a patient questionnaire. RESULTS: Respiratory burst capacity remained unchanged and phagocytotic activity increased significantly during APD (P<0.001) with the bicarbonate/lactate fluid. Effluent IL-6 release was significantly lower than with the lactate fluid (P<0.05). While in the effluent TGF-beta 1 was unaffected, AGE concentration was lower after bicarbonate/lactate treatment (P<0.05). Effluent CA125 concentration, an indicator of mesothelial cell integrity, was higher (P<0.05) in neutral effluents. Finally, patients' inflow pain diminished (P = 0.05) when using the neutral fluid. CONCLUSIONS: The use of a neutral PD fluid in APD improved patients' inflow pain as well as biocompatibility parameters reflecting enhanced phagocytotic activity of peritoneal macrophages, reduced constitutive inflammatory stimulation (IL-6), reduced AGE accumulation in the peritoneal cavity and better preservation of the mesothelial cell integrity. From the biocompatibility point of view, a neutral fluid with low GDP content can be recommended as the primary choice for APD.     

葡萄糖筛选试验在妊娠期糖尿病诊断及治疗中的价值

目的　探讨 5 0 g葡萄糖筛选试验 (GCT)在妊娠期糖尿病 (GDM )诊断及治疗中的价值。 方法　选择 2 0 0 0年 1月～ 2 0 0 3年 6月在我院行产前检查并分娩的 5 0 gGCT异常的孕妇 36 8例 ,按血糖值分为 5组 :≥7.8～ <8.0mmol/L为Ⅰ组 ,≥ 8.0～ <9.0mmol/L为Ⅱ组 ,≥ 9.0～ <10 .0mmol/L为Ⅲ组 ,≥ 10 .0～ <11.0mmol/L为Ⅳ组 ,≥ 11.0mmol/L为Ⅴ组。比较 5组 75 g口服葡萄糖耐量试验 (OGTT)异常的比例及需用胰岛素治疗的病例数的差异。结果　 5组GDM的发生率分别为 6 .9%、8.5 %、2 1.3%、4 7.8%和 85 .0 % ,75 gOGTT异常的发生率分别为 19.0 %、2 4 .2 %、5 1.1%、87.0 %和 90 .0 % ,且用胰岛素治疗的病例数随 5 0 gGCT血糖值的上升而增加。结论　 5 0 gGCT在GDM的诊断及治疗方案的预测方面均有重要价值。     

Cow's milk-specific immunoglobulin E levels as predictors of clinical reactivity in the follow-up of the cow's milk allergy infants

Background IgE‐mediated cow's milk proteins (CMPs) allergy shows a tendency to disappear with age. The sooner tolerance is detected, the earlier the substitute diets can be suspended and the quicker family emotional hardship is alleviated. Objective To analyse the specific IgE levels to cow's milk and its proteins, which help to separate tolerant from no tolerant children in the follow‐up of infants with allergy to cow's milk. Patients and methods Sixty‐six infants diagnosed with IgE‐mediated allergy to CMPs were included in this prospective follow‐up study. Periodic reassessments were carried out every 6 months until they were 2‐years old and then, annually, until tolerance arose or until the last reassessment in which tolerance had not been achieved. Non‐tolerant infants were followed, at least, for a period of 3 years. In each visit, the same skin tests and determination of specific IgE (CAP System FEIA) for milk and its proteins were carried out. The open challenge test was repeated unless a clear transgression to milk, which came to be positive, had taken place within the previous 3 months in each of the follow‐up visits. Specific IgE levels to milk and its proteins, in different moments of the follow‐up were analysed by means of the receiver‐operating characteristic curve to predict clinical reactivity. Results Throughout the follow‐up 45 (68%) infants became tolerant. The follow‐up mean for tolerant infants was 21.2 months whereas for non‐tolerant infants it was 58 months. The specific IgE levels which were predictors of the clinical reactivity (positive predictive value (PPV)90%), grew as the age of the infants increased: 1.5, 6 and 14 kU_A/L for milk in the age range 13–18 and 19–24 months and in the third year, respectively. Specific IgE levels to casein: 0.6, 3 and 5 kU_A/L, respectively, predicted clinical reactivity (PPV90%) in the different analysed moments of the follow‐up. The cut‐off points: 2.7, 9 and 24 kU_A/L for milk and 2, 4.2 and 9 kU_A/L for casein, respectively, predicted clinical reactivity with an accuracy 95% corresponding to a specificity of 90%. Conclusions Monitorization of specific IgE concentration for milk and casein by means of the CAP system in allergic children to CMPs allows us to predict, to a high degree of probability, clinical reactivity. Age factor must be taken into account to evaluate the specific IgE levels which are predictors of tolerance or clinical reactivity.     

Facilitating access to glucometer reagents increases blood glucose self-monitoring frequency and improves glycaemic control: a prospective study in insulin-treated diabetic patients.

AIMS: To investigate whether availability of glucometer reagents increases the frequency of self-blood glucose monitoring (SBGM) and improves glycaemic control in diabetic patients. METHODS: Sixty-two insulin-treated diabetic patients were randomized to two groups, matched for age, gender, education, income, type and duration of diabetes, years of insulin treatment, number of daily insulin injections, and haemoglobin (Hb)A1c. All patients were given a glucometer, but one group (no cost, NC) was provided glucometer test strips free of charge. The other group (control, C) had to purchase strips as they found it necessary. Both groups of patients were followed longitudinally at 2-monthly intervals for 12 months with measurement of blood glucose and HbA1c, and the frequency of SBGM was determined by downloading the glucometer memory. RESULTS: The SBGM frequency was significantly higher in the NC group vs. the C group during the first 4 months (2.0 +/- 0.2 tests/day vs. 1.4 +/- 0.1 tests/day, P<0.025). Mean HbA1c remained stable over the 12 months in the NC group, whereas an increase with time was observed in the C group. The difference in HbA1c between the two groups was significant (P<0.002) after 6 months. Random blood glucose measured at each visit and average glucose recorded by the glucometer were also lower in the NC group vs. the C group (P<0.005). There was a negative correlation between HbA1c and SBGM frequency, and HbA1c in patients testing at least twice a day was lower than in those testing less than twice a day (8.8 +/- 0.2% vs. 9.6 +/- 0.2%, P<0.001). CONCLUSIONS: In this prospective study, having easy access to glucometer strips provided free of charge to patients increased SBGM frequency. The relationship between HbA1c and SBGM frequency supports the view that SBGM is an essential tool in diabetes management.     

Role of Natural Killer Cell Subsets in Cardiac Allograft Rejection

To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4(+) T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8(+) T cells and NK1.1(+) cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2(+) NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function.     

Transplant Tolerance in Non-Human Primates: Progress, Current Challenges and Unmet Needs

Given the significant morbidity associated with current post-transplant immunosuppressive regimens, induction of immune tolerance continues to be an important goal of clinical organ transplantation. While many strategies for inducing tolerance have been successfully applied in murine models, significant barriers are faced when translating these approaches to the clinic. This has necessitated pre-clinical studies in the more closely related model system, the non-human primates (NHP). In this review, we will discuss the four most prominent strategies for inducing transplantation tolerance and highlight their relative success and shortcomings in NHP. These strategies are: (1) T-cell costimulation blockade (2) mixed chimerism induction (3) T-cell depletion and (4) tolerance induction through regulatory T-cells. After discussing the progress that has been made with each of these strategies, we will identify this field's most pressing unmet needs and discuss how we may best overcome the resulting barriers to tolerance induction.     

Comparison of the diagnostic criteria for diabetes mellitus, WHO-1985, ADA-1997 and WHO-1999 in the adult population of Asturias (Spain).

AIMS: To estimate the prevalence of diabetes mellitus with three diagnostic criteria (WHO-1985 and 1999 and ADA-1997), evaluate their concordance and analyse the sensitivity and specificity of the different screening strategies for diabetes. METHODS: A cross-sectional population study with two-step sampling. One thousand and 34 people were selected randomly. A 75-g oral glucose tolerance test (OGTT) was performed and venous blood samples were obtained fasting and at 2 h. RESULTS: The prevalence of known Type 2 diabetes mellitus (DM-2) is 4%[95% confidence interval (CI) 2.8, 5.1]. By WHO-1985 criteria the prevalence of unknown DM-2 is 5.9% (4.5, 7.4); by ADA-1997 criteria 3.5% (2.5, 4.6) and by WHO-1999 criteria 7.3% (5.8, 8.8). Diagnostic overlap and statistical concordance (coefficient K) are WHO-1985/ADA-1997 29.3%, K=0.42; WHO-1985/WHO-1999 80%, K=0.88; ADA-1997/WHO-1999 48%, K=0.63. If only fasting glucose was used (following ADA-1997), 36.3% of those with diabetes (2-h glucose > or =11.1 mmol/l) would be diagnosed. If OGTT was performed (i) in those with a fasting glucose between 6.1 mmol/l and 6.9 mmol/l (9.8% of the population) we would diagnose 66.6%, and (ii) in all those between 5.7 mmol/l and 6.9 mmol/l (18.9% of the population) 81.8% would be diagnosed. CONCLUSIONS: The ADA criteria decrease the prevalence of DM in the adult population of Asturias by 2.4% and concordance with the classical criteria (WHO-1985) was only 29.3%. Using fasting glucose only (ADA-1997) diagnoses 36.3% of those with diabetes. The recent recommendations of the WHO-1999 increases this to 66.6%. To improve the diagnostic strategy for diabetes and detect up to 81.8% of patients, we propose the use of OGTT for all those with a fasting glucose between 5.7 mmol/l and 6.9 mmol/l.