Effect of standing frames used in real life on bone remodeling in non-walking children with cerebral palsy.

Children with severe cerebral palsy are prone to low bone mineral density. No clear recommendation exists for an optimal use of standing frame to enhance bone health in this context. Used in real life, this study suggests for the first time that standing practice improved bone mineralization by limiting bone resorption. INTRODUCTION: To compare the bone health of children with severe cerebral palsy who use a static standing frame in real life to that of children who do not. METHODS: A total of 24 children with severe cerebral palsy GMFCS IV & V were included in the study and were divided into two groups: 13 were using a passive standing frame and 11 were not. We performed a single center retrospective cross-sectional study comparing the two groups using dual X-ray absorptiometry data and tests on biological samples, including bone remodeling factors. RESULTS: Total body (less head) bone mineral content was significantly higher in children who used a standing frame for an average of 30 min/day. This was confirmed in the lumbar spine. Although the total body bone mineral density (less head and proximal femur) densitometric data were not significantly higher, a positive trend favored the use of a standing frame in the children. Bone resorptive factors (CTX) were higher in the non-standing-frame group, whereas there was no difference among osteoformation factors. No difference in fracture history was found. CONCLUSIONS: We show that non-ambulant children with cerebral palsy who use a static standing frame in real life have better bone health, with lower bone resorption, than children who do not. Further studies are needed to determine how standing practice could impact bone mineralization over time in real life and to explore more bone remodeling factors.

Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy.

Achieving near normal glucose homeostasis implies that all components of dysglycemia that are present in diabetes states be eliminated. Reducing ambient/overall hyperglycemia is a pre-requisite to eliminate the risk of development and progression of diabetes complications. More controversially however, are the relative and related contributions of postprandial glucose excursions, glucose variability, hypoglycemia and the dawn phenomenon across the spectrum of dysglycemia. For instance, it is likely that the dawn phenomenon contributes to ambient hyperglycemia and that postprandial glucose excursions are at the cross road of ambient hyperglycemia and glucose variability with glucose fluctuations as causative risk factors for hypoglycemia. Proof-of-concept trials such as the ongoing FLAT-SUGAR study are necessary for gaining further insight into the possible harmful effects of some of these features such as excessive glycemic variability and glucose excursions, still considered to be of minor relevance by several diabetologists. Whether their role will be more thoroughly proven through further intervention trials with "hard" endpoints, remains to be seen. In the meantime more consideration should be given to medications aimed at concomitantly reducing ambient/overall hyperglycemia and those additional abnormal glycemic features of dysglycemia.

Application of medium-term metrics for assessing glucose homoeostasis: Usefulness, strengths and weaknesses.

This review aims to address the issue of whether or not the newer metrics, developed for continuous glucose monitoring [real-time CGM (rtCGM), intermittently scanned CGM (isCGM)], enhance assessment of the "glucose tetrad": Ambient hyperglycaemia, short-term glycaemic variability, postprandial glucose excursions and hypoglycaemia. The ever-increasing number of metrics offered with rtCGM and isCGM includes intermediate-term indicators referred to as "time in range" (TIR), the time spent in the range of 70-180mg/dL (TIR 70-180); time spent above the range of 180mg/dL (TAR>180); and time spent below the range of 70mg/dL or 54mg/dL (TBR<70 or TBR<54). The former two values are strongly correlated with HbA1c levels and can therefore serve as short- or medium-term markers of ambient hyperglycaemia, depending on whether glucose sensors are worn over periods of several days or weeks, respectively, whereas the latter indices (TBR<70 or<54) are more relevant for capturing hypoglycaemic events and quantifying their magnitude and duration, in contrast to random spot testing with self-monitoring of blood glucose. Nevertheless, although analyses of 24h glucose profiles by CGM provide a highly valuable method for quantifying postprandial glucose excursions and short-term glycaemic variability, neither of these factors can be fully represented by such TIR metrics. Thus, other metrics are clearly needed for more comprehensive assessment of glucose homoeostasis.

Glycaemic variabilities: Key questions in pursuit of clarity.

After years of intensive investigation, the definition of glycaemic variability remains unclear and the term variability in glucose homoeostasis might be more appropriate covering both short and long-term glycaemic variability. For the latter, we remain in the search of an accurate definition and related targets. Recent work leads us to consider that the within-subject variability of HbA1c calculated from consecutive determinations of HbA1c at regular time-intervals could be the most relevant index for assessing the long-term variability with a threshold value of 5% (%CV = SD of HbA1c/mean HbA1c) to separate stability from lability of HbA1c. Presently, no one can deny that short- and long-term glucose variability should be maintained within their lower ranges to limit the incidence of hypoglycaemia. Usually, therapeutic strategies aimed at reducing post-meal glucose excursions, i.e. the major contributor to daily glucose fluctuations, exert a beneficial effect on the short-term glucose variability. This explains the effectiveness of adjunct therapies with either GLP- receptor agonists or SGLT inhibitors in type 2 diabetes. In type 1 diabetes, the application of a CGM device alone reduces the short-term glycaemic variability. In contrast, sophisticated insulin delivery does not necessarily lead to such reductions despite marked downward shifts of 24-hour glycaemic profiles. Such contrasting observations raise the question as to whether the prolonged wear of CGM devices is or not the major causative factor for improvement in glucose variability among intensively insulin-treated persons with type 1 diabetes.

Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy.

AIMS/HYPOTHESIS: We examined whether type of diabetes and/or insulin treatment can modulate the impact of sustained hyperglycaemia and glycaemic variability as activators of oxidative stress. METHODS: This was an observational study in 139 patients with diabetes, 48 with type 1, 60 with type 2 treated by oral hypoglycaemic agents (OHAs) alone and 31 with type 2 treated with insulin plus OHAs. In addition, two groups of ten patients with type 2 diabetes were investigated either before and after introducing insulin treatment (add-on insulin group) or before and after add-on OHA therapy to metformin (add-on OHA group). Oxidative stress was estimated from 24 h urinary excretion rates of 8-isoprostaglandin F2alpha (8-iso-PGF2alpha). HbA(1c) was assessed and mean amplitude of glycaemic excursions (MAGE) was estimated by continuous monitoring. RESULTS: The 24 h excretion rate of 8-iso-PGF2alpha (median [range] picomoles per millimole of creatinine) was much higher (p < 0.0001) in type 2 diabetes patients treated with OHAs alone (112 [26-329]) than in the type 1 diabetes group (65 [29-193]) and the type 2 diabetes group treated with insulin (69 [30-198]). It was associated with HbA(1c) (F = 12.9, p = 0.0008) and MAGE (F = 7.7, p = 0.008) in non-insulin-treated, but not in insulin-treated patients. A significant reduction in 24 h excretion rate of 8-iso-PGF2alpha from 126 (47-248) to 62 (35-111] pmol/mmol of creatinine was observed in the add-on insulin group (p = 0.005) but not in the add-on OHA group. CONCLUSIONS/INTERPRETATION: In type 1 and type 2 diabetes, insulin exerts an inhibitory effect on oxidative stress, a metabolic disorder that is significantly activated by sustained hyperglycaemia and glucose variability in non-insulin-treated type 2 diabetes.

Outcomes of vaginal squamous cell carcinoma of patients treated with radiation therapy: a series of 37 patients from a single expert center.

INTRODUCTION: The aim is to assess the outcome of patients treated for vaginal carcinoma with radiation therapy in terms of long-term tolerance and survival. MATERIALS AND METHODS: This single-center retrospective study included patients with squamous cell carcinoma of the vagina treated with pelvic external beam radiation therapy (EBRT) with or without vaginal brachytherapy (VB) between 1990 and 2013. RESULTS: Thirty-seven patients were included with stage I (24%), II (60%), III (8%), or IV (8%) vaginal tumors. Median age was 66 years (range 27-86 years). Median tumor size was 4 cm (range 0.7-12 cm). Seven patients underwent first intention surgery. The 37 patients received pelvic EBRT (45 Gy) with inguinal irradiation in 57% of cases. Fifteen (41%) received concurrent chemotherapy. Low-dose supplemental VB was performed in 31 patients (84%) (median dose: 20 Gy). Median follow-up was 59 months (range 7-322 months). Four patients (11%) had late grade 3-4 complications. Relapse occurred in 11 patients (30%), five of them locally. The 5-year relapse-free and cancer-specific survival rates were 68% and 76%, respectively. Surgery and concurrent chemotherapy did not seem to have an impact on the course of the disease. CONCLUSION: In our experience, pelvic EBRT leads to prolonged survival with acceptable long-term toxicity in patients with squamous cell carcinoma of the vagina.

[Adjuvant irradiation in breast cancer patients with ATM gene heterozygous mutations: special focus on clinical efficacy/toxicity]. / Toxicité et efficacité de la radiothérapie adjuvante chez les patientes traitées pour un cancer du sein et porteuses d'une mutation hétérozygote du gène de l'ataxie-télangiectasie.

Dysfunction of the ataxia telangiectasia mutated (ATM) gene has been related to defective cell cycle control and genomic instability due to the impaired repair of DNA double strand breaks. Although increased radiosensitivity in ATM heterozygous patients has been suggested in preclinical data, clinical implication of ATM variant remains debated. Despite frequent in vitro hypersensitivity in patients with severe radiation-induced delayed toxicity, heterozygoty for ATM gene does not represent the major cause of unexpected complications after radiation therapy. This might be partially due to potential coexistence of alterations in additional genes that would play a role in development of late radiation-induced adverse response. Although several data suggest that some ATM polymorphisms would increase grade 3 subcutaneous fibrosis at lower doses compared with patients who did not possess these genetic alterations, the relationship between the presence of ATM mutations or sequence variants and radiation-induced toxicity remains controversial in part because of their biological and functional significance. Considering the lack of prospective data, patients with ATM mutation should be considered as candidates for both dose volume and dose reduction clinical trials.

Glucocentric risk factors for macrovascular complications in diabetes: Glucose 'legacy' and 'variability'-what we see, know and try to comprehend.

Recognizing the role of dysglycaemia, 'ambient' hyperglycaemia, 'metabolic memory' and glycaemic variability as risk factors for macrovascular diseases is mandatory for effective diabetes management. Chronic hyperglycaemia, also referred to as 'ambient hyperglycaemia', was only fully acknowledged as a risk factor for adverse cardiovascular events when the beneficial effects of intensive glucose-lowering strategies were consolidated in the extended follow-up (> 10 years) of patients included in the United Kingdom Prospective Diabetes Study (UKPDS) and Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study. These studies led to the concept of the glucose-lowering 'legacy effect' (metabolic memory), which depends on the duration and magnitude of glucose-lowering, and is not a 'forever' phenomenon, as demonstrated in the 15-year follow-up of the Veterans Affairs Diabetes Trial (VADT). The relatively weak evidence for linking long- and short-term glycaemic variability to vascular complications in patients with diabetes is mainly due to a reliance on observational and retrospective studies, and the lack of randomized interventional trials. However, hypoglycaemia may play an intermediary role in accentuating the link between glycaemic variability and vascular events.

A prospective multicenter study of 163 sleeve gastrectomies: results at 1 and 2 years.

BACKGROUND: Good results obtained after laparoscopic sleeve gastrectomy (LSG), in terms of weight loss and morbidity, have been reported in few recent studies. Our team has designed a multicenter prospective study for the evaluation of the effectiveness and feasibility of this operation as a restrictive procedure. METHODS: From January 2003 to September 2006, 163 patients (68% women) with an average age of 41.57 years, were operated on with a LSG. Indications for this procedure were morbid obese [body mass index (BMI)>40 kg/m2] or severe obese patients (BMI>35 kg/m2) with severe comorbidities (diabetes, sleep apnea, hypertension...) with high-volume eating disorders and superobese patients (BMI>50 kg/m2). RESULTS: The average BMI was 45.9 kg/m2. Forty-four patients (26.99%) were superobese, 84 (51.53%) presented with morbid obesity, and 35 (21.47%) were severe obese patients. Prospective evaluations of excess weight loss, mortality, and morbidity have been analyzed. Laparoscopy was performed in 162 cases (99.39%). No conversion to laparotomy had to be performed. There was no operative mortality. Perioperative complications occurred in 12 cases (7.36%). The reoperation rate was 4.90% and the postoperative morbidity was 6.74% due to six gastric fistulas (3.66%), in which four patients (2.44%) had a previous laparoscopic adjustable gastric banding. Long-term morbidity was caused by esophageal reflux symptoms (11.80%). The percentage of loss in excessive body weight was 48.97% at 6 months, 59.45% at 1 year (120 patients), 62.02% at 18 months, and 61.52% at 2 years (98 patients). No statistical difference was noticed in weight loss between obese and extreme obese patients. CONCLUSIONS: The sleeve gastrectomy seems to be a safe and effective restrictive bariatric procedure to treat morbid obesity in selected patients. LSG may be proposed for volume-eater patients or to prepare superobese patients for laparoscopic gastric bypass or laparoscopic duodenal switch. However, weight regained, quality of life, and evolution ofmorbidities due to obesity need to be evaluated in a long-term follow up.

Type 2 diabetes: a well-characterised but suboptimally controlled disease. Can we bridge the divide?

From a pathophysiological point of view, type 2 diabetes is a well-characterised disease, since the glycaemic disorders result from three main mechanisms (the De Fronzo's triumvirate): a defect of beta-cell function, decreased disposal of glucose in peripheral tissues and overproduction of glucose by the liver. Each defect is subject to 24-h circadian variations and to inevitable worsening with time. As a consequence, therapeutic strategies should reflect whether patients retain sufficient insulin secretion or suffer from a more severe secretory defect that progresses from being responsive to oral diabetic agents to the insulin-requiring stage. Identifying the different pathophysiological stages is a prerequisite for successful therapeutic strategies. This assessment can be done by considering on the one hand the HbA(1c) and on the other the glycaemic profiles. For the latter, either discontinuous (self-monitoring of blood glucose) or continuous glucose monitoring can be used. However, many difficulties remain for bridging the divide between well-understood pathophysiological concepts and suboptimal glycaemic control achieved in clinical practice. The main drawback is the difficulty in providing therapies at recommended doses to stochastic phenomena such as either intestinal absorption of carbohydrates or fluctuations in both pharmacokinetics and pharmacodynamics of hypoglycaemic agents.

Evaluation of a structured educational programme for type 2 diabetes patients seen in private practice.

AIM: Structured education is necessary in the management of a chronic disease such as diabetes and should be readily offered to patients in different settings. Our aim was to demonstrate the feasibility and advantages of a group education programme for type 2 diabetic patients in a private setting in France. METHODS: A programme of group education for patients with type 2 diabetes was initiated by a multidisciplinary group of volunteer healthcare providers, including general practitioners, specialists in diabetology and non-medical members. All volunteers received one day of training, and physicians were instructed to organize several sessions of group education for the type 2 diabetic patients who regularly attended their practice. The first 427 patients entering the programme were included in the study, and asked to fill in a questionnaire to assess their knowledge, beliefs and behaviours with regard to diabetes. Their physician filled in a medical form. Six months later, the same questionnaire and form were sent for follow-up information. RESULTS: At six months versus baseline, patients exhibited small, but consistent, improvements: (i) fasting glucose 142+/-42 mg/dL (P<0.04) vs 146+/-44 mg/dL (P<0.04); (ii) HbA(1c) 7.41+/-1.26% vs 7.57+/-1.33% (P<0.01); and (iii) all of the main parameters of diabetes self-management recorded in the study. The percentage of patients who inspected their feet at least once a week increased from 67 to 77% (P<0.001). Patients improved their knowledge of the disease and developed a more positive attitude towards their diabetes. CONCLUSION: Our study demonstrates that it is possible to organize educational sessions for diabetic patients in a private-practice setting. At six months, patients receiving these sessions showed benefits in terms of blood glucose control and other important markers of self-management of their disease.

The application of simple metrics in the assessment of glycaemic variability.

The assessment of glycaemic variability (GV) remains a subject of debate with many indices proposed to represent either short- (acute glucose fluctuations) or long-term GV (variations of HbA1c). For the assessment of short-term within-day GV, the coefficient of variation for glucose (%CV) defined as the standard deviation adjusted on the 24-h mean glucose concentration is easy to perform and with a threshold of 36%, recently adopted by the international consensus on use of continuous glucose monitoring, separating stable from labile glycaemic states. More complex metrics such as the Low Blood Glucose Index (LBGI) or High Blood Glucose Index (HBGI) allow the risk of hypo or hyperglycaemic episodes, respectively to be assessed although in clinical practice its application is limited due to the need for more complex computation. This also applies to other indices of short-term intraday GV including the mean amplitude of glycemic excursions (MAGE), Shlichtkrull's M-value and CONGA. GV is important clinically as exaggerated glucose fluctuations are associated with an enhanced risk of adverse cardiovascular outcomes due primarily to hypoglycaemia. In contrast, there is at present no compelling evidence that elevated short-term GV is an independent risk factor of microvascular complications of diabetes. Concerning long-term GV there are numerous studies supporting its association with an enhanced risk of cardiovascular events. However, this association raises the question as to whether the impact of long-term variability is not simply the consequence of repeated exposure to short-term GV or ambient chronic hyperglycaemia. The renewed emphasis on glucose monitoring with the introduction of continuous glucose monitoring technologies can benefit from the introduction and application of simple metrics for describing GV along with supporting recommendations.

Continuous glucose monitoring in patients with type 2 diabetes: Why? When? Whom?

The overall assessment of glycaemic control in patients with type 2 diabetes should normally include the monitoring of three parameters that are usually depicted as the 'glucose triad': HbA(1c), fasting plasma glucose (FPG) and postprandial glucose (PPG) excursions. However one additional marker, the so-called 'glucose variability' might be as important as the three others since it has been demonstrated that both upward and downward glucose fluctuations are potent activators of oxidative stress. Even though many methods have been proposed for assessing glucose fluctuations, the 'mean amplitude glucose excursions' (MAGE) index remains the 'gold standard'. However MAGE estimation requires the use of continuous glucose sensors. Despite the debate on the reliability and cost of the devices that permit glucose monitoring, we suggest that interventional trials designed to evaluate the effects of glucose fluctuations on diabetic complications should benefit from the use of continuous glucose monitoring systems (CGMSs). More prosaically, the use of these technologies could be extended to current clinical care of type 2 diabetic patients especially for motivating them to accept earlier insulin treatments in case of 'oral antidiabetic drug secondary failure', and further for choosing the most appropriate insulin regimen.

Addition of rapid-acting insulin to basal insulin therapy in type 2 diabetes: indications and modalities.

There are many reasons to believe that in the near future, the treatment of patients with Type 2 diabetes will be characterised by an increased use of insulin therapy. To ensure that insulin regimens are acceptable to patients, and implemented by physicians, they should be as simple and efficient as possible. Simplicity is synonymous with the regimen of once-daily basal insulin glargine given at any time of the day (at the same time each day). With such a strategy, the dose is adjusted by titrating to target fasting blood glucose values of 5.0 - 7.2 mmol/L (90 - 130 mg/dL). When these targets can no longer be achieved with reasonable doses of long-acting insulin, a rapid-acting insulin analogue should be added at meal times. A step-by-step strategy can be used; it is recommended that initially, a single daily prandial bolus of a rapid-acting insulin analogue is administered before the meal that leads to the highest post-meal blood glucose excursions. Further boluses can be added at other meal times as necessary, i.e, when post-meal blood glucose values remain above 10.0 mmol/L (180 mg/dL) and 7.8 mmol/L (140 mg/dL) at mid-morning and 2h-post-lunch or post-dinner times, respectively. This stepwise strategy may eventually lead to a standard basal-bolus regimen with 3 pre-meal injections of rapid-acting insulin analogues, a potentially small trade-off for achieving fairly-well controlled diabetes.

Contribution of postprandial glucose to chronic hyperglycaemia: from the "glucose triad" to the trilogy of "sevens".

Even though fasting and postprandial glucose are both contributors to the overall hyperglycaemia as observed in patients with type 2 diabetes, their respective contributions are varying with the degree of diabetic control. The contribution of postprandial glucose is predominant in patients with satisfactory control of diabetes (HbAlc < 7.3%) whereas the contribution of fasting glucose increases progressively with worsening diabetes. As a consequence an overall picture of the diabetic control should normally be based on the assessment of the "glucose triad" with its three components: HbAlc which integrates the diabetic control over a 3-month period, fasting and postprandial glucose. The two later are good indicators of the glycaemic regulation over the two main physiological periods of daytime: the fasting and postprandial states. Postprandial glucose concentrations should be more particularly tested at mid-morning time since in most patients this period corresponds to the highest glucose concentrations of daytime. However postprandial measurements at 2-h after lunch provide an evaluation of the overall diabetic control since we have demonstrated that glucose concentrations < 7 mmol/L at this time point are excellent predictors of HbAlc levels < 7% (specificity 2 90%). Therefore, in order to simplify the work of health care providers the "glucose triad" concept can be translated into the trilogy of "sevens": HbA1c goals < 7% and postprandial glucose targets < 7 mmol/L 2-h after lunch, both for assessing a satisfactory diabetic control, and fasting glucose < 7 mmol/L for defining the non-diabetic state.

Two phases of aging separated by the Smurf transition as a public path to death.

Aging's most obvious characteristic is the time dependent increase of an individual's probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined. To identify the very processes driving aging we have developed in the past years an assay to identify physiologically old individuals in a synchronized population of Drosophila melanogaster. Those individuals show an age-dependent increase of intestinal permeability followed by a high risk of death. Here we show that this physiological marker of aging is conserved in 3 invertebrate species Drosophila mojavensis, Drosophila virilis, Caenorhabditis elegans as well as in 1 vertebrate species Danio rerio. Our findings suggest that intestinal barrier dysfunction may be an important event in the aging process conserved across a broad range of species, thus raising the possibility that it may also be the case in Homo sapiens.

Plasma beta-thromboglobulin response to insulin-induced hypoglycemia in type I diabetic patients.

The effect of an insulin-induced hypoglycemia was examined in 14 type I diabetic patients. After an overnight blood glucose normalization, each patient received an additional intravenous bolus of 3 U regular insulin at 0900 h (time 0). Blood glucose was continuously recorded up to 180 min. Plasma samples were assayed for beta-thromboglobulin (beta TG, ng/ml), pancreatic glucagon (pg/ml), cortisol (microgram/dl), and growth hormone (ng/ml) 30 min before the insulin stress, at time 0, at blood glucose nadir, and at 180 min. The blood glucose fell from a baseline level of 85.0 +/- 3.2 mg/dl to a nadir value of 39.2 +/- 1.9 mg/dl (P less than 0.001) reached at an average time of 41.4 +/- 4.9 min. Plasma beta TG increased significantly (P less than 0.05) during the insulin stress: 93.4 +/- 23.7 ng/ml at nadir versus 42.5 +/- 5.9 at time 0. Plasma cortisol and growth hormone were significantly increased (P less than 0.02 and P less than 0.01) at nadir compared with time 0 values. Plasma pancreatic glucagon was higher at nadir than at time 0, but the difference was not significant. The present results indicate that in vivo platelet activation can be triggered by hypoglycemic episodes in insulin-treated diabetic patients.

An overview of the rationale for pharmacological strategies in type 2 diabetes: from the evidence to new perspectives.

Therapeutic strategies in type 2 diabetic patients should not only integrate both the targets and indications of the different therapies but should be also a compromise between the patient's and physician's goals and willingnesses. The rationale for therapeutic targets is based on recommendations that differ from one country to another. Even though HbA1c remains the "gold standard", monitoring of blood glucose at fasting and postprandial time-points is a complementary tool for estimating both the quality and safety of diabetic control. Despite the lack of available strong evidence-based data it seems that achieving glucose levels < 130 mg/dl at fasting and < 180 mg/dl or < 140 mg/dl over postbreakfast or postlunch periods, respectively, might be a reasonable goal in most countries. The choice of appropriate strategies for treating type 2 diabetic patients should ideally be based on pathophysiological considerations. However for practical reasons, decisions for initiating or completing antidiabetic treatments are usually made by using such simple parameters as HbA1c and plasma glucose levels. The bridge between pathophysiological and clinical rationales can be obtained from the analysis of the relative contributions of fasting and postprandial glucose to the overall hyperglycaemia. In patients with HbA1c < 7.3%, postprandial glucose makes the major contribution to the overall hyperglycaemia, whereas the contribution of fasting glucose becomes progressively predominant in patients with HbA1c > 7.3%. As a consequence of these observations, initiation of antidiabetic treatments or implementation of second-line therapies should be aimed at reducing either postprandial excursions or fasting hyperglycaemia according to whether HbA1c levels are found respectively below or above a cut-off value of 7.3%.

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

A thromboxane effect of a hydroxytyrosol-rich olive oil wastewater extract in patients with uncomplicated type I diabetes.

OBJECTIVE: To assess the antioxidant/non-antioxidant effects of a hydroxytyrosol (HT)-rich phenolic extract from olive mill wastewaters administered with a breakfast. DESIGN, SETTING AND SUBJECTS: Five type I diabetic patients received 25 mg of HT the first day and 12.5 mg/day the following 3 days. Blood sampling was carried out at T(0) (baseline) and T(4d) just before the breakfast + HT administration and at time points 1, 2, 3 and 4 h after T(0). Urines (24-h) were collected from T(0) to T(4d). Baseline HbA1c was generally inferior to 10%, glycemia was within the range 6-24 mmol/l, whereas total cholesterol, HDL-chol and triglycerides were normal. RESULTS: The major finding was the 46% decrease in the serum TXB(2) production after blood clotting at T(4d). Plasma vitamin A, E, beta-carotene were not changed. Vitamin C tended to increase (P = 0.075). Plasma antioxidant capacity was enhanced at T(0)+1 h only, whereas its main determinants (albumin, bilirubin, uric acid) were not modified. Urinary 8-isoPGF(2alpha) levels were highly variable and were not affected significantly by HT administration. CONCLUSION: The major effect of HT accounts for an antiaggregating platelet action, leading to a possible prevention of thrombotic and microthrombotic processes.