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Aim: Although newer technologies of insulin delivery in type 1 diabetes have facilitated an improvement in glycaemic control the risk of hypoglycaemia remains a threat. Therefore, it is important to define the thresholds of glycaemic variability below which the risk of hypoglycaemia can be eliminated or at least minimized., Methods: Randomized controlled trials conducted from 2017 to 2023 comparing Sensor-Augmented-Pumps and Augmented Insulin Delivery Systems (n = 16 and 22 studies, respectively) were selected. A weighted linear model of regression was used to compute the relationship between glycaemic variability and times spent below glucose range. The intercepts of regression lines with the abscissa axis (time below range = 0 %) defined the glycaemic variability thresholds., Results: Positive relationships were observed between the 2 metrics. The scatter plots indicated that the times spent below range never reached the value of 0 % and that the glycaemic variability never fell below 28 %. By extrapolating the regression lines, the glycaemic variability at intercepts with time below range < 70 mg/dL of 0 % was 30.1 % with sensor augmented pumps and 18.9 % with automated insulin delivery. For a time below range < 54 mg/dL of 0 % the respective glycaemic variability values were 32.7 % and 19.9 % (with sensor augmented pumps and automated insulin delivery, respectively)., Conclusions: Importantly, glycaemic variability targets and ambient hyperglycaemia are interdependent. Users of automated insulin delivery need to reach a glycaemic variability of 18 % to 20 % to minimize or eradicate the risk of hypoglycaemia. Such values are those observed in healthy non-diabetic people., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L Monnier, C Colette, S Aouinti, N Molinari and D Owens declare that they have no conflict of interest relevant to this article; E Renard has received consulting and speaker fees from A.Menarini Diagnostics, Abbott, Air Liquide SI, Astra Zeneca, Beckton-Dickinson, Boehringer-Ingelheim, Cellnovo, Dexcom Inc, Insulet Inc., Johnson & Johnson, Medtronic, Medirio, Novo-Nordisk, Roche, Sanofi-Aventis and research support from Abbott, Dexcom Inc., Insulet Inc., Roche,Tandem Diabetes Care; P-Y Benhamou has received speaker fees from Abbott, Eli Lilly, Novo-Nordisk, served on advisory board panels for Abbott, Insulet, Eli Lilly, Novo-Nordisk and is chief medical officer for Diabeloop., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Near normal glycaemic control in diabetes consists to target daily glucose fluctuations and quarterly HbA1c oscillations in addition to overall glucose exposure. Consequently, the prerequisite is to define simple, and mathematically undisputable key metrics for the short- and long-term variability in glucose homeostasis. As the standard deviations (SD) of either glucose or HbA1c are dependent on their means, the coefficient of variation (CV = SD/mean) should be applied instead as it that avoids the correlation between the SD and mean values. A CV glucose of 36% is the most appropriate threshold between those with stable versus labile glucose homeostasis. However, when near normal mean glucose concentrations are achieved a lower CV threshold of <27 % is necessary for reducing the risk for hypoglycaemia to a minimal rate. For the long-term variability in glucose homeostasis, a CV HbA1c < 5 % seems to be a relevant recommendation for preventing adverse clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Restricted-calorie diets are the most worldwide used treatments for obesity. Although such strategies are based on the first law of thermodynamics, the real life clinical practice demonstrates that the observed weight losses are divergent from those theoretically predicted. Loosely adherence to recommendations is one of the main causes for the limited efficacy of dieting, but many additional factors can be involved in the hurdles to weight loss. According to the second law of thermodynamics any restriction in dietary energy intake results in energy sparing with a diminution in the basal metabolic rate and a concomitant loss in the lean body mass. This "thrifty" energetic adaptation is associated with a progressive reduction in the difference between levels of energy intake and expenditure, thus resulting in a drastic fall in weight loss rates on the medium and long-term regardless of the dietary carbohydrate/fat ratio. This loss of efficacy is aggravated by the misadaptation of the production and action of anti-obesity hormones such as leptin. During the latest past decades the discovery of changes in the gut microbiota of obese people referred to as "obese dysbiosis" has raised the question as to whether these alterations can participate to diet-resistance. Combined with the behavioral and psychological barriers to low-calorie diets, there is a broad physiologic spectrum of evidence indicating that weight loss is a hard challenge. Consequently, the answer would be primarily to prevent the development of obesity and at worst to avoid its ominous progression from metabolically healthy to unhealthy stages., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

« Variability in glucose homoeostasis » is a better description than « glycaemic variability » as it encompasses two categories of dysglycaemic disorders: i) the short-term daily glucose fluctuations and ii) long-term weekly, monthly or quarterly changes in either HbA1c, fasting or postprandial plasma glucose. Presently, the relationship between the "variability in glucose homoeostasis" and diabetes complications has never been fully clarified because studies are either observational or limited to retrospective analysis of trials not primarily designed to address this issue. Despite the absence of definitive evidence from randomized controlled trials (RCTs), it is most likely that acute and long-term glucose homoeostasis "cycling", akin to weight and blood pressure "cycling" in obese and hypertensive individuals, are additional risk factors for diabetes complications in the presence of sustained ambient hyperglycaemia. As hypoglycaemic events are strongly associated with short- and long-term glucose variability, two relevant messages can be formulated. Firstly, due consideration should be given to avoid within-day glucose fluctuations in excess of 36% (coefficient of variation) at least for minimizing the inconvenience and dangers associated with hypoglycaemia. Secondly, it seems appropriate to consider that variability in glucose homoeostasis is not only associated with cardiovascular events but is also a causative risk factor via hypoglycaemic episodes as intermediary step. Untangling the" Gordian Knot", to provide confirmation about the impact of variability in glucose homoeostasis and diabetes complications remains a daunting prospect., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Masson SAS.)

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., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

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 HbA 1c ). 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., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Abstinence from eating and drinking from dawn to sunset characterizes the holy month of Ramadan. For the 50 million Muslims worldwide with diabetes who adhere to this religious fast, the practice results in marked changes in glucose homoeostasis. The sunset meal (Iftar) that breaks the fasting state is followed by exaggerated surges in blood glucose and sustained overnight hyperglycaemia in cases of nocturnal overfeeding. The predawn meal (Suhoor) frequently results in prolonged glucose decay over the daylight hours. These glycaemic disturbances are particularly marked in insulin-treated patients, in those with unsatisfactory diabetes control during the pre-Ramadan period and in patients who are poorly compliant with lifestyle recommendations. Whether such patients should be exempt from the Islamic fast remains an open debate, which might be partially resolved by long-term controlled studies using the technology of continuous glucose monitoring in large populations of patients with diabetes., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Both postprandial and fasting (basal) hyperglycaemia contribute to overall hyperglycaemia (ambient hyperglycaemia) in type 2 diabetes (T2D). Postprandial glucose is the main contributor in fairly well controlled individuals, whereas basal hyperglycaemia becomes the preponderant contributor in poorly controlled patients. A more generally acceptable description of the contribution of postprandial glucose is to simply say that the absolute impact of postprandial glucose to HbA1c remains constant at approximately 1% across the entire HbA1c spectrum of non-insulin-treated patients with T2D. While epidemiological and pathophysiological studies seem to indicate that excessive postprandial glucose excursions play a role in or are predictors of cardiovascular diseases, there is still currently a lack of clinical evidence that correcting post-meal hyperglycaemia can improve clinical outcomes. However, even in the absence of consensus, there are many reasons for thinking that excessive postprandial glucose might be an independent risk factor for diabetic complications as it contributes to both overall glucose exposure and glycaemic variability, especially in those who have HbA1c levels < 7.5-8%. Given that excessive glucose fluctuations from peaks to nadirs activate oxidative stress, it seems reasonable to consider that a key player in the pathogenesis of diabetic complications, according to the latest IDF guidelines, is post-meal glucose, thereby warranting its assessment and treatment when found at abnormally elevated levels. Nevertheless, healthcare professionals should bear in mind that targeting both post-meal and basal plasma glucose, giving equal consideration to both of them, is probably the best strategy for achieving optimal glycaemic control and thus preventing or reducing the risk of diabetic complications., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aim: The study was aimed at determining whether the dawn phenomenon in type 2 diabetes (T2D) can be predicted and quantified using simple and easily accessible glucose determinations., Methods: A total of 210 non-insulin-treated persons with T2D underwent continuous glucose monitoring (CGM). The dawn phenomenon was quantified as the absolute increment from the nocturnal glucose nadir to the pre-breakfast value (Δdawn, mg/dL). Pre-lunch (preL) and pre-dinner (preD) glucose, and their averaged values (preLD), were compared with the nocturnal nadir. These pre-meal values were subtracted from the pre-breakfast values. The differences obtained (Δpre-mealL, Δpre-meal D and Δpre-meal LD) were correlated with Δdawn values. The receiver operating characteristic (ROC) curve was used to select the optimal Δpre-meal value that best predicted a dawn phenomenon, set at a threshold of 20mg/dL., Results: All pre-meal glucose levels and differences from pre-breakfast values (Δpre-meal) significantly correlated (P<0.0001) with the nocturnal nadir and Δdawn values, respectively. The strongest correlations were observed for the parameters averaged at preL and preD time points: r=0.83 for preLD and r=0.58 for Δpre-meal LD. ROC curve analysis indicated that the dawn phenomenon at a threshold of 20mg/dL can be significantly predicted by a Δpre-meal LD cut off value of 10mg/dL. The relationship between Δdawn (Y, mg/dL) and Δpre-meal LD (X, mg/dL) was Y=0.49 X+15., Conclusion: The self-monitoring of preprandial glucose values at the three main mealtimes can predict the presence/absence of the dawn phenomenon, and permits reliable assessment of its magnitude without requiring continuous overnight glucose monitoring., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety. These attributes make GLP-1 agonists a treatment option in type 2 diabetes mellitus (T2DM). To optimise treatment choice, a detailed understanding of the effects of GLP-1 RAs on glucose homeostasis in individuals with T2DM is necessary. Although the various GLP-1 RAs share the same basic mechanisms of action, differences in pharmacokinetic/pharmacodynamic characteristics translate into differential effects on parameters of glycaemia. Head-to-head comparisons between long-acting non-prandial (liraglutide once daily and exenatide once weekly) and shorter-acting prandial (exenatide twice daily and lixisenatide once daily prandial) GLP-1 RAs confirm their differential effects on fasting plasma glucose (FPG) and post-prandial glucose (PPG). Liraglutide once daily and exenatide once weekly demonstrate greater reductions in FPG but lesser impacts on PPG excursions plasma than exenatide twice daily. Prandial GLP-1 RAs have a profound effect on post-prandial glycaemia, mediated by delaying gastric emptying, which is not subject to the tachyphylaxis occurring due to the sustained elevated plasma GLP-1 concentrations after treatment with long-acting GLP-1 RAs. Lixisenatide once-daily prandial, in contrast to liraglutide, strongly suppresses post-prandial glucagon secretion, further contributing to the more pronounced PPG-lowering effect found with lixisenatide. Evidence suggests that the GLP-1 RAs that predominantly target the prandial glucose excursions, such as exenatide twice daily and lixisenatide once-daily prandial, are therefore best used as combination therapy with basal insulin and will form an important new treatment option for individuals with T2DM., (Crown Copyright © 2013. Published by Elsevier Masson SAS. All rights reserved.)

The relationship between insulin and atherosclerosis is complex. People with type 2 diabetes are affected by three main glycaemic disorders: chronic hyperglycaemia; glycaemic variability; and iatrogenic hypoglycaemia. In addition to this triumvirate, the diabetic condition is characterized by lipid disorders, chronic low-grade inflammation and activation of oxidative stress. All these associated disorders reflect the insulin-resistant nature of type 2 diabetes and contribute to the development and progression of cardiovascular (CV) diseases. By both lowering plasma glucose and improving the lipid profile, insulin exerts beneficial effects on CV outcomes. In addition, insulin has several pleiotropic effects such as anti-inflammatory, antithrombotic and antioxidant properties. Insulin per se exerts an inhibitory effect on the activation of oxidative stress and seems able to counteract the pro-oxidant effects of ambient hyperglycaemia and glycaemic variability. However, insulin actions remain a subject of debate with respect to the risk of adverse CV events, which can increase in individuals exposed to high insulin doses. Evidence from the large-scale, long-term ORIGIN trial suggests that early implementation of insulin supplementation therapy in the course of glycaemic disorders, including type 2 diabetes, has a neutral impact on CV outcomes compared with standard management. Thus, the answer to the question "What impact does insulin have on atherosclerosis?" remains unclear, even though it is logical to deduce that insulin should be initiated as soon as possible and that small doses of insulin early on are better than higher doses later in the disease process., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Aim: The metabolic efficacy of adding prandial insulin in a stepwise manner to a straightforward basal-bolus regimen was compared in patients with type 2 diabetes mellitus (T2DM), suboptimally controlled by oral antidiabetic drugs (OADs) and once-daily basal insulin., Methods: In this international randomized, parallel-group, non-inferiority study, 811 patients with poorly controlled type 2 diabetes using basal insulin were switched to insulin glargine (GLAR) for 6 months while continuing OADs. Patients with HbA(1c) > 7% and FPG < 120 mg/dL (n=476) were then randomized to either group 1, GLAR+metformin (MET)+3×insulin glulisine (GLU), group 2, GLAR+MET+1-3×GLU, or group 3, GLAR+MET+insulin secretagogue (IS)+1-3×GLU, for 12 months. Objectives were to show the non-inferiority of efficacy of group 2 vs group 1 and vs group 3. Non-inferiority of group 2 vs group 1 was concluded if the upper limit of the 95% confidence interval (CI) for the HbA(1c) difference was ≤ to 0.4%., Results: The adjusted HbA(1c) difference of group 2 vs 1 for the per-protocol population crossed the non-inferiority margin (0.228, 95% CI: -0.018-0.473). There was significantly less weight gain in group 2 compared with group 1, but adverse events were otherwise similar between the two groups. In patients with HbA(1c) < 8% at baseline, non-inferiority was achieved in group 2 vs group 1., Conclusion: Although non-inferiority was not achieved, stepwise intensification of GLU added to GLAR showed efficacy close to that of the basal-bolus approach and with significantly less weight gain., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: To compare continuous glucose monitoring (CGM) profiles on vildagliptin versus sitagliptin in addition to metformin, in patients with inadequately controlled type 2 diabetes mellitus (HbA(1c) 6.5-8.0%)., Methods: A multicenter, prospective, randomised, open-label study with blinded endpoint analysis. CGM data acquired over three days--firstly on metformin alone and then 8 weeks after the addition of either vildagliptin (n=14) or sitagliptin (n=16)--were blinded and analyzed centrally., Results: In comparable populations with a mean baseline HbA1c of 7.1%, 24-hour glucose variability--measured by mean amplitude of glucose excursions and standard deviation of mean glucose concentration--showed similar improvement on both drugs versus metformin alone. In contrast, a series of predefined parameters reflecting daily glycaemic control--mean 24-hour blood glucose concentration, and the times spent in the optimal glycaemic range (70-140 mg/dL) and above the hyperglycaemic thresholds of 140 and 180 mg/dL together with the corresponding AUC values--were significantly improved from baseline only in the vildagliptin arm. In addition, overall hyperglycaemia (AUC[24 h] > 100 mg/dL) significantly dropped from baseline on vildagliptin [-37%] but not on sitagliptin [-9%], while postprandial hyperglycaemia (AUC[0-4 h] × 3) was significantly reduced on both, and basal hyperglycaemia (overall--postprandial hyperglycaemia was reduced only on vildagliptin [-41%; P = 0.04])., Conclusions: The addition of a DPP-4 inhibitor significantly reduced glycaemic variability with no difference between the two drugs. However, vildagliptin induced better circadian glycaemic control than sitagliptin with a significant decrease on overall hyperglycemia, mainly driven by reduction on basal hyperglycaemia., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Due to ongoing technological advances, the range of clinical applications for diffusion-weighted MR imaging has expanded to now include abdominal pathology. Current applications for liver pathology include two main directions. First, oncologic imaging with detection, characterization and follow-up of lesions. Second, evaluation of diffuse liver diseases, including hepatic fibrosis. The diagnostic impact and role of diffusion-weighted MR imaging remain under investigation, but appear promising. Because of its short acquisition time, sensitivity, and additional information it provides, diffusion-weighted MR imaging should be included in routine liver imaging protocols.

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.

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.

Cystic lesions of the pancreas, with an estimated prevalence of 20%, frequently are incidental findings at imaging on asymptomatic patients. Pseudocysts, typically in a setting of pancreatitis, should first be excluded. Characterization of cystic tumors is more complicated. Still, it is important to differentiate between benign and malignant lesions. Multi-detector row CT and MRI allow characterization of such lesions in over 75% of cases. Indeterminate lesions should undergo endoscopic US with biopsy/aspiration and fluid analysis, especially for mucin producing tumors (rounded with thick enhancing wall). When imaging fails to fully characterize a lesion, follow-up may be proposed for lesions less than 3 cm in size, that are either unilocular with thin nonenhancing wall (simple cyst) or lobulated multilocular with thin nonenhancing wall (serous cystadenoma, isolated side branch IPMTP). Follow-up imaging shows that these tumors usually show very little change over time. Management is based on comparing estimated patient survival without treatment to surgical risks (morbidity, mortality, functional sequelae from the procedure).

Purpose: The quality of magnetic resonance cholangiopancreatography (MRCP) images is frequently degraded by high signal from the gastrointestinal tract on heavily T2W images. The purpose of this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent in MRCP., Materials and Methods: Results from MRCP in 50 patients with PJ and 50 patients with paramagnetic contrast (ferumoxsil-Lumirem) were compared. Reviewers were blinded to the type of contrast agent. Exam quality was recorded with regards to signal suppression in the stomach, duodenum and proximal small bowel and with regards to pancreatic duct and biliary ducts visualization. In vitro, the signal characteristics of several commercially available brands of PJ were assessed using T1W, T2W and MRCP sequences. Signal intensity was correlated with the manganese concentration measured using atomic absorption spectrometry. Finally, the reviewers compared the taste of PJ and ferumoxsil., Results: On MRCP sequences, results were similar with regards to signal suppression in the stomach, duodenum and proximal small bowel with PJ and ferumoxsil. Visualization of the pancreatic duct, intrahgepatic bile ducts and CBD was similar with PJ and ferumoxsil. The signal intensity of commercially available brands of PJ on T2W and MRCP sequences correlated well with the measured manganese concentration on spectroscopy. Variations in manganese concentration were observed, with values ranging from 3.65 to 27.24 mg/L. The reviewers noted that PJ tasted "good" or "very good" and that ferumoxsil tasted "bad" or "very bad"., Conclusion: Ingestion of PJ provides effective signal suppression in the GI tract on MRCP, similar to paramagnetic contrast agents. Because manganese concentration is highly variable in commercially available PJ brands, a brand with high manganese concentration should be selected.

The imaging features of infectious and non-infectious pathologies in HIV patients with AIDS (less than 200 CD4/mm3) are illustrated. Opportunistic infections, tumors and vascular pathologies have variable appearances based on the degree of immunosuppression and patient compliance with opportunistic infection prophylaxis. Because of advances in retroviral treatments and wider use of anti-infectious prophylaxis, thoracic pathologies in AIDS patients are less frequent but must nonetheless be recognized, and diagnosis should be suggested in patients with unknown serologic status.

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.

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.

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.

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.

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%.

Intramural hematoma of the colon is a rare complication of blunt abdominal trauma. We report the case of a 32-year-old man who presented with abdominal pain related to blunt trauma. The initial diagnosis of post-traumatic intramural hematoma of the colon was performed at CT scan and proven at colonoscopy. Although the majority of cases warrant surgery, conservative therapy was proposed in the present case with spontaneous resolution of the hematoma demonstrated by CT scan.

Self-monitoring of blood glucose (SMBG) is recognized as necessary in insulin-treated diabetic patients. There is less evidence for the regular use of SMBG in non-insulin-using type 2 diabetic patients. The rationale for an appropriate regimen of SMBG might be to have at least one time-point of monitoring included within each of the 3 periods of daytime i.e. fasting, postprandial and postabsorptive periods. Interventional trials have indicated that a 4-to 5-point daily profile represents an optimal regimen for SMBG in type 1 diabetic patients with satisfactory diabetic control. This type of SMBG includes 4 daily glucose determinations (3 before each meal and one at bedtime) and one weekly monitoring at 3: 00 am. However additional determinations should be made within postprandial states, particularly when rapid insulin analogues or pump-treatments are used. In non-insulin-using type 2 diabetic patients, studies of diurnal glycemic profiles have indicated that postprandial glucose is an important contributor to HbA1c and that mid-morning hyperglycemia is the "weakest link" of metabolic control. Therefore mid-morning glucose testing should be recommended when HbA1c levels are not correctly controlled. Furthermore, extended postlunch determinations at 5: 00 pm can be helpful for checking both the quality and safety of diabetic control in such patients. The frequency and timing of SMBG depend both on the type (1 or 2) of diabetes and should be a compromise between optimal and minimal regimens.

Objectives: The Mediab study was conducted to estimate the medical care in French patients with type 2 diabetes mellitus managed by general practitioners on an ambulatory basis, but consIdered as requiring new treatment implementation., Methods: Five thousand one hundred and fourty eight diabetic patients without any treatment or treated with lifestyle measures either alone or combined with an oral antIdiabetic agent given as monotherapy were included in a cross-sectional study that was conducted on a nationwIde basis by using the ORP (R) methodology. The 4088 patients in whom HbA1c was determined with a reliable method were further classified into 3 categories according to whether HbA1c was<=6.5% (group I, n=525), ranging between 6.6 and 8% (group II, n=1699) or > 8% (group III, n=1864)., Results: A large proportion of patients (45.6%) exhibited HbA1c > 8%. Adherence to diet and regular physical activity were progressively decreasing while prevalence of diabetic complications was steadily increasing from group I to III, i.e. when diabetic control was worsening. The complications suffered from severe "underreporting". When complications were reported, the odds-ratio analysis showed that retinopathy is influenced by both the magnitude of glucose excess and the diabetes duration, while renal diseases and macroangiopathy depend mainly on diabetes duration. 38.1% of patients visited a diabetologist, but most of these patients were referred to the speciaList after the inclusion visit., Conclusions: Despite the development of guIdelines, a large percentage of patients remains poorly-controlled. Future actions should be based on: (i) better collaboration between general practitioners and diabetologists (ii) better detection of complications that suffer from severe "underreporting", (iii) reinforcement of lifestyle recommendations and of pharmacological treatments by shifting from mono- to multi-drug therapy, at earlier stages of the disease.

Objective: To evaluate the results of combination of D-Dimer test and simple clinical model for the diagnosis of deep vein thrombosis (DVT)., Materials and Methods: Inclusion: clinical suspicion of DVT. Non inclusion criteria were Clinical model performed by the referring physician included probability varying from high to low. D-Dimer test was performed by five different rapid techniques. Standard of reference was Doppler ultrasonography (DU) performed by a senior radiologist., Results: Eight hundred and fifty-four DU were performed on a 14 months time period, including 206 suspicion of pulmonary embolism, 109 postoperative time period, 120 non-included or excluded patients, 278 incomplete observations, 141 complete observations. DVT was present in 33 cases and absent in the other 108 cases (prevalence 23%). Sensitivity and negative predictive value of the five tests were between 82 and 97% and 90 et 97%. The most sensitive test had a specificity of 36% and a positive predictive value of 32%. Combination of clinical model and D-Dimer test did not improve the diagnostic accuracy., Conclusion: None of the test evaluated in the present study, even when combined with the clinical model results, did allow the exclusion of DVT.

A pulmonary artery pseudoaneurysm developed after placement of a Swan-Ganz catheter for liver surgery is described. This observation is unusual for two reasons. Pulmonary artery pseudoaneurysm was discovered on a simple post-operative chest radiograph. Spontaneous thrombosis and radiographic regression were observed.

Objective: The purpose of the present study was to determine the publication rate in Medline-indexed journals of papers originally presented at the Journées Françaises de Radiologie (JFR96)., Materials and Methods: Proceedings from the JFR 96 were reviewed by two observers in conference. A Medline search encompassing 1997-1999 was performed for the lead author of all abstracts of original papers. Publication year and the journal of publication were recorded., Results: 456 oral presentations were analysed, 39 papers were subsequently published corresponding to a publication rate of 8.5%. 10 papers were published in Radiology, 4 in European Radiology and 4 in the Journal de Radiologie, the other 21 in other journals. Publication rate was significantly higher for two sessions: Research session (publication rate was 22%) and Bone and Joint session (publication rate was 16%)., Conclusion: Less than 10% of abstracts presented at JFR 96 were subsequently published in Medline-indexed journals. This rate is lower than the publication rate of papers presented at other medical meetings.

Dietary interviews and food diaries are traditionally used for nutritional assessments. In clinical practice, these methods are time consuming, require high training, and thus remain poorly used. Furthermore, the results are frequently impaired by the underreporting phenomenon which can be due either to underrecording (failure to record what is eaten) or to undereating (volontary food restriction during the assessment period). These difficulties can be overcome by using rapid questionnaires based on 2 principles: 1) underreporting is less for proteins than for other macronutrients; 2) in developed countries, calories from proteins are relatively stable and contribute approximately to one sixth of the total daily energy intake. Estimations given by the rapid questionnaire lead to less misleading results than those provided by 7 day-food records. On the other hand, the rapid questionnaire gives an estimate of specific dietary behaviors such as nibbling, festive meals and consumption of salted entrées, sweet desserts and caloric beverages. In conclusion, helpful and simple recommendations for correcting main nutritional errors can be drawn from estimation of the above mentioned specific behaviors that correspond to a daily average of 500 kcalories.

Metabolic adaptation is part of the response to stress and participate to produce a favorable state for cure. Carbohydrate metabolism is profoundly altered with an increase in basal cellular glucose uptake and utilization and in endogenous glucose production; insulin sensitivity is decreased. Glucose tolerance is altered and hyperglycemia develops. This state of hyperglycemia is most obviously directed to satisfy the increased need of the injured organs and of the inflammatory cells. The role of the cytokines in association to the stress hormones is important to these metabolic adaptations. This article reviews the main features of glucose homeostasis and the potential mechanisms leading to stress induced insulin resistance.