The dawn phenomenon in type 2 diabetes: How to assess it in clinical practice?

International audienceAIM : 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

An update on the management of peripheral T-cell lymphoma and emerging treatment options

Peripheral T-cell lymphomas (PTCLs) comprise a rare and heterogeneous subset of non-Hodgkin’s lymphomas (NHLs) that arise from post-thymic T-cells or natural killer (NK)-cells at nodal or extranodal sites. Worldwide, PTCLs represent approximately 12% of all NHLs and the 2008 World Health Organization (WHO) classification includes over 20 biologically and clinically distinct T/NK-cell neoplasms that differ significantly in presentation, pathology, and response to therapy. Because of the rarity and heterogeneity of these diseases, large clinical trials have not been conducted and optimal therapy is not well defined. Most subtypes are treated with similar combination chemotherapy regimens as used for aggressive B-cell NHL, but with poorer outcomes. New treatment combinations and novel agents are currently being explored for PTCLs and this review highlights a number of options that appear promising

Respective Contributions of Glycemic Variability and Mean Daily Glucose as Predictors of Hypoglycemia in Type 1 Diabetes: Are They Equivalent?

To evaluate the respective contributions of short-term glycemic variability and mean daily glucose (MDG) concentration to the risk of hypoglycemia in type 1 diabetes. People with type 1 diabetes (n = 100) investigated at the University Hospital of Montpellier (France) underwent continuous glucose monitoring (CGM) on two consecutive days, providing a total of 200 24-h glycemic profiles. The following parameters were computed: MDG concentration, within-day glycemic variability (coefficient of variation for glucose [%CV]), and risk of hypoglycemia (presented as the percentage of time spent below three glycemic thresholds: 3.9, 3.45, and 3.0 mmol/L). MDG was significantly higher, and %CV significantly lower (both P &lt; 0.001), when comparing the 24-h glycemic profiles according to whether no time or a certain duration of time was spent below the thresholds. Univariate regression analyses showed that MDG and %CV were the two explanatory variables that entered the model with the outcome variable (time spent below the thresholds). The classification and regression tree procedure indicated that the predominant predictor for hypoglycemia was %CV when the threshold was 3.0 mmol/L. In people with mean glucose ≤7.8 mmol/L, the time spent below 3.0 mmol/L was shortest (P &lt; 0.001) when %CV was below 34%. In type 1 diabetes, short-term glycemic variability relative to mean glucose (i.e., %CV) explains more hypoglycemia than does mean glucose alone when the glucose threshold is 3.0 mmol/L. Minimizing the risk of hypoglycemia requires a %CV below 34%

Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes

International audienceOBJECTIVE:To define the threshold for excess glucose variability (GV), one of the main features of dysglycemia in diabetes.RESEARCH DESIGN AND METHODS:A total of 376 persons with diabetes investigated at the University Hospital of Montpellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groups-groups 1, 2a, 2b, and 3 (n = 82, 28, 65, and 79, respectively)-according to treatment: 1) diet and/or insulin sensitizers alone; 2) oral therapy including an insulinotropic agent, dipeptidyl peptidase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or 3) insulin. Group 4 included 122 persons with type 1 diabetes. Percentage coefficient of variation for glucose (%CV = [(SD of glucose)/(mean glucose)] × 100) and frequencies of hypoglycemia (interstitial glucose 36% were compared with those with %CV ≤36%.CONCLUSIONS:A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypoglycemia is significantly increased, especially in insulin-treated subjects

Photopatternable ionogels for electrochromic applications

This work describes the development of photopatternable ionogels based on a hybrid organic/inorganic sol–gel material and both phosphonium (trihexyltetradecylphosphonium dicyanamide [P6,6,6,14][dca], trihexyltetradecylphosphonium bis(trifluoromethanesulfonyl)-amide [P6,6,6,14][NTf2]) and imidazolium (1-ethyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate [emIm][FAP]) room temperature ionic liquids (RTILs). Ionogels were prepared via a two step process with the RTIL content varied between 40 and 80 w/w%, and characterised via Raman and Electrochemical Impedance Spectroscopy. 1 and 2 photon polymerisation was performed on the hybrid ionogels using photolithography, resulting in three dimensional structures that were characterised using scanning electron microscopy. Electrochromic ionogels were prepared by addition of ethyl viologen dibromide (EV) to an ionogel containing [emIm][FAP] and hybrid sol–gel material. This composition was photopolymerised on ITO electrodes by UV irradiation and subsequentially characterised via UV/Vis spectroelectrochemistry. It was also possible to fabricate a solid state electrochromic device based on EV and switch between the colourless (oxidised) and blue (reduced) forms using a perturbation signalof 1 V

Positron-emission tomography–based staging reduces the prognostic impact of early disease progression in patients with follicular lymphoma

Background: Previous studies reported that early progression of disease (POD) after initial therapy predicted poor overall survival (OS) in patients with follicular lymphoma (FL). Here, we investigated whether pre-treatment imaging modality had an impact on prognostic significance of POD. Methods: In this retrospective study, we identified 1088 patients with grade I–IIIA FL; of whom, 238 patients with stage II–IV disease were initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), and 346 patients were treated with rituximab-based chemotherapy. Patients (N = 484) from the FOLL05 study served as an independent validation cohort. We risk-stratified patients based on pre-treatment radiographic imaging (positron-emission tomography [PET] versus computed tomography [CT]) and early POD status using event-defining and landmark analyses. A competing risk analysis evaluated the association between early POD and histologic transformation. Results: In the discovery cohort, patients with POD within 24 months (PFS24) of initiating R-CHOP therapy had a 5-year OS of 57.6% for CT-staged patients compared with 70.6% for PET-staged patients. In the validation cohort, the 5-year OS for patients with early POD was 53.9% and 100% in CT- and PET-staged patients, respectively. The risk of histologic transformation in patients whose disease progressed within one year of initiating therapy was higher in CT-staged patients than in PET-staged patients (16.7% versus 6.3%, respectively), which was associated with a 9.7-fold higher risk of death. Conclusion: In FL, pre-treatment PET staging reduced the prognostic impact of early POD compared with CT staging. Patients with early POD and no histologic transformation have an extended OS with standard therapy

Review of methods for detecting glycemic disorders

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity

Mutual Mate Choice: When it Pays Both Sexes to Avoid Inbreeding

Theoretical models of sexual selection predict that both males and females of many species should benefit by selecting their mating partners. However, empirical evidence testing and validating this prediction is scarce. In particular, whereas inbreeding avoidance is expected to induce sexual conflicts, in some cases both partners could benefit by acting in concert and exerting mutual mate choice for non-assortative pairings. We tested this prediction with the gregarious cockroach Blattella germanica (L.). We demonstrated that males and females base their mate choice on different criteria and that choice occurs at different steps during the mating sequence. Males assess their relatedness to females through antennal contacts before deciding to court preferentially non-siblings. Conversely, females biased their choice towards the most vigorously courting males that happened to be non-siblings. This study is the first to demonstrate mutual mate choice leading to close inbreeding avoidance. The fact that outbred pairs were more fertile than inbred pairs strongly supports the adaptive value of this mating system, which includes no “best phenotype” as the quality of two mating partners is primarily linked to their relatedness. We discuss the implications of our results in the light of inbreeding conflict models