Rates of glycaemic deterioration in a real-world population with type 2 diabetes

Aims/hypothesis: There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on 'time to failure' methods, yet determining a 'coefficient of failure' has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and immunological variables associated with fast and slow rates of glycaemic deterioration. Methods: An observational cohort study was performed using the electronic medical records from participants in the Genetics of Diabetes Audit and Research in Tayside Study (GoDARTS). A model was derived based on an individual's observed HbA(1c) measures from the first eligible HbA(1c) after the diagnosis of diabetes through to the study end (defined as insulin initiation, death, leaving the area or end of follow-up). Each HbA(1c) measure was time-dependently adjusted for the effects of non-insulin glucose-lowering drugs, changes in BMI and corticosteroid use. GAD antibody (GADA) positivity was defined as GAD titres above the 97.5th centile of the population distribution. Results: The mean (95% CI) glycaemic deterioration for type 2 diabetes and GADA-positive individuals was 1.4 (1.3, 1.4) and 2.8 (2.4, 3.3) mmol/mol HbA(1c) per year, respectively. A younger age of diagnosis, lower HDL-cholesterol concentration, higher BMI and earlier calendar year of diabetes diagnosis were independently associated with higher rates of glycaemic deterioration in individuals with type 2 diabetes. The rate of deterioration in those diagnosed at over 70 years of age was very low, with 66% having a rate of deterioration of less than 1.1 mmol/mol HbA(1c) per year, and only 1.5% progressing more rapidly than 4.4 mmol/mol HbA(1c) per year. Conclusions/interpretation: We have developed a novel approach for modelling the progression of diabetes in observational data across multiple drug combinations. This approach highlights how glycaemic deterioration in those diagnosed at over 70 years of age is minimal, supporting a stratified approach to diabetes management

Response to "Influence of Diabetes on Antiplatelet Drug Efficacy"

Peer reviewe

Solitary wave trains in granular chains: Experiments, theory and simulations

The features of solitary waves observed in horizontal monodisperse chain of barely touching beads not only depend on geometrical and material properties of the beads but also on the initial perturbation provided at the edge of the chain. An impact of a large striker on a monodisperse chain, and similarly a sharp decrease of bead radius in a stepped chain, generates a solitary wave train containing many single solitary waves ordered by decreasing amplitudes. We find, by simple analytical arguments, that the unloading of compression force at the chain edge has a nearly exponential decrease. The characteristic time is mainly a function involving the grains' masses and the striker mass. Numerical calculations and experiments corroborate these findings.Comment: The original publication is available at http://www.springerlink.com (related papers at http://www.supmeca.fr/perso/jobs

The Relationship between AKI and CKD in Patients with Type 2 Diabetes:An Observational Cohort Study

Background There are few observational studies evaluating the risk of AKI in people with type 2 diabetes, and even fewer simultaneously investigating AKI and CKD in this population. This limits understanding of the interplay between AKI and CKD in people with type 2 diabetes compared with the nondiabetic population. Methods In this retrospective, cohort study of participants with or without type 2 diabetes, we used electronic healthcare records to evaluate rates of AKI and various statistical methods to determine their relationship to CKD status and further renal function decline. Results We followed the cohort of 16,700 participants (9417 with type 2 diabetes and 7283 controls without diabetes) for a median of 8.2 years. Those with diabetes were more likely than controls to develop AKI (48.6% versus 17.2%, respectively) and have preexisting CKD or CKD that developed during follow-up (46.3% versus 17.2%, respectively). In the absence of CKD, the AKI rate among people with diabetes was nearly five times that of controls (121.5 versus 24.6 per 1000 person-years). Among participants with CKD, AKI rate in people with diabetes was more than twice that of controls (384.8 versus 180.0 per 1000 person-years after CKD diagnostic date, and 109.3 versus 47.4 per 1000 person-years before CKD onset in those developing CKD after recruitment). Decline in eGFR slope before AKI episodes was steeper in people with diabetes versus controls. After AKI episodes, decline in eGFR slope became steeper in people without diabetes, but not among those with diabetes and preexisting CKD. Conclusions Patients with diabetes have significantly higher rates of AKI compared with patients without diabetes, and this remains true for individuals with preexisting CKD.on behalf of the BEAt-DKD Consortiu

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

Purpose: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. Methods: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. Results: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be amore limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. Conclusions: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching

2008: Sea surface temperature and salinity variability at Bermuda during the end of the Little Ice Age

[1] We use geochemical and isotope measurements on a 225-year old brain coral (Diploria labyrinthiformis) from the south shore of Bermuda (64°W, 32°N) to construct a record of decadal-to-centennial-scale climate variability. The coral was collected alive, and annual density bands visible in X radiographs delineate cold and warm seasons allowing for precise dating. Coral skeletons incorporate strontium (Sr) and calcium (Ca) in relative proportions inversely to the sea surface temperature (SST) in which the skeleton is secreted. Previous studies on this and other coral colonies from this region document the ability to reconstruct mean annual and wintertime SST using Sr/Ca measurements 18 O of seawater (dO w ), where dO w is proportional to sea surface salinity (SSS). We show in this study that mean annual and wintertime d 18 O of the carbonate (dO c ) are correlated to both SST and SSS, but a robust, quantitative measure of SSS is not found with present calibration data. In combination, however, the Sr/Ca and dO c qualitatively reconstruct lower salinities at the end of the Little Ice Age relative to modern day. Temperature changes agree with other records from the Bermuda region. Radiative and atmospheric forcing may explain some of the SST variability, but the scales of implied changes in SST and SSS indicate large-scale ocean circulation impacts as well