Rates, determinants and success of implementing deprescribing in people with type 2 diabetes:A scoping review

Background Individualizing goals for people with type 2 diabetes may result in deintensification of medication, but a comprehensive picture of deprescribing practices is lacking. Aims To conduct a scoping review in order to assess the rates, determinants and success of implementing deprescribing of glucose-, blood pressure- or lipid-lowering medications in people with diabetes. Methods A systematic search on MEDLINE and Embase between January 2007 and January 2019 was carried out for deprescribing studies among people with diabetes. Outcomes were rates of deprescribing related to participant characteristics, the determinants and success of deprescribing, and its implementation. Critical appraisal was conducted using predefined tools. Results Fourteen studies were included; eight reported on rates, nine on determinants and six on success and implementation. Bias was high for studies on success of deprescribing. Deprescribing rates ranged from 14% to 27% in older people with low HbA(1c)levels, and from 16% to 19% in older people with low systolic blood pressure. Rates were not much affected by age, gender, frailty or life expectancy. Rates were higher when a reminder system was used to identify people with hypoglycaemia, which led to less overtreatment and fewer hypoglycaemic events. Most healthcare professionals accepted the concept of deprescribing but differed on when to conduct it. Deprescribing glucose-lowering medications could be successfully conducted in 62% to 75% of participants with small rises in HbA(1c). Conclusions Deprescribing of glucose-lowering medications seems feasible and acceptable, but was not widely implemented in the covered period. Support systems may enhance deprescribing. More studies on deprescribing blood pressure- and lipid-lowering medications in people with diabetes are needed

M-I coupling across the auroral oval at dusk and midnight: repetitive substorm activity driven by interplanetary coronal mass ejections (CMEs)

We study substorms from two perspectives, i.e., magnetosphere–ionosphere coupling across the auroral oval at dusk and at midnight magnetic local times. By this approach we monitor the activations/expansions of basic elements of the substorm current system (Bostrøm type I centered at midnight and Bostrøm type II maximizing at dawn and dusk) during the evolution of the substorm activity. Emphasis is placed on the R1 and R2 types of field-aligned current (FAC) coupling across the Harang reversal at dusk. We distinguish between two distinct activity levels in the substorm expansion phase, i.e., an initial transient phase and a persistent phase. These activities/phases are discussed in relation to polar cap convection which is continuously monitored by the polar cap north (PCN) index. The substorm activity we selected occurred during a long interval of continuously strong solar wind forcing at the interplanetary coronal mass ejection passage on 18 August 2003. The advantage of our scientific approach lies in the combination of (i) continuous ground observations of the ionospheric signatures within wide latitude ranges across the auroral oval at dusk and midnight by meridian chain magnetometer data, (ii) snapshot satellite (DMSP F13) observations of FAC/precipitation/ion drift profiles, and (iii) observations of current disruption/near-Earth magnetic field dipolarizations at geostationary altitude. Under the prevailing fortunate circumstances we are able to discriminate between the roles of the dayside and nightside sources of polar cap convection. For the nightside source we distinguish between the roles of inductive and potential electric fields in the two substages of the substorm expansion phase. According to our estimates the observed dipolarization rate (δ Bz/δt) and the inferred large spatial scales (in radial and azimuthal dimensions) of the dipolarization process in these strong substorm expansions may lead to 50–100 kV enhancements of the cross-polar-cap potential due to inductive electric field coupling

Transitions between states of magnetotail-ionosphere coupling and the role of solar wind dynamic pressure: the 25 July 2004 interplanetary CME case

In a case study, we investigate transitions between fundamental magnetosphere–ionosphere (M-I) coupling modes during storm-time conditions (SYM-H between −100 and −160 nT) driven by an interplanetary coronal mass ejection (ICME). We combine observations from the near tail, at geostationary altitude (GOES-10), and electrojet activities across the auroral oval at postnoon-to-dusk and midnight. After an interval of strong westward electrojet (WEJ) activity, a 3 h long state of attenuated/quenched WEJ activity was initiated by abrupt drops in the solar wind density and dynamic pressure. The attenuated substorm activity consisted of brief phases of magnetic field perturbation and electron flux decrease at GOES-10 near midnight and moderately strong conjugate events of WEJ enhancements at the southern boundary of the oval, as well as a series of very strong eastward electrojet (EEJ) events at dusk, during a phase of enhanced ring current evolution, i.e., enhanced SYM-H deflection within −120 to −150 nT. Each of these M-I coupling events was preceded by poleward boundary intensifications and auroral streamers at higher oval latitudes. We identify this mode of attenuated substorm activity as being due to a magnetotail state characterized by bursty reconnection and bursty bulk flows/dipolarization fronts (multiple current wedgelets) with associated injection dynamo in the near tail, in their braking phase. The latter process is associated with activations of the Bostrøm type II (meridional) current system. A transition to the next state of M-I coupling, when a full substorm expansion took place, was triggered by an abrupt increase of the ICME dynamic pressure from 1 to 5 nPa. The brief field deflection events at GOES-10 were then replaced by a 20 min long interval of extreme field stretching (Bz approaching 5 nT and Bx ≈ 100 nT) followed by a major dipolarization (Δ Bz ≈ 100 nT). In the ionosphere the latter stage appeared as a full-size stepwise poleward expansion of the WEJ. It thus appears that the ICME passage led to fundamentally different M-I coupling states corresponding to different levels of dynamic pressure (Pdyn) under otherwise very similar ICME conditions. Full WEJ activity, covering a wide latitude range across the auroral oval in the midnight sector, was attenuated by the abrupt dynamic pressure decrease and resumed after the subsequent abrupt increase

PCV83 Cost-Effectiveness of Statins for Primary Prevention in Newly Diagnosed Type 2 Diabetes Patients in the Netherlands

Background: Patients with type 2 diabetes have an increased risk of cardiovascular events, which can be reduced by statin treatment. Objectives: The aim of this study is to determine if statin treatment for primary prevention started at the time of type 2 diabetes diagnosis is cost-effective, taking non-adherence and different age groups into account. Methods: A cost-effectiveness analysis has been performed using a Markov model with a time horizon of 10 years. The 10-years cardiovascular risk was estimated in a Dutch population of primary prevention patients with newly diagnosed diabetes from the GIANTT database (Groningen Initiative to Analyse Type 2 Diabetes Treatment) using the UKPDS risk engine. Statin adherence of a Dutch type 2 diabetes population was measured as pill days covered (PDC) in the IADB pharmacy research database. PDC of ≥ 80% and ≤ 20% were associated with full and no efficacy of the treatment. Cost-effectiveness was measured in costs per quality-adjusted life-year (QALY) from the healthcare payers perspective, also stratified for cardiovascular risk and age. A probabilistic sensitivity analysis was performed. Results: Characteristics of 4,683 primary prevention type 2 diabetes patients were inserted into the UKPDS risk engine. The mean 10-years risk of the population was 23% for coronary heart disease (CHD), 14% for fatal CHD, 10% for stroke and 2% for fatal stroke. PDC in the type 2 diabetes population was 81%, 77% and 75% in years one, two and three, respectively. In general, statin treatment was highly cost-effective at around €2,500 per QALY. Favorable cost-effectiveness was robust in sensitivity analysis. Differences in age and 10-years cardiovascular risk showed large differences in cost-effectiveness ranging from more than €800,000 per QALY to being cost saving. Conclusions: Statin treatment for primary prevention in patients newly diagnosed with type 2 diabetes is costeffective. Due to large differences in cost-effectiveness according to different risk groups, the efficiency of the treatment could be increased by focusing on patients with higher cardiovascular risk and higher ages

No significant association of type 2 diabetes-related genetic risk scores with glycated haemoglobin levels after initiating metformin or sulphonylurea derivatives

AIM: To explore the added value of diabetes-related genetic risk scores (GRSs) to readily available clinical variables in the prediction of glycated haemoglobin (HbA1c) levels after initiation of glucose-regulating drugs. MATERIALS AND METHODS: We conducted a cohort study in people with type 2 diabetes (T2DM) from the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database who initiated metformin (MET) or sulphonylurea derivatives (SUs) and for whom blood samples were genotyped. The primary outcome was HbA1c level at 6 months, adjusted for baseline HbA1c. GRSs were based on single nucleotide polymorphisms linked to insulin sensitivity, β-cell activity, and T2DM risk in general. Associations were analysed using multiple linear regression to assess whether adding the GRSs increased the explained variance in a prediction model that included age, gender, diabetes duration and cardio-metabolic biomarkers. RESULTS: We included 282 patients initiating MET and 89 patients initiating SUs. In the MET prediction model, diabetes duration of >3 months when starting MET was associated with 2.7-mmol/mol higher HbA1c level. For SUs, no significant clinical predictors were identified. Addition of the GRS linked to insulin sensitivity (for MET), β-cell activity (for SUs) and T2DM risk (for both) to the models did not improve the explained variance significantly (22% without vs. 22% with GRS) for the MET and (14% without vs. 14% with GRS) for the SUs model, respectively. CONCLUSION: This study did not indicate a significant effect of GRS related to T2DM in general or to the drugs' mechanism of action for prediction of inter-individual HbA1c variability in the short term after initiation of MET or SU therapy

Sex disparities in treatment patterns after metformin initiation among patients with type 2 diabetes mellitus

PURPOSE: To assess sex differences in treatment patterns after metformin initiation among type 2 diabetes mellitus (T2D) patients.METHODS: A cohort study was conducted using the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) primary care database. Patients aged ≥18 years initiating metformin were followed 2-5 years. Markov modeling was conducted to estimate treatment transition rates and calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) comparing men with women adjusted for age, HbA1c level at initiation, and cardiovascular disease history. Kaplan-Meier analyses and Cox proportional-hazards models were used to determine the time to and likelihood of getting treatment intensification. HbA1c levels at initiation and intensification were compared using Mann-Whitney U tests.RESULTS: In total, 11 508 metformin initiators were included (50.1% women). The most common transition after initiation was a dose increase (probability women 0.52, men 0.59, no significant difference). Women were more likely than men to switch to any other non-insulin hypoglycemic agent after initiation (aHR 1.66; 95% CI 1.31-2.12), after dose increase (aHR 1.48; 95% CI 1.10-1.98) and after dose decrease (aHR 2.64; 95% CI 1.28-5.46). Time to intensification was longer, time to switching was shorter, and HbA1c levels at initiation and intensification were lower for women than men.CONCLUSIONS: Sex disparities were observed in treatment transitions after metformin initiation. Women more often switched treatment than men, which suggest that prescribers acknowledge more tolerance or other problems for metformin in women. Men intensified treatment earlier and at higher HbA1c levels, indicative of a higher need for treatment intensification.</p