Use of personalised risk-based screening schedules to optimise workload and sojourn time in screening programmes for diabetic retinopathy:A retrospective cohort study

Background: National guidelines in most countries set screening intervals for diabetic retinopathy (DR) that are insufficiently informed by contemporary incidence rates. This has unspecified implications for interval disease risks (IDs) of referable DR, disparities in ID between groups or individuals, time spent in referable state before screening (sojourn time), and workload. We explored the effect of various screening schedules on these outcomes and developed an open-access interactive policy tool informed by contemporary DR incidence rates. Methods and findings: Scottish Diabetic Retinopathy Screening Programme data from 1 January 2007 to 31 December 2016 were linked to diabetes registry data. This yielded 128,606 screening examinations in people with type 1 diabetes (T1D) and 1,384,360 examinations in people with type 2 diabetes (T2D). Among those with T1D, 47% of those without and 44% of those with referable DR were female, mean diabetes duration was 21 and 23 years, respectively, and mean age was 26 and 24 years, respectively. Among those with T2D, 44% of those without and 42% of those with referable DR were female, mean diabetes duration was 9 and 14 years, respectively, and mean age was 58 and 52 years, respectively. Individual probability of developing referable DR was estimated using a generalised linear model and was used to calculate the intervals needed to achieve various IDs across prior grade strata, or at the individual level, and the resultant workload and sojourn time. The current policy in Scotland—screening people with no or mild disease annually and moderate disease every 6 months—yielded large differences in ID by prior grade (13.2%, 3.6%, and 0.6% annually for moderate, mild, and no prior DR strata, respectively, in T1D) and diabetes type (2.4% in T1D and 0.6% in T2D overall). Maintaining these overall risks but equalising risk across prior grade strata would require extremely short intervals in those with moderate DR (1–2 months) and very long intervals in those with no prior DR (35–47 months), with little change in workload or average sojourn time. Changing to intervals of 12, 9, and 3 months in T1D and to 24, 9, and 3 months in T2D for no, mild, and moderate DR strata, respectively, would substantially reduce disparity in ID across strata and between diabetes types whilst reducing workload by 26% and increasing sojourn time by 2.3 months. Including clinical risk factor data gave a small but significant increment in prediction of referable DR beyond grade (increase in C-statistic of 0.013 in T1D and 0.016 in T2D, both p < 0.001). However, using this model to derive personalised intervals did not have substantial workload or sojourn time benefits over stratum-specific intervals. The main limitation is that the results are pertinent only to countries that share broadly similar rates of retinal disease and risk factor distributions to Scotland. Conclusions: Changing current policies could reduce disparities in ID and achieve substantial reductions in workload within the range of IDs likely to be deemed acceptable. Our tool s

Incidence of Hospitalization for Heart Failure and Case-Fatality Among 3.25 Million People With and Without Diabetes Mellitus

Background: Recent clinical trials of new glucose-lowering treatments have drawn attention to the importance of hospitalisation for heart failure as a complication of diabetes. However, the epidemiology is not well described, particularly for type 1 diabetes. We examined the incidence and case-fatality of heart failure hospitalisations in the entire population aged 30 and older resident in Scotland during 2004 to 2013. Methods: Date and type of diabetes diagnosis were linked to heart failure hospitalisations and deaths using the national Scottish registers. Incidence rates and case-fatality were estimated in regression models (quasi-Poisson and logistic regression respectively). All estimates are adjusted for age, sex, socio-economic status and calendar-year. Results: Over the 10-year period of the study, among 3.25 million people there were 91,429, 22,959 and 1,313 incident heart failure events among those without diabetes, with type 2, and type 1 diabetes respectively. The crude incidence rates of heart failure hospitalisation were therefore 2.4, 12.4 and 5.6 per 1000 person-years for these three groups. Heart failure hospitalisation incidence was higher in people with diabetes, regardless of type, than in people without. Relative differences were smallest for older men, in whom the difference was nonetheless large (men aged 80, rate ratio 1.78; 95% CI 1.45 to 2.19). Rates declined similarly, by 0.2% per calendar-year, in people with type 2 diabetes and without diabetes. Rates fell faster, however, in those with type 1 diabetes (2.2% per calendar-year, RR for type 1/calendar-year interaction 0.978; 95% CI 0.959 to 0.998). 30-day case-fatality was similar among people with type 2 diabetes and without diabetes, but was higher in type 1 diabetes for men (OR 0.96; 95% CI 0.95 to 0.96) and women (OR 0.98; 95% CI 0.97 to 0.98). Case-fatality declined over time for all groups (3.3% per calendar-year, OR per calendar-year 0.967; 95% CI 0.961 to 0.973). Conclusions: Despite falling incidence, particularly in type 1 diabetes, heart failure remains around 2-fold higher than in people without diabetes, with higher case-fatality in those with type 1 diabetes. These findings support the view that heart failure is an under-recognised and important complication in diabetes, particularly for type 1 disease

The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus:a real-world observational study

Aims/hypothesis: Dapagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is indicated for improving glycaemic control in type 2 diabetes mellitus. Whether its effects on HbA1c and other variables, including safety outcomes, in clinical trials are obtained in real-world practice needs to be established. Methods: We used data from the comprehensive national diabetes register, the Scottish Care Information-Diabetes (SCI-Diabetes) collaboration database, available from 2004 to mid-2016. Data within this database were linked to mortality data from the General Registrar, available from the Information Services Division (ISD) of the National Health Service in Scotland. We calculated crude within-person differences between pre- and post-drug-initiation values of HbA1c, BMI, body weight, systolic blood pressure (SBP) and eGFR. We used mixed-effects regression models to adjust for within-person time trajectories in these measures. For completeness, we evaluated safety outcomes, cardiovascular disease events, lower-limb amputation and diabetic ketoacidosis, focusing on cumulative exposure effects, using Cox proportional hazard models, though power to detect such effects was limited. Results: Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA1c was −10.41 mmol/mol (−0.95%) after 3 months’ exposure. The crude change after 12 months was −12.99 mmol/mol (−1.19%) but considering the expected rise over time in HbA1c gave a dapagliflozin-exposure-effect estimate of −15.14 mmol/mol (95% CI −15.87, −14.41) (−1.39% [95% CI −1.45, −1.32]) at 12 months that was maintained thereafter. A drop in SBP of −4.32 mmHg (95% CI −4.84, −3.79) on exposure within the first 3 months was also maintained thereafter. Reductions in BMI and body weight stabilised by 6 months at −0.82 kg/m2 (95% CI −0.87, −0.77) and −2.20 kg (95% CI −2.34, −2.06) and were maintained thereafter. eGFR declined initially by −1.81 ml min−1 [1.73 m]−2 (95% CI −2.10, −1.52) at 3 months but varied thereafter. There were no significant effects of cumulative drug exposure on safety outcomes. Conclusions/interpretation: Dapagliflozin exposure was associated with reductions in HbA1c, SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA1c and SBP over the period of study

Effect of serum sample storage temperature on metabolomic and proteomic biomarkers

Prospective biomarker studies can be used to identify biomarkers predictive of disease onset. However, if serum biomarkers are measured years after their collection, the storage conditions might affect analyte concentrations. Few data exists concerning which metabolites and proteins are affected by storage at - 20 degrees C vs - 80 degrees C. Our objectives were to document analytes affected by storage of serum samples at - 20 degrees C vs - 80 degrees C, and to identify those indicative of the storage temperature. We utilized liquid chromatography tandem mass spectrometry and Luminex to quantify 300 analytes from serum samples of 16 Finnish individuals with type 1 diabetes, with split-aliquot samples stored at - 80 degrees C and - 20 degrees C for a median of 4.2 years. Results were validated in 315 Finnish and 916 Scottish individuals with type 1 diabetes, stored at -20 degrees C and at - 80 degrees C, respectively. After quality control, we analysed 193 metabolites and proteins of which 120 were apparently unaffected and 15 clearly susceptible to storage at - 20 degrees C vs - 80 degrees C. Further, we identified serum glutamate/glutamine ratio greater than 0.20 as a biomarker of storage at - 20 degrees C vs - 80 degrees C. The results provide a catalogue of analytes unaffected and affected by storage at - 20 degrees C vs - 80 degrees C and biomarkers indicative of suboptimal storage.Peer reviewe