Background We aimed to ascertain the cumulative risk of fatal or critical care unit-treated COVID-19 in people with diabetes and compare it with that of people without diabetes, and to investigate risk factors for and build a crossvalidated predictive model of fatal or critical care unit-treated COVID-19 among people with diabetes. MethodsIn this cohort study, we captured the data encompassing the first wave of the pandemic in Scotland, from March 1, 2020, when the first case was identified, to July 31, 2020, when infection rates had dropped sufficiently that shielding measures were officially terminated. The participants were the total population of Scotland, including all people with diabetes who were alive 3 weeks before the start of the pandemic in Scotland (estimated Feb 7, 2020). We ascertained how many people developed fatal or critical care unit-treated COVID-19 in this period from the Electronic Communication of Surveillance in Scotland database (on virology), the RAPID database of daily hospitalisations, the Scottish Morbidity Records-01 of hospital discharges, the National Records of Scotland death registrations data, and the Scottish Intensive Care Society and Audit Group database (on critical care). Among people with fatal or critical care unit-treated COVID-19, diabetes status was ascertained by linkage to the national diabetes register, Scottish Care Information Diabetes. We compared the cumulative incidence of fatal or critical care unit-treated COVID-19 in people with and without diabetes using logistic regression. For people with diabetes, we obtained data on potential risk factors for fatal or critical care unit-treated COVID-19 from the national diabetes register and other linked health administrative databases. We tested the association of these factors with fatal or critical care unit-treated COVID-19 in people with diabetes, and constructed a prediction model using stepwise regression and 20-fold cross-validation. Findings Of the total Scottish population onMarch 1, 2020 (n=5 463 300), the population with diabetes was 319 349 (5•8%), 1082 (0•3%) of whom developed fatal or critical care unit-treated COVID-19 by July 31, 2020, of whom 972 (89•8%) were aged 60 years or older. In the population without diabetes, 4081 (0•1%) of 5 143 951 people developed fatal or critical care unit-treated COVID-19. As of July 31, the overall odds ratio (OR) for diabetes, adjusted for age and sex, was 1•395 (95% CI 1•304-1•494; p<0•0001, compared with the risk in those without diabetes. The OR was 2•396 (1•815-3•163; p<0•0001) in type 1 diabetes and 1•369 (1•276-1•468; p<0•0001) in type 2 diabetes. Among people with diabetes, adjusted for age, sex, and diabetes duration and type, those who developed fatal or critical care unit-treated COVID-19 were more likely to be male, live in residential care or a more deprived area, have a COVID-19 risk condition, retinopathy, reduced renal function, or worse glycaemic control, have had a diabetic ketoacidosis or hypoglycaemia hospitalisation in the past 5 years, be on more...

OBJECTIVE To quantify the relationship of residual C-peptide secretion to glycemic outcomes and microvascular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS C-peptide was measured in an untimed blood sample in the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) cohort of 6,076 people with type 1 diabetes monitored for an average of 5.2 years. RESULTS In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 vs. &lt;5 pmol/L were as follows: insulin dose at baseline, 9% lower (P = 2 × 10−17); HbA1c during follow-up, 4.9 mmol/mol lower (P = 3 × 10−13); hazard ratio for hospital admission for diabetic ketoacidosis during follow-up, 0.44 (P = 0.0001); odds ratio for incident retinopathy, 0.51 (P = 0.0003). Effects on the risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/L). In regression models contrasting C-peptide 30 to &lt;200 pmol/L with &lt;5 pmol/L, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (P = 6 × 10−8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (P = 0.03). CONCLUSIONS These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the Diabetes Control and Complications Trial (DCCT) intensively treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/L. This has obvious implications for the design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.

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 HbA 1c 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 HbA 1c , 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 HbA 1c 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 HbA 1c 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/m 2 (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 HbA 1c , SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA 1c and SBP over the period of study.