Use of insulin glargine and cancer incidence in Scotland: a study from the

Abstract Aims/hypothesis The aim of the present study was to examine whether patients with diabetes in Scotland using insulin glargine have a greater cancer risk than patients using other types of insulin. Methods We used a nationwide diabetes clinical database that covers the majority of the Scottish population with diagnosed diabetes, and examined patients with diabetes who were exposed to any insulin therapy between 1 January 2002 and 31 December 2005. Among these we defined a fixed cohort based on exposure during a 4 month period in 2003 (n=36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users across the period (n=12,852 in whom 381 cancers occurred). Records from these cohorts were linked to cancer registry data up to the end of 2005. We used Cox proportional hazards models for survival analyses. Results Those receiving any insulin glargine (n=3,959) had the same incidence rate for all cancers as those not receiving insulin glargine (HR 1.02, 95% CI 0.77-1.36, p=0.9 in the fixed cohort) The subset of patients using insulin glargine alone (n=447) had a significantly higher incidence of all cancers than those using other insulins only (n=32,295) (HR 1.55, 95% CI 1.01-2.37, p=0.045), and those using insulin glargine with other insulins (n=3,512) had a slightly lower incidence (HR 0.81, 95% CI 0.55-1.18, p=0.26). There were important differences in baseline characteristics between these three groups, although the risk ratios were broadly unaltered on adjustment for these. Overall, there was no increase in breast cancer rates associated with insulin glargine use (HR 1.49, 95% CI 0.79-2.83, though insulin glargine only users had a higher rate than those using non-glargine insulin only (HR 3.39, 95% CI 1.46-7.85, p=0.004). Among type 2 diabetic incident insulin users, no significant difference between the three groups was observed with respect to all cancer or breast cancer. All the above HRs are adjusted for age, calendar time prior cancer and type of diabetes, as appropriate, and are stratified according to sex. Conclusions/interpretation Overall, insulin glargine use was not associated with an increased risk of all cancers or site-specific cancers in Scotland over a 4 year time frame. Given the overall data, we consider the excess of cases of all cancers and breast cancer in the subgroup of insulin glargine only users to more likely reflect allocation bias rather than an effect of insulin glargine itself

A genome-wide association study suggests an association of Chr8p21.3 (GFRA2) with diabetic neuropathic pain

BACKGROUND: Neuropathic pain, caused by a lesion or a disease affecting the somatosensory system, is one of the most common complications in diabetic patients. The purpose of this study is to identify genetic factors contributing to this type of pain in a general diabetic population. METHOD: We accessed the Genetics of Diabetes Audit and Research Tayside (GoDARTS) datasets that contain prescription information and monofilament test results for 9439 diabetic patients, among which 6927 diabetic individuals were genotyped by Affymetrix SNP6.0 or Illumina OmniExpress chips. Cases of neuropathic pain were defined as diabetic patients with a prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain and in whom monofilament test result was positive for sensory neuropathy in at least one foot. Controls were individuals who did not have a record of receiving any opioid analgesics. Imputation of non‐genotyped SNPs was performed by IMPUTE2, with reference files from 1000 Genomes Phase I datasets. RESULTS: After data cleaning and relevant exclusions, imputed genotypes of 572 diabetic neuropathic pain cases and 2491 diabetic controls were used in the Fisher's exact test. We identified a cluster in the Chr8p21.3, next to GFRA2 with a lowest p‐value of 1.77 × 10(−7) at rs17428041. The narrow‐sense heritability of this phenotype was 11.00%. CONCLUSION: This genome‐wide association study on diabetic neuropathic pain suggests new evidence for the involvement of variants near GFRA2 with the disorder, which needs to be verified in an independent cohort and at the molecular level

Risk of severe COVID-19 in patients with inflammatory rheumatic diseases treated with immunosuppressive therapy in Scotland

Objective: To investigate the association of severe coronavirus disease 2019 (COVID-19) in patients with inflammatory rheumatic diseases (IRDs) treated with immunosuppressive drugs. Method: A list of 4633 patients on targeted – biological or targeted synthetic – DMARDs in March 2020 was linked to a case– control study that includes all cases of COVID-19 in Scotland. Results: By 22 November 2021, 433 of the 4633 patients treated with targeted DMARDS had been diagnosed with COVID-19, of whom 58 had been hospitalized. With all those in the population not on DMARDs as the reference category, the rate ratio for hospitalized COVID-19 associated with DMARD treatment was 2.14 [95% confidence interval (CI) 2.02–2.26] in those on conventional synthetic (cs) DMARDs, 2.01 (95% CI 1.38–2.91) in those on tumour necrosis factor (TNF) inhibitors as the only targeted agent, and 3.83 (95% CI 2.65–5.56) in those on other targeted DMARDs. Among those on csDMARDs, rate ratios for hospitalized COVID-19 were lowest at 1.66 (95% CI 1.51–1.82) in those on methotrexate and highest at 5.4 (95% CI 4.4–6.7) in those on glucocorticoids at an average dose > 10 mg/day prednisolone equivalent. Conclusion: The risk of hospitalized COVID-19 is elevated in IRD patients treated with immunosuppressive drugs compared with the general population. Of these drugs, methotrexate, hydroxychloroquine, and TNF inhibitors carry the lowest risk. The highest risk is associated with prednisolone. A larger study is needed to estimate reliably the risks associated with each class of targeted DMAR

End stage renal disease and survival in people with diabetes:a national database linkage study

© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. Funding This work was supported by the Wellcome Trust through the Scottish Health Informatics Programme (SHIP). The SHIP is collaboration between the Universities of Aberdeen, Dundee, Edinburgh, Glasgow and St Andrews and the Information Services Division of National Health Service National Service Scotland. Funding for diabetes register linkage and data extraction was provided by the Chief Scientist’s Office of the Scottish Government. The Scottish Diabetes Research Network receives financial support from National Health Services Research Scotland. The Scottish Renal Registry is funded by the Information Services Division of National Health Service National Services Scotland but relies heavily on the goodwill of the contributing renal units who spent a large amount time working with Scottish Renal Registry staff to ensure that the data held within the register are accurate and complete.Peer reviewedPublisher PD

Efficacy and Safety of Alirocumab as Add-on Therapy in High–Cardiovascular-Risk Patients With Hypercholesterolemia Not Adequately Controlled With Atorvastatin (20 or 40 mg) or Rosuvastatin (10 or 20 mg)::Design and Rationale of the ODYSSEY OPTIONS Studies

The phase 3 ODYSSEY OPTIONS studies (OPTIONS I, NCT01730040; OPTIONS II, NCT01730053) are multicenter, multinational, randomized, double-blind, active-comparator, 24-week studies evaluating the efficacy and safety of alirocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, as add-on therapy in ∼ 650 high-cardiovascular (CV)-risk patients whose low-density lipoprotein cholesterol (LDL-C) levels are ≥100 mg/dL or ≥70 mg/dL according to the CV-risk category, high and very high CV risk, respectively, with atorvastatin (20–40 mg/d) or rosuvastatin (10–20 mg/d). Patients are randomized to receive alirocumab 75 mg via a single, subcutaneous, 1-mL injection by prefilled pen every 2 weeks (Q2W) as add-on therapy to atorvastatin (20–40 mg) or rosuvastatin (10–20 mg); or to receive ezetimibe 10 mg/d as add-on therapy to statin; or to receive statin up-titration; or to switch from atorvastatin to rosuvastatin (OPTIONS I only). At week 12, based on week 8 LDL-C levels, the alirocumab dose may be increased from 75 mg to 150 mg Q2W if LDL-C levels remain ≥100 mg/dL or ≥70 mg/dL in patients with high or very high CV risk, respectively. The primary efficacy endpoint in both studies is difference in percent change in calculated LDL-C from baseline to week 24 in the alirocumab vs control arms. The studies may provide guidance to inform clinical decision-making when patients with CV risk require additional lipid-lowering therapy to further reduce LDL-C levels. The flexibility of the alirocumab dosing regimen allows for individualized therapy based on the degree of LDL-C reduction required to achieve the desired LDL-C level

Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study

<p>Background: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.</p> <p>Methods and Findings: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005–2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4–3.8, p<0.001) than men (2.3: 2.0–2.7, p<0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2–3.0, p<0.001) in men and 2.7 (2.2–3.4, p<0.001) in women. Between 2005–2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were <40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60–69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA1c of <7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used.</p> <p>Conclusions: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed.</p&gt

Rates of referable eye disease in the Scottish National Diabetic Retinopathy Screening Programme

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Peer reviewedPublisher PD