Persistence with Insulin Therapy in Patients with Type 2 Diabetes in France: An Insurance Claims Study

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-016-0185-8"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> There are currently no enhanced digital features for this article. If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional enhanced digital features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:</p> <p>• Summary Slides</p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p> <p> </p

Use of Fibrates Monotherapy in People with Diabetes and High Cardiovascular Risk in Primary Care: A French Nationwide Cohort Study Based on National Administrative Databases

<div><p>Background and Aim</p><p>According to guidelines, diabetic patients with high cardiovascular risk should receive a statin. Despite this consensus, fibrate monotherapy is commonly used in this population. We assessed the frequency and clinical consequences of the use of fibrates for primary prevention in patients with diabetes and high cardiovascular risk.</p><p>Design</p><p>Retrospective cohort study based on nationwide data from the medical and administrative databases of French national health insurance systems (07/01/08-12/31/09) with a follow-up of up to 30 months.</p><p>Methods</p><p>Lipid-lowering drug-naive diabetic patients initiating fibrate or statin monotherapy were identified. Patients at high cardiovascular risk were then selected: patients with a diagnosis of diabetes and hypertension, and >50 (men) or 60 (women), but with no history of cardiovascular events. The composite endpoint comprised myocardial infarction, stroke, amputation, or death.</p><p>Results</p><p>Of the 31,652 patients enrolled, 4,058 (12.8%) received a fibrate. Age- and gender-adjusted annual event rates were 2.42% (fibrates) and 2.21% (statins). The proportionality assumption required for the Cox model was not met for the fibrate/statin variable. A multivariate model including all predictors was therefore calculated by dividing data into two time periods, allowing Hazard Ratios to be calculated before (HR_<540) and after 540 days (HR_>540) of follow-up. Multivariate analyses showed that fibrates were associated with an increased risk for the endpoint after 540 days: HR_<540 = 0.95 (95% CI: 0.78–1.16) and HR_>540 = 1.73 (1.28–2.32).</p><p>Conclusion</p><p>Fibrate monotherapy is commonly prescribed in diabetic patients with high cardiovascular risk and is associated with poorer outcomes compared to statin therapy.</p></div

Predictors of the combined outcome in age- and gender-adjusted Cox models.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval. P-values were calculated using the Cox-proportional hazard model.</p><p>Predictors of the combined outcome in age- and gender-adjusted Cox models.</p

Manganese Superoxide Dismutase (<i>SOD2</i>) Polymorphisms, Plasma Advanced Oxidation Protein Products (AOPP) Concentration and Risk of Kidney Complications in Subjects with Type 1 Diabetes

<div><p>Aims</p><p>Oxidative stress is involved in the pathophysiology of diabetic nephropathy. Manganese superoxide dismutase (SOD2) catalyses the dismutation of superoxide, regulates the metabolism of reactive oxygen species in the mitochondria and is highly expressed in the kidney. Plasma concentration of advanced oxidation protein products (AOPP), a marker of oxidative stress, was found to be increased in patients with kidney disease. We investigated associations of <i>SOD2</i> allelic variations, plasma SOD activity and AOPP concentration with diabetic nephropathy in type 1 diabetic subjects.</p><p>Methods</p><p>Eight SNPs in the <i>SOD2</i> region were analysed in 1285 Caucasian subjects with type 1 diabetes from the SURGENE prospective study (n = 340; 10-year follow-up), GENESIS (n = 501) and GENEDIAB (n = 444) cross-sectional studies. Baseline plasma concentration of AOPP and SOD activity were measured in GENEDIAB participants. Hazard ratio (HR) and odds ratio (OR) were determined for incidence and prevalence of nephropathy. Analyses were adjusted or stratified by retinopathy stages.</p><p>Results</p><p>In the SURGENE cohort, the T-allele of rs4880 (V16A) was associated with the incidence of renal events (new cases, or the progression to a more severe stage of nephropathy; HR 1.99, 95% CI 1.24–3.12, p = 0.004) and with the decline in estimated glomerular filtration rate (eGFR) during follow-up. Similar associations were observed for rs2758329 and rs8031. Associations were replicated in GENESIS/GENEDIAB cohorts, in the subset of participants without proliferative retinopathy, and were confirmed by haplotype analyses. Risk allele and haplotype were also associated with higher plasma AOPP concentration and lower SOD activity.</p><p>Conclusions</p><p><i>SOD2</i> allelic variations were associated with the incidence and the progression of diabetic nephropathy, with a faster decline in eGFR and with plasma AOPP concentration and SOD activity in subjects with type 1 diabetes. These results are consistent with a role for <i>SOD2</i> in the protection against oxidative stress and kidney disease in type 1 diabetes.</p></div

SURGENE cohort: Genotype frequencies of <i>SOD2</i> polymorphisms by incidence of renal events during follow-up.

<p>SNPs are sorted in 5′ to 3′ order. Hazards ratio for the major allele in a recessive model (MM vs Xm) determined in Cox proportional hazards survival regressive model, adjusted for sex, age, duration of diabetes, treatment by ACE inhibitors and retinopathy stages. Retinopathy was coded as an ordinal polytomic covariate: absent (1), non-proliferative (2), pre-proliferative (3), or proliferative retinopathy (4). MAF: minor allele frequency. p≤0.01 is significant.</p

Kaplan-Meier survival (renal event-free) curve during follow-up in the SURGENE cohort by <i>SOD2</i> rs4880 genotypes: TT (n = 108), TC (n = 158), CC (n = 74).

<p>Y-axis represents the absence of renal events defined as new cases of microalbuminuria or progression to a more severe stage of nephropathy.</p

Final Cox models with a cut-off time at 540 days.

<p>Abbreviations: HR, hazard ratio; CI, confidence interval. P-values were calculated using the Cox-proportional hazard model.</p><p>Final Cox models with a cut-off time at 540 days.</p

A. Study scheme. B. Flow chart of patients with diabetes and high cardiovascular risk in primary care initiating fibrate or statin monotherapy.

<p>A. Study scheme. B. Flow chart of patients with diabetes and high cardiovascular risk in primary care initiating fibrate or statin monotherapy.</p

Variation of eGFR (ml/min.year⁻¹) during follow-up in the SURGENE cohort by <i>SOD2</i> rs4880 genotypes: TT (n = 108), TC (n = 158), CC (n = 74).

<p>Results expressed as means ± SEM.</p

Survival curves for death and cardiovascular events in patients treated with statin or fibrate monotherapy.

<p>Survival curves for death and cardiovascular events in patients treated with statin or fibrate monotherapy.</p