Use of incretin agents and risk of pancreatic cancer: A population-based cohort study

Marine protected areas (MPA) are rapidly being established to minimize the impact of anthropogenic disturbances, yet, while climate change is acknowledged as a growing threat, very limited research exists about how to directly incorporate climate-related disturbances into MPA design. Using the conservation planning software Marxan and the Indo-west Pacific as a study region, an illustrative approach is developed here that incorporates climate change projections into the process of identifying priority areas for marine conservation. Conservation targets were set at 10% and 30% of areas that continually held sea-surface temperatures less than 1 °C above maximum non-extreme historic temperatures (derived from satellite imagery from 1984-2009). This approach allowed for continuity in conservation objectives across both space and time by identifying the geographic extent of thermal stress in the region and illustrating how conditions would change in future years. Achievement of targets was found to be flexible, but some areas were more important than others for achieving these targets. Interannual trend analyses were carried out for three climate models under two climate change scenarios to examine spatial and temporal patterns of thermal stress. Spatial patterns of thermal stress varied throughout the region. Results of the conservation approach were compared to the trend results to see whether the trends might be a simpler approach for accounting for climate change impacts in conservation planning (i.e., one feature could be used instead of more than 1000). The interannual analyses had a low overlap with the Marxan results, and hence are not a suitable substitute for the approach shown here. This study showed that inclusion of climate-related disturbances in marine conservation planning is feasible and should become common practice, together with targets for biodiversity. © 2012 Elsevier Ltd

Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group : population based cohort study

OBJECTIVE: To determine the association between use of sulphonylureas and risk of hypoglycaemia in relation to renal function and sulphonylurea metabolic group compared with use of metformin. DESIGN: Population based cohort study using routinely collected data from general practices in England. SETTING: Clinical Practice Research Datalink (CPRD) database, 2004-12. PARTICIPANTS: 120 803 new users of a non-insulin antidiabetic agent with at least one prescription and aged 18 years or more. The first prescription defined start of follow-up. Patients were followed until the end of data collection, a record for hypoglycaemia, or a blood glucose level of less than 3.0 mmol/L. MAIN OUTCOME MEASURES: Associations between sulphonylurea dose, renal impairment, type of sulphonylurea used, and risk of hypoglycaemia, were determined using Cox proportional hazard models. Adjustments were made for age, sex, lifestyle, comorbidity, and drug use. RESULTS: The risk of hypoglycaemia in current users of sulphonylureas only was significantly increased compared with current users of metformin only (adjusted hazard ratio 2.50, 95% confidence interval 2.23 to 2.82). The higher risk in current users of sulphonylureas only was further increased in patients with an estimated glomerular filtration rate of less than 30 mL/min/1.73 m(2) (4.96, 3.76 to 6.55). The risk of hypoglycaemia was also significantly higher in patients with a high sulphonylurea dose (3.12, 2.68 to 3.62) and in current users of glibenclamide (7.48, 4.89 to 11.44). Gliclazide, the sulphonylurea of first choice, showed a similar risk of hypoglycaemia compared with other sulphonylureas. CONCLUSIONS: Sulphonylurea treatment in patients with a renal function of less than 30 mL/min/1.73 m(2) should be considered with caution. Moreover, an increased risk of hypoglycaemic events was observed among all users of sulphonylureas. This contrasts with several guidelines that recommend gliclazide as first choice sulphonylurea, and therefore requires further investigation

"Use of sodium-glucose co-transporter 2 inhibitors, changes in body mass index and risk of fracture:a population-based cohort study"

Aims: Sodium-glucose co-transporter-2 (SGLT-2) inhibitor-induced weight loss might play a role in the debated elevated fracture risk with these agents. The aim of the current study was to investigate the association between SGLT-2 inhibitor use, changes in body mass index (BMI) and fracture risk. Methods: A retrospective cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD) GOLD (2013–2018). The study population (N = 34,960) consisted of adults with diabetes initiating a sulphonylurea or SGLT-2 inhibitor. Cox proportional hazards models estimated hazard ratios (HRs) for major osteoporotic fracture with SGLT-2 inhibitor use versus sulphonylurea use, stratified by change in BMI, average daily dose and cumulative dose. Analyses were adjusted for age, sex, lifestyle variables, comorbidities, and concomitant drug use. Results: SGLT-2 inhibitor use was not associated with an increased fracture risk compared to sulphonylurea use (adjusted HR 1.19; 95% confidence interval (CI): 0.80–1.79). This finding remained consistent after stratification by BMI change. However, the highest cumulative dose category was associated with an increased fracture risk (adjusted HR: 2.10, 95 %CI: 1.11–3.99). Conclusion: SGLT-2 inhibitor use was not associated with increased osteoporotic fracture risk, irrespective of change in BMI. However, a high cumulative dose could be an important risk factor

HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients

We investigated whether HLA-A*24 typing complements screening for HLA-DQ and for antibodies (Abs) against insulin, GAD, IA-2 (IA-2A), and zinc transporter-8 (ZnT8A) for prediction of rapid progression to type 1 diabetes (T1D). Persistently Ab+ siblings/offspring (n = 288; aged 0-39 years) of T1D patients were genotyped for HLA-DQA1-DQB1 and HLA-A*24 and monitored for development of diabetes within 5 years of first Ab+. HLA-A*24 (P = 0.009), HLA-DQ2/DQ8 (P = 0.001), and positivity for IA-2A ± ZnT8A (P < 0.001) were associated with development of T1D in multivariate analysis. The 5-year risk increased with the number of the above three markers present (n = 0: 6%; n = 1: 18%; n = 2: 46%; n = 3: 100%). Positivity for one or more markers identified a subgroup of 171 (59%) containing 88% of rapid progressors. The combined presence of HLA-A*24 and IA-2A+ ± ZnT8A+ defined a subgroup of 18 (6%) with an 82% diabetes risk. Among IA-2A+ 6 ZnT8A+ relatives, identification of HLA-A*24 carriers in addition to HLA-DQ2/DQ8 carriers increased screening sensitivity for relatives at high Ab-and HLA-inferred risk (64% progression; P = 0.002). In conclusion, HLA-A*24 independently predicts rapid progression to T1D in Ab+ relatives and complements IA-2A, ZnT8A, and HLA-DQ2/DQ8 for identifying participants in immunointervention trials. © 2013 by the American Diabetes Association.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Use of incretin agents and risk of pancreatic cancer: A population-based cohort study

Marine protected areas (MPA) are rapidly being established to minimize the impact of anthropogenic disturbances, yet, while climate change is acknowledged as a growing threat, very limited research exists about how to directly incorporate climate-related disturbances into MPA design. Using the conservation planning software Marxan and the Indo-west Pacific as a study region, an illustrative approach is developed here that incorporates climate change projections into the process of identifying priority areas for marine conservation. Conservation targets were set at 10% and 30% of areas that continually held sea-surface temperatures less than 1 °C above maximum non-extreme historic temperatures (derived from satellite imagery from 1984-2009). This approach allowed for continuity in conservation objectives across both space and time by identifying the geographic extent of thermal stress in the region and illustrating how conditions would change in future years. Achievement of targets was found to be flexible, but some areas were more important than others for achieving these targets. Interannual trend analyses were carried out for three climate models under two climate change scenarios to examine spatial and temporal patterns of thermal stress. Spatial patterns of thermal stress varied throughout the region. Results of the conservation approach were compared to the trend results to see whether the trends might be a simpler approach for accounting for climate change impacts in conservation planning (i.e., one feature could be used instead of more than 1000). The interannual analyses had a low overlap with the Marxan results, and hence are not a suitable substitute for the approach shown here. This study showed that inclusion of climate-related disturbances in marine conservation planning is feasible and should become common practice, together with targets for biodiversity. © 2012 Elsevier Ltd