Poorly controlled type 2 diabetes mellitus is associated with a decreased risk of incident gout: a population-based case-control study

OBJECTIVE The aim of this study was to explore the risk of incident gout in patients with type 2 diabetes mellitus (T2DM) in association with diabetes duration, diabetes severity and antidiabetic drug treatment. METHODS We conducted a case-control study in patients with T2DM using the UK-based Clinical Practice Research Datalink (CPRD). We identified case patients aged ≥18 years with an incident diagnosis of gout between 1990 and 2012. We matched to each case patient one gout-free control patient. We used conditional logistic regression analysis to calculate adjusted ORs (adj. ORs) with 95% CIs and adjusted our analyses for important potential confounders. RESULTS The study encompassed 7536 T2DM cases with a first-time diagnosis of gout. Compared to a diabetes duration <1 year, prolonged diabetes duration (1-3, 3-6, 7-9 and ≥10 years) was associated with decreased adj. ORs of 0.91 (95% CI 0.79 to 1.04), 0.76 (95% CI 0.67 to 0.86), 0.70 (95% CI 0.61 to 0.86), and 0.58 (95% CI 0.51 to 0.66), respectively. Compared to a reference A1C level of <7%, the risk estimates of increasing A1C levels (7.0-7.9, 8.0-8.9 and ≥9%) steadily decreased with adj. ORs of 0.79 (95% CI 0.72 to 0.86), 0.63 (95% CI 0.55 to 0.72), and 0.46 (95% CI 0.40 to 0.53), respectively. Neither use of insulin, metformin, nor sulfonylureas was associated with an altered risk of incident gout. CONCLUSIONS Increased A1C levels, but not use of antidiabetic drugs, was associated with a decreased risk of incident gout among patients with T2DM.

Diabetes, use of antidiabetic drugs, and the risk of glioma

BACKGROUND Prior epidemiologic studies suggest inverse relations between diabetes and glioma risk, but the underlying mechanisms, including use of antidiabetic drugs, are unknown. METHODS We therefore performed a matched case-control analysis using the Clinical Practice Research Datalink (CPRD). We identified incident glioma cases diagnosed between 1995 and 2012 and matched each case with 10 controls on age, gender, calendar time, general practice, and years of active history in the CPRD. We performed conditional logistic regression to estimate odds ratios (ORs) with 95% CIs, adjusted for body mass index and smoking. RESULTS We identified 2005 cases and 20 050 controls. Diabetes was associated with decreased risk of glioma (OR = 0.74; 95% CI = 0.60-0.93), particularly glioblastoma (OR = 0.69; 95% CI = 0.51-0.94). Glioblastoma risk reduction was markedly pronounced among diabetic men (OR = 0.60; 95% CI = 0.40-0.90), most apparently for those with diabetes of long-term duration (OR for >5 vs 0 y = 0.46; 95% CI = 0.26-0.82) or poor glycemic control (OR for HbA1c ≥8 vs <6.5% = 0.20; 95% CI = 0.06-0.70). In contrast, the effect of diabetes on glioblastoma risk was absent among women (OR = 0.85; 95% CI = 0.53-1.36). No significant associations with glioma were found for use of metformin (OR for ≥30 vs 0 prescriptions = 0.72; 95% CI = 0.38-1.39), sulfonylureas (OR = 0.71; 95% CI = 0.39-1.30), or insulin (OR = 0.79; 95% CI = 0.37-1.69). CONCLUSIONS Antidiabetic treatment appears to be unrelated to glioma, but long-term diabetes duration and increased HbA1c both show decreased glioma risk. Stronger findings in men than women suggest low androgen levels concurrent with diabetes as a biologic mechanism.

Heart failure in young adults

Heart failure (HF) is a major health concern affecting 15 million people in Europe and around 900 000 people in the U.K. HF predominantly affects the elderly, with the mean age of patients with a diagnosis of HF between 70 and 80 years. Most previous HF studies have accordingly focused on older patients. Although HF is less common in younger adults (<65 years), 15% to 20% of patients hospitalised with HF are younger than 60 years of age. Very few studies have described the characteristics of younger adults with HF and its outcome. The aims of this thesis are to describe the clinical characteristics of younger adults with HF, explore the epidemiology of HF in younger adults and determine their short- and long-term outcomes. This was made possible by access multiple databases consisting of large patient cohorts with HF. The first chapter is a systematic literature review of younger adults with HF. Gaps in the current literature were identified and the thesis focused on some of these. The CHARM study allows detail characterisations of younger adults with HF. It recorded characteristics of patients with HF, including symptoms and signs of HF, electrocardiographic changes, chest radiographic findings, and also left ventricular ejection fraction. HF hospitalisations and its precipitating factors were also recorded systematically. Younger adults were more likely to have a third heart sound and hepatomegaly, but less likely to have pulmonary crackles and peripheral oedema. Similarly, radiological findings in younger adults were less likely to show interstitial pulmonary oedema or pleural effusion. Interestingly, younger adults aged <40 years not only have similar HF hospitalisation rate to older patients, however during their presentation with decompensated HF, they were less likely to have clinical pulmonary oedema and radiological signs of HF. Physicians managing younger adults with HF need to be aware of this. Younger adults were also less compliant with medications and lifestyle restriction resulting in hospitalisation with decompensated HF. Fortunately, despite these challenges, mortality rates in younger adults with HF were lower compared to older patients. To further substantiate the findings from the CHARM study, the MAGGIC study, a meta-analysis consists of over 40 000 patients with HF from large observational studies and randomised controlled trials, was examined. In both databases, the commonest aetiology of HF in younger adults was dilated cardiomyopathy. The ejection fraction was the lowest in younger adults. Similar to the CHARM study, mortality rates in younger adults were lower compared to older patients. However, in the MAGGIC study, by stratifying mortality into patients with preserved ejection fraction and with reduced ejection fraction, younger patients with preserved ejection fraction have a much lower mortality rate compared to patients with reduced ejection fraction. Findings from clinical trials are not always reflective of the real life clinical practice. The U.K. Clinical Practice Research Datalink (CPRD), a large and well-validated primary care database with 654 practices contributing information into the database representing approximated 8% of the U.K. population, is a rich dataset offering a unique opportunity to examine the characteristics, treatments, and outcomes of younger adults with HF in the community. In contrast to the CHARM and MAGGIC studies, younger adults aged <40 years were stratified into 20-29 and 30-39 years in the CPRD analysis. This is possible due to the larger number of younger adults with HF. Further stratifying the younger age groups demonstrated heterogeneity among younger adults with HF. In contrast to previous data showing younger adults have lower co-morbidities, the proportions of depression, chronic kidney disease, asthma, and any connective tissue disease were high among patients aged 20-29 years in the analysis from the CPRD. Surprisingly, the treatment rates for angiotensin converting enzyme (ACE) inhibitor, and aldosterone antagonist were the lowest in patients aged 20-29 years. With the exception of patients aged ≥80 years, treatment rate with beta-blocker was also the lowest in patients aged 20-29 years. With over two decades of follow up, long-term mortality rates in younger adults with HF can be determined. The mortality rates continued to decline from 1988 to 2011. Physicians managing younger adults with HF can now use this contemporary data to provide prognostic information to patients and their family. A hospital administrative database is the logical next platform to explore younger adults with HF. The Alberta Ministry of Health database links an outpatient database to a hospitalisation database providing ample data to examine the relationship between outpatient clinic visits and hospital admissions in younger adults with HF. Following a diagnosis of HF in the outpatient setting, younger adults were admitted to the hospital with decompensated HF much sooner than older patients. Younger adults also presented to emergency department more frequently following their first hospitalisation for HF. In conclusion, this thesis presented the characteristics and outcomes of younger adults with HF, and helped to extend our current understanding on this important topic. I hope the data presented here will benefit not only physicians looking after younger adults with HF, but also patients and their family.

Inteligencia territorial para la recuperación de las dinámicas socio-productivas en la subregión de Lengupá (Boyacá, Colombia)

Este documento corresponde al ejercicio preliminar de la línea de investigación en dinámicas territoriales, y es uno de los artículos científicos propuestos como resultado del Proyecto de investigación “Inteligencia territorial para la recuperación de las dinámicas socio-productivas de la subregión de Lengupá”. Por lo tanto, presenta los resultados de la fase exploratoria, correspondiente al diagnóstico regional en el marco de los enfoques teóricos desde los cuales la región es estudiada. A continuación, se presentarán los dos pilares fundamentales de ésta investigación: el territorio y la Inteligencia Territorial. En el caso del territorio, este proceso de investigación parte de un diferenciación previa respecto al lugar y al espacio, debido a que en el territorio se dan relaciones históricas y de poder en una relación dialéctica, entre los atributos ecológicos y culturales, teniendo en cuenta el planteamiento de Sasquet, (2015) cuando menciona que para comprender el territorio es necesario comprender el espacio geográfico, territorialidad humana, en escala subregional y a través del tiempo.