Retinal microvascular calibre and risk of incident diabetes: the multi-ethnic study of atherosclerosis

Aim

To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.

Methods

The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45-84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.

Results

After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12-2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37-5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.

Conclusion

Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways.     

Effect of pulmonary exacerbations on long-term lung function decline in cystic fibrosis

It is unknown what proportion of long-term lung function decline in cystic fibrosis (CF) is explained by pulmonary exacerbations. The aim of this study was to determine how exacerbations requiring hospitalisation contribute to the course of CF lung disease. This was a retrospective cohort study. The primary outcome was the rate of decline of forced expiratory volume in 1 s (FEV(1)) % predicted. Out of 851 subjects, 415 (48.8%) subjects had ≥ 1 exacerbation. After adjustment for confounders, the annual rate of FEV(1) decline in those without an exacerbation was 1.2% per yr (95% CI 1.0-1.5), compared with 2.5% per yr (95% CI 2.1-2.8) in those with an exacerbation. The proportion of overall FEV(1) decline associated with ≥ 1 exacerbation was 52% (95% CI 35.0-68.9). For a given number of exacerbations, the annual rate of FEV(1) decline was greatest in subjects with ≤ 6 months between exacerbations. Half of FEV(1) decline seen in CF patients was associated with pulmonary exacerbations. Time between exacerbations, specifically ≤ 6 months between exacerbations, plays an important contribution to overall lung function decline. These findings support using time to next exacerbation as a clinical end-point for CF trials.     

Changes in circumpapillary retinal vessel density after acute primary angle closure episode via OCT angiography

Purpose

To investigate the changes and evaluate the diagnosis value of circumpapillary vessel density (VD) in cases of acute primary angle closure (APAC).

Design

Case–control study.

Methods

APAC patients with a history of unilateral acute attack were enrolled. The eyes with acute episode constituted the case group while the contralateral eyes without attack consisted of the control group. Ophthalmic examinations including slit-lamp examination, best-corrected visual acuity, intraocular pressure and visual field were carried out. Retinal nerve fiber layer (RNFL), macular ganglion cell complex (GCC) were measured by spectral-domain optical coherence tomography, while VD was assessed by optical coherence tomography angiography.

Results

The whole en face image vessel density (wiVD), circumpapillary vessel density (cpVD) and inside disk VD for both all vessels and capillary were all significantly lower in the APAC eyes compared to the fellow eyes (P?<?0.01 for all). In APAC eyes, the wiVD, inside disk VD and cpVD both for all vessels and capillary were all positively correlated with RNFL and GCC thicknesses but negatively correlated with the mean deviation (MD), pattern standard deviation (PSD) and the duration of acute attack (all P?<?0.01). From the ROC curve, the cpVD_cap, wiVD_cap, cpVD_all and wiVD_all all showed comparable diagnostic ability with RNFL, GCC and MD to differentiate eyes with APAC from the fellow eyes (all P?>?0.05). The inside disk VD_cap and VD_all demonstrated significant lower diagnostic ability than the cpVD_cap, wiVD_cap, cpVD_all and wiVD_all (all P?<?0.001).

Conclusions

In APAC eyes, circumpapillary VD decreased significantly compared with the fellow unaffected eyes. They were significantly correlated with thicknesses of RNFL and GCC, and visual field MD and PSD in the APAC eyes. The patients with longer duration of acute attack were more likely to have lower cpVD. For APAC, the diagnostic ability of wiVD and cpVD was similar with RNFL, GCC and MD and was higher than inside disk VD.

     

Factors influencing the acquisition of Stenotrophomonas maltophilia infection in cystic fibrosis patients

BackgroundStenotrophomonas maltophilia is one of the most common multi-drug resistant organisms causing pulmonary infections in CF patients. It is unknown whether S. maltophilia infection follows the same pattern and shares similar risk factors for acquisition as described for Pseudomonas aeruginosa.MethodsWe examined all clinical events from 1997 to 2008 in the Toronto CF Database to identify risk factors for the acquisition of S. maltophilia and to define distinct patterns of infection.ResultsWe followed 601 patients over 12 years, during which time one quarter of subjects had at least one positive culture for S. maltophilia; the incidence rate was slightly higher in children (11.6/100 person years) compared with adults (10.6/100 person years). Using multi-variable Cox proportional hazards models, steeper rate of FEV₁ decline was a significant risk factor for S. maltophilia acquisition, whereas new infections were less likely to occur with greater oral antibiotic use and a history of Burkholderia cepacia complex infection.ConclusionsThis study illustrates the evolution of S. maltophilia infection over time in a large cohort of adults and children with CF. Younger CF patients, and those with greater lung function decline were at increased risk of S. maltophilia infection. The use of oral antibiotics to maintain lung function may be a way of decreasing the risk of infection. However, the optimal management of CF patients with persistent S. maltophilia infection is not yet known and requires further studies.     

Chronic Stenotrophomonas maltophilia infection and mortality or lung transplantation in cystic fibrosis patients

BackgroundChronic Stenotrophomonas maltophilia infection is an independent risk factor for severe pulmonary exacerbations in cystic fibrosis (CF) patients. The goal of this study was to determine the effect of chronic S. maltophilia infection on mortality and the need for lung transplantation in a longitudinal study of children and adults with CF.MethodsThis was a cohort study of CF patients from the Hospital for Sick Children and St Michael's Hospital (Toronto, Canada) from 1997 to 2008. A Cox Regression model was used to estimate the hazard ratio (HR) to time of death or lung transplantation adjusting for age, gender, genotype, pancreatic status, CF related diabetes (CFRD), forced expiratory volume in 1 s (FEV₁), body mass index, number of pulmonary exacerbations, Pseudomonas aeruginosa, Burkholderia cepacia complex, Aspergillus and chronic S. maltophilia infection.ResultsA total of 687 patients were followed over the 12 year study period; 95 patients underwent a lung transplantation (of which 26 died) and an additional 49 patients died (total 144 events). In a Cox Regression model adjusting for baseline FEV₁, baseline infection with B. cepacia complex (HR 1.72, 95% CI 1.09–2.71) and baseline chronic S. maltophilia infection (HR 2.80, 95% CI 1.65–4.76) were significantly associated with death or lung transplant. However, in a time-varying model, infection with B. cepacia complex and chronic S. maltophilia infection were no longer significant.ConclusionsBaseline chronic S. maltophilia infection is associated with an almost three-fold increased risk of death or lung transplant in CF patients. It is still unclear, however, whether chronic S. maltophilia infection is simply a marker of severity of disease and ultimate mortality or whether it is causally related to disease progression.