CXCR4 Antagonism attenuates the development of diabetic cardiac fibrosis

Heart failure (HF) is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice) or type II diabetes (Israeli Sand-rats) and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow) to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

Compliance with recommendations from a screening programme for diabetic retinopathy

METHODS: General practitioner compliance with recommendations for patient follow-up after participation in a screening programme for diabetic retinopathy was assessed. Six months after screening with non-mydriatic retinal photography in four areas of Victoria, the genera practitioner of each participant was surveyed if the participant reported no examination for diabetic retinopathy in the past 2 years and if the results of the screening indicated the need for further assessment. RESULTS: Overall, 208 of 253 (82%) completed questionnaires were analysed. A total of 123 (59%) patients were referred by their doctors for further assessment and 97 (79%) of those referred were reported to have complied with the referral. Of the 85 (41%) patients who were not referred for further assessment, 31 (36%) were reported by their doctors to be already under regular review by an ophthalmologist. CONCLUSIONS: Compliance with genera practitioner referrals suggests that this screening programme was effective and a useful means by which to remind general practitioners of the importance of regular eye examinations for people with diabetes.

Use of focus groups to identify health promotion strategies for the early detection of diabetic retinopathy

BACKGROUND: People with diabetes do not regularly utilise eye services for the early prevention of vision loss due to diabetic eye disease. A community-based screening program has been initiated in Victoria to address this issue. To encourage people to take preventive eye health care measures, the most effective health promotion strategies were identified. METHODS: Thirty-three health professionals were invited to attend focus groups. A sample of 35 people with diabetes was approached by their GPs or diabetes educators because of their motivation to participate in diabetes activities. Each group consisted of 10 members. Discussion points included the type of education messages available to people with diabetes; use of eye services among the participants with diabetes; and strategies required promoting the screening service. RESULTS: Five focus groups were conducted. The discussions highlighted that a great deal could be achieved by using local community networks to promote the benefits of early detection of diabetic retinopathy and local screening program. The group members recommended that particular attention be directed to general practitioners and their distribution of materials to patients. Key issues for planning and implementing the program were highlighted. The groups urged development of strategies to encourage people with diabetes in rural Victoria to participate in a program for the early detection of diabetic retinopathy.

Screening for diabetic retinopathy using a non-mydriatic retinal camera in rural Victoria

PURPOSE: To develop a screening programme for the early detection of diabetic retinopathy using non-mydriatic retinal photography. METHODS: A community based screening service was offered to all people with known diabetes mellitus in selected townships in the LaTrobe and Goulburn Valleys in Victoria. At the local examination centre, basic sociodemographic information was collected as well as details of previous use of eye care services for the early detection of diabetic retinopathy. The examination included visual acuity (VA), glycosylated haemoglobin level and Polaroid photographs of each fundus using a Canon CR5-45NM non-mydriatic retinal camera (Canon, Tochigiken, Japan). Dilating drops were not used. Photographs were subsequently reviewed and letters were sent to all participants (with copies to their general practitioners) with recommendations for appropriate follow up. RESULTS: A total of 1177 people with diabetes attended the screening service, which is estimated to be 40% of the total population with known diabetes in the study area. The mean age was 65 years (range 20-94 years); 559 (48%) people reported not having a dilated fundus examination within the past 2 years; 345 (29%) people had never had a dilated fundus examination. Of the 2354 eyes, 2126 (90%) of the photographs were gradable. A total of 704 people (60%) had normal VA and no evidence of diabetic retinopathy, 209 people (18%) had diabetic retinopathy, 101 people (9%) had evidence of other fundus pathology, 42 people (3%) had reduced acuity (< 6/18) in one or both eyes (with no fundus pathology evident) and 121 people (10%) had ungradable photographs in one or both eyes. CONCLUSIONS: The present study demonstrates the usefulness of a screening programme with non-mydriatic retinal photography as an adjunct to current eye care services for the early detection of diabetic retinopathy.

Examination compliance and screening for diabetic retinopathy: a 2-year follow-up study

Early detection and timely treatment of diabetic retinopathy can preserve vision, yet many people with diabetes do not have their eyes examined regularly. The purpose of this study was to examine eye care practices of people with diabetes who had not previously accessed eye care services on a regular basis. Screening with non-mydriatic retinal photography for diabetic retinopathy was initiated in 1996, and targeted people with diabetes who did not access eye care services on a regular basis. Each test area was revisited 2 years after the initial screening. Patients that did not attend the biennial screening were followed up by mail survey. Although none of the participants in this study had been previously accessing eye care services on a regular basis, 87% did so after attending the screening. These results indicate that mobile screening with non-mydriatic photography, as an adjunct to current eye care services, has the potential to increase examination compliance for diabetic retinopathy and to achieve sustained behaviour change.

Recruitment methods for community-based screening for diabetic retinopathy

Regular screening of all people with diabetes is the most efficient and cost-effective way to detect early stages of diabetic retinopathy so that laser treatment can be performed at the optimal time. A major aim of the Program for the Early Detection of Diabetic Retinopathy was to increase compliance with guidelines for screening for diabetic retinopathy. This community-based screening program used non-mydriatic retinal photography and was initiated in four areas of Victoria, Australia from 1996-1998. Recruitment strategies included targeted mail-outs, provision of the program brochure in English and the main languages spoken in the areas and media promotion in ethnic newspapers and on ethnic radio stations. In Victoria, only 55% of the population with diabetes currently access eye care services at the recommended intervals. This program was able to increase compliance with guidelines to 70% among people with diabetes that had not had a recent eye examination. A total of 1,197 people with diabetes were screened for diabetic retinopathy. Of the 1,197 people who were screened, 620 (15% of the estimated number of people with diabetes) had not had their eyes examined in the past two years. This pilot study identified strategies to encourage people with diabetes to have their eyes examined at the recommended intervals.