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1.  Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme 
Diabetologia  2013;56(8):1716-1725.
Aims/hypothesis
The aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening.
Methods
This was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy.
Results
The study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years.
Conclusions/interpretation
Transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-013-2928-7) contains peer reviewed but unedited supplementary material, which is available to authorised users.
doi:10.1007/s00125-013-2928-7
PMCID: PMC3699707  PMID: 23689796
Diabetes; Diabetic retinopathy; Maculopathy; Retinal screening; Screening intervals
2.  Four-Year Incidence of Diabetic Retinopathy in a Spanish Cohort: The MADIABETES Study 
PLoS ONE  2013;8(10):e76417.
Objective
To evaluate the incidence of diabetic retinopathy in patients with Type 2 Diabetes Mellitus, to identify the risk factors associated with the incidence of retinopathy and to develop a risk table to predict four-year retinopathy risk stratification for clinical use, from a four-year cohort study.
Design
The MADIABETES Study is a prospective cohort study of 3,443 outpatients with Type 2 Diabetes Mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).
Results
The cumulative incidence of retinopathy at four-year follow-up was 8.07% (95% CI = 7.04–9.22) and the incidence density was 2.03 (95% CI = 1.75–2.33) cases per 1000 patient-months or 2.43 (95% CI = 2.10–2.80) cases per 100 patient-years. The highest adjusted hazard ratios of associated risk factors for incidence of diabetic retinopathy were LDL-C >190 mg/dl (HR = 7.91; 95% CI = 3.39–18.47), duration of diabetes longer than 22 years (HR = 2.00; 95% CI = 1.18–3.39), HbA1c>8% (HR = 1.90; 95% CI = 1.30–2.77), and aspirin use (HR = 1.65; 95% CI = 1.22–2.24). Microalbuminuria (HR = 1.17; 95% CI = 0.75–1.82) and being female (HR = 1.12; 95% CI = 0.84–1.49) showed a non-significant increase of diabetic retinopathy. The greatest risk is observed in females who had diabetes for more than 22 years, with microalbuminuria, HbA1c>8%, hypertension, LDL-Cholesterol >190 mg/dl and aspirin use.
Conclusions
After a four-year follow-up, the cumulative incidence of retinopathy was relatively low in comparison with other studies. Higher baseline HbA1c, aspirin use, higher LDL-Cholesterol levels, and longer duration of diabetes were the only statistically significant risk factors found for diabetic retinopathy incidence. This is the first study to demonstrate an association between aspirin use and diabetic retinopathy risk in a well-defined cohort of patients with Type 2 Diabetes Mellitus at low risk of cardiovascular events. However, further studies with patients at high cardiovascular and metabolic risk are needed to clarify this issue.
doi:10.1371/journal.pone.0076417
PMCID: PMC3798464  PMID: 24146865
3.  Diabetic retinopathy at diagnosis of type 2 diabetes in Scotland 
Diabetologia  2012;55(9):2335-2342.
Aims/hypothesis
The aim of this study was to examine the prevalence of and risk factors for diabetic retinopathy in people with newly diagnosed type 2 diabetes mellitus, using Scottish national data.
Methods
We identified individuals diagnosed with type 2 diabetes mellitus in Scotland between January 2005 and May 2008 using data from the national diabetes database. We calculated the prevalence of retinopathy and ORs for risk factors associated with retinopathy at first screening.
Results
Of the 51,526 people with newly diagnosed type 2 diabetes mellitus identified, 91.4% had been screened by 31 December 2010. The median time to first screening was 315 days (interquartile range [IQR] 111–607 days), but by 2008 the median was 83 days (IQR 51–135 days). The prevalence at first screening of any retinopathy was 19.3%, and for referable retinopathy it was 1.9%. For individuals screened after a year the prevalence of any retinopathy was 20.5% and referable retinopathy was 2.3%. Any retinopathy at screening was associated with male sex (OR 1.19, 95% CI 1.14, 1.25), HbA1c (OR 1.07, 95% CI 1.06, 1.08 per 1% [11 mmol/mol] increase), systolic BP (OR 1.06, 95% CI 1.05, 1.08 per 10 mmHg increase), time to screening (OR for screening >1 year post diagnosis = 1.12, 95% CI 1.07, 1.17) and obesity (OR 0.87, 95% CI 0.82, 0.93) in multivariate analysis.
Conclusions/interpretation
The prevalence of retinopathy at first screening is lower than in previous UK studies, consistent with earlier diagnosis of diabetes. Most newly diagnosed type 2 diabetic patients in Scotland are screened within an acceptable interval and the prevalence of referable disease is low, even in those with delayed screening.
doi:10.1007/s00125-012-2596-z
PMCID: PMC3411303  PMID: 22688348
Diabetic retinopathy; Diabetic retinopathy screening; Scotland; Type 2 diabetes
4.  Incidence and Progression of Diabetic Retinopathy During 17 Years of a Population-Based Screening Program in England 
Diabetes Care  2012;35(3):592-596.
OBJECTIVE
To estimate the incidence of diabetic retinopathy in relation to retinopathy grade at first examination and other prognostic characteristics.
RESEARCH DESIGN AND METHODS
This was a dynamic cohort study of 20,686 people with type 2 diabetes who had annual retinal photography up to 14 times between 1990 and 2006. Cumulative and annual incidence rates were estimated using life tables, and risk factors for progression were identified using Cox regression analysis.
RESULTS
Of 20,686 patients without proliferative diabetic retinopathy (PDR) or sight-threatening maculopathy at their first retinal examination (baseline), 16,444 (79%) did not have retinopathy, 3,632 (18%) had nonproliferative retinopathy, and 610 (2.9%) had preproliferative retinopathy. After 5 years, few patients without retinopathy at baseline developed preproliferative retinopathy (cumulative incidence 4.0%), sight-threatening maculopathy (0.59%), or PDR (0.68%); after 10 years, the respective cumulative incidences were 16.4, 1.2, and 1.5%. Among those with nonproliferative (background) retinopathy at baseline, after 1 year 23% developed preproliferative retinopathy, 5.2% developed maculopathy, and 6.1% developed PDR; after 10 years, the respective cumulative incidences were 53, 9.6, and 11%. Patients with nonproliferative retinopathy at baseline were five times more likely to develop preproliferative, PDR, or maculopathy than those without retinopathy at baseline (adjusted hazard ratio 5.0 [95% CI 4.4–5.6]).
CONCLUSIONS
Few patients without diabetic retinopathy at the initial screening examination developed preproliferative retinopathy, PDR, or sight-threatening maculopathy after 5–10 years of follow-up. Screening intervals longer than a year may be appropriate for such patients.
doi:10.2337/dc11-0943
PMCID: PMC3322726  PMID: 22279031
5.  The 3 Year Incidence and Cumulative Prevalence of Retinopathy 
American journal of ophthalmology  2007;143(6):970-976.
Purpose
To describe the 3 year incidence and cumulative prevalence of retinopathy and its risk factors.
Design
Population-based, prospective cohort study in four U.S. communities
Methods
In the Atherosclerosis Risk in Communities Study, 981 participants had retinal photography of one randomly selected eye at the 3rd examination (1993-95) and 3 years later at the 4th examination (1996). Photographs were graded on both occasions for retinopathy signs (e.g., microaneurysm, retinal hemorrhage, cotton wool spots). Incidence was defined as participants without retinopathy at the 3rd examination who developed retinopathy at the 4th examination, and cumulative prevalence was defined to include incident retinopathy as well as participants who had retinopathy at both the 3rd and 4th examinations.
Results
The 3-year incidence anad cumulative prevalence of any retinopathy in the whole cohort was 3.8% and 7.7%, respectively. In multivariable analysis, incident retinopathy was related to higher mean arterial blood pressure (OR 1.5, 95% CI 1.0, 2.3, per standard deviation increase in risk factor levels), fasting serum glucose (OR 1.6, 95% CI, 1.3, 2.1), serum total cholesterol (OR 1.4, 95% CI, 1.0, 2.0), and plasma fibrinogen (OR 1.4, 95% CI, 1.1, 1.9). Among persons without diabetes, the 3 year incidence and cumulative prevalence of non-diabetic retinopathy was 2.9% and 4.3%, respectively. Incident non-diabetic retinopathy was related to higher mean arterial blood pressure (OR 1.4, 95% CI, 0.9, 2.3) and fasting serum glucose (OR 1.5, 95% CI, 1.0, 2.3). Among persons with diabetes, the 3-year incidence and cumulative prevalence of diabetic retinopathy was 10.1% and 27.2%, respectively.
Conclusions
Retinopathy signs occur frequently in middle-aged people, even in those without diabetes. Hypertension and hyperglycemia are risk factors for incident retinopathy.
doi:10.1016/j.ajo.2007.02.020
PMCID: PMC1950734  PMID: 17399675
6.  Prevalence of Diabetic Retinopathy in the United States, 2005–2008 
Context
The prevalence of diabetes in the United States has increased. People with diabetes are at risk for diabetic retinopathy. No recent national population-based estimate of the prevalence and severity of diabetic retinopathy exists.
Objectives
To describe the prevalence and risk factors of diabetic retinopathy among US adults with diabetes aged 40 years and older.
Design, Setting, and Participants
Analysis of a cross-sectional, nationally representative sample of the National Health and Nutrition Examination Survey 2005–2008 (N=1006). Diabetes was defined as a self-report of a previous diagnosis of the disease (excluding gestational diabetes mellitus) or glycated hemoglobin A1c of 6.5% or greater. Two fundus photographs were taken of each eye with a digital nonmydriatic camera and were graded using the Airlie House classification scheme and the Early Treatment Diabetic Retinopathy Study severity scale. Prevalence estimates were weighted to represent the civilian, noninstitutionalized US population aged 40 years and older.
Main Outcome Measurements
Diabetic retinopathy and vision-threatening diabetic retinopathy.
Results
The estimated prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was 28.5% (95% confidence interval [CI], 24.9%–32.5%) and 4.4% (95% CI, 3.5%–5.7%) among US adults with diabetes, respectively. Diabetic retinopathy was slightly more prevalent among men than women with diabetes (31.6%; 95% CI, 26.8%–36.8%; vs 25.7%; 95% CI, 21.7%–30.1%; P=.04). Non-Hispanic black individuals had a higher crude prevalence than non-Hispanic white individuals of diabetic retinopathy (38.8%; 95% CI, 31.9%–46.1%; vs 26.4%; 95% CI, 21.4%–32.2%; P=.01) and vision-threatening diabetic retinopathy (9.3%; 95% CI, 5.9%–14.4%; vs 3.2%; 95% CI, 2.0%–5.1%; P=.01). Male sex was independently associated with the presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% CI, 1.39–3.10), as well as higher hemoglobin A1c level (OR, 1.45; 95% CI, 1.20–1.75), longer duration of diabetes (OR, 1.06 per year duration; 95% CI, 1.03–1.10), insulin use (OR, 3.23; 95% CI, 1.99–5.26), and higher systolic blood pressure (OR, 1.03 per mm Hg; 95% CI, 1.02–1.03).
Conclusion
In a nationally representative sample of US adults with diabetes aged 40 years and older, the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy was high, especially among Non-Hispanic black individuals.
doi:10.1001/jama.2010.1111
PMCID: PMC2945293  PMID: 20699456
7.  The relation of atherosclerotic cardiovascular disease to retinopathy in people with diabetes in the Cardiovascular Health Study 
Aims: To describe the association of retinopathy with atherosclerosis and atherosclerotic risk factors in people with diabetes.
Methods: 296 of the 558 people classified as having diabetes by the American Diabetes Association criteria, from a population based cohort of adults (ranging in age from 69 to 102 years) living in four United States communities (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were studied from 1997 to 1998. Lesions typical of diabetic retinopathy were determined by grading a 45° colour fundus photograph of one eye of each participant, using a modification of the Airlie House classification system.
Results: Retinopathy was present in 20% of the diabetic cohort, with the lowest prevalence (16%), in those 80 years of age or older. Retinopathy was detected in 20.3% of the 296 people with diabetes; 2.7% of the 296 had signs of proliferative retinopathy and 2.1% had signs of macular oedema. The prevalence of diabetic retinopathy was higher in black people (35.4%) than white (16.0%). Controlling for age, sex, and blood glucose, retinopathy was more frequent in black people than white (odds ratio (OR) 2.26, 95% confidence interval (CI) 1.01, 5.05), in those with longer duration of diabetes (OR (per 5 years of diabetes) 1.42, 95% CI 1.18, 1.70), in those with subclinical cardiovascular disease (OR 1.49, 95% CI 0.51, 4.31), or coronary heart disease or stroke (OR 3.23, 95% CI 1.09, 9.56) than those without those diseases, in those with higher plasma low density lipoprotein (LDL) cholesterol (OR (per 10 mg/dl of LDL cholesterol) 1.12, 95% CI 1.02, 1.23), and in those with gross proteinuria (OR 4.76, 95% CI 1.53, 14.86).
Conclusion: Data from this population based study suggest a higher prevalence of retinopathy in black people than white people with diabetes and the association of cardiovascular disease, elevated plasma LDL cholesterol, and gross proteinuria with diabetic retinopathy. However, any conclusions or explanations regarding associations described here must be made with caution because only about one half of those with diabetes mellitus were evaluated.
PMCID: PMC1770969  PMID: 11801510
diabetes; diabetic retinopathy; atherosclerosis; dyslipidaemia
8.  Use of mobile screening unit for diabetic retinopathy in rural and urban areas. 
BMJ : British Medical Journal  1993;306(6871):187-189.
OBJECTIVES--To compare the effectiveness of a mobile screening unit with a non-mydriatic polaroid camera in detecting diabetic retinopathy in rural and urban areas. To estimate the cost of the service. DESIGN--Prospective data collection over two years of screening for diabetic retinopathy throughout Tayside. SETTING--Tayside region, population 390,000, area 7770 km2. SUBJECTS--961 patients in rural areas and 1225 in urban areas who presented for screening. MAIN OUTCOME MEASURES--Presence of diabetic retinopathy, need for laser photocoagulation, age, duration of diabetes, and diabetic treatment. RESULTS--Compared with diabetic patients in urban areas, those in rural areas were less likely to attend a hospital based diabetic clinic (46% (442) v 86% (1054), p < 0.001); less likely to be receiving insulin (260 (27%) v 416 (34%), p < 0.001 and also after correction for differences in age distribution); more likely to have advanced (maculopathy or proliferative retinopathy) diabetic retinopathy (13% (122) v 7% (89), p < 0.001); and more likely to require urgent laser photocoagulation for previously unrecognised retinopathy (1.4% (13) v 0.5% (6), p < 0.02). The screening programme cost 10 pounds per patient screened and 1000 pounds per patient requiring laser treatment. CONCLUSION--The mobile diabetic eye screening programme detected a greater prevalence of advanced retinopathy in diabetic patients living in rural areas. Patients in rural areas were also more likely to need urgent laser photocoagulation. Present screening procedures seem to be less effective in rural areas and rural patients may benefit more from mobile screening units than urban patients.
PMCID: PMC1676588  PMID: 8443485
9.  Long-Term Risk of Incident Type 2 Diabetes and Measures of Overall and Regional Obesity: The EPIC-InterAct Case-Cohort Study 
PLoS Medicine  2012;9(6):e1001230.
A collaborative re-analysis of data from the InterAct case-control study conducted by Claudia Langenberg and colleagues has established that waist circumference is associated with risk of type 2 diabetes, independently of body mass index.
Background
Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).
Methods and Findings
The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5–22.4 kg/m2) with a low WC (<94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI≥35 kg/m2) and a high WC (>102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50–103 per 1,000 person-years in men and 28–74 per 1,000 person-years in women).
Conclusions
WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 350 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone that the pancreas releases after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest form of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing sugar from the blood become insulin resistant. Type 2 diabetes can be controlled with diet and exercise, and with drugs that help the pancreas make more insulin or that make cells more sensitive to insulin. The long-term complications of diabetes, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about 10 years compared to people without diabetes.
Why Was This Study Done?
A high body mass index (BMI, a measure of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is a strong predictor of type 2 diabetes. Although the risk of diabetes is greatest in obese people (who have a BMI of greater than 30 kg/m2), many of the people who develop diabetes are overweight—they have a BMI of 25–30 kg/m2. Healthy eating and exercise reduce the incidence of diabetes in high-risk individuals, but it is difficult and expensive to provide all overweight and obese people with individual lifestyle advice. Ideally, a way is needed to distinguish between people with high and low risk of developing diabetes at different levels of BMI. Waist circumference is a measure of fat distribution that has the potential to quantify diabetes risk among people with different BMIs because it estimates the amount of fat around the abdominal organs, which also predicts diabetes development. In this case-cohort study, the researchers use data from the InterAct study (which is investigating how genetics and lifestyle interact to affect diabetes risk) to estimate the long-term risk of type 2 diabetes associated with BMI and waist circumference. A case-cohort study measures exposure to potential risk factors in a group (cohort) of people and compares the occurrence of these risk factors in people who later develop the disease and in a randomly chosen subcohort.
What Did the Researchers Do and Find?
The researchers estimated the association of BMI and waist circumference with type 2 diabetes from baseline measurements of the weight, height, and waist circumference of 12,403 people who subsequently developed type 2 diabetes and a subcohort of 16,154 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC). Both risk factors were independently associated with type 2 diabetes risk, but waist circumference was a stronger risk factor in women than in men. Obese men (BMI greater than 35 kg/m2) with a high waist circumference (greater than 102 cm) were 22 times more likely to develop diabetes than men with a low normal weight (BMI 18.5–22.4 kg/m2) and a low waist circumference (less than 94 cm); obese women with a waist circumference of more than 88 cm were 31.8 times more likely to develop type 2 diabetes than women with a low normal weight and waist circumference (less than 80 cm). Importantly, among overweight people, waist circumference measurements identified a subgroup of overweight people (those with a high waist circumference) whose 10-year cumulative incidence of type 2 diabetes was similar to that of obese people.
What Do These Findings Mean?
These findings indicate that, among people of European descent, waist circumference is independently and strongly associated with type 2 diabetes, particularly among women. Additional studies are needed to confirm this association in other ethnic groups. Targeted measurement of waist circumference in overweight individuals (who now account for a third of the US and UK adult population) could be an effective strategy for the prevention of diabetes because it would allow the identification of a high-risk subgroup of people who might benefit from individualized lifestyle advice.
Additional Information
Please access these web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001230.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health care professionals, and the general public, including detailed information on diabetes prevention (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (including some information in Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes, about the prevention of type 2 diabetes, and about obesity; it also includes peoples stories about diabetes and about obesity
The charity Diabetes UK also provides detailed information for patients and carers, including information on healthy lifestyles for people with diabetes, and has a further selection of stories from people with diabetes; the charity Healthtalkonline has interviews with people about their experiences of diabetes
More information on the InterAct study is available
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention and about obesity (in English and Spanish)
doi:10.1371/journal.pmed.1001230
PMCID: PMC3367997  PMID: 22679397
10.  Use of eye care services by people with diabetes: the Melbourne Visual Impairment Project 
AIM—The use of eye care services by people with and without diabetes was investigated in the Melbourne Visual Impairment Project (VIP), a population based study of eye disease in a representative sample of Melbourne residents 40 years of age and older.
METHODS—A comprehensive interview was employed to elicit information on history of diabetes, medication use, most recent visit to an ophthalmologist and optometrist, and basic demographic details. Presence and extent of diabetic retinopathy was determined by dilated fundus examination.
RESULTS—The Melbourne VIP comprised 3271 people who ranged in age from 40 to 98 years; 46.2% of them were male. Of 3189 people who had the fundus examination and knew their diabetes status, 162 (5.1%) reported having been previously diagnosed with diabetes and, of these, 37 (22.2%) were found to have diabetic retinopathy. Seven people (4.3%) had developed diabetes before age 30. The mean duration of diabetes was 9.2 years. People with diabetes were significantly more likely to have visited an ophthalmologist ever or in the past 2 years than people without diabetes. However, 31.8% of people with diabetes had never visited an ophthalmologist. The proportion of people who had never seen an ophthalmologist was 47.1% for people without diabetes, 34.2% for people with diabetes but without diabetic retinopathy, and 25% for people with diabetic retinopathy. Sixty one per cent of people with diabetic retinopathy had seen an ophthalmologist in the past year and a further 3% within the past 2 years. People with diabetes were not significantly more likely to have visited an optometrist than people without diabetes (p=0.51). Overall, 37.7% of people with diabetes and 32.9% of people without diabetes had visited an optometrist within the past year (χ2=2.25, 1 df, p=0.13). Information concerning retinal examinations was available for 135 individuals (83.3% of people with diabetes). Only 74 (54.8%) could recall ever having a dilated fundus examination; 10 (14%) by an optometrist, 62 (86%) by an ophthalmologist, and five (7%) by a general practitioner. Of those 68 people who had seen an ophthalmologist in the past 2 years, 48 (71%) reported a dilated fundus examination during that time. This compares with 28 (43%) reported dilated fundus examinations in the 65 people who had seen an optometrist in the past 2 years. This finding is statistically significant (χ2=10.2, 1 df, p<0.005).
CONCLUSION—These results indicate that nearly half of people with diabetes in Melbourne are not receiving adequate screening or follow up for diabetic retinopathy, despite universal health care.

 Keywords: diabetes; diabetic retinopathy; screening guidelines
PMCID: PMC1722538  PMID: 9640191
11.  Retinal Vascular Geometry Predicts Incident Retinopathy in Young People With Type 1 Diabetes 
Diabetes Care  2011;34(7):1622-1627.
OBJECTIVE
To examine the association between retinal vascular geometry and subsequent development of incident retinopathy in young patients with type 1 diabetes.
RESEARCH DESIGN AND METHODS
A prospective cohort study of 736 people with type 1 diabetes aged 12 to 20 years, retinopathy-free at baseline, attending an Australian tertiary care hospital. Retinopathy was determined from seven-field retinal photographs according to the modified Airlie House Classification. Retinal vascular geometry, including length/diameter ratio (LDR) and simple tortuosity (ST), was quantified in baseline retinal photographs. Generalized estimating equations were used to determine risk of retinopathy associated with baseline LDR and ST, adjusting for other factors.
RESULTS
After a median 3.8 (interquartile range 2.4–6.1) years of follow-up, incident retinopathy developed in 287 of 736 (39%). In multivariate analysis, lower arteriolar LDR (odds ratio 1.8 [95% CI 1.2–2.6]; 1st vs. 4th quartile) and greater arteriolar ST (1.5 [1.0–2.2]; 4th vs. 1st quartile) predicted incident retinopathy after adjusting for diabetes duration, sex, A1C, blood pressure, total cholesterol, and BMI. In subgroup analysis by sex, LDR predicted incident retinopathy in male and female participants (2.1 [1.1–4.0] and 1.7 [1.1–2.7]; 1st vs. 4th quartiles, respectively) and greater arteriolar ST predicted incident retinopathy in male participants (2.4 [1.1–4.4]; 4th vs. 1st quartile) only.
CONCLUSIONS
Lower arteriolar LDR and greater ST were independently associated with incident retinopathy in young people with type 1 diabetes. These vascular geometry measures may serve as risk markers for diabetic retinopathy and provide insights into the early structural changes in diabetic microvascular complications.
doi:10.2337/dc10-2419
PMCID: PMC3120178  PMID: 21593293
12.  Diagonal ear lobe crease in diabetic south Indian population: Is it associated with Diabetic Retinopathy?. Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular-genetics Study (SN-DREAMS, Report no. 3) 
BMC Ophthalmology  2009;9:11.
Background
To report the prevalence of ear lobe crease (ELC), a sign of coronary heart disease, in subjects (more than 40 years old) with diabetes and find its association with diabetic retinopathy.
Methods
Subjects were recruited from the Sankara Nethralaya Diabetic Retinopathy Epidemiology And Molecular-genetics Study (SN-DREAMS), a cross-sectional study between 2003 and 2006; the data were analyzed for the1414 eligible subjects with diabetes. All patients' fundi were photographed using 45° four-field stereoscopic digital photography. The diagnosis of diabetic retinopathy was based on the modified Klein classification. The presence of ELC was evaluated on physical examination.
Results
The prevalence of ELC, among the subjects with diabetes, was 59.7%. The ELC group were older, had longer duration of diabetes, had poor glycemic control and had a high socio-economic status compared to the group without ELC and the variables were statistically significant. There was no statistical difference in the prevalence of diabetic retinopathy in two groups. On multivariate analysis for any diabetic retinopathy, the adjusted OR for women was 0.69 (95% CI 0.51-0.93) (p = 0.014); for age >70 years, 0.49 (95% CI 0.26-0.89) (p = 0.024); for increasing duration of diabetes (per year increase), 1.11(95% CI 1.09-1.14) (p < 0.0001); and for poor glycemic control (per unit increase in glycosylated heamoglobin), 1.26 (95% CI 1.19-1.35) (p < 0.0001). For sight-threatening diabetic retinopathy, no variable was significant on multivariable analysis. In predicting any diabetic retinopathy, the presence of ELC had sensitivity of 60.4%, and specificity, 40.5%. The area under the ROC curve was 0.50 (95% CI 0.46-0.54) (p 0.02).
Conclusion
The ELC was observed in nearly 60% of the urban south Indian population. However, the present study does not support the use of ELC as a screening tool for both any diabetic retinopathy and sight-threatening retinopathy.
doi:10.1186/1471-2415-9-11
PMCID: PMC2762956  PMID: 19788727
13.  Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: prospective cohort study 
Objective To examine the relation between blood pressure and the development of early retinopathy in adolescents with childhood onset type 1 diabetes.
Design Prospective cohort study.
Setting Diabetes Complications Assessment Service at the Children’s Hospital at Westmead, Sydney, Australia.
Participants 1869 patients with type 1 diabetes (54% female) screened for retinopathy with baseline median age 13.4 (interquartile range 12.0-15.2) years, duration 4.9 (3.1-7.0) years, and albumin excretion rate of 4.4 (3.1-6.8) μg/min plus a subgroup of 1093 patients retinopathy-free at baseline and followed for a median 4.1 (2.4-6.6) years.
Main outcome measures Early background retinopathy; blood pressure.
Results Overall, retinopathy developed in 673 (36%) participants at any time point. In the retinopathy-free group, higher systolic blood pressure (odds ratio 1.01, 95% confidence interval 1.003 to 1.02) and diastolic blood pressure (1.01, 1.002 to 1.03) were predictors of retinopathy, after adjustment for albumin excretion rate (1.27, 1.13 to 1.42), haemoglobin A1c (1.08, 1.02 to 1.15), duration of diabetes (1.16, 1.13 to 1.19), age (1.13, 1.08 to 1.17), and height (0.98, 0.97 to 0.99). In a subgroup of 1025 patients with albumin excretion rate below 7.5 μg/min, the cumulative risk of retinopathy at 10 years’ duration of diabetes was higher for those with systolic blood pressure on or above the 90th centile compared with those below the 90th centile (58% v 35%, P=0.03). The risk was also higher for patients with diastolic blood pressure on or above the 90th centile compared with those below the 90th centile (57% v 35%, P=0.005).
Conclusions Both systolic and diastolic blood pressure are predictors of retinopathy and increase the probability of early retinopathy independently of incipient nephropathy in young patients with type 1 diabetes.
doi:10.1136/bmj.a918
PMCID: PMC2526183  PMID: 18728082
14.  The prevalence and severity of diabetic retinopathy, associated risk factors and vision loss in patients registered with type 2 diabetes in Luganville, Vanuatu 
Aim
To determine the prevalence and severity of diabetic retinopathy in patients with type 2 diabetes in Luganville, the second largest town in Vanuatu. Additionally, to investigate risk factors for retinopathy and the effect of retinopathy on visual acuity (VA) within this group.
Method
All 83 registered patients with type 2 diabetes in Luganville, a town of 13 121 people, were invited for an interview and anthropometric measurements. A questionnaire including assessment of hypertension and glycaemic control, which are known risk factors for diabetic retinopathy, was administered. This sample accounted for approximately 1.07% of Luganville's adult population. Presenting VA was measured. The retina was photographed with a non‐mydriatic fundus camera and images later independently graded for the extent of retinopathy.
Results
68 (82%) of the 83 patients attended. The mean (SD) age was 54 (11) years and 31 (46%) were male. Diabetic retinopathy was present in 36 (52.9%) of the sample. Sight‐threatening retinopathy requiring urgent referral was present in 15 (22.1%) patients. Presenting VA was worse than 6/12 in the better eye in n = 32 (47%) and in up to half of these cases the principal cause was retinopathy. In addition, four people had uniocular blindness resulting from diabetes. The mean body mass index was lower in those patients with diabetes with retinopathy than in those without (p = 0.010), but there were no other significant differences between the two groups and, specifically, no difference in the frequency of retinopathy risk factors. 42 (61.8%) patients had hypertension (⩾135/85 mm Hg) or were taking antihypertensive therapy.
Conclusions
The prevalence of registered patients with diabetes in Luganville's adult population was 1.07%. Diabetic retinopathy was highly prevalent in the sample (in 36, 52.9%), and in 15 (22.1%) there was a significant threat to sight, with up to 25% of the sample possibly already affected by decreased VA or blindness resulting from diabetes‐related eye disease. Retinopathy risk factors were also prevalent. A diabetes screening programme with baseline ophthalmic assessment and follow‐up are urgently needed to enable timely intervention and treatment.
doi:10.1136/bjo.2006.104174
PMCID: PMC1994739  PMID: 17077115
15.  Prevalence and risk factors for diabetic retinopathy in rural India. Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study III (SN-DREAMS III), report no 2 
Objective
The study was aimed at estimating the prevalence of type 2 diabetes mellitus and diabetic retinopathy in a rural population of South India.
Design
A population-based cross-sectional study.
Participants
13 079 participants were enumerated.
Methods
A multistage cluster sampling method was used. All eligible participants underwent comprehensive eye examination. The fundi of all patients were photographed using 45°, four-field stereoscopic digital photography, and an additional 30° seven-field stereo digital pairs were taken for participants with diabetic retinopathy. The diagnosis of diabetic retinopathy was based on Klein's classification.
Main outcome measures
Prevalence of diabetes mellitus and diabetic retinopathy and associated risk factors.
Results
The prevalence of diabetes in the rural Indian population was 10.4% (95% CI 10.39% to 10.42%); the prevalence of diabetic retinopathy, among patients with diabetes mellitus, was 10.3% (95% CI 8.53% to 11.97%). Statistically significant variables, on multivariate analysis, associated with increased risk of diabetic retinopathy were: gender (men at greater risk; OR 1.52; 95% CI 1.01 to 2.29), use of insulin (OR 3.59; 95% CI 1.41 to 9.14), longer duration of diabetes (15 years; OR 6.01; 95% CI 2.63 to 13.75), systolic hypertension (OR 2.14; 95% CI 1.20 to 3.82), and participants with poor glycemic control (OR 3.37; 95% CI 2.13 to 5.34).
Conclusions
Nearly 1 of 10 individuals in rural South India, above the age of 40 years, showed evidence of type 2 diabetes mellitus. Likewise, among participants with diabetes, the prevalence of diabetic retinopathy was around 10%; the strongest predictor being the duration of diabetes.
doi:10.1136/bmjdrc-2013-000005
PMCID: PMC4212556  PMID: 25452856
Retinopathy; Incidence
16.  Can the Retinal Screening Interval Be Safely Increased to 2 Years for Type 2 Diabetic Patients Without Retinopathy? 
Diabetes Care  2012;35(8):1663-1668.
OBJECTIVE
In the U.K., people with diabetes are typically screened for retinopathy annually. However, diabetic retinopathy sometimes has a slow progression rate. We developed a simulation model to predict the likely impact of screening patients with type 2 diabetes, who have not been diagnosed with diabetic retinopathy, every 2 years rather than annually. We aimed to assess whether or not such a policy would increase the proportion of patients who developed retinopathy-mediated vision loss compared with the current policy, along with the potential cost savings that could be achieved.
RESEARCH DESIGN AND METHODS
We developed a model that simulates the progression of retinopathy in type 2 diabetic patients, and the screening of these patients, to predict rates of retinopathy-mediated vision loss. We populated the model with data obtained from a National Health Service Foundation Trust. We generated comparative 15-year forecasts to assess the differences between the current and proposed screening policies.
RESULTS
The simulation model predicts that implementing a 2-year screening interval for type 2 diabetic patients without evidence of diabetic retinopathy does not increase their risk of vision loss. Furthermore, we predict that this policy could reduce screening costs by ∼25%.
CONCLUSIONS
Screening people with type 2 diabetes, who have not yet developed retinopathy, every 2 years, rather than annually, is a safe and cost-effective strategy. Our findings support those of other studies, and we therefore recommend a review of the current National Institute for Health and Clinical Excellence (NICE) guidelines for diabetic retinopathy screening implemented in the U.K.
doi:10.2337/dc11-2282
PMCID: PMC3402259  PMID: 22566535
17.  Event Rates, Hospital Utilization, and Costs Associated with Major Complications of Diabetes: A Multicountry Comparative Analysis 
PLoS Medicine  2010;7(2):e1000236.
Philip Clarke and colleagues examined patient-level data for over 11,000 participants with type 2 diabetes from 20 countries and find that major complications of diabetes significantly increased hospital use and costs across settings.
Background
Diabetes imposes a substantial burden globally in terms of premature mortality, morbidity, and health care costs. Estimates of economic outcomes associated with diabetes are essential inputs to policy analyses aimed at prevention and treatment of diabetes. Our objective was to estimate and compare event rates, hospital utilization, and costs associated with major diabetes-related complications in high-, middle-, and low-income countries.
Methods and Findings
Incidence and history of diabetes-related complications, hospital admissions, and length of stay were recorded in 11,140 patients with type 2 diabetes participating in the Action in Diabetes and Vascular Disease (ADVANCE) study (mean age at entry 66 y). The probability of hospital utilization and number of days in hospital for major events associated with coronary disease, cerebrovascular disease, congestive heart failure, peripheral vascular disease, and nephropathy were estimated for three regions (Asia, Eastern Europe, and Established Market Economies) using multiple regression analysis. The resulting estimates of days spent in hospital were multiplied by regional estimates of the costs per hospital bed-day from the World Health Organization to compute annual acute and long-term costs associated with the different types of complications. To assist, comparability, costs are reported in international dollars (Int$), which represent a hypothetical currency that allows for the same quantities of goods or services to be purchased regardless of country, standardized on purchasing power in the United States. A cost calculator accompanying this paper enables the estimation of costs for individual countries and translation of these costs into local currency units. The probability of attending a hospital following an event was highest for heart failure (93%–96% across regions) and lowest for nephropathy (15%–26%). The average numbers of days in hospital given at least one admission were greatest for stroke (17–32 d across region) and heart failure (16–31 d) and lowest for nephropathy (12–23 d). Considering regional differences, probabilities of hospitalization were lowest in Asia and highest in Established Market Economies; on the other hand, lengths of stay were highest in Asia and lowest in Established Market Economies. Overall estimated annual hospital costs for patients with none of the specified events or event histories ranged from Int$76 in Asia to Int$296 in Established Market Economies. All complications included in this analysis led to significant increases in hospital costs; coronary events, cerebrovascular events, and heart failure were the most costly, at more than Int$1,800, Int$3,000, and Int$4,000 in Asia, Eastern Europe, and Established Market Economies, respectively.
Conclusions
Major complications of diabetes significantly increase hospital use and costs across various settings and are likely to impose a high economic burden on health care systems.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, nearly 250 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone produced by the pancreas. Blood sugar control fails in people with diabetes because they make no insulin (type 1 diabetes) or, more commonly, because the fat and muscle cells that usually respond to insulin by removing excess sugar from the blood have become insulin insensitive (type 2 diabetes). Type 2 diabetes can be prevented and controlled by eating a healthy diet and exercising regularly. It can also be treated with drugs that help the pancreas make more insulin or that increase insulin sensitivity. Major long-term complications of diabetes include kidney failure and an increased risk of cardiovascular problems such as heart attacks, heart failure, stroke, and problems with the blood vessels in the arms and legs. Because of these complications, the life expectancy of people with diabetes is about ten years shorter than that of people without diabetes.
Why Was This Study Done?
Diabetes imposes considerable demands on health care systems but little is known about the direct medical costs associated with treating this chronic disease in low- and middle-income countries where more than three-quarters of affected people live. In particular, although estimates have been made of the overall resources devoted to the treatment of diabetes, very little is known about how the different long-term complications of diabetes contribute to health care costs in different countries. Public-health experts and governments need this information to help them design effective and sustainable policies for the prevention and treatment of diabetes. In this study, the researchers estimate the resource use associated with diabetes-related complications in three economic regions using information collected in the Action in Diabetes and Vascular Disease (ADVANCE) study. This multinational clinical trial is investigating how drugs that control blood pressure and blood sugar levels affect the long-term complications of diabetes.
What Did the Researchers Do and Find?
The researchers recorded diabetes-related complications, hospital admissions for these complications, and length of hospital stays in 11,140 patients with severe diabetes from 20 countries who participated in the ADVANCE study. They used “multiple regression analysis” to estimate the number of days spent in hospital for diabetes-related complications in Asia, Eastern Europe, and the Established Market Economies (Canada, Australia, New Zealand, and several Western European countries). Finally, they calculated the economic costs of each complication using regional estimates of the costs per bed-day from the World Health Organization's CHOICE project (CHOosing Interventions that are Cost Effective). Nearly everyone in the study who developed heart failure attended a hospital, but only 15%–26% of people attended a hospital for kidney problems. The chances of hospitalization for any complication were lowest in Asia and highest in the Established Market Economies; conversely, lengths of stay were longest in Asia and shortest in the Established Market Economies. Finally, the estimated annual hospital costs for patients who had a coronary event, stroke, or heart failure were more than Int$1,800, Int$3,000, and Int$4,000 in Asia, Eastern Europe, and the Established Market Economies, respectively (the international dollar, Int$, is a hypothetical currency that has the same purchasing power in all countries), compared to Int$76, Int$156, and Int$296 for patients who experienced none of these events.
What Do These Findings Mean?
Because the ADVANCE trial had strict entry criteria, the findings of this study may not be generalizable to the broader population of people with diabetes. Nevertheless, given the lack of information about the costs associated with diabetes-related complications in low- and middle-income countries, these findings provide important new information about the patterns of hospital resource use and costs in these countries. Specifically, these findings show that the major complications of diabetes greatly increase hospital use and costs in all three economic regions considered and impose a high economic burden on health care systems that is likely to increase as the diabetes epidemic develops. Importantly, these findings should help policy makers anticipate the future health care costs associated with diabetes and should help them evaluate which therapies aimed at preventing diabetes-related complications will reduce these costs most effectively.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000236.
The International Diabetes Federation provides information about all aspects of diabetes
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health care professionals, and the general public (in English and Spanish)
The UK National Health Service also provides information for patients and caregivers about type 2 diabetes (in several languages)
Information about the ADVANCE study is available
The World Health Organization's CHOICE Web site provides information about the analysis of the cost effectiveness of health care interventions
doi:10.1371/journal.pmed.1000236
PMCID: PMC2826379  PMID: 20186272
18.  Gene-Lifestyle Interaction and Type 2 Diabetes: The EPIC InterAct Case-Cohort Study 
PLoS Medicine  2014;11(5):e1001647.
In this study, Wareham and colleagues quantified the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. The authors found that the relative effect of a type 2 diabetes genetic risk score is greater in younger and leaner participants, and the high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
Please see later in the article for the Editors' Summary
Background
Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention.
Methods and Findings
The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10−4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10−3) and waist circumference (p for interaction  = 7.49×10−9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score.
Conclusions
The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, more than 380 million people currently have diabetes, and the condition is becoming increasingly common. Diabetes is characterized by high levels of glucose (sugar) in the blood. Blood sugar levels are usually controlled by insulin, a hormone released by the pancreas after meals (digestion of food produces glucose). In people with type 2 diabetes (the commonest type of diabetes), blood sugar control fails because the fat and muscle cells that normally respond to insulin by removing excess sugar from the blood become less responsive to insulin. Type 2 diabetes can often initially be controlled with diet and exercise (lifestyle changes) and with antidiabetic drugs such as metformin and sulfonylureas, but patients may eventually need insulin injections to control their blood sugar levels. Long-term complications of diabetes, which include an increased risk of heart disease and stroke, reduce the life expectancy of people with diabetes by about ten years compared to people without diabetes.
Why Was This Study Done?
Type 2 diabetes is thought to originate from the interplay between genetic and lifestyle factors. But although rapid progress is being made in understanding the genetic basis of type 2 diabetes, it is not known whether the consequences of adverse lifestyles (for example, being overweight and/or physically inactive) differ according to an individual's underlying genetic risk of diabetes. It is important to investigate this question to inform strategies for prevention. If, for example, obese individuals with a high level of genetic risk have a higher risk of developing diabetes than obese individuals with a low level of genetic risk, then preventative strategies that target lifestyle interventions to obese individuals with a high genetic risk would be more effective than strategies that target all obese individuals. In this case-cohort study, researchers from the InterAct consortium quantify the combined effects of genetic and lifestyle factors on the risk of type 2 diabetes. A case-cohort study measures exposure to potential risk factors in a group (cohort) of people and compares the occurrence of these risk factors in people who later develop the disease with those who remain disease free.
What Did the Researchers Do and Find?
The InterAct study involves 12,403 middle-aged individuals who developed type 2 diabetes after enrollment (incident cases) into the European Prospective Investigation into Cancer and Nutrition (EPIC) and a sub-cohort of 16,154 EPIC participants. The researchers calculated a genetic type 2 diabetes risk score for most of these individuals by determining which of 49 gene variants associated with type 2 diabetes each person carried, and collected baseline information about exposure to lifestyle risk factors for type 2 diabetes. They then used various statistical approaches to examine the combined effects of the genetic risk score and lifestyle factors on diabetes development. The effect of the genetic score was greater in younger individuals than in older individuals and greater in leaner participants than in participants with larger amounts of body fat. The absolute risk of type 2 diabetes, expressed as the ten-year cumulative incidence of type 2 diabetes (the percentage of participants who developed diabetes over a ten-year period) increased with increasing genetic score in normal weight individuals from 0.25% in people with the lowest genetic risk scores to 0.89% in those with the highest scores; in obese people, the ten-year cumulative incidence rose from 4.22% to 7.99% with increasing genetic risk score.
What Do These Findings Mean?
These findings show that in this middle-aged cohort, the relative association with type 2 diabetes of a genetic risk score comprised of a large number of gene variants is greatest in individuals who are younger and leaner at baseline. This finding may in part reflect the methods used to originally identify gene variants associated with type 2 diabetes, and future investigations that include other genetic variants, other lifestyle factors, and individuals living in other settings should be undertaken to confirm this finding. Importantly, however, this study shows that young, lean individuals with a high genetic risk score have a low absolute risk of developing type 2 diabetes. Thus, this sub-group of individuals is not a logical target for preventative interventions. Rather, suggest the researchers, the high absolute risk of type 2 diabetes associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001647.
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals and the general public, including detailed information on diabetes prevention (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and about living with diabetes; it also provides people's stories about diabetes
The charity Diabetes UK provides detailed information for patients and carers in several languages, including information on healthy lifestyles for people with diabetes
The UK-based non-profit organization Healthtalkonline has interviews with people about their experiences of diabetes
The Genetic Landscape of Diabetes is published by the US National Center for Biotechnology Information
More information on the InterAct study is available
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention (in English and Spanish)
doi:10.1371/journal.pmed.1001647
PMCID: PMC4028183  PMID: 24845081
19.  Short Report: Complications Delay in diabetic retinopathy screening increases the rate of detection of referable diabetic retinopathy 
Diabetic Medicine  2013;31(1):439-442.
Aims
To assess whether there is a relationship between delay in retinopathy screening after diagnosis of Type 2 diabetes and level of retinopathy detected.
Methods
Patients were referred from 88 primary care practices to an English National Health Service diabetic eye screening programme. Data for screened patients were extracted from the primary care databases using semi-automated data collection algorithms supplemented by validation processes. The programme uses two-field mydriatic digital photographs graded by a quality assured team.
Results
Data were available for 8183 screened patients with diabetes newly diagnosed in 2005, 2006 or 2007. Only 163 with Type 1 diabetes were identified and were insufficient for analysis. Data were available for 8020 with newly diagnosed Type 2 diabetes. Of these, 3569 were screened within 6 months, 2361 between 6 and 11 months, 1058 between 12 and 17 months, 366 between 18 and 23 months, 428 between 24 and 35 months, and 238 at 3 years or more after diagnosis. There were 5416 (67.5%) graded with no retinopathy, 1629 (20.3%) with background retinopathy in one eye, 753 (9.4%) with background retinopathy in both eyes and 222 (2.8%) had referable diabetic retinopathy. There was a significant trend (P = 0.0004) relating time from diagnosis to screening detecting worsening retinopathy. Of those screened within 6 months of diagnosis, 2.3% had referable retinopathy and, 3 years or more after diagnosis, 4.2% had referable retinopathy.
Conclusions
The rate of detection of referable diabetic retinopathy is elevated in those who were not screened promptly after diagnosis of Type 2 diabetes.
doi:10.1111/dme.12313
PMCID: PMC4232880  PMID: 24093530
20.  Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R) 
Diabetologia  2011;55(3):671-680.
Aims/hypothesis
We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus.
Methods
The study population consisted of 4,994 persons aged ≥67 years, who participated in the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA1c ≥6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses.
Results
The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA1c, insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria.
Conclusions/interpretation
Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.
doi:10.1007/s00125-011-2395-y
PMCID: PMC3269506  PMID: 22134840
Diabetes mellitus; Microalbuminuria; Non-diabetic; Old age; Population sample; Random; Retinopathy
21.  Diabetic retinopathy in people aged 70 years or older. The Oulu Eye Study 
AIMS—To evaluate the presence and severity of diabetic retinopathy and the value of retinopathy screening in people aged 70 years or older.
METHODS—In a population based study on 500 of 560 eligible (89%) people aged 70 years or older, signs of diabetic retinopathy were evaluated through dilated pupils by an ophthalmologist using photographic and/or ophthalmoscopic methods.
RESULTS—23% of the study population (113/500) had diabetes mellitus. Signs of diabetic retinopathy were found in 24 people (21% of the diabetic population). Retinopathy changes were graded as mild to moderate non-proliferative retinopathy (NPDR) in 40 eyes (18 people), severe NPDR (preproliferative) in five eyes (four people), and proliferative in three eyes (two people). Preproliferative or proliferative changes were present in four people (3.5% of the diabetic population) and diabetic maculopathy was diagnosed in nine (8% of the diabetic population). Laser treatment was considered to be indicated in seven people for maculopathy, and in two for proliferative changes. In four people the visual acuity was reduced to a low vision level as a result of diabetic retinopathy.
CONCLUSION—In spite of the high prevalence of diabetes mellitus in the elderly population, the prevalence of vision threatening diabetic retinopathy, particularly proliferative retinopathy, is low. Ophthalmoscopically, reliable information on fundus changes could be obtained in 94%, but photographs were gradable in only 76% of the diabetic population. Therefore, the value of photographic screening for diabetic retinopathy in this age group is poor in comparison with younger age groups.


PMCID: PMC1722143  PMID: 9135385
22.  Retinal blood flow in diabetic retinopathy. 
BMJ : British Medical Journal  1992;305(6855):678-683.
OBJECTIVES--(a) To report on the basic parameters of retinal blood flow in a population of diabetic patients with and without retinopathy and non-diabetic controls; (b) to formulate a haemodynamic model for the pathogenesis of diabetic retinopathy from this and other studies. DESIGN--Laser-Doppler velocimetry and computerised image analysis to determine retinal blood flow in a large cross sectional study. SETTING--Diabetic retinopathy outpatient clinic. SUBJECTS--24 non-diabetic controls and 76 diabetic subjects were studied (63 patients with insulin dependent diabetes, 13 with non-insulin dependent diabetes). Of the diabetic subjects, 12 had no diabetic retinopathy, 27 had background retinopathy, 13 had pre-proliferative retinopathy, 12 had proliferative retinopathy, and 12 had had pan-retinal photocoagulation for proliferative retinopathy. MAIN OUTCOME MEASURES--Retinal blood flow (microliters/min) and conductance (rate of flow per unit of perfusion pressure). RESULTS--In comparison with non-diabetic controls (9.52 microliters/min) and diabetic patients with no diabetic retinopathy (9.12 microliters/min) retinal blood flow was significantly increased in all grades of untreated diabetic retinopathy (background 12.13 microliters/min, pre-proliferative 15.27 microliters/min, proliferative 13.88 microliters/min). There was a significant decrease in flow after pan-retinal photocoagulation in comparison with all the other groups studied (4.48 microliters/min). Conductance of the retinal circulation was higher in the untreated diabetic retinopathy groups. These results were independent of age, sex, type of diabetes, duration of diabetes, glycated haemoglobin concentration, blood glucose concentration, blood pressure, and intraocular pressure. CONCLUSIONS--Retinal blood flow is significantly increased in diabetic retinopathy in comparison with non-diabetic controls and diabetic subjects with no retinopathy. This has implications for controlling hypertension and hyperglycaemia as a strategy in reducing morbidity from diabetic retinopathy.
PMCID: PMC1882919  PMID: 1393111
23.  Quality-assured screening for diabetic retinopathy delivered in primary care in Ireland: an observational study 
The British Journal of General Practice  2013;63(607):e134-e140.
Background
At present, there is no national population-based retinopathy screening programme for people in Ireland who have diabetes, such as those operating in the UK for over a decade.
Aim
To evaluate a community-based initiative that utilised existing resources in general practice and community optometry/ophthalmology services to provide screening for diabetic retinopathy.
Design and setting
Cross-sectional study using electronic ophthalmic patient screening records in community optometry clinics in Cork, Ireland.
Method
A purposive sample of 32 practices was recruited from Diabetes in General Practice, a general practice-led initiative in the South of Ireland. Practices invited all adult patients registered with diabetes to participate in free retinopathy screening (n = 3598), provided by 15 community optometry practices and two community ophthalmologists. Data were recorded on an electronic database used by optometrists and the performance was benchmarked against proposed national standards for retinopathy screening.
Result
In total, 30 practices participated (94%). After 6 months, 49% of patients (n = 1763) had been screened, following one invitation letter and no reminder. Forty-three per cent of those invited consented to their data being used in the study and subsequent analyses are based on that sample (n = 1542). The mean age of the patients screened was 65 years (standard deviation = 13.0 years), 57% were male (n = 884), and 86% had type 2 diabetes (n = 1320). In total, 26% had some level of retinopathy detected (n = 395); 21% had background retinopathy (n = 331), 3% had pre-proliferative retinopathy (n = 53), and 0.7% had proliferative retinopathy (n = 11).
Conclusion
The detection of retinopathy among 26% of those screened highlights the need for a national retinopathy screening programme in Ireland. Significant learning, derived from the implementation of this initiative, will inform the national programme.
doi:10.3399/bjgp13X663091
PMCID: PMC3553639  PMID: 23561692
diabetic retinopathy; general practice; optometry; quality assurance; primary care; screening
24.  Prevalence of diabetic retinopathy in patients with diabetes mellitus diagnosed after the age of 70 years 
AIMS/BACKGROUND—A hospital based prevalence study was undertaken to estimate the prevalence of diabetic retinopathy (DR) in patients diagnosed as having diabetes mellitus after the age of 70 years. The prevalence of visually threatening retinopathy at the time of diagnosis of diabetes was also determined. The association between prevalence of DR and duration of diabetes mellitus, mode of treatment, HbA1c levels, presence of hypertension, and sex of patient was examined and a comparison was drawn between this study and earlier prevalence studies of DR in older type II diabetics.
METHODS—Using data on the Irish Diabetic Retinopathy Register located in the Mater Misericordiae Hospital, Dublin, all patients who were diagnosed as having type II diabetes mellitus after the age of 70 years were invited to attend for ophthalmic review. Medical records were examined to determine the duration of diabetes mellitus, mode of treatment, recent HbA1c levels, and the presence of systemic hypertension.
RESULTS—Of the 150 patients examined, 21 (14%) had some form of DR and 10 of these patients (6.6%) had visually threatening retinopathy or previously treated visually threatening retinopathy. Five patients (3.3%) presented with visually threatening retinopathy at the time of diagnosis of diabetes. Those patients with DR had a significantly higher median duration of diabetes (5.0 years) compared with those patients without DR (3.5 years). A significantly higher proportion of patients with DR required treatment with insulin and a correspondingly lower proportion of patients without DR were controlled on diet alone. There was no significant association between prevalence of DR and HbA1c levels, systemic hypertension, or sex of patient. There was a lower overall prevalence of DR in comparison with earlier studies.
CONCLUSIONS—The prevalence of DR in these elderly type II diabetics is lower than that previously reported in patients with type II disease but a small percentage of patients had visually threatening retinopathy at presentation. Longer duration of diabetes and insulin use were associated with a significantly increased prevalence of DR. All elderly type II diabetic patients require thorough ophthalmic examination near to the time of first presentation and thereafter at regular intervals.


PMCID: PMC1722137  PMID: 9135386
25.  Visual and anatomical outcomes following vitrectomy for complications of diabetic retinopathy: The DRIVE UK Study 
Eye  2012;26(4):510-516.
Introduction
End-stage diabetic eye disease is an important cause of severe visual impairment in the working-age group. With the increasing availability of refined surgical techniques as well as the early diagnosis of disease because of screening, one would predict that the prevalence of this condition is decreasing and the visual outcome is improving.
Aim
To study the prevalence and visual outcome following vitrectomy for complications of diabetic retinopathy.
Materials and methods
This study identified the patients who underwent vitrectomy from January 2007 to December 2009 because of diabetes-related complications in South East London. Data collected included baseline demographics, best-corrected visual acuity, indication for the vitrectomy, complication, outcome, and duration of follow-up.
Results
The prevalence of people requiring vitrectomy who are registered in the diabetes register of this region was 2 per 1000 people with diabetes. Vitrectomy was required in 185 eyes of 158 patients during this period. These included 83 Caucasians, 51 Afro-Caribbeans, 17 South Asians, and 7 from other ethnic groups. There were 58 patients with type I diabetes and 100 with type II, with a mean duration of diabetes of 23 and 16.5 years, respectively. The reason for vitrectomy included tractional retinal detachment (TRD) in 109 eyes, non-clearing vitreous haemorrhage (NCVH) in 68 eyes, and other causes in 8 eyes. In all, 50% of the eyes with TRD and NCVH, and 87% of the eyes with NCVH improved by at least three ETDRS lines at 12 months. Poor predictors of visual success included longer duration of diabetes (OR: 0.69), use of insulin (OR: 0.04), presence of ischaemic heart disease (OR: 0.04), delay in surgery (OR: 0.59), and the failure to attend clinic appointments (OR: 0.58). Preoperative use of intravitreal bevacizumab in eyes with TRD undergoing vitrectomy showed a marginal beneficial effect on co-existent maculopathy (P=0.08) and required less laser intervention post procedure, but did not affect the number of episodes of late-onset vitreous haemorrhage post vitrectomy (P=0.81).
Conclusion
Visual outcome has improved significantly in eyes with complications due to diabetic retinopathy compared with the previously reported Diabetic Vitrectomy Study.
doi:10.1038/eye.2011.321
PMCID: PMC3325558  PMID: 22222268
pars plana vitrectomy; proliferative diabetic retinopathy; tractional retinal detachment; non-clearing vitreous haemorrhage

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