To estimate the ten-year incidence of dry eye in an older population and examine its association with various risk factors.
The 43 to 86 year old population of Beaver Dam, WI, was examined in 1988 to ...1990 (n = 4926) and 1993 to 1995 (n = 3722). Dry eye data were first collected in 1993 to 1995. Subsequent examinations or interviews occurred in 1998 to 2000 (n = 2827) and 2003 to 2005 (n = 2124). The incidence cohort comprised 2414 subjects not reporting dry eye in 1993 to 1995. Risk factor information, ascertained in 1993 to 1995, included demographics, medical history, cardiovascular disease risk factors, medications, and life-style factors. Ten-year cumulative incidence was estimated by the product-limit method.
Over the 10-year period, 482 subjects developed a history of dry eye for an incidence of 21.6% (95% confidence interval, 19.9 to 23.3%). Incidence increased significantly (p < 0.001) with age. Incidence was greater in women (25.0%) than men (17.2%, p < 0.001). After adjusting for age, incidence was greater (p < 0.05) in subjects with arthritis, allergy or thyroid disease not treated with hormone, using antihistamines, antianxiety medications, antidepressants, oral steroids or vitamins, and poorer self-rated health. Incidence was less (p < 0.05) in subjects consuming alcohol. It was not significantly associated with blood pressure, hypertension, serum total or high density lipoprotein cholesterol, body mass, diabetes, gout, osteoporosis, cardiovascular disease, smoking, caffeine use, or taking calcium channel blockers or anticholesterol medications. In a multivariable model with time-varying covariates, increased incidence was associated with age, female gender, poorer self-rated health, antidepressant or oral steroid use, and thyroid disease untreated with hormone. It was lower for those using angiotensin-converting enzyme inhibitors or with a sedentary lifestyle.
Dry eye incidence is substantial. However, there are few associated risk factors. Some drugs (antihistamines, antianxiety drugs, antidepressants, oral steroids) are associated with greater risk, while angiotensin-converting enzyme inhibitors may be associated with lower risk.
Diabetes mellitus is a disease with considerable morbidity and mortality worldwide. Breakdown of the blood–retinal barrier and leakage from the retinal vasculature leads to diabetic macular edema, an ...important cause of vision loss in patients with diabetes. Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes, insulin therapies for control of glucose metabolism cannot prevent long-term retinal complications. The phenomenon of temporary paradoxical worsening of diabetic macular edema after insulin treatment has been observed in a number of studies. In prospective studies on non–insulin-dependent (type 2) diabetes mellitus patients, a change in treatment from oral drugs to insulin was often associated with a significant increased risk of retinopathy progression and visual impairment. Although insulin therapies are critical for regulation of the metabolic disease, their role in the retina is controversial. In this study with diabetic mice, insulin treatment resulted in increased vascular leakage apparently mediated by betacellulin and signaling via the epidermal growth factor (EGF) receptor. In addition, treatment with EGF receptor inhibitors reduced retinal vascular leakage in diabetic mice on insulin. These findings provide unique insight into the role of insulin signaling in mediating retinal effects in diabetes and open new avenues for therapeutics to treat the retinal complications of diabetes mellitus.
To describe the relationship of retinal arteriolar and venular calibers to the long-term incidence of microvascular and macrovascular complications in people with type 2 diabetes.
Population-based ...prospective study.
One thousand three hundred seventy persons diagnosed to have diabetes at > or =30 years of age in south central Wisconsin participated in the baseline examination from 1980 to 1982, 987 in the 4-year follow-up, and 533 in the 10-year follow-up.
Computer-assisted grading was used to determine the average caliber of retinal arterioles (central retinal arteriolar equivalent CRAE) and retinal venules (central retinal venular equivalent CRVE) at all examinations.
Incidence and progression of diabetic retinopathy; incidence of proliferative diabetic retinopathy and macular edema; incidence of nephropathy, neuropathy, and lower extremity amputation; and ischemic heart disease, stroke, and overall mortality.
While adjusting for other factors, smaller CRAE was associated with the 14-year cumulative incidence of lower extremity amputation (odds ratio OR, first vs. second to fourth quartiles, 2.20; 95% confidence interval CI, 1.14-4.24; P = 0.02), 22-year all-cause mortality (hazard ratio HR, 1.18; 95% CI, 1.02-1.38; P = 0.03), and 22-year stroke mortality (HR, 1.47; 95% CI, 1.04-2.07; P = 0.03) but not with the other end points. Larger CRVE was associated with the 14-year incidence of diabetic nephropathy (OR, fourth vs. first to third quartiles, 2.08; 95% CI, 1.47-2.94; P<0.001) and 22-year stroke mortality (HR, 1.71; 95% CI, 1.20-2.44; P = 0.003) but with none of the other end points.
Retinal vessel caliber is independently associated with risk of incident nephropathy, lower extremity amputation, and stroke mortality in persons with type 2 diabetes. Measurement of retinal vessel caliber from photographs may provide additional information for the prediction of these events.
The purpose of the study was to estimate the 14-year incidence of visual loss in a diabetic population and to examine its relationship to potential risk factors.
Cohort study.
A population-based ...sample of younger onset diabetic persons diagnosed younger than 30 years of age and taking insulin (n = 880) were examined at baseline, 4 years, 10 years, and 14 years.
Visual acuity (VA) as measured by the Early Treatment Diabetic Retinopathy Study protocol was performed.
Visual impairment (VI), defined as a VA of 20/40 or worse in the better eye; blindness, defined as a VA of 20/200 or worse in the better eye; and doubling of the visual angle were measured.
Cumulative 14-year incidences of VI, doubling of the visual angle, and blindness were 12.7%, 14.2%, and 2.4%, respectively. In univariate analyses, loss of vision as measured by doubling of the visual angle is associated with older age, longer duration of diabetes, higher glycosylated hemoglobin, higher systolic and diastolic blood pressure, presence of proteinuria, more pack-years smoked, presence of macular edema, and more severe retinopathy. In logistic regression analyses, incidence of doubling of the visual angle is associated independently with retinopathy (odds ratio OR, 1.07; 95% confidence interval CI, 1.03, 1.11 for each level), glycosylated hemoglobin (OR, 1.46; 95% CI, 1.28, 1.66 for each 1%), proteinuria (OR, 2.32; 95% CI, 1.39, 3.88 for presence), and age (OR, 1.45; 95% CI, 1.20, 1.75 for 10 years). In addition, a change in glycosylated hemoglobin from baseline to the 4-year examination is associated with loss of vision (OR, 1.15; 95% CI, 1.02, 1.30 for a 1% increase).
Loss of vision continues to be significant in persons with diabetes. These results suggest that prevention of retinopathy through control of glycemia will have a beneficial effect on visual outcome.
To examine the 14-year incidence and progression of diabetic retinopathy and macular edema and its relation to various risk factors.
Population-based incidence study.
The study was conducted in an ...11-county area in southern Wisconsin.
Six hundred thirty-four insulin-taking persons with diabetes diagnosed before age 30 years participated in baseline, 4-year, 10-year, and 14-year follow-up examinations.
The 14-year progression of retinopathy, progression to proliferative retinopathy, and incidence of macular edema were detected by masked grading of stereoscopic color fundus photographs using the modified Airlie House classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme.
The 14-year rate of progression of retinopathy was 86%, regression of retinopathy was 17%, progression to proliferative retinopathy was 37%, and incidence of macular edema was 26%. Progression of retinopathy was more likely with less severe retinopathy, being male, having higher glycosylated hemoglobin or diastolic blood pressure at baseline, an increase in the glycosylated hemoglobin level, and an increase in diastolic blood pressure level from the baseline to the 4-year follow-up. Increased risk of proliferative retinopathy or incidence of macular edema was associated with more severe baseline retinopathy, higher glycosylated hemoglobin at baseline, and an increase in the glycosylated hemoglobin between the baseline and 4-year follow-up examination. The increased risk of proliferative retinopathy was associated with the presence of hypertension at baseline, whereas the increased risk of a participant having macular edema develop was associated with the presence of gross proteinuria at baseline. Lower glycosylated hemoglobin at baseline was associated with improvement in retinopathy.
These data suggest relatively high 14-year rates of progression of retinopathy and incidence of macular edema. These data also suggest that a reduction of hyperglycemia and hypertension may result in a beneficial decrease in the progression to proliferative retinopathy.
To describe retinal vascular caliber and correlates in people with type 2 diabetes.
Population-based study.
Thirteen hundred seventy persons diagnosed to have diabetes at or after 30 years of age in ...an 11-county area in south central Wisconsin from 1980 to 1982.
Retinal photographs of 7 standard fields were taken; light box grading was done to determine retinopathy severity. Computer-assisted grading was done from a digitized image of field 1 to determine the central retinal arteriolar equivalent (CRAE; arteriolar caliber) and central retinal venular equivalent (CRVE; venular caliber).
Retinal arteriolar and venular calibers.
In multivariable analyses in persons with panretinal photocoagulation excluded, while controlling for refractive error, CRAE was associated independently with age (per 10 years, beta = -2.0 microm), mean arterial blood pressure (BP) (per 10 mmHg, beta = -2.2 microm), smoking status (current vs. never smoked, beta = 5.6 microm), and intraocular pressure (IOP) (per 1 mmHg, beta = 0.2 microm). The CRVE was associated independently with age (per 10 years, beta = -2.5 microm), mean arterial BP (per 10 mmHg, beta = -2.1 microm), smoking status (current vs. never smoked, beta = 11.6 microm), pack-years smoked (per 10 pack-years, beta = 1.0 microm), body mass index (per kg/m2, beta = 0.3 mm), pulse rate (per 10 beats/minute, beta = 1.5 microm), retinopathy severity (per 1 level, beta = 1.05 microm), and IOP (per 10 mmHg, beta = -0.5 microm). Smaller CRAEs and CRVEs were found in eyes with panretinal photocoagulation treatment than in eyes without such treatment.
In persons with type 2 diabetes, variations in retinal vascular caliber are related to various systemic and ocular factors. Understanding these relationships may provide further insights into early retinal vascular changes in diabetes.
To examine the association of performance-based measures of visual functioning with the occurrence of falls, fractures, physical outcomes, and limitations in an older population.
A population-based ...study of Beaver Dam, Wisconsin, of persons who were 43 to 86 years of age was performed from 1988 through 1990 (n = 4926), 1993 through 1995 (n = 3722), and 1998 through 2000 (n = 2962).
Participants in the Beaver Dam Eye Study at the 1993 through 1995 examination.
Historical information was obtained by interview at each examination. Current binocular visual acuity, best-corrected visual acuity, near acuity, log contrast sensitivity, and visual sensitivity (threshold) were measured by standard protocols at the 5-year follow-up (1993–1995) of the cohort. Outcomes were ascertained at the 10-year follow-up examination (1998–2000).
History of physical limitations, falls, fractures, and change in time to walk a measured course.
The incidence of outcomes was as follows: nursing home residence, 4.6%; not driving at night, 9.7%; any fracture, 11.0%; two or more falls, 7.5%; fear of falling, 11.9%; and use of walking aids, 3.6%. The increase in time to walk a 10-foot course was 0.14 seconds. Age was associated with higher incidence of virtually every outcome and with time to walk a measured course. Incidence of not driving at night, any fracture, and fear of falling were more common in women after adjusting for age. We evaluated the relationship of outcomes to current binocular vision, best-corrected vision, near vision, contrast sensitivity, and visual sensitivity (threshold), as measured by perimetry (the latter four for the better eye). When controlling for confounders in multivariable models, the odds ratios of nursing home placement for the poorest categories of function were 3.20 (95% confidence interval CI, 1.85, 5.56) for current binocular vision, 4.23 (95% CI, 2.34, 7.64) for best-corrected visual acuity in the better eye, 5.00 (95% CI, 2.28, 10.94) for near vision, and 2.40 (95% CI, 1.46, 3.92) for contrast sensitivity. The odds ratio for not driving at night for the poorest category of visual sensitivity was 2.22 (95% CI, 1.31, 3.75). The odds ratios for any fractures for the categories of poorest function were 1.75 (95% CI, 1.02, 2.99) for current binocular acuity, 2.00 (95% CI, 1.10, 3.62) for best-corrected vision in the better eye, 3.04 (95% CI, 1.34, 6.86) for near vision, and 1.64 (95% CI, 1.05, 2.56) for visual sensitivity. The odds ratios for 2 or more falls in the past year for the poorest categories of visual function were 2.02 (95% CI, 1.13, 3.63) for current binocular acuity and 1.85 (95% CI, 1.10, 3.12) for visual sensitivity. The incidence of fear of falling was associated with the poorest category of best-corrected acuity (odds ratio, 2.95; 95% CI, 1.52, 5.70), and use of walking aids was associated with visual sensitivity (odds ratio, 3.51; 95% CI, 1.72, 7.18). Change in time to walk the measured course was not significantly associated with any of the visual functions.
Visual function is associated with some physical outcomes and limitations 5 years later in middle- to older-aged adults. These associations are likely to be related, in part, to the presence of other medical conditions.
Hyperglycemia is implicated in the development and progression of microvascular complications in type 1 diabetes. In contrast, the association between hyperglycemia and macrovascular complications or ...mortality in type 1 diabetes is not clear. The authors studied a population-based cohort of 879 individuals with type 1 diabetes from Wisconsin, free of cardiovascular disease and end-stage renal disease at the baseline examination (1980–1982). The main outcome of interest was all-cause (n = 201) and cardiovascular (n = 132) mortality as of December 31, 2001. Elevated glycosylated hemoglobin levels were associated with all-cause and cardiovascular mortality, independent of duration of diabetes, smoking, hypertension, and proteinuria. The multivariable relative risks comparing the highest quartile of glycosylated hemoglobin (≥12.1%) with the lowest quartile (≤9.4%) were 2.42 (95% confidence interval: 1.54, 3.82; p-trend = 0.0006) for all-cause mortality and 3.28 (95% confidence interval: 1.77, 6.08; p-trend < 0.0001) for cardiovascular mortality. This association was present among both sexes and persisted in subgroup analyses by categories of diabetes duration, smoking, body mass index, proteinuria, and retinopathy. These data suggest that hyperglycemia is associated with all-cause and cardiovascular mortality among individuals with type 1 diabetes.
OBJECTIVE:--The purpose of this study was to examine the relationship of glycemic control and exogenous and endogenous insulin levels with all-cause and cause-specific mortality (ischemic heart ...disease and stroke) in an older-onset diabetic population. RESEARCH DESIGN AND METHODS--The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an ongoing, prospective, population-based cohort study of individuals with diabetes first examined in 1980-1982. A stratified sample of all individuals with diabetes diagnosed at 30 years of age or older was labeled "older-onset" (n = 1,370). Those participating in the 1984-1986 examination phase (n = 1,007) were included in the analysis. Endogenous insulin was determined by measurements of plasma C-peptide (in nanomoles per liter), and exogenous insulin was calculated in units per kilogram per day. Glycemic control was determined by levels of glycosylated hemoglobin (HbA₁). RESULTS:--After 16 years of follow-up, 824 individuals died (all-cause mortality); 358 deaths involved ischemic heart disease and 137 involved stroke. C-peptide and HbA₁ were significantly associated with all-cause and ischemic heart disease mortality in our study. The hazard ratio (95% CI) values for all-cause mortality were 1.12 (1.07-1.17) per 1% increase in HbA₁, 1.20 (0.85-1.69) per 1 unit · kg⁻¹ · day⁻¹ increase in exogenous insulin, and 1.15 (1.04-1.29) per 1 nmol/l increase in C-peptide and for ischemic heart disease mortality were 1.14 (1.06-1.22), 1.50 (0.92-2.46), and 1.19 (1.02-1.39) for HbA₁, exogenous insulin, and C-peptide, respectively, after adjusting for relevant confounders. C-peptide was associated with stroke mortality only among men (1.65 1.07-2.53). CONCLUSIONS:--Our results show that individuals with higher endogenous insulin levels are at higher risk of all-cause, ischemic heart disease, and stroke mortality.
The aim of this report is to describe the prevalence of retinopathy and its associations with atherosclerosis and vascular risk factors in people with diabetes.
Cross-sectional study.
Persons with ...diabetes, having gradable fundus photographs, from a biracial population-based cohort of adults (ages 51–72 years), and living in four United States communities (Forsyth County, North Carolina; the city of Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland) were studied from 1993 to 1995.
Lesions typical of diabetic retinopathy were detected by grading a 45° color fundus photograph of one eye of each participant, using a modification of the Airlie House classification system.
Severity of diabetic retinopathy (none, minimal nonproliferative, moderate nonproliferative, severe nonproliferative, and proliferative) and macular edema.
Retinopathy was detected in 328/1600 (20.5%) of those with diabetes; 114/1724 (6.6%) had hard exudate, 28/1600 (1.8%) had proliferative diabetic retinopathy, and 27/1662 (1.6%) had macular edema. The prevalence of diabetic retinopathy was higher in blacks (27.7%) compared with whites (16.7%). Controlling for duration of diabetes, serum glucose, systolic blood pressure, and type of diabetes medications taken, severity of retinopathy was associated with carotid artery intima-media wall thickness (odds ratio OR/0.1-mm thickness 1.09; 95% confidence interval CI, 1.01, 1.17;
P = 0.01), serum albumin (OR/0.1 g/dl 0.94; 95% CI, 0.88, 0.99;
P = 0.02), but not race (OR blacks versus whites,1.24; 95% CI, 0.88, 1.75;
P = 0.21). Severity of diabetic retinopathy was not associated with coronary artery disease or stroke history or any of the plasma lipids studied. Controlling for age, gender, duration of diabetes, serum glucose, and type of diabetes medications taken, the presence of retinal hard exudates was associated with plasma low-density lipoprotein cholesterol (OR/10 mg/dl 1.18; 95% CI, 1.09, 1.29;
P < 0.001), and plasma Lp(a) (OR/10 mg/dl 1.02; 95% CI, 1.00, 1.05;
P = 0.04) but not race or blood pressure.
These data suggest that plasma lipids are associated with the presence of hard exudate and that carotid artery intima-media wall thickness is associated with retinopathy, but other manifestations of atherosclerosis and most of its risk factors are not associated with severity of diabetic retinopathy.
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