Biomedical subjects
B E Klein
Publications and source records attributed to B E Klein.
Diet and nuclear lens opacities.
Relations between diet and nuclear opacities in the lens of the eye were investigated in a population-based cohort of middle-aged and older adults who lived in Beaver Dam, Wisconsin. Nuclear sclerosis was assessed from photographs of the lens taken during 1988-1990 in 1,919 persons in the Beaver Dam Eye Study. Diets in the past (1978-1980) were assessed retrospectively with the use of a food frequency questionnaire in home interviews. Relations with intake of foods and nutrients were evaluated using logistic regression analyses. In men, after controlling for age, smoking, and heavy drinking, intakes of numerous nutrients in the highest versus lowest quintile were associated with 40-50 percent reduced odds of more severe nuclear sclerosis. Relations with some nutrients (vitamins A, C, and E, riboflavin, thiamin, niacin) were at least partly explained by previously identified inverse associations with multivitamin use. Relations with other nutrients (folate, alpha-carotene, and dietary fiber) appeared to reflect associations with intake of foods, particularly vegetables. Inverse associations with individual nutrients and foods were often weaker or nonexistent in women. These data indicate that the intake of vitamin supplements (in men and women) and certain foods (particularly in men) may explain associations of several nutrients with risk for nuclear sclerosis.
Factors associated with having eye examinations in persons with diabetes.
OBJECTIVES: To estimate compliance with guidelines on ocular examinations for diabetic persons, to examine factors that affect compliance, and to determine reasons for noncompliance. DESIGN: Cross-sectional population study. SETTING: Primary care setting. PATIENTS: The population is 765 diabetic persons with younger onset and 533 with older onset who participated in the 1990 to 1992 follow-up examination of the Wisconsin Epidemiologic Study of Diabetic Retinopathy. MEASUREMENTS: A medical history was taken in which subjects were asked about eye examinations by ophthalmologists and optometrists. RESULTS: Sixty-four percent of the younger-onset group and 62% of the older-onset group had had a dilated eye examination in the previous year. Persons in both groups were more likely to have had a dilated examination if they had a longer duration of diabetes, more severe retinopathy, a history of glaucoma or cataract, and health insurance that covered eye examinations. Persons with younger-onset diabetes were more likely to have had an examination if they were older, were visually impaired, and had more education or higher income. Persons in the older-onset group were more likely to have had an examination if they were female or taking insulin. In those not having an eye examination, 79% and 71% of the younger- and older-onset groups, respectively, reported not having had one because they had no problems with their eyes, and 31% and 35% reported not having been told they needed one. Thirty-two percent and 11% said they were too busy, and 30% and 12% said they could not afford an examination. CONCLUSIONS: Diabetic persons should be educated as to the need for eye care; the results show that barriers to eye care exist in the form of affordability and lack of time.
Age-related eye disease and survival. The Beaver Dam Eye Study.
OBJECTIVE: To investigate the relationship of cataract, age-related maculopathy, glaucoma, and visual impairment to survival in the population-based Beaver Dam Eye Study. DESIGN: In this population-based study, visual acuity was measured with use of standardized protocols. At baseline, stereoscopic color fundus photographs and color slit-lamp and retroillumination photographs were graded in a masked fashion to determine the presence of age-related maculopathy and cataract, respectively. Deaths were ascertained by contacting family members, daily review of obituaries, and use of vital status records. PARTICIPANTS: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, were identified and examined between 1988 and 1990. RESULTS: From the time of the baseline examination until a median of 4 years later, 9.5% (467/4926) of the population had died. After correcting for age and sex, poorer survival was associated with more severe nuclear sclerosis (5-year survival of 88.9% for the most severe compared with 94.1% for the least severe stage) and visual impairment (5-year survival of 87.5% for impaired compared with 91.8% for unimpaired vision). However, after controlling for systemic factors, only more severe nuclear sclerosis in people without diabetes was significantly associated with poorer survival (hazard ratio per level of severity, 1.19; 95% confidence interval, 1.00 to 1.40). CONCLUSIONS: These data suggest that after controlling for age and sex, nuclear sclerotic cataract severity, cataract surgery, and visual impairment are risk indicators for poorer survival. Cortical cataract, posterior subcapsular cataract, glaucoma, and age-related maculopathy were unrelated to poorer survival.
A cohort study of the relationship of diabetic retinopathy to blood pressure.
OBJECTIVE: To determine whether blood pressure at baseline was associated with incidence or progression of diabetic retinopathy during a 10-year interval in a population-based cohort. PARTICIPANTS: A probability sample of all persons receiving primary care for diabetes in an 11-county area of southern Wisconsin were invited to participate in the study examinations in 1980 to 1982, 1984 to 1986, and 1990 to 1992. PROCEDURES: Blood pressure measurements, height, weight, ocular photographs, and glycosylated hemoglobin measurements were obtained and ocular examinations and a medical history interview were performed at each evaluation. MAIN OUTCOME MEASURES: Fundus photographs of seven standard photographic fields were obtained and graded according to the modified Airlie House Classification scheme. End points were incidence, any progression, or progression to proliferative diabetic retinopathy. RESULTS: At the baseline examination, 996 subjects were determined to have younger-onset diabetes and 1370 subjects had older-onset diabetes compared with 891 and 987, respectively, at the 4-year follow-up examination and 765 and 533, respectively, at the 10-year follow-up examination. In discrete linear logistic analyses, a 10-mm Hg increase in systolic blood pressure was significantly associated with incidence of retinopathy in subjects with younger-onset diabetes 10 years after the baseline examination (odds ratio, 1.27; 95% confidence interval, 1.03 to 1.57). No consistent association of blood pressure and retinopathy in subjects with older-onset diabetes was observed. Mortality did not affect the relationship of blood pressure and retinopathy. CONCLUSION: Increased systolic blood pressure at baseline was associated with a modest subsequent increased risk of incidence of diabetic retinopathy in subjects with younger-onset diabetes.
Dietary fat and age-related maculopathy.
OBJECTIVE: To describe the relationship between type and level of fat in the diet and the prevalence of age-related maculopathy. DESIGN: Retrospective population-based study. SETTING AND PARTICIPANTS: Residents of Beaver Dam, Wis, between the ages of 45 and 84 years, participating in the Beaver Dam Eye Study and Nutritional Factors in Eye Disease Study. DATA COLLECTION: Presence and severity of age-related maculopathy were determined from masked grading of fundus photographs taken from 1988 through 1990. Diets in the past (1978 through 1980) were assessed retrospectively using a food frequency questionnaire during in-person home interviews. RESULTS: Persons with intake of saturated fat and cholesterol in the highest compared with the lowest quintile had 80% and 60% increased odds for early age-related maculopathy, respectively, after adjusting for age and intake of beer. These relationships were not influenced by adjusting for several other potential confounding variables (carotenoid intake, intake of vitamins C or E in supplements, smoking, body mass index, time spent outdoors in the summer, gender, and history of diabetes, hypertension, or cardiovascular disease). Odds ratios for late age-related maculopathy were in similar directions but were not statistically significant. CONCLUSIONS: High intake of saturated fat and cholesterol is associated with increased risk for early age-related maculopathy in the Beaver Dam population. This supports the hypothesis that atherosclerosis or its risk factors are related to age-related maculopathy. Confirmation of this finding in other populations and in prospective studies is needed.
Retinal microaneurysm counts and 10-year progression of diabetic retinopathy.
OBJECTIVE: To determine the relationship of change in the number of retinal microaneurysms to the 10-year progression to significant retinopathy, proliferative retinopathy, and clinically significant macular edema. DESIGN: Population-based study of persons with younger- and older-onset diabetes with 10 years of follow-up. SETTING AND PATIENTS: Eleven-county area in southern Wisconsin, where 189 patients with diabetes who had only retinal microaneurysms in photographs at baseline participated in 4- and 10-year follow-up examinations. OUTCOME MEASURES: Ten-year incidence of moderate nonproliferative diabetic retinopathy or worse, proliferative retinopathy, or clinically significant macular edema as determined by masked grading of stereoscopic color fundus photographs of seven standard fields. RESULTS: The increase in the number of retinal microaneurysms and the ratio of the number of retinal microaneurysms at the 4-year follow-up to the number at baseline were positively associated with incidence of proliferative retinopathy or clinically significant macular edema at the 10-year follow-up. Proliferative retinopathy was approximately 4.6 times and clinically significant macular edema was approximately 9.1 times more likely to develop at 10-year follow-up in eyes in which the number of microaneurysms increased by 16 or more from baseline to the 4-year follow-up than in eyes with no increase. Proliferative retinopathy was 3.4 times and clinically significant macular edema was 6.7 times more likely to develop at 10-year follow-up in eyes that had ratios of 3 or greater of the number of retinal microaneurysms at the 4-year follow-up to the number at baseline than in eyes in which the ratios were smaller. These relationships remained after controlling for the level of glycosylated hemoglobin and type of diabetes. CONCLUSIONS: Microaneurysm counts using stereoscopic color fundus photographs are an early important measure of progression of retinopathy and may serve as a surrogate end point for severe change in some clinical trials.
Serum antioxidants and age-related macular degeneration in a population-based case-control study.
OBJECTIVE: To investigate relationships between levels of tocopherols and carotenoids in the serum and age-related macular degeneration (ARMD). DESIGN: A nested case-control study within a population-based cohort. PARTICIPANTS: Cases included a sample of subjects with retinal pigment abnormalities with the presence of soft drusen (n = 127) or with late ARMD (geographic atrophy [n = 9]) or neovascular and exudative macular degeneration (n = 31). An equal number of controls (167 pairs) were selected from among participants in the Beaver Dam Eye Study. The controls had no photographic evidence of soft drusen, retinal pigment abnormalities, or late ARMD and were matched with cases for age, sex, and current smoking status. DATA COLLECTION: Presence and severity of ARMD were determined from masked grading of fundus photographs obtained from 1988 to 1990. Levels of individual carotenoids and tocopherols were determined in serum collected at the same time. RESULTS: Average levels of individual carotenoids were similar in cases and controls. Average levels of vitamin E (alpha-tocopherol) were lower in people with exudative macular degeneration (P = .03). However, the difference was no longer statistically significant after controlling for levels of cholesterol in the serum. Persons with levels of lycopene, the most abundant carotenoid in the serum, in the lowest quintile were twice as likely to have ARMD. Levels of the carotenoids that compose macular pigment (lutein with zeaxanthin) in the serum were unrelated to ARMD. CONCLUSIONS: Very low levels of one (lycopene) but not other dietary carotenoids or tocopherols were related to ARMD. Lower levels of vitamin E in subjects with exudative macular degeneration compared with controls may be explained by lower levels of serum lipids.
Hypertension and lens opacities from the Beaver Dam Eye Study.
PURPOSE: To examine the relationship between hypertension and lens opacities, and the use of antihypertensive agents. METHODS: A total of 4,926 adults, 43 to 84 years of age, living in Beaver Dam, Wisconsin, at the time of a private census, were invited to participate in a study that included a medical interview and an examination that included ocular photography. All study procedures and photographic grading were done according to standard protocols. RESULTS: According to analysis with the Liang-Zeger multiple logistic regression model, people with hypertension were more likely to have posterior subcapsular opacities than people without hypertension (odds ratio, 1.39; 95% confidence interval, 1.05, 1.84). Specific medications for hypertension did not meaningfully affect the risk. Hypertension was associated with increased risk in both those with and without diabetes. CONCLUSIONS: Hypertension is associated with increased risk of posterior subcapsular opacities. The pathophysiologic mechanisms that may explain the relationship are unknown. Incidence data will give a better indication of temporal relationship between hypertension, medications to lower blood pressure, and lens opacities.
Incidence of cataract surgery in the Wisconsin Epidemiologic Study of Diabetic Retinopathy.
PURPOSE: We studied the incidence of cataract extraction in people with diabetes of long duration to determine which factors are associated with higher risk of surgery. METHODS: We recruited a probability sample of all persons receiving care for diabetes in an 11-county area of southern Wisconsin for a prevalence study of diabetic retinopathy. All 2,366 subjects were examined between September 1980 and June 1982. During the slit-lamp examinations, presence of the lens, whether natural or prosthetic, was noted. The subjects were reexamined four and ten years after the initial prevalence study. Occurrence of cataract extraction in the interim between examinations was recorded. RESULTS: In the younger-onset group there was an 8.3% (95% confidence interval, 6.2%, 10.8%) cumulative incidence, and in the older-onset group there was a 24.9% (95% confidence interval, 21.3%, 28.5%) cumulative incidence of cataract surgery in the ten-year interval. Characteristics statistically significantly related to cataract surgery in the younger-onset group in multivariate analysis were age, severity of diabetic retinopathy, and proteinuria. In the older-onset group, age and use of insulin were associated with increased risk. CONCLUSIONS: These data indicate that cataract surgery is a relatively frequent occurrence in people with diabetes. This finding needs to be considered to plan for health care for people with diabetes.
Alcohol use and age-related maculopathy in the Beaver Dam Eye Study.
PURPOSE: Because there are few epidemiologic data examining the relationship between alcohol use and age-related maculopathy, we investigated this relationship via the population-based Beaver Dam Eye Study. METHODS: Alcohol consumption in the year before examination was determined by a standardized questionnaire. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs. RESULTS: While controlling for other factors, consumption of beer in the past year was related to greater odds of increased retinal pigment degeneration (odds ratio, 1.13; 95% confidence interval, 1.02, 1.25) and exudative macular degeneration (odds ratio, 1.41; 95% confidence interval, 1.05, 1.88). Current consumption of neither wine nor liquor was related to early or late age-related maculopathy. CONCLUSIONS: These data suggest a relationship between beer consumption and greater odds of having exudative macular degeneration. Whether this is from a toxic effect specific to beer or from other unknown confounders cannot be determined.
Physical activity and the risk of progression of retinopathy or the development of proliferative retinopathy.
OBJECTIVE: To determine if physical activity is associated with the 6-year risk of progression of retinopathy or incidence of proliferative retinopathy. RESEARCH DESIGN AND METHODS: Participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy who were free of proliferative retinopathy at the 1984 to 1986 examination and in whom diabetes had developed when younger than 30 years of age (n = 606) were evaluated after a 6-year follow-up period. Stereoscopic fundus photographs were graded for the presence and severity of retinopathy. Physical activity was assessed by a questionnaire. RESULTS: There were no associations between any of the measures of physical activity and two-step progression of retinopathy or the development of proliferative retinopathy during the follow-up period. No associations were seen even for those with more severe preproliferative retinopathy at the 1984 to 1986 examination or for the subset engaging in strenuous activity such as weight lifting. CONCLUSIONS: Physical activity does not appear to be associated with either an increased or decreased risk of progression of retinopathy or the development of proliferative retinopathy in people with insulin-dependent diabetes mellitus.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema.
BACKGROUND: As part of a population-based study of diabetes mellitus, the incidence of macular edema over a 10-year period and its relation to various risk factors are examined. METHODS: There were 891 younger-onset people with a diagnosis of having had diabetes before 30 years of age who were taking insulin at baseline examination and 987 older-onset people with a diagnosis of having had diabetes at 30 years of age or older who participated in baseline and 4-year examinations. Of these, 765 younger-onset and 533 older-onset people also participated in a 10-year examination. The presence of macular edema at baseline and follow-up examinations was determined from gradings of stereoscopic fundus photographs. RESULTS: The incidence of macular edema over the 10-year period was 20.1% in the younger-onset group, 25.4% in the older-onset group taking insulin, and 13.9% in the older-onset group not taking insulin. The incidence of macular edema over the 10-year period was associated with higher levels of glycosylated hemoglobin and more severe retinopathy in both younger- and older-onset groups, and with being female and increased diastolic blood pressure in the older-onset group. CONCLUSIONS: These data suggest a relatively high incidence of macular edema. The authors' data also suggest that a reduction in hyperglycemia may result in a beneficial decrease in the incidence of macular edema.
Association of dietary and life-style factors with sex hormones in postmenopausal women.
We examined the relations between endogenous sex hormones and alcohol intake, dietary constituents, and life-style factors in a population-based sample of 253 postmenopausal women not using replacement hormones. Estrone, dihydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), and free and total testosterone were measured in serum. Age and years since menopause were negatively associated with dihydroepiandrosterone sulfate and positively associated with sex hormone-binding globulin levels. Higher relative weight was strongly and negatively associated with sex hormone-binding globulin. Other factors were only very weakly associated with sex hormones. Since, except for weight, few potentially modifiable factors appear to influence these hormone profiles, it may be that behaviors earlier in life mediate hormone levels and subsequent disease risk.
Does insulin-like growth factor I predict incidence and progression of diabetic retinopathy?
We evaluated the relationship of insulin-like growth factor (IGF)-I to incidence and progression of diabetic retinopathy over a 6-year interval in a large population-based study of diabetes in southern Wisconsin. Participants included people with younger-onset diabetes (n = 66 adolescents, n = 661 adults > or = 18 years of age) and older-onset diabetes (n = 285 for those using insulin, n = 248 for those not using insulin). Fundus photographs were graded in a masked fashion using standardized protocols to determine the severity of retinopathy in each eye. Serum IGF-I levels were measured during 1984-1986 using a double-antibody radioimmunoassay. Mean IGF-I was highest in adolescents (499.1 micrograms/l), lower in younger-onset adult (280.1 micrograms/l), and lowest in the older-onset group (205.7 and 221.2 micrograms/l for older-onset group using insulin and not using insulin, respectively). The incidence of retinopathy was not significantly higher in people with higher IGF-I levels in any group. The odds of developing diabetic retinopathy in 6 years for each 10 micrograms/l increase in IGF-I after controlling for age, glycosylated hemoglobin, and duration of diabetes at baseline was 1.21 (95% confidence interval [CI] 0.95-1.54) for adolescents; 1.00 (95% CI 0.93-1.08) for younger-onset adults; 0.93 (95% CI 0.85-1.02) for the older-onset group using insulin; and 0.99 (95% CI 0.95-1.04) for the older-onset group not using insulin. In summary, IGF-I was not associated with 6-year incidence or progression of diabetic retinopathy in any of the groups.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XVI. The relationship of C-peptide to the incidence and progression of diabetic retinopathy.
The relationship between plasma C-peptide and the 6-year incidence and progression of diabetic retinopathy was examined in a population-based study in Wisconsin. Individuals with younger-onset (n = 548) and older-onset (n = 459) diabetes were included. C-peptide was measured by radioimmunoassay with Heding's M1230 antiserum. Retinopathy was determined from stereoscopic fundus photographs. Younger- and older-onset insulin-using individuals with undetectable or low plasma C-peptide (< 0.3 nmol/l) at baseline had the highest incidence and rates of progression of retinopathy, whereas older-onset individuals with C-peptides > 0.3 nmol/l had the lowest incidence and rates of progression of retinopathy. However, within each group (younger-onset using insulin, older-onset using insulin, and older-onset not using insulin), after we controlled for other characteristics associated with retinopathy, there was no relationship between higher levels of C-peptide at baseline and lower 6-year incidence or progression of retinopathy. These data suggest that glycemic control, and not C-peptide, is related to the incidence and progression of diabetic retinopathy.
Ten-year incidence of gross proteinuria in people with diabetes.
There are few population-based epidemiological data describing the long-term incidence of gross proteinuria in people with diabetes. We performed a population-based study in southern Wisconsin of individuals with diabetes diagnosed at either < 30 years of age and taking insulin (younger-onset, n = 666) or > or = 30 years of age either taking (older-onset taking insulin, n = 376) or not taking insulin (older-onset not taking insulin, n = 418). The presence of gross proteinuria (> or = 0.3 g/l) was determined by means of a reagent strip. The incidence of proteinuria in the 10-year interval was 28% in the younger-onset group, it was 40% in the older-onset group taking insulin, and it was 33% in the older-onset group not taking insulin. After we controlled for other risk factors, the 10-year incidence of proteinuria was significantly related to higher glycosylated hemoglobin level and diastolic blood pressure at baseline and to an increase in glycosylated hemoglobin level and an increase in diastolic blood pressure from baseline to the 4-year follow-up in the younger-onset group and to higher glycosylated hemoglobin level, higher systolic blood pressure, and higher total pack-years of cigarettes smoked at baseline and an increase in systolic blood pressure from baseline to the 4-year follow-up in the older-onset groups. These data suggest that modification of three factors--hyperglycemia, high blood pressure, and smoking--may lead to a reduction in the long-term incidence of proteinuria.
Older-onset diabetes and lens opacities. The Beaver Dam Eye Study.
PURPOSE: To determine the prevalence of lens opacities in older-onset diabetic persons. METHODS: A study of age-related eye disease in a population (n = 4926) of adults in Beaver Dam, Wisconsin. Study participants were examined and interviewed according to protocol. Photographs were taken of the lenses of both eyes of all study participants. Photographs were graded in a standard fashion. Diabetes was defined by history, doctors' records and serum glucose criteria. RESULTS: Persons who were diabetic were significantly more likely to have cortical lens opacities (age-adjusted odds ratio 1.72, 95% CI 1.29-2.30 for right eyes) and were more likely to have previously undergone cataract surgery (age-adjusted odds ratio 2.01, 95% CI 1.43-2.82 for either eye) than people without diabetes. Longer duration of diabetes significantly increased the odds of having cortical opacity. CONCLUSION: Older-onset diabetes is associated with increased frequency of a specific age-related lens change, cortical opacity. It is also associated with increased frequency of cataract surgery.