Showing papers by "Ronald Klein published in 1995"

Hyperglycemia and microvascular and macrovascular disease in diabetes.

Abstract: In summary, over the past 16 years, since the publication of Kelly West's book, epidemiological study has provided better insight into the relation of hyperglycemia and diabetic complications. Data from the WESDR demonstrate a strong consistent relationship between hyperglycemia and the incidence and progression of microvascular (diabetic retinopathy, loss of vision, and nephropathy) and macrovascular (amputation and cardiovascular disease mortality) complications in people with IDDM and NIDDM (Figs. 19 and 20). The DCCT has demonstrated that intensive insulin therapy will reduce the incidence and progression of microvascular complications in people with IDDM (22). A number of further challenges await laboratory scientists and epidemiologists regarding hyperglycemia in people with diabetes. There is a need to understand the relation of hyperglycemia to pathogenetic mechanisms that lead to the development of specific complications, to develop new methods to detect and physiologically treat hyperglycemia, and to develop better methods of primary and secondary prevention of diabetic complications in people with IDDM and NIDDM.

The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity.

Abstract: Purpose To investigate the relationship of age-related maculopathy, cataract, and glaucoma to visual acuity in the population-based Beaver Dam Eye Study. Methods A cross-sectional, population-based study was performed in people 43 through 86 years of age residing in Beaver Dam, Wisconsin, who were identified between 1987 and 1988 and examined (n = 4926) between 1988 and 1990. Of those who participated, 99.4% were white. Visual acuity was measured (n = 4886) using a modification of the Early Treatment Diabetic Retinopathy Study protocol. Stereoscopic color fundus photographs and slit lamp and retroillumination photographs of the lens were graded in a masked fashion using standardized protocols to determine the presence of age-related maculopathy and central cataract. Results Fifty-seven percent of those who were legally blind had late age-related maculopathy in both eyes. The frequency of visual acuity of 20/200 or worse was not significantly different in eyes with exudative macular degeneration (48%) than in eyes with pure geographic atrophy (42%). While controlling for other factors (age, central cataract, and glaucoma) in participants with both gradable age-related maculopathy and visual acuity measurable in at least one eye (n = 4716), investigators found that each of the early age-related maculopathy lesions was associated with a decrease in visual acuity of approximately two letters or fewer when compared to eyes without these lesions. Late age-related maculopathy was associated with a decrease of approximately seven lines of letters read correctly. Conclusion These data demonstrate that exudative macular degeneration and pure geographic atrophy are the most important causes of legal blindness in this population and that early age-related maculopathy, central cataract, and glaucoma had a small effect on visual acuity.

Methodology for retinal photography and assessment of diabetic retinopathy: the EURODIAB IDDM complications study.

Abstract: We present the methodology for 45 degrees retinal photography and detail the development, application and validation of a new system of 45 degrees field grading standards for the assessment of diabetic retinopathy. The systems were developed for the EURODIAB IDDM Complications Study, part of a European Community funded Concerted Action Programme into the epidemiology and prevention of diabetes (EURODIAB). Assessment of diabetic retinopathy was carried out centrally by a trained reader of colour retinal photographs using the newly-developed system. The system proved to be acceptably accurate, repeatable repeatable and relatively simple to apply. It compared well with the recognised 'gold standard' 7-field 30 degrees stereo photography (assessed using a modified Airlie House classification scheme), against which the new system was validated in a series of 48 eyes. Selection was as a stratified random sample based on clinical retinopathy status: 5, no retinopathy; 25, non-proliferative retinopathy; 16, proliferative or photocoagulated; plus 2, eyes with potentially confounding lesions (vein occlusion). Simple presence of retinal lesions was correctly detected by both systems in 43 of the 48 eyes, giving 100% agreement on detection. Both systems correctly identified the two known cases of confounding vein occlusion. In eyes with diabetic retinopathy (n = 41), when severity was expressed in three groups: mild background, moderate/severe background and proliferative/photocoagulated, at least one grader (out of five) using the new system matched the verified results in 38 out of 31 (93%) eyes and three or more graders matched in 31 (76%) eyes.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum antioxidants and age-related macular degeneration in a population-based case-control study

Abstract: 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 (α-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.

Dietary fat and age-related maculopathy

Abstract: 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.

Smoothing spline ANOVA for exponential families, with application to the Wisconsin Epidemiological Study of Diabetic Retinopathy : the 1994 Neyman Memorial Lecture

Abstract: Let y i , i = 1,..., n, be independent observations with the density of y i of the form h(y i , f i ) = exp[y i f i - b(f i ) + c(y i )], where b and c are given functions and b is twice continuously differentiable and bounded away from 0. Let i t = f(t(i)), where t = (t 1 ,..., t d ) ∈ T (1) ⊗...⊗ T (d) = T, the T (α) are measurable spaces of rather general form and f is an unknown function on T with some assumed smoothness properties. Given (y i , t(i), i = 1,..., n), it is desired to estimate f(t) for t in some region of interest contained in T. We develop the fitting of smoothing spline ANOVA models to this data of the form f(t) = C + Σ α f α (t α ) + Σ α< βfαβ (t α , t β ) +.... The components of the decomposition satisfy side conditions which generalize the usual side conditions for parametric ANOVA. The estimate of f is obtained as the minimizer, in an appropriate function space, of L(y,f) + Σ α λ α J α (f α ) + Σ α<β λ αβ J αβ (f αβ ) +..., where L(y,f) is the negative log likelihood of y = (y 1 ,..., y n )' given f, the J α , J αβ ,... are quadratic penalty functionals and the ANOVA decomposition is terminated in some manner. There are five major parts required to turn this program into a practical data analysis tool: (1) methods for deciding which terms in the ANOVA decomposition to include (model selection), (2) methods for choosing good values of the smoothing parameters λ α , λ αβ ,..., (3) methods for making confidence statements concerning the estimate, (4) numerical algorithms for the calculations and, finally, (5) public software. In this paper we carry out this program, relying on earlier work and filling in important gaps. The overall scheme is applied to Bernoulli data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy to model the risk of progression of diabetic retinopathy as a function of glycosylated hemoglobin, duration of diabetes and body mass index. It is believed that the results have wide practical application to the analysis of data from large epidemiologic studies.

Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population

Abstract: Objective: To investigate the relationship of various retinal lesions to systemic hypertension in the population-based Beaver Dam Eye Study. Design: In this cross-sectional population-based study, blood pressure was measured using standardized protocols. Using standardized protocols, stereoscopic color fundus photographs were graded in a masked fashion to determine the presence of retinopathy (defined as retinal microaneurysms only, blot hemorrhages only, hemorrhages and/or microaneurysms, cotton-wool spots, hard exudates, intraretinal microvascular abnormalities, venous beading, and retinal new vessels), retinal arteriolar narrowing, and arteriovenous nicking. Participants: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, between 1987 and 1988 were examined between 1988 and 1990. People with diabetes or retinal vascular occlusions were excluded. Results: Retinopathy was present in 336 subjects (7.8%), arteriolar narrowing in 582 subjects (13.5%), and arteriovenous nicking in 95 subjects (2.2%) in the nondiabetic population. Hypertension was associated with increased frequency of retinopathy, arteriolar narrowing, and arteriovenous nicking. After adjusting for age, hypertension was associated with the presence of retinopathy (in men: relative risk [RR], 1.47; 95% confidence interval [CI], 1.10 to 1.96; in women: RR, 1.69; 95% CI, 1.26 to 2.27), arteriolar narrowing (in men: RR, 1.34; 95% CI, 1.03 to 1.74; in women: RR, 1.37; 95% CI, 1.14 to 1.64), and arteriovenous nicking (in men: RR, 1.87; 95% CI, 0.99 to 3.54; in women: RR, 1.65; 95% CI, 1.00 to 2.73). Retinopathy, arteriolar narrowing, and arteriovenous nicking were more frequent in those subjects whose blood pressure was elevated despite use of antihypertensive medications compared with those subjects whose blood pressure was controlled with antihypertensive medications or those who were normotensive. Conclusions: These data suggest that retinopathy and retinal arteriolar narrowing are common in people with hypertension. Further longitudinal study is necessary to evaluate the public health significance of these retinal lesions regarding possibly increased risk of renal and cardiovascular disease.

Age-Related Eye Disease and Survival: The Beaver Dam Eye Study

Abstract: 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.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy-Reply

Abstract: In reply Drs Batchelder and Barricks suggest that our data on the long-term incidence and progression of retinopathy contradict rather than support the guidelines 1 of yearly dilated retinal examinations 5 years after diagnosis of insulindependent diabetes mellitus (IDDM) in people younger than 30 years of age and 1 year after diagnosis of non—insulindependent diabetes mellitus (NIDDM) in people 30 years of age or older. 2 They suggest that the guidelines do not take into account the epidemiologic observations that people with any type of diabetes and no retinopathy or minimal retinopathy consisting of only microaneurysms are unlikely to progress to vision-threatening retinopathy over a 4-year period. 3-5 They suggest that the "screening interval should be tailored to a patient's risk" and that our "data do not suggest any difference in effectiveness for screening intervals of 1, 2, or even 4 years for this group of lowrisk patients." In 1991,

Diet and Nuclear Lens Opacities

Abstract: 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.

Older-onset diabetes and lens opacities. The Beaver Dam Eye Study

Abstract: 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 denned 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 assoc...

Retinal Microaneurysm Counts and 10-Year Progression of Diabetic Retinopathy

Abstract: 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 youngerand 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.

Factors associated with having eye examinations in persons with diabetes.

Abstract: 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.

Association of dietary and life-style factors with sex hormones in postmenopausal women.

Abstract: 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.

Relation of Sex Hormones and Dehydroepiandrosterone Sulfate (DHEA-SO4) to Cardiovascular Risk Factors in Postmenopausal Women

Abstract: Sex hormones play a major role in determining the risk of cardiovascular disease. While several studies have shown that reduced sex hormone-binding globulin is associated with an atherogenic pattern of lipoproteins and increased glucose concentrations in premenopausal women, little data are available examining the association of sex hormone-binding globulin and sex hormones with cardiovascular risk factors in postmenopausal women, a group with high rates of cardiovascular disease. The investigators hypothesized that in postmenopausal women decreased sex hormone-binding globulin and increased testosterone would be associated with an atherogenic pattern of cardiovascular risk factors. The sex hormone-binding globulin, total and free testosterone, estrone, and dehydroepiandrosterone sulfate (DHEA-SO4) in 253 postmenopausal women who were not taking hormones were measured in a population-based study, the Beaver Dam Eye Study (Beaver Dam, Wisconsin, 1988-1990). Sex hormone-binding globulin was significantly inversely correlated with body mass index (r = -0.53, p 0.001), glycosylated hemoglobin (r = -0.34, p < 0.001), and diastolic blood pressure (r = -0.25, p < 0.001), and positively correlated with high density lipoprotein cholesterol (HDL cholesterol) (r = 0.31, p < 0.001), and HDL cholesterol/total cholesterol (r = 0.31, p < 0.001). Total (r = -0.20, p < 0.01) and free (r = -0.14, p < 0.05) testosterone were significantly inversely correlated with HDL cholesterol/total cholesterol ratio. Total testosterone concentrations were also significantly positively correlated with total cholesterol (r = 0.15), body mass index (r = 0.16), and systolic (r = 0.17) and diastolic (r = 0.18) blood pressures (all p < 0.01). DHEA-SO4 was not associated with any of the metabolic variables, while estrone was inversely associated only with the HDL cholesterol/total cholesterol ratio (r = 0.13, p < 0.05). The authors conclude that increased androgenization in postmenopausal women is associated with atherogenic changes in cardiovascular risk factors.

The progression of retinopathy over 2 years : the Pittsburgh epidemiology of diabetes complications (EDC) study

Abstract: This study examined potential risk factors for the incidence and progression of retinopathy in a large representative cohort of childhood onset insulin-dependent diabetic patients. Participants in the Epidemiology of Diabetes Complications (EDC) Study underwent a full clinical examination at baseline and again at a 2-year follow-up. Retinopathy status was ascertained using stereo fundus photographs graded according to the modified Airlie House System. The study population is based on a large cohort of childhood-onset insulin-dependent diabetic patients, seen within 1 year of diagnosis at the Children's Hospital of Pittsburgh between January 1950 and May 1980. A total of 657 subjects participated at baseline (1986-1988), with 80% of eligible survivors taking part in the follow-up examination. This report concerns risk factors associated with the progression of diabetic retinopathy over a 2-year period, and the interaction of these factors with the presence of nephropathy. Analyses showed that baseline diastolic blood pressure was significantly associated with the incidence of any retinopathy, while glycosylated hemoglobin, baseline severity of retinopathy, serum triglycerides, and, to a lesser extent, higher levels of low-density lipoprotein (LDL) cholesterol and fibrinogen were associated with the progression of retinopathy. Progression to proliferative retinopathy was related to higher LDL cholesterol, fibrinogen, serum triglycerides, albumin excretion rate, and glycosylated hemoglobin (GHb). Risk factors varied with the presence of nephropathy. In the absence of nephropathy, GHb was a significant predictor of progression, whilst this was not the case in the presence of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

A Cohort Study of the Relationship of Diabetic Retinopathy to Blood Pressure

Abstract: Objective: To determine whether blood pressure at base-line 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.

Serum Carotenoids and Tocopherols and Severity of Nuclear and Cortical Opacities

Abstract: Purpose To determine whether higher levels of individual carotenoids and tocopherols in the serum are related to less severe nuclear and cortical opacities within the general population Methods Levels of individual carotenoids and tocopherols in the serum were determined in 400 randomly selected persons aged 50 to 84 years participating in the Nutritional Factors in Eye Disease Study of Beaver Dam, Wisconsin Severity of nuclear and cortical opacities was assessed from lens slit lamp and retroillumination photographs taken at the same time Relationships between serum levels of nutrients and prevalence of these opacities were evaluated using logistic regression analysis accounting for known possible confounders Results Higher levels of individual or total carotenoids or a-tocopherol in the serum were not associated with less severe nuclear or cortical opacities overall However, associations differed between men and women and within specific population subgroups A significant trend for lower odds for either type of opacity with increasing levels of /3-carotene in the serum was observed in men For nuclear sclerosis, this protective association with /^-carotene was found in younger but not older men Higher levels of three other carotenoids (a-carotene, /?-cryptoxanthin, and lutein) in serum were significantly related to lower odds for nuclear sclerosis only in men who smoked In contrast to these inverse associations observed in some subgroups, higher levels of some carotenoids and a-tocopherol often were direcdy associated with nuclear sclerosis, particularly in women Conclusions Higher levels of carotenoids and tocopherols are not consistently associated with less severe opacities in the general population Invest Ophthalmol Vis Sci 1995;36:276-288 Opacities in the nuclear and cortical region become more common with age Identification of factors that delay their occurrence may eventually reduce the number of cataract extractions performed and might also help identify factors that contribute to the slowing of other degenerative processes of aging Higher dietary levels of nutrients with roles in oxidant defense systems may protect against lens opacification1 ' 2 Studies in experimental animals us

Ten-Year Incidence of Gross Proteinuria in People With Diabetes

Abstract: 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 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.

The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVI. The Relationship of C-Peptide to the Incidence and Progression of Diabetic Retinopathy

Abstract: 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 Heeling9s M1230 antiserum Retinopathy was determined from stereoscopic fundus photographs Younger- and older-onset insulinusing individuals with undetectable or low plasma Cpeptide ( 03 nmol/1 had the lowest incidence and rates of progression of retinopathy However, within each group (youngeronset using insulin, older-onset using insulin, and olderonset 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

Does insulin-like growth factor I predict incidence and progression of diabetic retinopathy ?

Abstract: 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.

A comparison of methods for correlated ordinal measures with ophthalmic applications.

Abstract: For many clinical trials and epidemiologic investigations in the field of ophthalmology, paired ordinal data are often collected through the detailed grading of retinal photographs. One method for analysis of these data is the extension of the generalized estimating equation (GEE) methodology to multinomial data with cumulative link functions. Prior to the development of this advanced technique, however, ophthalmologists developed a method of combining the ordinal responses of both eyes of a patient into a single person-level response on a new ordinal scale. A relationship between the regression coefficients of these two methods is derived as a function of the correlation between eyes. We investigate the applicability of this result and the relationship of the standard errors in simulation experiments and in an example from the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Insulin-like growth factor-I is related to glycemic control in children and adolescents with newly diagnosed insulin-dependent diabetes.

Abstract: To address the relationship of insulin-like growth factor-I (IGF-I) to diabetes control, we determined IGF-I levels in 137 subjects age 17 yr and younger with recently diagnosed insulin-dependent diabetes mellitus in a population-based cohort study between 3 and 11 months after diagnosis (mean 4.9 months). Initial determinations of IGF-I, 24-h urine C-peptide and microalbuminuria, age, sex, height, weight, body mass index, pubertal stage, and glycosylated hemoglobin (GHb) were obtained. IGF-I levels ranged from 11-439 ng/mL, were strongly related to age (r = 0.74, P or = 10 yr of age; P = 0.50), and it did not change between prepubertal and pubertal subjects (P = 0.95). IGF-I was not related to 24-h urine C-peptide or microalbuminuria. These results suggest that lower IGF-I levels are related to poorer metabolic control of diabetes in the period following insulin-dependent diabetes mellitus diagnosis in all young persons regardless of age or pubertal status.