Epidemiologic Study Of Diabetic Retinopathy Research Articles

Self-rated health and diabetes of long duration. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

To evaluate the self-reported quality of life in individuals with diabetes of long duration. An interview was administered 14 years after baseline to two cohorts of individuals with diabetes who have been followed in an epidemiological study periodically since 1980. Responses to the Medical Outcomes Study Short Form 36 as related to complications of diabetes, age, glycosylated hemoglobin level, and other characteristics were assessed. Physical function, physical role, general health scales, and a general question about health were related to diabetes characteristics in older- and younger-onset individuals. Symptoms of sensory neuropathy were associated with the four measures in both younger- (n = 645) and older-onset (n = 292) individuals. Other descriptive variables in the younger-onset group were the presence of nephropathy, cardiovascular disease, smoking, peak expiratory flow, physical activity, and glycosylated hemoglobin. Hypoglycemic reactions were of only borderline significance and that for only one scale (physical role). In older-onset individuals, cardiovascular disease, physical activity, and sex were descriptive of responses to the quality-of-life questions. Factors related to diabetes contribute to self-assessed health. some of these factors may be modifiable, which, if altered, may lead to improved quality of life.

The impact of cardiovascular disease on people with diabetes: the potential for prevention

The impact of cardiovascular disease on people with diabetes: the potential for prevention

Is obesity related to microvascular and macrovascular complications in diabetes? The Wisconsin Epidemiologic Study of Diabetic Retinopathy

Is obesity related to microvascular and macrovascular complications in diabetes? The Wisconsin Epidemiologic Study of Diabetic Retinopathy

Sex hormones and DHEA-SO4 in relation to ischemic heart disease mortality in diabetic subjects. The Wisconsin Epidemiologic Study of Diabetic Retinopathy.

Sex hormones are associated with atherogenic changes in lipoproteins and changes in glucose and insulin metabolism, yet few data are available on the relationship of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to ischemic heart disease (IHD) in diabetic subjects, a group with very high levels of IHD. We examined the relation of total and free testosterone, sex hormone binding globulin, estrone, estradiol, and DHEA-SO4 to the 5-year IHD mortality in the older-onset diabetic subjects in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) in a matched diabetic subject-control design (two control subjects for every diabetic subject). In men (n = 123), none of the sex hormones or DHEA-SO4 significantly predicted IHD mortality. In women (n = 120), lower levels of DHEA-SO4 (P < 0.01) and total testosterone (P = 0.07) predicted IHD mortality. These results were essentially unchanged after adjustment for duration of diabetes, GHb, diuretic use, and serum creatinine, which are major predictors of IHD mortality in the WESDR. Finding lower testosterone levels in diabetic subjects of IHD in women is contrary to data on risk factors, which suggests that increased androgen activity may be associated with worse IHD risk factors. This study suggests that alterations in sex hormones and DHEA-SO4 are unlikely to explain a major proportion of the variation in IHD mortality in diabetic subjects.

A global odds ratio regression model for bivariate ordered categorical data from ophthalmologic studies.

In typical clinical trials or epidemiologic studies of a bilateral eye disease, the primary outcome data consist of pairs of ordered categorical responses that tend to be highly correlated. In such studies, interest often centres in associating the outcome data with a grouping variable such as the treatment indicator or the exposure status and other person- and eye-specific covariates. In this paper, we propose a latent variable regression model to analyse such bivariate ordered categorical data. We use as a joint distribution for bivariate latent random variables the cross ratio distribution proposed by Plackett, which results in modelling the dependency between the fellow eyes with the global odds ratio. We illustrate the proposed model with data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a study that seeks to identify risk factors among younger-onset diabetics.

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

Let $y_i, i = 1, \dots, n$, 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 $f_i = f(t(i))$, where $t = (t_1, \dots, t_d) \epsilon \mathsf{T}^{(1)} \otimes \dots \otimes \mathsf{T}^{(d)} = \mathsf{T}$, the $\mathsf{T}^{(\alpha)}$ are measurable spaces of rather general form and f is an unknown function on $\mathsf{T}$ with some assumed "smoothness" properties. Given ${y_i, t(i), i = 1, \dots, n}$, it is desired to estimate $f(t)$ for t in some region of interest contained in $\mathsf{T}$. We develop the fitting of smoothing spline ANOVA models to this data of the form $f(t) = C + \sum_{\alpha} f_{\alpha}(t_{\alpha}) + \sum_{\alpha < \beta} f_{\alpha \beta} (t_{\alpha}, t_{\beta}) + \dots$. 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 $\mathsf{L}(y, f) + \sum_{\alpha} \lambda_{\alpha} J_{\alpha}(f_{\alpha}) + \sum_{\alpha <\beta} \lambda_{\alpha \beta} J_{\alpha \beta}(f_{\alpha \beta}) + \dots$, where $\mathsf{L}(y, f)$ is the negative log likelihood of $y = (y_1, \dots, y_n)'$ given f, the $J_{\alpha}, J_{\alpha \beta}, \dots$ 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 $\lambda_{\alpha}, \lambda_{\alpha \beta}, \dots$, (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 epidemiological studies.

Analyzing Bivariate Ordinal Data Using a Global Odds Ratio

Abstract A moment method is proposed for regression analysis of bivariate ordered categorical data using the global odds ratio as the measure of association. For modeling the margins, this method utilizes the stochastic ordering implicit in the data. This method allows for covariate effects in modeling the association between responses. An application of the proposed model is illustrated using the ophthalmological data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy for identifying risk factors among younger onset diabetics. This model is also extended to a longitudinal data setting with more than two repeated measures.

Analyzing Bivariate Ordinal Data Using a Global Odds Ratio

Abstract A moment method is proposed for regression analysis of bivariate ordered categorical data using the global odds ratio as the measure of association. For modeling the margins, this method utilizes the stochastic ordering implicit in the data. This method allows for covariate effects in modeling the association between responses. An application of the proposed model is illustrated using the ophthalmological data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy for identifying risk factors among younger onset diabetics. This model is also extended to a longitudinal data setting with more than two repeated measures.

Physical Activity and the Risk of Progression of Retinopathy or the Development of Proliferative Retinopathy

To determine if physical activity is associated with the 6-year risk of progression of retinopathy or incidence of proliferative retinopathy. 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. 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. 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. XVI. The relationship of C-peptide to the incidence and progression of diabetic retinopathy

The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XVI. The relationship of C-peptide to the incidence and progression of diabetic retinopathy

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.

A bivariate cumulative probit regression model for ordered categorical data.

This paper proposes a latent variable regression model for bivariate ordered categorical data and develops the necessary numerical procedure for parameter estimation. The proposed model is an extension of the standard bivariate probit model for dichotomous data to ordered categorical data with more than two categories for each margin. In addition, the proposed model allows for different covariates for the margins, which is characteristic of data from typical ophthalmological studies. It utilizes the stochastic ordering implicit in the data and the correlation coefficient of the bivariate normal distribution in expressing intra-subject dependency. Illustration of the proposed model uses data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy for identifying risk factors for diabetic retinopathy among younger-onset diabetics. The proposed regression model also applies to other clinical or epidemiological studies that involve paired organs.

A Comparison of the Study Populations in the Diabetes Control and Complications Trial and the Wisconsin Epidemiologic Study of Diabetic Retinopathy

We compared the Diabetes Control and Complications Trial (DCCT) cohort with patients who had insulin-dependent diabetes mellitus (IDDM) in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) to determine whether the DCCT cohort was similar to the patients with IDDM in the general population and whether the DCCT results are generalizable to a nonresearch population. Demographic and clinical characteristics were compared between the DCCT study cohort and the WESDR cohort of patients with IDDM with age at onset of diabetes at younger than 30 years and followed up from 1980 to 1986. The DCCT eligibility criteria were applied to the WESDR cohort, and patients were identified who fulfilled the major criteria of the DCCT primary prevention and secondary intervention cohorts. Conventionally treated subjects in the DCCT primary prevention and secondary intervention cohorts were compared with their respective WESDR groups with regard to clinical characteristics, progression of retinopathy, and development of gross proteinuria. Comparison of the DCCT primary prevention and secondary intervention cohorts at baseline with the respective WESDR groups revealed an older age and an older age at diagnosis, a lower hemoglobin A1c (HbA1c) level, and more frequent injections and monitoring in the DCCT cohorts, but there were few other substantive differences. The progression of retinopathy and the association with baseline HbA1c level were similar for the conventionally treated DCCT and WESDR cohorts, except for a lower rate of progression in the DCCT secondary intervention cohort compared with that of the WESDR cohort, perhaps because of the lower HbA1c level. At baseline, patients in the DCCT cohort were generally similar to patients with IDDM in the population-based WESDR cohort, except for differences in the levels of HbA1c that diminished over time as the HbA1c levels in the WESDR cohort decreased. The demographic similarities between the DCCT and WESDR cohorts, the similar rates of progression of retinopathy in conventionally treated patients, and the similar associations between the HbA1c levels and progression of retinopathy in the DCCT and WESDR cohorts support the validity of generalizing the DCCT results to patients with IDDM in the general population.

A comparison of the study populations in the Diabetes Control and Complications Trial and the Wisconsin Epidemiologic Study of Diabetic Retinopathy

A comparison of the study populations in the Diabetes Control and Complications Trial and the Wisconsin Epidemiologic Study of Diabetic Retinopathy

Lp(a) is not related to retinopathy in diabetic subjects.

To examine the association between Lp(a) concentrations and the severity of retinopathy in 22 younger-onset and 48 older-onset diabetic subjects from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of diabetic retinopathy. We used a subset of the WESDR population with standardized protocols and stereoscopic color fundus photography to determine the severity of diabetic retinopathy in relation to Lp(a) concentrations. Lp(a) concentrations were measured by a monoclonal anti-Lp(a) antibody. Lp(a) levels were not significantly different between younger-onset or older-onset subjects with and without retinopathy. Our results do not support a link between higher levels of Lp(a) and severe retinopathy in either younger-onset or older-onset diabetic subjects but this needs confirmation in larger prospective studies.

Incidence of Cataract Surgery in the Wisconsin Epidemiologic Study of Diabetic Retinopathy

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. 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. 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. 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.

Self-rated health and mortality in people with diabetes.

This study examined whether self-rated health is an independent and significant predictor of mortality in people with diabetes, using data collected in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Participants were asked to rate their health in comparison with others their age. A proportional hazards model was used to regress survival time on self-rated health and a number of covariates measuring physical health. People with younger onset diabetes (n = 891) who rated their health relative to their peers as "worse" or "don't know" were no more likely to die than those rating their health as "the same" or "better" when physical health status was controlled. In contrast, those with older onset diabetes (n = 987) who rated their health as "worse" or "don't know" were almost twice as likely to die as those rating their health as "the same" or "better" when physical health status was controlled. Self-rated health is a significant predictor of mortality in people with older onset diabetes but not in those with younger onset diabetes when physical health status is controlled.

Sex Hormones and the Incidence of Severe Retinopathy in Male Subjects with Type I Diabetes

Diabetic retinopathy rarely occurs before puberty, suggesting that changes in sex hormones may influence the development of this condition. The authors measured total testosterone, free testosterone, sex hormone-binding globulin, estradiol, and dehydroepiandrosterone-sulfate levels in 44 men with type I diabetes participating in the 1984 to 1986 re-examination phase of the Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based study of diabetic complications. The mean age was 32.7 years, and the mean duration of diabetes was 15.4 years. Subjects who progressed to proliferative or preproliferative retinopathy 6 years later (cases, n = 22) were compared with subjects who had little or no progression (controls, n = 22). Both groups were matched on initial level of retinopathy. Seven stereoscopic retinal photographs of each eye were obtained at both examinations, and the photographs were read by the University of Wisconsin Reading Center. Sex hormone-binding globulin concentrations (nmol/l) were significantly lower (reflecting increased androgenicity) in cases than in controls (22.4 +/- 11.4 versus 32.5 +/- 19.8; P = 0.04). No other statistically significant differences in hormone levels were observed. Neither serum testosterone nor other sex hormones were related to the incidence of severe retinopathy. The relationship to low-serum sex hormone-binding globulin suggests that increased androgenicity may be associated with the progression of retinopathy in male subjects with type I diabetes.

Prevalence of Microalbuminuria in Older-Onset Diabetes

To examine the prevalence of microalbuminuria and the relationships of microalbuminuria to blood pressure and other risk factors. Individuals diagnosed with diabetes at > or = 30 yr of age either taking insulin (n = 435) or not taking insulin (n = 363), who were participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were examined during 1984-1986. Random urine samples were collected and an agglutination inhibition test was used to determine the presence of microalbuminuria, which is defined as > or = 0.03 g/L but < 0.3 g/L. The frequency of microalbuminuria was 29.2% in those individuals taking insulin and 22.0% in those not taking insulin. Microalbuminuria was significantly associated with the male sex, older age, higher systolic blood pressure, higher GHb, use of insulin, higher recent alcohol consumption, and a history of cardiovascular disease. These findings suggest a relationship between controllable risk factors, blood pressure and GHb, and microalbuminuria in older-onset diabetic individuals.

The Association of Microalbuminuria with Diabetic Retinopathy: The Wisconsin Epidemiologic Study of Diabetic Retinopathy

To investigate the relationship between microalbuminuria and the presence and severity of diabetic retinopathy in a large population-based cohort of individuals with diabetes. Microalbuminuria was measured by an agglutination inhibition assay in random urine samples obtained from participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (n = 1139) who did not have hematuria, gross proteinuria, or a history of renal disease. Retinopathy was determined from stereoscopic color fundus photographs graded according to a modification of the Airlie House Classification System. Younger-onset (diagnosed with diabetes before 30 years of age) and older-onset (diagnosed with diabetes when 30 years of age or older) individuals with microalbuminuria were more likely to have retinopathy than those without microalbuminuria. Younger-onset individuals who had microalbuminuria at the time of examination were more likely to have proliferative retinopathy than younger-onset subjects with normoalbuminuria. These relationships remained after controlling for glycemia, hypertension, duration of diabetes, and other potential confounders. Microalbuminuria is associated cross-sectionally with the presence of retinopathy in persons with diabetes and with the presence of proliferative disease in younger-onset individuals. These data suggest that microalbuminuria may be a marker for the risk of proliferative retinopathy developing. If longitudinal studies confirm these findings, individuals with insulin-dependent diabetes mellitus (IDDM) who have microalbuminuria may benefit from ophthalmologic follow-up.