Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brown, J. B.
Right arrow Articles by Summers, K. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, J. B.
Right arrow Articles by Summers, K. H.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes Care 26:2637-2642, 2003
© 2003 by the American Diabetes Association, Inc.

Pathophysiology/Complications
Original Article

Diabetic Retinopathy

Contemporary prevalence in a well-controlled population

Jonathan Betz Brown, MPP, PHD1, Kathryn L. Pedula, MS1 and Kent H. Summers, PHD2

1 Center for Health Research, Kaiser Permanente Northwest Region, Portland, Oregon
2 US Health Outcomes Evaluation Group, Eli Lilly and Company, Indianapolis, Indiana

Address correspondence and reprint requests to Jonathan B. Brown, MPP, PhD, Senior Investigator, Center for Health Research, 3800 N. Interstate Ave., Portland, OR 97227-1110. E-mail: jonathan.brown{at}kpchr.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
OBJECTIVE—To measure the extent to which modern intensified risk factor control has lessened the duration-specific prevalence of diabetic retinopathy and, therefore, has decreased the risk of blindness in Americans with type 2 diabetes.

RESEARCH DESIGN AND METHODS—Intensified control of blood glucose and blood pressure has prevented diabetic retinopathy in randomized controlled trials. There is as yet no confirmation that subsequent treatment intensification in the community has had the same result. We identified all 6,993 members of a health maintenance organization, Kaiser Permanente Northwest (KPNW), who, in 1997–1998, had dilated retinal examinations and verifiable data of diagnosis of type 2 diabetes. We plotted prevalence by time since diagnosis for background diabetic retinopathy (BDR) and proliferative diabetic retinopathy (PDR) and compared these results to identically derived 1980–1982 results from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). We estimated multivariate predictive models.

RESULTS—Mean (± SD) HbA1c in KPNW was 7.84 ± 1.26% versus 10.37% (standardized) in the WESDR. KPNW blood pressure averaged 138.6 ± 13.8/79.5 ± 7.4 mmHg compared with 147.0/79.0 in the WESDR. BDR was much less prevalent in KPNW, but PDR prevalence appeared unchanged. BDR preceded diagnosis in 20.8% of the WESDR subjects but only 2.0% of KPNW subjects. However, in both populations, the first cases of PDR appeared similarly, soon after diagnosis.

CONCLUSIONS—Earlier diagnosis and more aggressive control of blood glucose and blood pressure decreased the duration-adjusted prevalence of background, but not of sight-threatening proliferative retinopathy. More population-based research is needed to replicate and explain this unexpected finding. Detecting and treating PDR should not be neglected on the assumption that risk-factor control has minimized its prevalence.

Abbreviations: ADR, accelerated diabetic retinopathy • BDR, background diabetic retinopathy • DCCT, Diabetes Control and Complications Trial • ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification • KPNW, Kaiser Permanente Northwest • ME, macular edema • PDR, proliferative diabetic retinopathy • WESDR, Wisconsin Epidemiologic Study of Diabetic Retinopathy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
Diabetic retinopathy is the third most common cause of blindness in the U.S. and the leading cause of new blindness in individuals 20–74 years of age (1). Retinopathy threatens sight once proliferative diabetic retinopathy (PDR) or macular edema (ME) appears (2). Among individuals at high risk in the 1960s through 1980s, randomized trials showed that annual examination plus laser photocoagulation could halve the incidence of blindness (3,4). Computer modeling subsequently showed that periodic screening was cost-effective (5,6). Annual or biennial screening is now a standard of care (7,8).

In the 1990s, randomized trials confirmed that control of hyperglycemia and hypertension could prevent retinopathy (9–13). These findings accelerated a movement toward intensified risk-factor control (14). The resulting improvements, however, fueled speculation that annual retinal screening was no longer justified in many patients (15,16). Quality measurement organizations lengthened the screening interval for non–insulin-using patients with relatively good HbA1c levels.

To assess the contemporary threat from retinopathy, we compared the contemporary prevalence of background diabetic retinopathy (BDR) and PDR to the prevalence in a historical population—participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). WESDR measured baseline diabetic retinopathy in 1980–1982, before aggressive risk-factor control was widespread (17).


   RESEARCH DESIGN AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
Research setting and study population
The subjects of this study were members of a long-established nonprofit group-model health maintenance organization called Kaiser Permanente Northwest (KPNW) and had type 2 diabetes. The methods used to create the KPNW Diabetes Registry are described elsewhere (14). Validation studies have shown the registry to be over 99% sensitive and 99% specific for diagnosed diabetes (14).

Inclusion criteria for the present study were 1) type 2 diabetes, 2) known date of diagnosis, 3) 2 full years of health plan eligibility in 1997 and 1998, and 4) at least one KPNW dilated retinal examination between 1 January 1997 and 31 December 1998. Diagnosis date was not calculated unless registrants had a full year of health plan membership without any indication of diabetes before entering the registry. Case subjects who were diagnosed before 1988, when only inpatient data were available, also were excluded. Subjects with type 1 diabetes were excluded to allow comparison with the older-onset WESDR cohort (18). We also excluded individuals known to be blind (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 369.4).

Ascertainment of retinal status
We identified retinal status from inpatient discharge diagnoses but primarily from encounter and problem-list diagnoses in KPNW’s comprehensive electronic medical record, which began in 1995 and 1996. To ascertain BDR, PDR, and ME, we considered a range of potential ICD-9-CM codes and, to validate local coding practices, compared code-specific prevalences in the study population to prevalences in an age- and sex-matched population of KPNW members without diabetes. We also checked coding against an independent study that compared KPNW outpatient diagnostic coding in 1999 to detailed descriptions in 500 individual medical records.

We ultimately defined PDR as the occurrence of ICD-9-CM codes 362.02 (PDR) or 379.23 (vitreous hemorrhage). These codes had high positive and negative predictive value for PDR in the 1999 validation study. To avoid overdiagnosing PDR, we ignored other codes that KPNW clinicians sometimes used for this condition. We defined background (nonproliferative) diabetic retinopathy by ICD-9-CM codes 362.01 (BDR), 250.5 (diabetes with ophthalmic manifestations), or 362.10 (background retinopathy unspecified). The latter code identified some cases of nondiabetic retinopathy (based on comparison with nondiabetic control subjects). For this and other reasons, we believe our coding somewhat overestimated BDR prevalence. We identified ME by the code 362.83 (retinal edema). This code proved to be very specific for ME but excluded a number of subjects whose ME was coded as BDR with a free-text annotation of ME.

Measurement of predictor variables
KPNW’s HbA1c results were based on the Diamat high-performance liquid chromatography method, the standard method used in the Diabetes Control and Complications Trial (DCCT) and the U.K. Prospective Diabetes Study. We calculated long-term average HbA1c (glycemic burden) and long-term mean lipid levels as the average of all values recorded from 1993 through 1998. We calculated mean blood pressure as the average of all blood pressure measurements recorded during 1997 and 1998. Individuals were considered to have had hypertension and insulin therapy if, at any time between 1987 and 1998, inclusive, they purchased an antihypertensive medication or insulin from KPNW. We calculated duration of therapy as the number of years between an individual’s first and last purchases, using pharmacy data that extended back through 1987.

Analytic methods
To compare the duration-specific prevalence of diabetic retinopathy in 1997–1998 in KPNW to the duration-adjusted prevalence in 1980–1981 in southern Wisconsin, we plotted retinal status by duration of diabetes, just as the WESDR investigators did in two publications (18,19). These graphs do not show true cumulative incidence because they exclude retinopathy that may have occurred in individuals who died before the observation windows. Therefore, incidence is increasingly underestimated as duration increases.

The WESDR results were estimated from Fig. 2 of the third WESDR report (18), which displays data separately for insulin-using and non–insulin-using WESDR cohorts. The WESDR methods have been detailed elsewhere (17–21). Briefly, WESDR recruited subjects from lists of patients with diabetes created by 452 of the 457 primary care physicians practicing in southern Wisconsin in 1979. The investigators identified all patients who had been diagnosed after age 30 years and then excluded 34.5%, usually because of the absence of two confirmatory glucose tests. Random probability sampling was then applied within six strata defined by current use of insulin (yes or no) and tertiles of time since diagnosis, with fourfold oversampling in strata with disease durations >15 years. Of the recruitment sample, 76% completed the baseline examination (n = 1,370), which included seven-field fundus photography. Photographs were graded centrally by trained, blinded reviewers.

We estimated trend lines from annual mean prevalences using the Trend function in Microsoft Excel. To identify correlates of retinal disease progression, we estimated multivariate logistic models on all cases with fully complete data. We converted WESDR glycated hemoglobin values to the DCCT standard by the formula DCCT = 0.003 + 0.935 x WESDR (21).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
We identified 11,985 individuals with type 2 diabetes who were members of KPNW throughout all of 1997 and 1998. Of these, 8,368 (70%) had a known post-1987 date of diabetes diagnosis. A total of 6,999 (84% of the 8,368) had retinal examinations during 1997 and 1998. Of these, six were found to be blind and were excluded, leaving 6,993 subjects.

Characteristics of the study sample are displayed in Table 1, together with baseline characteristics of the older-onset WESDR comparison sample, when known. Average age (± SD) was 61.9 ± 11.8 years (compared with 66.6 years in the WESDR), and 51% were male. Average age at diagnosis was 58.8 ± 11.8 years (vs. 54.8 years in the WESDR). Average duration of disease was 2.8 ± 2.6 years, much less than the 11.9 years reported by the WESDR. During the 6 years ending 31 December 1998, 98.5% had had at least one HbA1c measurement and a large majority had multiple tests in each membership year. Mean HbA1c was 7.84 ± 1.26% vs. 10.37% in the WESDR.


View this table:
[in this window]
[in a new window]
  		Table 1— Population characteristics: KPNW type 2 diabetes (1997–1998) and combined WESDR older cohorts (1980–1982)

 
Total cholesterol results were available for 6,547 subjects (93.6%). The average mean total cholesterol was 220.3 ± 42 mg/dl (5.68 ± 1.08 mmol/l). During 1997 and 1998, patients averaged more than 10 medical care visits per year at which a blood pressure measurement was taken. All but 18 subjects had at least one blood pressure recorded. Systolic and diastolic blood pressures averaged 138.6 ± 13.8 and 79.5 ± 7.4 mmHg, respectively, compared with 147.0 and 79.0 mmHg in the WESDR.

Of the study population, 76% (5,105 of 6,993) purchased an antihypertensive medication during the 11-year study period, with a mean duration of use of 5.86 ± 4.0 years. Sixteen percent of the study sample used insulin. For these 1,119 individuals, the mean number of years on insulin was 2.8 ± 2.5. By sampling design, insulin use in the combined WESDR cohort was much higher (49%).

Ascertainment bias
The 16% of the study-eligible KPNW population who did not receive a retinal examination at KPNW during the study window were not statistically significantly different with respect to sex (males 53.0%, P = 0.42) or glycemic control (HbA1c 7.93 vs. 7.84%, P = 0.06), but they were younger (58.6 vs. 61.9 years, P < 0.0001) and more recently diagnosed (duration 2.5 vs. 2.8 years, P = 0.001). In addition, they were less likely to be using insulin (12.7 vs. 16.1%, P < 0.0001), had lower systolic blood pressure (137.6 vs. 138.6 mmHg, P = 0.022), and had higher diastolic pressure (80.2 vs. 79.5 mmHg, P = 0.0001).

Duration-specific prevalence
Table 2 details the prevalence of retinal disease by diabetes duration in the KPNW population. Prevalence increased with disease duration, with BDR more prevalent than PDR and PDR more prevalent than ME. (The bulge in year 1 is due to backlog additions to the registry in 1996 made possible by newly available electronic medical record data, i.e., individuals not yet using antihyperglycemic drugs or supplies.) Figure 1 plots these data for BDR and PDR against duration-specific prevalence for the insulin-using and non–insulin-using older-onset WESDR cohorts in 1980–1981. For PDR (Fig. 1A), duration-specific KPNW prevalence approximates the prevalences for the non–insulin-using WESDR group. For BDR, however, KPNW prevalence is much less than in either WESDR cohort. The best-fitting trend lines for PDR were linear and, for the WESDR BDR data, quadratic.


View this table:
[in this window]
[in a new window]
  		Table 2— Rates of BDR, PDR, and ME by years since diabetes diagnosis

 


View larger version (37K):
[in this window]
[in a new window]
  		Figure 1— A: PDR; B: BDR. Smooth lines are calculated trend lines and jagged lines connect data summarized by years since diagnosis. Black, square data points and lines are from the older insulin-using WESDR population (WESDR-IU). Light gray diamonds and lines represent data from the older non–insulin-using WESDR population (WESDR-NIU). Medium gray circles and lines represent data from the KPNW population with type 2 diabetes (KPNW). The lines connecting annual data from the KPNW population are dashed. Equations describe their adjacent trend lines.

 
Correlates of retinal disease
Table 3 shows the results of three multivariate logistic models that regressed the occurrence of BDR, PDR, and ME on medical history variables. Of the 10 factors, 7 included in the BDR model returned statistically significant adjusted odds ratios (ORs). The OR for hypertension treatment was 1.69; for each 1-ml increase in mean systolic pressure, 1.02; and for hypertension treatment duration, 0.96. A 1 percentage point increase in mean long-term HbA1c was associated with an OR of 1.44. Insulin use was associated with an OR of 1.52 and each year of insulin use with an OR of 1.09. The OR associated with a year of diabetes duration was 1.23. Age, sex, and mean total cholesterol had small, not statistically significant associations.


View this table:
[in this window]
[in a new window]
  		Table 3— Results of multiple logistic regressions of retinal status on risk factors

 
In a second analysis of 6,391 subjects for the presence of PDR (versus either no retinopathy or BDR), the odds associated with insulin therapy became nonsignificant, whereas the duration of insulin therapy remained significant at 1.15. The odds associated with a unit change in HbA1c dropped somewhat to 1.33. Odds for diabetes duration, mean systolic blood pressure, and hypertension treatment duration became nonsignificant. The OR for hypertension treatment increased to 2.02.

In the multivariate model for ME (versus no ME), mean systolic pressure (OR 1.03/mmHg) and diabetes duration (OR 1.14/year) were significant predictors. However, the strongest correlate of ME by far was coexistent PDR (OR 26.63). ORs changed little when we removed PDR from the model.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
We set out to measure the extent to which modern intensified medical practices have slowed the progression of diabetic retinal disease, as randomized clinical trials (9–13) would predict. We compared results from an earlier foundational study of diabetic retinopathy, the WESDR, to contemporary data from a population that had an extended history of improved glucose and blood pressure control. We found a much lower duration-specific prevalence of BDR in the more recent data but a surprisingly unchanged prevalence of PDR. This finding suggests that the risk of blindness from PDR is not appreciably lower in modern patients despite dramatic improvements in mean risk-factor control.

We cannot rule out the possibility that less precise visualization and coding by KPNW clinicians affected our results. As previously described, we designed our ICD-CM-9 coding scheme conservatively to underestimate the prevalence of PDR and overestimate the prevalence of BDR. An independent review of 500 medical records for the year 1999 confirmed high positive and negative predictive values for our PDR assignment rules. Nevertheless, cases of advanced BDR may have been up-coded to PDR, and cases of early BDR may have been missed.

Similarly, lack of data on the 13% of the Kaiser Permanente population without a known date of diagnosis and on the 15% of the remainder without retinal examinations could have biased our PDR prevalence estimates upward if omitted cases had had less severe retinopathy. Diabetes diagnosis date could not be determined for individuals who joined the health plan with diabetes already diagnosed or who were diagnosed before 1988. The causes of missing examination dates included use of non–Kaiser-Permanente eye specialists, language and cultural barriers, forgetfulness, disorganization, and other causes of nonadherence to medical advice. (Most patients who were late for examinations received postcards and ultimately telephone reminders.)

Both study groups were population-based, WESDR by design, and KPNW by virtue of its large and representative (22) market share and remarkably stable membership (14), but probably differed in many respects beyond their hugely different glucose and blood pressure levels. Improved survival is one possible explanation of increased PDR in the KPNW population. Substantial improvement in age- and sex-adjusted mortality has been documented for the KPNW registry (14). Computer simulation models of diabetes (23–25) indicate that improved survival increases the prevalence of retinal disease by increasing the time available for its occurrence. However, simulation generally predicts increases in both background and proliferative disease. Our analysis revealed an apparent decrease in BDR.

The KPNW decrease in duration-specific BDR is partly attributable to earlier diagnosis of diabetes. Backward extrapolation of the cumulative prevalence function for BDR provides an indirect measure of the average delay between diabetes onset and diagnosis (26). The x-intercepts for BDR in Fig. 1B indicate that, relative to diagnosis, diabetes onset occurred ~4 years earlier in WESDR than in KPNW. If the x-intercept of the KPNW curve in Fig. 1B were shifted left 4 years, BDR prevalence in KPNW would approach (but not equal) the prevalence observed in the non–insulin-using WESDR cohort.

An intriguing aspect of the KPNW-WESDR comparison is that PDR prevalence does not follow BDR in shifting to the right in response to earlier diagnosis. Other researchers also have observed that time to PDR is independent of time to BDR (27). Our data raise the possibility that something occurring as a result of diagnosis helps trigger PDR. If so, a mechanism worth considering is accelerated diabetic retinopathy (ADR). Since the early 1980s, 13 studies have documented accelerated progression of PDR after the rapid intensification of glucose control (28–41). ADR has been observed in both type 1 and type 2 diabetic patients and has led to both transient and permanent progression, up to and including blindness. Further research is necessary to evaluate this hypothesis (42). An alternative explanation is that the U.K. Prospective Diabetes Study results have been misinterpreted (43), and intensified blood pressure and glycemic control actually do not prevent PDR in type 2 disease.

We conclude that earlier diagnosis of type 2 diabetes and more aggressive control of blood glucose and blood pressure have probably greatly decreased the duration-specific prevalence of background diabetic retinopathy since the WESDR, in settings where these actions have occurred. However, the duration-specific prevalence of sight-threatening proliferative retinopathy remains elevated. These findings should be confirmed by studies using expertly graded fundus photographs and in cohorts with longer follow-up. The possible role of ADR should be tested. In the meantime, detecting and treating PDR should not be neglected or de-emphasized.


   Acknowledgments
 
The authors wish to acknowledge the contributions of Kristin Marciante, PharmD, PhD, who conducted the validation of KPNW retinal diagnoses against complete medical records as part of her dissertation research, and Jennifer Coury for editorial support.


   Footnotes
 
J.B.B. and K.L.P. have received research funding from Eli Lilly. K.H.S. holds stock in Eli Lilly.

A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

See accompanying editorial, p. 2691.

Received for publication October 24, 2002. Accepted for publication April 18, 2003.


   References
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

  1. National Society to Prevent Blindness: Vision Problems in the US. New York, Prevent Blindness America, 1980
  2. Aiello LP, Gardner TW, King GL, Blankenship G, Cavallerano JD, Ferris FL, Klein R: Diabetic retinopathy. Diabetes Care 21:143–156, 1998[Medline]
  3. The Diabetic Retinopathy Study Research Group: Photocoagulation treatment of proliferative diabetic retinopathy: clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. Ophthalmology 88:583–600, 1981[Medline]
  4. Early Treatment Diabetic Retinopathy Study Research Group: Early photocoagulation for diabetic retinopathy. ETDRS report no. 9. Ophthalmology 98:766–785, 1991[Medline]
  5. Javitt JC, Aiello LP: Cost-effectiveness of detecting and treating diabetic retinopathy. Ann Intern Med 124:164–169, 1996[Abstract/Free Full Text]
  6. Javitt JC, Aiello LP, Chiang Y, Ferris FL III, Canner JK, Greenfield S: Preventative eye care in people with diabetes is cost-saving to the federal government: implications for health-care reform. Diabetes Care 17:909–917, 1994[Abstract]
  7. National Committee on Quality Assurance: Technical Specifications. Washington, DC, HEDIS, 1998
  8. American Diabetes Association: Diabetic retinopathy (Position Statement). Diabetes Care 22 (Suppl. 1):S70–S73, 1999
  9. Diabetes Control and Complications Trial Research Group: The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 44:968–983, 1995[Abstract]
  10. Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M: Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 28:103–117, 1995[Medline]
  11. UKPDS Group: UKPDS 33: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet 352:837–851, 1998[Medline]
  12. UKPDS Group: UKPDS 38: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. BMJ 317:703–713, 1998[Abstract/Free Full Text]
  13. UKPDS Group: UKPDS 34: Effect of intensive blood-glucose control with metformin on complications on overweight patients with type 2 diabetes. Lancet 532:854–865, 1998
  14. Brown JB, Nichols GA, Glauber HS: Case-control study of 10 years of comprehensive diabetes care. West J Med 172:85–90, 2000[Medline]
  15. Vijan S, Hofer TP, Hayward RA: Cost-utility analysis of screening intervals for diabetic retinopathy in patients with type 2 diabetes mellitus. JAMA 283:889–896, 2000[Abstract/Free Full Text]
  16. Javitt JC: How often should patients with diabetes be screened for retinopathy? JAMA 284:437–438, 2000[Free Full Text]
  17. Klein R, Klein BEK, Moss SE: The Wisconsin epidemiologic study of diabetic retinopathy: A review. Diabetes Metab Rev 5:559–570, 1989[Medline]
  18. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL: The Wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 102:527–532, 1984[Abstract]
  19. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL: The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol 102:520–526, 1984[Abstract]
  20. Klein R, Klein BEK, Moss SE, DeMets DL, Kaufman I, Voss PS: Prevalence of diabetes mellitus in Southern Wisconsin. Am J Epidemiol 119:54–61, 1984[Abstract/Free Full Text]
  21. Klein R, Klein BE, Moss SE, Cruickshanks KJ: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 105:1801–1815, 1998[Medline]
  22. Greenlick M, Freeborn D, Pope C: Health Care Research in an HMO: Two Decades of Discovery. Baltimore, MD, Johns Hopkins University, 1998
  23. Eastman RC: Is intensive glycemic control worth the expense? Cleveland Clin J Med 64:410–413, 1997[Medline]
  24. Brown JB, Russell A, Chan W, Pedula K, Aickin M: The global diabetes model: user friendly version 3.0. Diabetes Res Clin Pract 50 (Suppl. 3):S15–S46, 2000
  25. Brown JB, Palmer AJ, Bisgaard P, Chan W, Pedula K, Russell A: The Mt. Hood challenge: cross-testing two diabetes simulation models. Diabetes Res Clin Pract 50 (Suppl. 3):S57–S64, 2000
  26. Harris MI, Klein R, Welborn TA, Knuman MW: Onset of NIDDM occurs at least 4–7 years before clinical diagnosis. Diabetes Care 15:815–819, 1992[Abstract]
  27. Vitale S, Maguire MG, Murphy RP, Hiner C, Rourke L, Sackett C, Patz A: Interval between onset of mild nonproliferative and proliferative retinopathy in type 1 diabetes. Arch Ophthalmol 115:194–198, 1997[Abstract]
  28. Agardh CD, Eckert B, Agardh E: Irreversible progression of severe retinopathy in young type I insulin-dependent diabetes mellitus patients after improved metabolic control. J Diabetes Complications 6:96–100, 1992[Medline]
  29. Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, Sandvik L, Aagenaes O: Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin-dependent diabetes mellitus: the Oslo Study. BMJ 290:811–815, 1985
  30. Dandona P, Bolger JP, Boag F, Fonesca V, Abrams JD: Rapid development and progression of proliferative retinopathy after strict diabetic control. BMJ 290:895–896, 1985
  31. Diabetes Control and Complications Trial Research Group: Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 116:874–886, 1998[Abstract/Free Full Text]
  32. Diabetes Control and Complications Trial: The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. Arch Ophthalmol 113:36–51, 1995[Abstract]
  33. Henricsson M, Janzon L, Groop L: Progression of retinopathy after change of treatment from oral antihyperglycemic agents to insulin in patients with NIDDM. Diabetes Care 18:1571–1576, 1995[Abstract]
  34. Kroc Collaborative Study Group: Blood glucose control and the evolution of diabetic retinopathy and albuminuria. N Engl J Med 311:365–372, 1985
  35. Lauritzen T, Frost-Larsen K, Larsen HW, Deckert T: Effect of 1 year of near-normal blood glucose levels on retinopathy in insulin-dependent diabetics. Lancet 29:200–203, 1983
  36. Moskalets E, Galstyan G, Starostina E, Antsiferov M, Chantelau E: Association of blindness to intensification of glycemic control in insulin-dependent diabetes mellitus. J Diabetes Complications 8:45–50, 1994[Medline]
  37. Roysarkar TI, Gupta A, Dash RJ, Dogra MR: Effect of insulin therapy on progression of retinopathy in noninsulin-dependent diabetes mellitus. Am J Ophthalmol 115:569–574, 1993[Medline]
  38. van Ballegooie E, Hooymans JM, Timmerman Z, Reitsma WD, Sluiter WJ, Schweitzer NM, Doorenbos H: Rapid deterioration of diabetic retinopathy during treatment with continuous subcutaneous insulin infusion. Diabetes Care 7:236–242, 1984[Abstract]
  39. Henricsson M, Berntorp K, Berntorp E, Fernlund P, Sundkvist G: Progression of retinopathy after improved metabolic control in type 2 diabetic patients: relation to IGF-1 and hemostatic variables. Diabetes Care 22:1944–1949, 1999[Abstract/Free Full Text]
  40. Henricsson M, Nilsson A, Janzon L, Groop L: The effect of glycaemic control and the introduction of insulin therapy on retinopathy in non-insulin-dependent diabetes mellitus. Diabet Med 14:123–131, 1997[Medline]
  41. Efron B: Regression and ANOVA with zero-one data: measures of residual variation. J Am Stat Assoc 73:113–121, 1978
  42. Brown JB, Nichols G: Glycemic control before and after changes in anti-hyperglycemic therapy in type 2 diabetes. Am J Manag Care 9:213–217, 2003[Medline]
  43. Ewart RM: The case against aggressive treatment of type 2 diabetes: critique of the UK prospective diabetes study. BMJ 323:854–858, 2001[Free Full Text]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
G. Pambianco, T. Costacou, D. Ellis, D. J. Becker, R. Klein, and T. J. Orchard
The 30-year natural history of type 1 diabetes complications: the pittsburgh epidemiology of diabetes complications study experience.
Diabetes, May 1, 2006; 55(5): 1463 - 1469.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Guan, C. Hudson, T. Wong, M. Kisilevsky, R. K. Nrusimhadevara, W. C. Lam, M. Mandelcorn, R. G. Devenyi, and J. G. Flanagan
Retinal Hemodynamics in Early Diabetic Macular Edema
Diabetes, March 1, 2006; 55(3): 813 - 818.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
N. Emanuele, J. Sacks, R. Klein, D. Reda, R. Anderson, W. Duckworth, C. Abraira, and for the Veterans Affairs Diabetes Trial Group
Ethnicity, Race, and Baseline Retinopathy Correlates in the Veterans Affairs Diabetes Trial
Diabetes Care, August 1, 2005; 28(8): 1954 - 1958.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
R. Klein
Has the Frequency of Proliferative Diabetic Retinopathy Declined in the U.S.?
Diabetes Care, September 1, 2003; 26(9): 2691 - 2692.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brown, J. B.
Right arrow Articles by Summers, K. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brown, J. B.
Right arrow Articles by Summers, K. H.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum