The Diabetic Retinopathy Clinical Research NetworkThe Diabetic Retinopathy

Clinical Research Network

Effect of Diabetes Education

During Retinal Ophthalmology Visits

on Diabetes Control (Protocol M)

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Rationale for Diabetes Education During Retina Examination

Rationale for Diabetes Education During Retina Examination

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Ocular complications often can be observed before substantial vision loss and may be a highly motivating finding for an individual to be vigilant about glycemic control.

Educational intervention at the ophthalmology office may have additional impact beyond the current standard of diabetes education at other medical offices.

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Primary Objective• Determine if glycemic control in individuals

with type 1 or type 2 diabetes can be improved with subject-specific diabetes education and risk assessment during retina examinations

Compare mean change in HbA1c from baseline to 1 year in the intervention vs. control groups; within 2 cohorts 1. More Frequent Cohort- seen for standard care

more frequently than every 12 months2. Annual Cohort- for standard care every 12

months

Protocol M: Primary Objective

Study DesignStudy Design

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Participants meeting all of the following criteria*:• At least 18 years old with Type 1 or type 2 diabetes

Cluster Randomized Trial (N = 1875)

Primary Outcome: Mean Change in HbA1c from baseline to 1 year†

*Only participants with a central laboratory measured HbA1c ≥ 6.0% will be included in the primary analysis†Parallel analyses were performed on all outcomes for the data collected at 3 months and 2 years. Results were similar to 1 year and are not included.

Secondary Outcomes: Diabetes care knowledge assessments PAID and SCI-2, BMI, and BP

Control Intervention Control Intervention

AnnualMore

Frequent

42 participating sites 34 randomized by site (Cluster Unit = Site) 8 randomized by investigator (Cluster Unit = subset

of investigators at site)50 Clusters

25 Assigned to Intervention 25 Assigned to Control

Recruitment Goal 900 in each cohort

Participants were included in the more frequent cohort if at least one retinal visit occurred between baseline and 1 year, otherwise they were included in the annual cohort.

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Randomization

Enrollment and Follow-up Enrollment and Follow-up

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More FrequentN = 990

Control N = 502

InterventionN = 488

Dropped = 62 Deaths = 6

Completed = 434

Dropped = 62 Deaths = 6

Completed = 43412-Month Visit

Enrollment and Follow-up Enrollment and Follow-up

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AnnualN = 756

Control N = 368

InterventionN = 388

Dropped = 59 Deaths = 4

Completed = 300

Dropped = 57 Deaths = 11

Completed = 32012-Month Visit

TreatmentTreatment

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Usual Care

HbA1c- immediate feedback Personalized risk assessment

including retinopathy level, HbA2c, and BP

Feedback to PCP Supplemental diabetes

management materials for home use

Testing with supplemental education by investigator as needed

Email follow-up with link to view personalized risk assessment reports

Control

Intervention

ResultsResults

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Participant Baseline Characteristics

Participant Baseline Characteristics

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More Frequent Annual

Control Intervention Control Intervention

Gender: Women 50% 55% 58% 58%

Median Age 64 65 61 63

Race/Ethnicity: White

63% 58% 63% 55%

Type 1 Diabetes 12% 11% 16% 13%

Type 2 Diabetes 88% 86% 82% 84%

Mean HbA1c 8.3 8.6 8.3 8.4

Ocular Baseline CharacteristicsOcular Baseline Characteristics

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More Frequent Annual

Control Intervention Control Intervention

Visual Acuity 20/20 or better (in the better seeing eye)

32% 31% 51% 52%

DME on clinical exam (worse of 2 eyes)

40% 34% 5% 5%

Patient Knowledge of HbA1c(N = 631)*

Patient Knowledge of HbA1c(N = 631)*

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4 5 6 7 8 9 10 11 12 13 14 15 16 17 18456789

101112131415161718

Central Lab Measured HbA1c

Las

t K

no

wn

Hb

A1c

*Among those who had a last known date within the last 6 months

In Office vs Central Lab HbA1c(N = 867)

In Office vs Central Lab HbA1c(N = 867)

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4 6 8 10 12 14 16456789

101112131415161718

Central Lab Measured HbA1c

Las

t K

no

wn

Hb

A1c

More Frequent CohortMore Frequent Cohort

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More Frequent CohortNumber of Follow Up Retina Visits Prior to 12 Month Visit

More Frequent CohortNumber of Follow Up Retina Visits Prior to 12 Month Visit

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Control†

N = 424Intervention†

N = 423

4 or more visits* 42% 32%

Median # of visits* 2 3

*Case report forms captures this information for clinical center visits at the DRCR.net site that enrolled the participant.

† Includes only participants who completed the 12 month primary outcome visit and had a non-missing central lab value (i.e., participants in the primary analysis

More Frequent CohortNumber of Follow Up Interventions Prior to 12 Month Visit

More Frequent CohortNumber of Follow Up Interventions Prior to 12 Month Visit

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# Follow up interventions*

InterventionN = 411

0 22%

1 42%

2 26%

3 11%

*Based on follow up visits where in office HbA1c was recorded.

More Frequent Cohort12 Month Primary Analysis

More Frequent Cohort12 Month Primary Analysis

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Central Lab HbA1cControl N = 424

InterventionN = 423

Mean at Baseline 8.3 8.5

Mean at 12M 8.2 8.3

Mean change from baseline to 12M -0.1 -0.3

Mean difference (Cont-Int)* -0.09

95% Confidence Interval* -0.29, +0.12

P-value* 0.35

*From a repeated measures model adjusting for baseline HbA1c and fitting a correlation between patients within site, assuming the correlation is the same for any pair of patients at a given site, and the within site correlation is the same at all sites. P-value from adjusted model (race, education level, income) = 0.29

More Frequent CohortPrimary Analysis of HbA1c at 1 Year

More Frequent CohortPrimary Analysis of HbA1c at 1 Year

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Control N = 424

InterventionN = 423

% with HbA1c < 7.0% 23% 23%% with HbA1c > 10.0% 11% 14%% with relative decrease in HbA1c ≥ 10% 21% 25%

% with absolute decrease in HbA1c ≥ 0.5% 31% 36%

% with absolute increase in HbA1c ≥ 0.5% 26% 26%

More Frequent Cohort12 Month Secondary Outcomes

More Frequent Cohort12 Month Secondary Outcomes

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Control N = 430

InterventionN = 418

Mean Change in Mean Arterial BP (mmHg)

-1 -1

Mean Change in Body Mass Index (kg/m2)

+0.1 -0.1

Annual CohortLimited to participants with a baseline central lab HbA1c ≥6.0%

Annual CohortLimited to participants with a baseline central lab HbA1c ≥6.0%

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Annual Cohort12 Month Primary Analysis

Annual Cohort12 Month Primary Analysis

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Central Lab HbA1cControl N = 289

InterventionN = 297

Mean at Baseline 8.2 8.4

Mean at 12M 8.2 8.3

Mean change from baseline to 12M 0.0 -0.1

Mean difference (Cont-Int)* 0.04

95% Confidence Interval* -0.18, +0.26

P-value* 0.68

*From a repeated measures model adjusting for baseline HbA1c and fitting a correlation between patients within site, assuming the correlation is the same for any pair of patients at a given site, and the within site correlation is the same at all sites. P-value from adjusted model (race, education level, income) = 0.52

Annual Cohort12 Month Secondary Outcomes

Annual Cohort12 Month Secondary Outcomes

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Control N = 321

InterventionN = 340

Mean Change in Mean Arterial BP (mmHg)

-1 0

Mean Change in Body Mass Index (kg/m2)

0.0 -0.2

Sensitivity AnalysisSensitivity Analysis Results were similar when annual cohort was

pooled with more frequent cohort. Sensitivity analyses were consistent with the

primary analysis results, including• using all available measurements (POC or PC)

when central lab value not available• excluding N = 48 (3%) cases where abnormal

hemoglobin variant observed• imputing for missing 1-year data • evaluating separately by cluster type (site-level or

investigator-level)

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Sensitivity AnalysisSensitivity Analysis Results were also consistent when

stratified by predefined baseline subgroups of interest • A1c, last known A1c, annual income, diabetes

type, DR severity, VA, and DME

An interaction between site and treatment group was not identified

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Discussion

Individualized assessment of diabetes complication risks during ophthalmology visits did not alter glycemic control, compared with usual care.

The lack of intervention effect in this study could reflect the standard care given by this specialized investigator group which is highly attuned to evidence-based retinal care for individuals with diabetes, and possibly already providing patient education at a level where the prescribed intervention would not add incremental benefit. 29

Discussion

DiscussionDiscussion The similarity of A1c between intervention

and control groups at one year emphasizes the challenge and need for additional approaches other than those employed in this study, including :

1. Personalized retinal imaging

2. Displaying images of severe diabetic complications

3. Exposure to individuals who have experienced these debilitating complications

4. More frequent educational interaction

5. Additional communication with primary diabetes care providers.

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ConclusionConclusion The addition of personalized education and risk

assessment during ophthalmology visits in this study did not improve glycemic control,

long-term optimization of glycemic control is still clearly a cornerstone of diabetes care.

These results suggest that optimizing glycemic control remains a substantive challenge requiring more extensive interventional paradigms than examined in this study and further research into new technologies and models of behavioral change.

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Conclusion Conclusion Until more successful approaches are

found, ophthalmologists and all other diabetes care providers should continue their efforts to maximize education, assessment, systemic control and treatment of complications for patients with diabetes.

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