Validation of Time in Range as an Outcome Measure for Diabetes Clinical Trials.

OBJECTIVE: This study evaluated the association of time in range (TIR) of 70-180 mg/dL (3.9-10 mmol/L) with the development or progression of retinopathy and development of microalbuminuria using the Diabetes Control and Complications Trial (DCCT) data set in order to validate the use of TIR as an outcome measure for clinical trials. RESEARCH DESIGN AND METHODS: In the DCCT, blood glucose concentrations were measured at a central laboratory from seven fingerstick samples (seven-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. Retinopathy progression was assessed every 6 months and urinary microalbuminuria development every 12 months. Proportional hazards models were used to assess the association of TIR and other glycemic metrics, computed from the seven-point fingerstick data, with the rate of development of microvascular complications. RESULTS: Mean TIR of seven-point profiles for the 1,440 participants was 41 ± 16%. The hazard rate of development of retinopathy progression was increased by 64% (95% CI 51-78), and development of the microalbuminuria outcome was increased by 40% (95% CI 25-56), for each 10 percentage points lower TIR (P < 0.001 for each). Results were similar for mean glucose and hyperglycemia metrics. CONCLUSIONS: Based on these results, a compelling case can be made that TIR is strongly associated with the risk of microvascular complications and should be an acceptable end point for clinical trials. Although hemoglobin A1c remains a valuable outcome metric in clinical trials, TIR and other glycemic metrics-especially when measured with continuous glucose monitoring-add value as outcome measures in many studies.

The Association of Biochemical Hypoglycemia with the Subsequent Risk of a Severe Hypoglycemic Event: Analysis of the DCCT Data Set.

OBJECTIVE: To evaluate the association of biochemical hypoglycemia with subsequent severe hypoglycemia (SH) events using the Diabetes Control and Complications Trial (DCCT) data set. RESEARCH DESIGN AND METHODS: The frequency of biochemical hypoglycemia (percentage of values <70 and <54 mg/dL [3.9 and 3.0 mmol/L) was assessed using DCCT blood glucose concentrations measured at a central laboratory from seven finger-stick samples (7-point testing: pre- and 90-min postmeals and at bedtime) collected during 1 day every 3 months. SH events required a change in mental status necessitating the involvement of another individual to provide treatment. A Poisson model accounting for repeated measures from each participant was used to assess the association of biochemical hypoglycemia frequency, computed from the 7-point finger-stick data, with the development of SH events. RESULTS: The risk of SH during a 3-month period was substantially higher (P < 0.001) when there was at least one hypoglycemic blood glucose value in the preceding 7-point profile, with similar results seen for both the 70 mg/dL (rate ratio = 3.0 [95% confidence interval: 2.6-3.3]) and 54 mg/dL (rate ratio = 2.7 [95% confidence interval: 2.4-3.1]) thresholds. CONCLUSIONS: The occurrence of biochemical hypoglycemia <70 or <54 mg/dL is associated with an increased risk of SH. For this reason as well as the deleterious effects of hypoglycemia on glucose counter-regulation and hypoglycemia awareness, cognition, quality of life, and arrhythmias, it is important in diabetes management to avoid hypoglycemic glucose levels as much as possible.

Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous Glucose Monitoring.

While A1C is well established as an important risk marker for diabetes complications, with the increasing use of continuous glucose monitoring (CGM) to help facilitate safe and effective diabetes management, it is important to understand how CGM metrics, such as mean glucose, and A1C correlate. Estimated A1C (eA1C) is a measure converting the mean glucose from CGM or self-monitored blood glucose readings, using a formula derived from glucose readings from a population of individuals, into an estimate of a simultaneously measured laboratory A1C. Many patients and clinicians find the eA1C to be a helpful educational tool, but others are often confused or even frustrated if the eA1C and laboratory-measured A1C do not agree. In the U.S., the Food and Drug Administration determined that the nomenclature of eA1C needed to change. This led the authors to work toward a multipart solution to facilitate the retention of such a metric, which includes renaming the eA1C the glucose management indicator (GMI) and generating a new formula for converting CGM-derived mean glucose to GMI based on recent clinical trials using the most accurate CGM systems available. The final aspect of ensuring a smooth transition from the old eA1C to the new GMI is providing new CGM analyses and explanations to further understand how to interpret GMI and use it most effectively in clinical practice. This Perspective will address why a new name for eA1C was needed, why GMI was selected as the new name, how GMI is calculated, and how to understand and explain GMI if one chooses to use GMI as a tool in diabetes education or management.

Optimal Sampling Duration for Continuous Glucose Monitoring to Determine Long-Term Glycemic Control.

OBJECTIVE: To determine the minimum sample of continuous glucose monitoring (CGM) data needed to accurately reflect 3 months of glycemic control. RESEARCH DESIGN AND METHODS: Three months of CGM data were collected on 257 individuals (age 10-78 years) with type 1 diabetes in two studies (one using the Abbott FreeStyle Libre Pro™ and the other using the Dexcom™ G4). Correlations were calculated between the full 3 months and incremental sampling periods of CGM data. RESULTS: Correlation to the full 3 months of data improved with an increasing number of days of data collection, plateauing by about 14 days, with an R2 value of 0.84-0.86 for mean glucose, time at 70-180 mg/dL, and time >180 mg/dL, with lower values for time <70 mg/dL (0.76) and coefficient of variation (0.70). CONCLUSIONS: Fourteen days of CGM data provide a good estimation of glucose metrics for a 3-month period.

Sex- and age-dependent effects of celiac disease on growth and weight gain in children with type 1 diabetes: Analysis of the type 1 diabetes Exchange Clinic Registry.

BACKGROUND: Celiac disease (CD) is common in patients with type 1 diabetes (T1D) and effects of CD on growth in children with T1D remain unclear. METHODS: We analyzed heights, weights, and body mass index (BMI) in 215 matched pediatric CD/control pairs in the T1D Exchange Clinic Registry. CD was defined by a clinic-reported diagnosis and positive celiac serology (n = 80) and/or positive small bowel biopsy (n = 135). Cases and controls were matched by age (mean: 14 years), diabetes duration (median: 7 years), sex (57% female), and clinic site. There were 5569 height/weight measurements. RESULTS: Gluten was restricted for varying periods of time in 61% of females and 51% of males with CD. Females with CD were shorter than female controls at all ages (P = 0.01). Weight z-scores were initially lower in preschool females with CD but similar to controls by middle childhood. Males with CD were initially shorter but adult heights were similar. Height in both sexes and weight in males were lower in CD participants diagnosed at younger age. Growth in T1D children with biopsy-proven CD, 76% of them were gluten-restricted, was comparable to that of T1D controls. CONCLUSION: Concurrent CD impairs linear growth in T1D females at all stages of development and in young T1D males. Young females with CD have lower weights, but both sexes have similar weights by middle childhood. Children younger at CD onset remain shorter throughout childhood; males younger at CD onset have persistently lower weights. Long-term gluten restriction may restore weight gain and linear growth in children with CD and T1D.

Continuous Glucose Monitoring Versus Usual Care in Patients With Type 2 Diabetes Receiving Multiple Daily Insulin Injections: A Randomized Trial.

Background: Continuous glucose monitoring (CGM), which studies have shown is beneficial for adults with type 1 diabetes, has not been well-evaluated in those with type 2 diabetes receiving insulin. Objective: To determine the effectiveness of CGM in adults with type 2 diabetes receiving multiple daily injections of insulin. Design: Randomized clinical trial. (The protocol also included a type 1 diabetes cohort in a parallel trial and subsequent second trial.) (ClinicalTrials.gov: NCT02282397). Setting: 25 endocrinology practices in North America. Patients: 158 adults who had had type 2 diabetes for a median of 17 years (interquartile range, 11 to 23 years). Participants were aged 35 to 79 years (mean, 60 years [SD, 10]), were receiving multiple daily injections of insulin, and had hemoglobin A1c (HbA1c) levels of 7.5% to 9.9% (mean, 8.5%). Intervention: Random assignment to CGM (n = 79) or usual care (control group, n = 79). Measurements: The primary outcome was HbA1c reduction at 24 weeks. Results: Mean HbA1c levels decreased to 7.7% in the CGM group and 8.0% in the control group at 24 weeks (adjusted difference in mean change, -0.3% [95% CI, -0.5% to 0.0%]; P = 0.022). The groups did not differ meaningfully in CGM-measured hypoglycemia or quality-of-life outcomes. The CGM group averaged 6.7 days (SD, 0.9) of CGM use per week. Limitation: 6-month follow-up. Conclusion: A high percentage of adults who received multiple daily insulin injections for type 2 diabetes used CGM on a daily or near-daily basis for 24 weeks and had improved glycemic control. Because few insulin-treated patients with type 2 diabetes currently use CGM, these results support an additional management method that may benefit these patients. Primary Funding Source: Dexcom.

Effect of initiating use of an insulin pump in adults with type 1 diabetes using multiple daily insulin injections and continuous glucose monitoring (DIAMOND): a multicentre, randomised controlled trial.

BACKGROUND: The benefit of initiation of insulin pump therapy (continuous subcutaneous insulin infusion; CSII) in patients with type 1 diabetes using continuous glucose monitoring (CGM) has not been studied. We aimed to assess glycaemic outcomes when switching from multiple daily injections (MDI) to CSII in adults with type 1 diabetes using CGM. METHODS: In this multicentre, randomised controlled trial, 75 adults with type 1 diabetes in the CGM group of the DIAMOND trial were randomly assigned via the study website using a computer-generated sequence to continue MDI or switch to CSII, with continuation of CGM, for 28 weeks. The primary outcome was CGM-measured time in the glucose concentration range of 70-180 mg/dL (3·9-10·0 mmol/L). This study is registered with ClinicalTrials.gov, number NCT02282397. FINDINGS: Between April 14, 2015, and May 5, 2016, 37 participants were randomly assigned to the CGM plus CSII group and 38 participants were randomly assigned to the CGM plus MDI group. The study was completed by 36 (97%) of 37 participants in the CGM plus CSII group and 35 (92%) of 38 participants in the CGM plus MDI group. Mean CGM use was 6·7 days per week (SD 0·8) in the CGM plus CSII group and 6·9 days per week (0·3) in the CGM plus MDI group (p=0·86). No participants in the CGM plus CSII group who completed the trial discontinued CSII. Over the follow-up period, mean time in the glucose concentration range of 70-180 mg/dL (3·9-10·0 mmol/L) was 791 min per day (SD 157) in the CGM plus CSII group and 741 min per day (225) in the CGM plus MDI group (adjusted mean treatment group difference: 83 min, 95% CI 17-149; p=0·01). Participants in the CGM plus CSII group had a greater reduction in CGM-measured mean glucose (p=0·005) and hyperglycaemia (on four metrics: p=0·007 for >180 mg/dL [>10·0 mmol/L], p=0·02 for >250 mg/dL [>13·9 mmol/L], p=0·04 for >300 mg/dL [>16·6 mmol/L], and p=0·02 for the area under the curve for 180 mg/dL [10·0 mmol/L]), but also an increase in CGM-measured hypoglycaemia (p=0·0001 for <70 mg/dL [<3·9 mmol/L], p=0·0002 for <60 mg/dL [<3·3 mmol/L], p=0·0009 for <50 mg/dL [<2·8 mmol/L], p=0·0002 for the area over the curve for 70 mg/dL [3·9 mmol/L]). Mean HbA1c change from baseline to 28 weeks was 0·3% (SD 0·9; 3·3 mmol/mol [SD 9·8]) in the CGM plus CSII group and 0·1% (0·4; 1·1 mmol/mol [4·4]) in the CGM plus MDI group (p=0·32). Severe hypoglycaemia occurred in one participant in the CGM plus MDI group, and diabetic ketoacidosis and severe hyperglycaemia occurred in one participant each in the CGM plus CSII group. INTERPRETATION: Our findings show that glycaemic control measured by time in the glucose range of 70-180 mg/dL (3·9-10·0 mmol/L) is improved by initiation of CSII in adults with type 1 diabetes. However, biochemical hypoglycaemia also was increased in the study, which will be important to consider when incorporating these results into clinical practice. FUNDING: Dexcom.

Hypoglycemic Event Frequency and the Effect of Continuous Glucose Monitoring in Adults with Type 1 Diabetes Using Multiple Daily Insulin Injections.

INTRODUCTION: The benefits of continuous glucose monitoring (CGM) in type 1 diabetes have been established among adults using insulin pumps. The DIAMOND randomized clinical trial examined the effectiveness of using CGM in improving glycemic control in participants using insulin injections. The frequency of hypoglycemic events in this trial has not been previously examined. METHODS: Adults with type 1 diabetes using multiple daily insulin injections (MDI) with A1C values of 7.5% to 9.9% and not using CGM were randomized to adopt CGM (CGM group, n = 105) or continue with usual care (control group, n = 53). CGM data were collected from both groups at the beginning of the study and after 3 and 6 months. A hypoglycemic event was defined as a series of at least CGM values less than 3.0 mmol/L, separated by 20 min or more, with no intervening values of 3.0 mmol/L or more. Hypoglycemic event rates per 24 h were compared using a linear model adjusted for the baseline event rate per 24 h, baseline A1C, and site as a random effect. RESULTS: In the CGM group, the median hypoglycemic event rate fell by 30% (0.23 per 24 h at baseline and 0.16 per 24 h at follow-up) while in the control group the rate was nearly unchanged (0.31 per 24 h at baseline and 0.30 per 24 h at follow-up; p value = 0.03). CONCLUSION: In the DIAMOND randomized controlled trial, participants in the CGM group experienced a greater reduction in hypoglycemic event rate than participants receiving usual care in the control group. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02282397.

Continuous Glucose Monitoring in Older Adults With Type 1 and Type 2 Diabetes Using Multiple Daily Injections of Insulin: Results From the DIAMOND Trial.

OBJECTIVE: The objective was to determine the effectiveness of real-time continuous glucose monitoring (CGM) in adults ≥ 60 years of age with type 1 (T1D) or type 2 (T2D) diabetes using multiple daily insulin injections (MDI). METHODS: A multicenter, randomized trial was conducted in the United States and Canada in which 116 individuals ≥60 years (mean 67 ± 5 years) with T1D (n = 34) or T2D (n = 82) using MDI therapy were randomly assigned to either CGM (Dexcom™ G4 Platinum CGM System® with software 505; n = 63) or continued management with self-monitoring blood glucose (SMBG; n = 53). Median diabetes duration was 21 (14, 30) years and mean baseline HbA1c was 8.5 ± 0.6%. The primary outcome, HbA1c at 24 weeks, was obtained for 114 (98%) participants. RESULTS: HbA1c reduction from baseline to 24 weeks was greater in the CGM group than Control group (-0.9 ± 0.7% versus -0.5 ± 0.7%, adjusted difference in mean change was -0.4 ± 0.1%, P < .001). CGM-measured time >250 mg/dL ( P = .006) and glycemic variability ( P = .02) were lower in the CGM group. Among the 61 in the CGM group completing the trial, 97% used CGM ≥ 6 days/week in month 6. There were no severe hypoglycemic or diabetic ketoacidosis events in either group. CONCLUSION: In adults ≥ 60 years of age with T1D and T2D using MDI, CGM use was high and associated with improved HbA1c and reduced glycemic variability. Therefore, CGM should be considered for older adults with diabetes using MDI.

REPLACE-BG: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Well-Controlled Type 1 Diabetes.

OBJECTIVE: To determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: A randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only (n = 149) or CGM+BGM (n = 77) group. The primary outcome was time in range (70-180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%. RESULTS: CGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively (P < 0.001). Mean time in 70-180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI -2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group. CONCLUSIONS: Use of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.

Effect of Continuous Glucose Monitoring on Glycemic Control in Adults With Type 1 Diabetes Using Insulin Injections: The DIAMOND Randomized Clinical Trial.

Importance: Previous clinical trials showing the benefit of continuous glucose monitoring (CGM) in the management of type 1 diabetes predominantly have included adults using insulin pumps, even though the majority of adults with type 1 diabetes administer insulin by injection. Objective: To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections. Design, Setting, and Participants: Randomized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practices in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A1c (HbA1c) levels of 7.5% to 9.9%. Interventions: Random assignment 2:1 to CGM (n = 105) or usual care (control group; n = 53). Main Outcomes and Measures: Primary outcome measure was the difference in change in central-laboratory-measured HbA1c level from baseline to 24 weeks. There were 18 secondary or exploratory end points, of which 15 are reported in this article, including duration of hypoglycemia at less than 70 mg/dL, measured with CGM for 7 days at 12 and 24 weeks. Results: Among the 158 randomized participants (mean age, 48 years [SD, 13]; 44% women; mean baseline HbA1c level, 8.6% [SD, 0.6%]; and median diabetes duration, 19 years [interquartile range, 10-31 years]), 155 (98%) completed the study. In the CGM group, 93% used CGM 6 d/wk or more in month 6. Mean HbA1c reduction from baseline was 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group and 0.5% and 0.4%, respectively, in the control group (repeated-measures model P < .001). At 24 weeks, the adjusted treatment-group difference in mean change in HbA1c level from baseline was -0.6% (95% CI, -0.8% to -0.3%; P < .001). Median duration of hypoglycemia at less than <70 mg/dL was 43 min/d (IQR, 27-69) in the CGM group vs 80 min/d (IQR, 36-111) in the control group (P = .002). Severe hypoglycemia events occurred in 2 participants in each group. Conclusions and Relevance: Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA1c level during 24 weeks. Further research is needed to assess longer-term effectiveness, as well as clinical outcomes and adverse effects. Trial Registration: clinicaltrials.gov Identifier: NCT02282397.

The relationship between neuropsychological assessment, numeracy, and functional status in older adults with type 1 diabetes.

While data are accumulating on the association between neuropsychological performance and real-world endpoints, less is known about the association with medical self-management skills. The self-management of type 1 diabetes (T1D) is often complex, and mismanagement can result in hypoglycaemia and hyperglycaemia and associated morbidity and mortality. The T1D Exchange conducted a case-control study evaluating factors associated with severe hypoglycaemia in older adults (≥ 60 years old) with longstanding T1D (≥ 20 years). A battery of neuropsychological and functional assessments was administered, including measures of diabetes-specific self-management skill (diabetes numeracy) and instrumental activities of daily living (IADL). After adjusting for confounding variables, diabetes numeracy was related to memory and complex speeded attention; while IADL were associated with simple processing speed, executive functioning, complex speeded attention and dominant hand dexterity. The severity of overall cognitive deficit was uniquely associated with both diabetes numeracy and IADL, when controlling for age, education, frailty and depression. This study demonstrates that the cognitive deficits in older adults with T1D have functional implications for both diabetes management and IADL. Further research is needed to determine specific interventions to maximise diabetes self-management in older adults with declining cognition.

Autoimmune Diseases in Children and Adults With Type 1 Diabetes From the T1D Exchange Clinic Registry.

BACKGROUND AND AIMS: Type 1 diabetes (T1D) is associated with other autoimmune diseases (AIDs), but the prevalence and associated predictive factors for these comorbidities of T1D across all age groups have not been fully characterized. MATERIALS AND METHODS: Data obtained from 25 759 participants with T1D enrolled in the T1D Exchange Registry were used to analyze the types and frequency of AIDs as well as their relationships to gender, age, and race/ethnicity. Diagnoses of autoimmune diseases, represented as ordinal categories (0, 1, 2, 3, or more AIDs) were obtained from medical records of Exchange Registry participants. RESULTS: Among the 25 759 T1D Exchange participants, 50% were female, 82% non-Hispanic white, mean age was 23.0 ± 16.9 years and mean duration of diabetes was 11 years. Of these participants, 6876 (27%) were diagnosed with at least one AID. Frequency of two or more AIDs increased from 4.3% in participants aged younger than 13 years to 10.4% in those aged 50 years or older. The most common AIDs were thyroid (6097, 24%), gastrointestinal (1530, 6%), and collagen vascular diseases (432, 2%). Addison's disease was rare (75, 0.3%). The prevalence of one or more AIDs was increased in females and non-Hispanic whites and with older age. CONCLUSIONS: In the T1D Exchange Clinic Registry, a diagnosis of one or more AIDs in addition to T1D is common, particularly in women, non-Hispanic whites, and older individuals. Results of this study have implications for both primary care and endocrine practice and will allow clinicians to better anticipate and manage the additional AIDs that develop in patients with T1D.

The effect of donor diabetes history on graft failure and endothelial cell density 10 years after penetrating keratoplasty.

OBJECTIVE: To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PK) in the Cornea Donor Study. DESIGN: Multicenter, prospective, double-masked, controlled clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing PK for a moderate risk condition, principally Fuchs' dystrophy or pseudophakic or aphakic corneal edema, were enrolled by 105 surgeons from 80 clinical sites in the United States. METHODS: Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained before surgery (baseline) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD. MAIN OUTCOME MEASURES: Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD. RESULTS: There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD, or ECD values longitudinally over time in unadjusted analyses, nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 patients receiving a cornea from a donor with diabetes versus 26% in the 891 patients receiving a cornea from a donor without diabetes (95% confidence interval for the difference, -10% to 6%; unadjusted P=0.60). Baseline ECD (P=0.71), 10-year ECD (P>0.99), and changes in ECD over 10 years (P=0.86) were similar comparing donor groups with and without diabetes. CONCLUSIONS: The study results do not suggest an association between donor diabetes and PK outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool. Thus, the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty, or both, warrants further study with more precise measures of diabetes and its complications.

A mathematical model to predict endothelial cell density following penetrating keratoplasty with selective dropout from graft failure.

PURPOSE: We constructed several mathematical models that predict endothelial cell density (ECD) for patients after penetrating keratoplasty (PK) for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). METHODS: In a subset (n = 591) of Cornea Donor Study participants, postoperative ECD was determined by a central reading center. Various statistical models were considered to estimate the ECD trend longitudinally over 10 years of follow-up. A biexponential model with and without a logarithm transformation was fit using the Gauss-Newton nonlinear least squares algorithm. To account for correlated data, a log-polynomial model was fit using the restricted maximum likelihood method. A sensitivity analysis for the potential bias due to selective dropout was performed using Bayesian analysis techniques. RESULTS: The three models using a logarithm transformation yield similar trends, whereas the model without the transform predicts higher ECD values. The adjustment for selective dropout turns out to be negligible. However, this is possibly due to the relatively low rate of graft failure in this cohort (19% at 10 years). Fuchs' dystrophy and pseudophakic/aphakic corneal edema (PACE) patients had similar ECD decay curves, with the PACE group having slightly higher cell densities by 10 years. CONCLUSIONS: Endothelial cell loss after PK can be modeled via a log-polynomial model, which accounts for the correlated data from repeated measures on the same subject. This model is not significantly affected by the selective dropout due to graft failure. Our findings warrant further study on how this may extend to ECD following endothelial keratoplasty.