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

A Mathematical Model to Predict Endothelial Cell Density Following Penetrating Keratoplasty With Selective Dropout From Graft Failure

Citation: Riddlesworth TD, Kollman C, Lass JH, et al. A mathematical model to predict endothelial cell density following penetrating keratoplasty with selective dropout from graft failure. Invest Ophthalmol Vis Sci. 2014;55:8409-8415. DOI:10.1167/ iovs.14-15683 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 ¼ 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

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 \u3e180 mg/dL [\u3e10·0 mmol/L], p=0·02 for \u3e250 mg/dL [\u3e13·9 mmol/L], p=0·04 for \u3e300 mg/dL [\u3e16·6 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/dL [ 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

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

ObjectiveTo 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 methodsA 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%.ResultsCGM 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.ConclusionsUse 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

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 HbA 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 ( 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