Kellee M. Miller

Randomized Trial Evaluating Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema

OBJECTIVE Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). DESIGN Multicenter, randomized clinical trial. PARTICIPANTS A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. METHODS Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (> or =24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. MAIN OUTCOME MEASURES Best-corrected visual acuity and safety at 1 year. RESULTS The 1-year mean change (+/-standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9+/-11, P<0.001) and ranibizumab + deferred laser group (+9+/-12, P<0.001) but not in the triamcinolone + prompt laser group (+4+/-13, P=0.31) compared with the sham + prompt laser group (+3+/-13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. CONCLUSIONS Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.

Current State of Type 1 Diabetes Treatment in the U.S.: Updated Data From the T1D Exchange Clinic Registry

To examine the overall state of metabolic control and current use of advanced diabetes technologies in the U.S., we report recent data collected on individuals with type 1 diabetes participating in the T1D Exchange clinic registry. Data from 16,061 participants updated between 1 September 2013 and 1 December 2014 were compared with registry enrollment data collected from 1 September 2010 to 1 August 2012. Mean hemoglobin A1c (HbA1c) was assessed by year of age from <4 to >75 years. The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and 8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c decreased from 8.3% (67 mmol/mol) in 2–4-year-olds to 8.1% (65 mmol/mol) at 7 years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds. Subsequently, mean HbA1c values decline gradually until ∼30 years of age, plateauing at 7.5–7.8% (58–62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain all too common complications of treatment, especially in older (SH) and younger patients (DKA). Insulin pump use increased slightly from enrollment (58–62%), and use of continuous glucose monitoring (CGM) did not change (7%). Although the T1D Exchange registry findings are not population based and could be biased, it is clear that there remains considerable room for improving outcomes of treatment of type 1 diabetes across all age-groups. Barriers to more effective use of current treatments need to be addressed and new therapies are needed to achieve optimal metabolic control in people with type 1 diabetes.

The T1D Exchange Clinic Registry

CONTEXT The T1D Exchange includes a clinic-based registry, a patient-centric web site called Glu, and a biobank. OBJECTIVE The aim of the study was to describe the T1D Exchange clinic registry and provide an overview of participant characteristics. DESIGN Data obtained through participant completion of a questionnaire and chart extraction include diabetes history, management, and monitoring; general health; lifestyle; family history; socioeconomic factors; medications; acute and chronic diabetic complications; other medical conditions; and laboratory results. SETTING Data were collected from 67 endocrinology centers throughout the United States. PATIENTS We studied 25,833 adults and children with presumed autoimmune type 1 diabetes (T1D). RESULTS Participants ranged in age from less than 1 to 93 yr, 50% were female, 82% were Caucasian, 50% used an insulin pump, 6% used continuous glucose monitoring, and 16% had a first-degree family member with T1D. Glycosylated hemoglobin at enrollment averaged 8.3% and was highest in 13 to 25 yr olds. The prevalence of renal disease was ≤4% until T1D was present for at least 10 yr, and retinopathy treatment was ≤2% until T1D was present for at least 20 yr. A severe hypoglycemic event (seizure or coma) in the prior 12 months was reported by 7% of participants and diabetic ketoacidosis in the prior 12 months by 8%. CONCLUSIONS The T1D Exchange clinic registry provides a database of important information on individuals with T1D in the United States. The rich dataset of the registry provides an opportunity to address numerous issues of relevance to clinicians and patients, including assessments of associations between patient characteristics and diabetes management factors with outcomes.

Most Youth With Type 1 Diabetes in the T1D Exchange Clinic Registry Do Not Meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines

OBJECTIVE To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids. RESEARCH DESIGN AND METHODS Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ≥1 year. RESULTS American Diabetes Association HbA1c targets of <8.5% for those younger than 6 years, <8.0% for those 6 to younger than 13 years old, and <7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of <85th percentile. CONCLUSIONS Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.

Evidence of a Strong Association Between Frequency of Self-Monitoring of Blood Glucose and Hemoglobin A1c Levels in T1D Exchange Clinic Registry Participants

OBJECTIVE Despite substantial evidence of the benefit of frequent self-monitoring of blood glucose (SMBG) in type 1 diabetes, certain insurers limit the number of test strips that they will provide. The large database of the T1D Exchange clinic registry provided an opportunity to evaluate the relationship between the number of SMBG measurements per day and HbA1c levels across a wide age range of children and adults. RESEARCH DESIGN AND METHODS The analysis included 20,555 participants in the T1D Exchange clinic registry with type 1 diabetes ≥1 year and not using a continuous glucose monitor (11,641 younger than age 18 years and 8,914 18 years old or older). General linear models were used to assess the association between the number of SMBG measurements and HbA1c levels after adjusting for potential confounding variables. RESULTS A higher number of SMBG measurements per day were associated with non-Hispanic white race, insurance coverage, higher household income, and use of an insulin pump for insulin delivery (P < 0.001 for each factor). After adjusting for these factors, a higher number of SMBG measurements per day was strongly associated with a lower HbA1c level (adjusted P < 0.001), with the association being present in all age-groups and in both insulin pump and injection users. CONCLUSIONS There is a strong association between higher SMBG frequency and lower HbA1c levels. It is important for insurers to consider that reducing restrictions on the number of test strips provided per month may lead to improved glycemic control for some patients with type 1 diabetes.

Factors predictive of use and of benefit from continuous glucose monitoring in type 1 diabetes.

OBJECTIVE To evaluate factors associated with successful use of continuous glucose monitoring (CGM) among participants with intensively treated type 1 diabetes in the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Randomized Clinical Trial. RESEARCH DESIGN AND METHODS The 232 participants randomly assigned to the CGM group (165 with baseline A1C ≥7.0% and 67 with A1C <7.0%) were asked to use CGM on a daily basis. The associations of baseline factors and early CGM use with CGM use ≥6 days/week in the 6th month and with change in A1C from baseline to 6 months were evaluated in regression models. RESULTS The only baseline factors found to be associated with greater CGM use in month 6 were age ≥25 years (P < 0.001) and more frequent self-reported prestudy blood glucose meter measurements per day (P < 0.001). CGM use and the percentage of CGM glucose values between 71 and 180 mg/dl during the 1st month were predictive of CGM use in month 6 (P < 0.001 and P = 0.002, respectively). More frequent CGM use was associated with a greater reduction in A1C from baseline to 6 months (P < 0.001), a finding present in all age-groups. CONCLUSIONS After 6 months, near-daily CGM use is more frequent in intensively treated adults with type 1 diabetes than in children and adolescents, although in all age-groups near-daily CGM use is associated with a similar reduction in A1C. Frequency of blood glucose meter monitoring and initial CGM use may help predict the likelihood of long-term CGM benefit in intensively treated patients with type 1 diabetes of all ages.

Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry.

CONTEXT Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D). OBJECTIVE Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D. DESIGN AND SETTING We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology centers. PATIENTS Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D for ≥2 years. RESULTS Higher frequencies of SH and DKA were associated with lower socioeconomic status (P < .001). SH was strongly associated with diabetes duration (P < .001), with 18.6% of those with diabetes ≥40 years having an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of 7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels <7.0% (<53 mmol/mol) or >7.5% (>58 mmol/mol). DKA frequency increased with higher HbA1c levels (P < .001), with 21.0% of those with HbA1c ≥10.0% (≥86 mmol/mol) having an event in the past 12 months. CONCLUSIONS SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those with HbA1c ≥10.0% (≥86 mmol/mol), should be largely preventable. In contrast, SH, most frequent with diabetes ≥40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly in patients with very low HbA1c levels.

Real-time continuous glucose monitoring among participants in the T1D Exchange clinic registry.

OBJECTIVE To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]). RESEARCH DESIGN AND METHODS Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days. RESULTS Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ≥26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (≥6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ≤15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year. CONCLUSIONS CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D Exchange clinic registry

Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) are common serious acute complications of type 1 diabetes (T1D). The aim of this study was to determine the frequency of SH and DKA and identify factors related to their occurrence in the T1D Exchange pediatric and young adult cohort.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison

Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries.