Nicole C. Foster

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.

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.

Insulin pump use in young children in the T1D Exchange clinic registry is associated with lower hemoglobin A1c levels than injection therapy

Insulin delivery via injection and continuous subcutaneous insulin infusion (CSII) via insulin pump were compared in a cross‐sectional study (n = 669) and retrospective longitudinal study (n = 1904) of young children (<6 yr) with type 1 diabetes (T1D) participating in the T1D Exchange clinic registry. Use of CSII correlated with longer T1D duration (p < 0.001), higher parental education (p < 0.001), and annual household income (p < 0.006) but not with race/ethnicity. Wide variation in pump use was observed among T1D Exchange centers even after adjusting for these factors, suggesting that prescriber preference is a substantial determinant of CSII use. Hemoglobin A1c (HbA1c) was lower in pump vs. injection users (7.9 vs. 8.5%, adjusted p < 0.001) in the cross‐sectional study. In the longitudinal study, HbA1c decreased after initiation of CSII by 0.2%, on average (p < 0.001). Frequency of a severe hypoglycemia (SH) event did not differ in pump vs. injection users (p = 0.2). Frequency of ≥1 parent‐reported diabetic ketoacidosis (DKA) event in the prior year was greater in pump users than injection users (10 vs. 8%, p = 0.04). No differences between pump and injection users were observed for clinic‐reported DKA events. Children below 6 yr have many unique metabolic characteristics, feeding behaviors, and care needs compared with older children and adolescents. These data support the use of insulin pumps in this youngest age group, and suggest that metabolic control may be improved without increasing the frequency of SH, but care should be taken as to the possibly increased risk of DKA.

Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry.

Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes‐related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre‐adolescence‐to‐adolescence and adolescence‐to‐young adulthood, and the demographic and clinical factors associated with these changes.

Optical treatment of strabismic and combined strabismic-anisometropic amblyopia.

OBJECTIVE To determine visual acuity improvement in children with strabismic and combined strabismic-anisometropic (combined-mechanism) amblyopia treated with optical correction alone and to explore factors associated with improvement. DESIGN Prospective, multicenter, cohort study. PARTICIPANTS We included 146 children 3 to <7 years old with previously untreated strabismic amblyopia (n = 52) or combined-mechanism amblyopia (n = 94). METHODS Optical treatment was provided as spectacles (prescription based on a cycloplegic refraction) that were worn for the first time at the baseline visit. Visual acuity with spectacles was measured using the Amblyopia Treatment Study HOTV visual acuity protocol at baseline and every 9 weeks thereafter until no further improvement in visual acuity. Ocular alignment was assessed at each visit. MAIN OUTCOME MEASURES Visual acuity 18 weeks after baseline. RESULTS Overall, amblyopic eye visual acuity improved a mean of 2.6 lines (95% confidence interval [CI], 2.3-3.0), with 75% of children improving ≥ 2 lines and 54% improving ≥ 3 lines. Resolution of amblyopia occurred in 32% (95% CI, 24%-41%) of the children. The treatment effect was greater for strabismic amblyopia than for combined-mechanism amblyopia (3.2 vs 2.3 lines; adjusted P = 0.003). Visual acuity improved regardless of whether eye alignment improved. CONCLUSIONS Optical treatment alone of strabismic and combined-mechanism amblyopia results in clinically meaningful improvement in amblyopic eye visual acuity for most 3- to <7-year-old children, resolving in at least one quarter without the need for additional treatment. Consideration should be given to prescribing refractive correction as the sole initial treatment for children with strabismic or combined-mechanism amblyopia before initiating other therapies. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Rates of Diabetic Ketoacidosis: International Comparison With 49,859 Pediatric Patients With Type 1 Diabetes From England, Wales, the U.S., Austria, and Germany

OBJECTIVE Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly advanced, yet differing, health care systems with an aim to identify factors associated with DKA admissions. RESEARCH DESIGN AND METHODS Data from 49,859 individuals <18 years with type 1 diabetes duration ≥1 year from the Prospective Diabetes Follow-up Registry (DPV) initiative (n = 22,397, Austria and Germany), the National Paediatric Diabetes Audit (NPDA; n = 16,314, England and Wales), and the T1D Exchange (T1DX; n = 11,148, U.S.) were included. DKA was defined as ≥1 hospitalization for hyperglycemia with a pH <7.3 during the prior year. Data were analyzed using multivariable logistic regression models. RESULTS The frequency of DKA was 5.0% in DPV, 6.4% in NPDA, and 7.1% in T1DX, with differences persisting after demographic adjustment (P < 0.0001). In multivariable analyses, higher odds of DKA were found in females (odds ratio [OR] 1.23, 99% CI 1.10–1.37), ethnic minorities (OR 1.27, 99% CI 1.11–1.44), and HbA1c ≥7.5% (≥58 mmol/mol) (OR 2.54, 99% CI 2.09–3.09 for HbA1c from 7.5 to <9% [58 to <75 mmol/mol] and OR 8.74, 99% CI 7.18–10.63 for HbA1c ≥9.0% [≥75 mmol/mol]). CONCLUSIONS These multinational data demonstrate high rates of DKA in childhood type 1 diabetes across three registries/audits and five nations. Females, ethnic minorities, and HbA1c above target were all associated with an increased risk of DKA. Targeted DKA prevention programs could result in substantial health care cost reduction and reduced patient morbidity and mortality.

Continuous Glucose Monitoring in Patients With Type 1 Diabetes Using Insulin Injections

Continuous glucose monitoring (CGM) has been demonstrated in randomized trials to improve glucose control in patients with type 1 diabetes (T1D) (1–3); however, most of the participants in these trials have used a pump for insulin delivery, and the use of CGM in T1D patients receiving insulin by injection has not been well studied. We used the T1D Exchange registry database to assess the impact of CGM on HbA1c in insulin injection users. Details on the informed consent process, eligibility criteria, and data collection methods have been previously published (4). Participants were defined as CGM users if CGM was used for real-time diabetes management during the 30 days prior to the clinic visit. Among the 17,731 registry participants with T1D duration >1 year who had a clinic visit between June 2014 and October 2015, 6,222 (35%) used injections alone, 8,783 (50%) used pump alone, 2,316 (13%) used pump with CGM, and 410 (2%) used injections with CGM. A Dexcom CGM was being used by …

Intranasal Glucagon for Treatment of Insulin-Induced Hypoglycemia in Adults With Type 1 Diabetes: A Randomized Crossover Noninferiority Study

OBJECTIVE Treatment of severe hypoglycemia with loss of consciousness or seizure outside of the hospital setting is presently limited to intramuscular glucagon requiring reconstitution immediately prior to injection, a process prone to error or omission. A needle-free intranasal glucagon preparation was compared with intramuscular glucagon for treatment of insulin-induced hypoglycemia. RESEARCH DESIGN AND METHODS At eight clinical centers, a randomized crossover noninferiority trial was conducted involving 75 adults with type 1 diabetes (mean age, 33 ± 12 years; median diabetes duration, 18 years) to compare intranasal (3 mg) versus intramuscular (1 mg) glucagon for treatment of hypoglycemia induced by intravenous insulin. Success was defined as an increase in plasma glucose to ≥70 mg/dL or ≥20 mg/dL from the glucose nadir within 30 min after receiving glucagon. RESULTS Mean plasma glucose at time of glucagon administration was 48 ± 8 and 49 ± 8 mg/dL at the intranasal and intramuscular visits, respectively. Success criteria were met at all but one intranasal visit and at all intramuscular visits (98.7% vs. 100%; difference 1.3%, upper end of 1-sided 97.5% CI 4.0%). Mean time to success was 16 min for intranasal and 13 min for intramuscular (P < 0.001). Head/facial discomfort was reported during 25% of intranasal and 9% of intramuscular dosing visits; nausea (with or without vomiting) occurred with 35% and 38% of visits, respectively. CONCLUSIONS Intranasal glucagon was highly effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes. Although the trial was conducted in a controlled setting, the results are applicable to real-world management of severe hypoglycemia, which occurs owing to excessive therapeutic insulin relative to the impaired or absent endogenous glucagon response.

Depression in Adults in the T1D Exchange Clinic Registry

OBJECTIVE Little is known about the frequency of depression in adults with type 1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange clinic registry allowed us to explore depression in a large, heterogeneous sample. RESEARCH DESIGN AND METHODS Participants ≥18 years old (N = 6,172; median age 34 years; median diabetes duration 16 years; 55% female; and 89% non-Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a validated, reliable measure of current depression. Probable major depression was defined in four ways: PHQ-8 ≥10, PHQ-8 ≥12, per diagnostic algorithm, and as a continuous variable. Characteristics and clinical outcomes of those with and without depression were compared using logistic and linear regression models. RESULTS A total of 4.6–10.3% of participants were classified as probable major depression depending on how defined. Participants classified as depressed were more likely female, nonwhite race/ethnicity, to have a lower household income and lower education level, to exercise less often, to miss insulin doses, and to have one or more complications (neuropathy, nephropathy, treatment for retinopathy, or cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the depressed versus not depressed groups (8.4 ± 1.7% [68 ± 8.6 mmol/mol] vs. 7.8 ± 1.4% [62 ± 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed participants. CONCLUSIONS In the T1D Exchange clinic registry, adults with probable major depression have worse clinical outcomes than those not depressed. Whether identification and treatment of depression improves diabetes outcomes requires study. Depression is common in T1D, and better identification and treatment of this comorbid condition is needed.

Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes

OBJECTIVE Treatment of severe hypoglycemia outside of the hospital setting is limited to intramuscular glucagon requiring reconstitution prior to injection. The current study examined the safety and dose-response relationships of a needle-free intranasal glucagon preparation in youth aged 4 to <17 years. RESEARCH DESIGN AND METHODS A total of 48 youth with type 1 diabetes completed the study at seven clinical centers. Participants in the two youngest cohorts (4 to <8 and 8 to <12 years old) were randomly assigned to receive either 2 or 3 mg intranasal glucagon in two separate sessions or to receive a single, weight-based dose of intramuscular glucagon. Participants aged 12 to <17 years received 1 mg intramuscular glucagon in one session and 3 mg intranasal glucagon in the other session. Glucagon was given after glucose was lowered to <80 mg/dL (mean nadir ranged between 67 and 75 mg/dL). RESULTS All 24 intramuscular and 58 of the 59 intranasal doses produced a ≥25 mg/dL rise in glucose from nadir within 20 min of dosing. Times to peak plasma glucose and glucagon levels were similar under both intramuscular and intranasal conditions. Transient nausea occurred in 67% of intramuscular sessions versus 42% of intranasal sessions (P = 0.05); the efficacy and safety of the 2- and 3-mg intranasal doses were similar in the youngest cohorts. CONCLUSIONS Results of this phase 1, pharmacokinetic, and pharmacodynamic study support the potential efficacy of a needle-free glucagon nasal powder delivery system for treatment of hypoglycemia in youth with type 1 diabetes. Given the similar frequency and transient nature of adverse effects of the 2- and 3-mg intranasal doses in the two youngest cohorts, a single 3-mg intranasal dose appears to be appropriate for use across the entire 4- to <17-year age range.