Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk of (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb+; (2) when people who are IAb+ are initially identified there is a need for confirmation using a second sample; (3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care.

Twelve-month psychosocial outcomes of continuous glucose monitoring with behavioural support in parents of young children with type 1 diabetes.

AIM: Managing type 1 diabetes in young children can cause significant stress for parents. Continuous glucose monitoring (CGM) may reduce parental burden. The Strategies to Enhance CGM Use in Early Childhood (SENCE) trial randomized parents of children (ages 2 to <8 years) with type 1 diabetes to CGM with family behavioural intervention (CGM + FBI), CGM alone (Standard-CGM) or blood glucose monitoring for 26 weeks before receiving CGM + FBI (BGM-Crossover). This report assesses changes in psychosocial outcomes for all groups over 52 weeks. METHODS: CGM + FBI (n = 45), Standard-CGM (n = 42) and BGM-Crossover (n = 44) participants completed psychosocial assessments at baseline, 26 weeks and 52 weeks. Repeated measures linear regression models evaluated change within and between treatment groups. RESULTS: The BGM-Crossover group reported improved diabetes burden (Δ -6.9, 95% CI [-11.3, -2.6], p = 0.003), fear of hypoglycaemia (Δ -6.4, CI [-10.1, -2.6], p = 0.002) and technology satisfaction (Δ 7.3, CI [2.4, 12.2], p = 0.005) from 26 to 52 weeks, similar to published findings in the CGM + FBI group over the first 26 weeks. The Standard-CGM group reported increased technology satisfaction (Δ 7.3, CI [0.6, 14.0], p = 0.027) from baseline to 52 weeks. The CGM + FBI group reported less diabetes burden and fear of hypoglycaemia from baseline to 52 weeks, but changes were not statistically significant. Scores from 26 to 52 weeks did not deteriorate. CONCLUSIONS: Parents demonstrated psychosocial benefits following FBI that appeared to maintain without additional intervention. CGM-focused education with behavioural support likely helps parents of young children with type 1 diabetes reduce burden and worry in the short- and long-term.

Development and delivery of a brief family behavioral intervention to support continuous glucose monitor use in young children with type 1 diabetes.

BACKGROUND: Despite potential glycemic benefits of continuous glucose monitor (CGM) use in young children with type 1 diabetes, psychosocial and behavioral challenges may interfere with sustained use. We developed a 5-session family behavioral intervention (FBI) to support CGM use. OBJECTIVE: We report on the multi-step development of the FBI, training interventionists, implementation in a 14-site clinical trial, and participant satisfaction. METHODS: A multidisciplinary team created the FBI based on mixed-methods (i.e., survey data, qualitative research) preliminary work with parents of young children. Investigators trained non-physician staff to deliver the 5 sessions per an intervention manual. Trial participants received the FBI either during the first (FBI group, n = 50) or second 6-months (Crossover group, n = 44) of the 1-year trial. Investigators listened to session recordings to rate intervention fidelity, and participants rated satisfaction with the FBI. RESULTS: The complete 5-session FBI was delivered to 89% of participants, in-person (73%) or by telephone (23%). Sessions lasted 23 min on average, and fidelity was high across sessions. Over 80% of participants rated very high satisfaction with all aspects of the FBI and offered few recommendations for improvement. CONCLUSIONS: Having been developed based on experiences and input of families of young children with type 1 diabetes, the FBI represented a novel behavioral approach to enhance sustained CGM use during a challenging developmental period. Evidence of strong feasibility and acceptability supports its potential for implementation in research and clinical care. As diabetes technologies evolve, the FBI may continue to be refined to address parents' most relevant concerns.

Differences between patients with type 1 diabetes with optimal and suboptimal glycaemic control: A real-world study of more than 30 000 patients in a US electronic health record database.

AIMS: To use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States. MATERIALS AND METHODS: Retrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] <7.0% vs. ≥7.0% [53 mmol/mol]) at the closest measurement to the index date. RESULTS: Of 31 430 adults with T1D, 79.9% had suboptimal glycaemic control (mean HbA1c 8.8% [73 mmol/mol]). These patients were more likely to be younger, African American, uninsured or on Medicaid, obese, smokers, have uncontrolled hypertension and have depression. Despite worse glycaemic control and increased CV risk factors of uncontrolled hypertension, obesity and smoking, rates of coronary heart disease and stroke were not higher in these patients. Patients with suboptimal glycaemic control also experienced more diabetes complications (including SH, DKA and microvascular disease) and utilized more emergency care, with more emergency department visits and inpatient stays. CONCLUSION: This real-world study of >30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.

Undertreatment of cardiovascular risk factors in the type 1 diabetes exchange clinic network (United States) and the prospective diabetes follow-up (Germany/Austria) registries.

AIM: To examine the control of cardiovascular risk factors in type 1 diabetes (T1D) registries from the United States and Germany/Austria. MATERIALS AND METHODS: Data on individuals aged ≥12 years with T1D for ≥1 year, from the T1D Exchange Clinic Network (T1DX, United States) and the Prospective Diabetes Follow-up Registry (DPV, Germany/Austria) from 1 January 2016 to 31 March 2018 were analysed. Linear and logistic regression models adjusted for age groups, sex, duration of diabetes and minority status were used to compare clinical characteristics and achievement of diabetes management targets between registries. RESULTS: The cohort consisted of 47 936 patients (T1DX, n = 19 442; DPV, n = 28 494). Achievement of HbA1c goals (<7.0%, ages 18-65 years; all others, <7.5%) was better in the DPV for those aged <65 years (all P < .001). However, more older adults (aged ≥65 years) in the T1DX achieved an HbA1c goal of <7.5% compared with DPV (70% vs. 50%, P < .001). The frequency of patients with overweight (53% vs. 51%, P < .001) and obesity (19% vs. 9%, P < .001) was higher in T1DX. The frequency of meeting blood pressure goals (84% vs. 66%, P < .001) and lipid goals (73% vs. 62%, P < .001) was higher in T1DX; this was observed across all age groups (all P < .001). Few young adults aged <26 years received antihypertensive and lipid-lowering medications, respectively, despite indications in both registries (T1DX: 5% and 3%, DPV: 3% and 1%). CONCLUSION: A minority of patients with T1D achieve glycaemic targets and the majority are inadequately treated for hypertension and dyslipidaemia. This highlights the need for improved diabetes and cardiovascular risk management strategies in T1D.

"I'm essentially his pancreas": Parent perceptions of diabetes burden and opportunities to reduce burden in the care of children <8 years old with type 1 diabetes.

BACKGROUND: Across all age groups, management of type 1 diabetes (T1D) places substantial responsibility and emotional burden upon families. This study explored parent perceptions of the burdens of caring for very young children with T1D. METHODS: Semi-structured qualitative interviews were conducted with parents (85% mothers) of 79 children with T1D, aged 1 to <8 years old, from four diverse pediatric diabetes clinical centers. Interviews were transcribed, coded, and analyzed using hybrid thematic analysis to derive central themes. RESULTS: Youth (77% White) had T1D for ≥6 months: age (M ± SD) 5.2 ± 1.5 years, diabetes duration 2.4 ± 1.3 years, and A1c 63 ± 10 mmol/mol (7.9 ± 0.9%); 66% used an insulin pump and 61% used CGM. Three major themes emerged related to diabetes burdens: (a) the emotional burden of diabetes on themselves and their children, (b) the burden of finding, training, and trusting effective secondary caregivers to manage the child's diabetes, and (c) suggestions for how more comprehensive, personalized diabetes education from healthcare providers for parents and secondary caregivers could help reduce parent burden and worry. CONCLUSIONS: In families with very young children with T1D, parental perceptions of the burden of managing diabetes are common and could be mitigated by tailored education programs that increase parent knowledge, bolster parents' confidence in themselves, and increase trust in their secondary caregivers to manage diabetes. Reduced parental burden and increased caregiver knowledge may positively impact child's glycemic control, as well as improve parent and child quality of life.

Effect of Continuous Glucose Monitoring on Glycemic Control in Adolescents and Young Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Adolescents and young adults with type 1 diabetes exhibit the worst glycemic control among individuals with type 1 diabetes across the lifespan. Although continuous glucose monitoring (CGM) has been shown to improve glycemic control in adults, its benefit in adolescents and young adults has not been demonstrated. Objective: To determine the effect of CGM on glycemic control in adolescents and young adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted between January 2018 and May 2019 at 14 endocrinology practices in the US including 153 individuals aged 14 to 24 years with type 1 diabetes and screening hemoglobin A1c (HbA1c) of 7.5% to 10.9%. Interventions: Participants were randomized 1:1 to undergo CGM (CGM group; n = 74) or usual care using a blood glucose meter for glucose monitoring (blood glucose monitoring [BGM] group; n = 79). Main Outcomes and Measures: The primary outcome was change in HbA1c from baseline to 26 weeks. There were 20 secondary outcomes, including additional HbA1c outcomes, CGM glucose metrics, and patient-reported outcomes with adjustment for multiple comparisons to control for the false discovery rate. Results: Among the 153 participants (mean [SD] age, 17 [3] years; 76 [50%] were female; mean [SD] diabetes duration, 9 [5] years), 142 (93%) completed the study. In the CGM group, 68% of participants used CGM at least 5 days per week in month 6. Mean HbA1c was 8.9% at baseline and 8.5% at 26 weeks in the CGM group and 8.9% at both baseline and 26 weeks in the BGM group (adjusted between-group difference, -0.37% [95% CI, -0.66% to -0.08%]; P = .01). Of 20 prespecified secondary outcomes, there were statistically significant differences in 3 of 7 binary HbA1c outcomes, 8 of 9 CGM metrics, and 1 of 4 patient-reported outcomes. The most commonly reported adverse events in the CGM and BGM groups were severe hypoglycemia (3 participants with an event in the CGM group and 2 in the BGM group), hyperglycemia/ketosis (1 participant with an event in CGM group and 4 in the BGM group), and diabetic ketoacidosis (3 participants with an event in the CGM group and 1 in the BGM group). Conclusions and Relevance: Among adolescents and young adults with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in glycemic control over 26 weeks. Further research is needed to understand the clinical importance of the findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03263494.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Dyslipidaemia and statin use in individuals aged 10 to <40 years in the T1D Exchange clinic registry.

For individuals aged 10 to <40 years with type 1 diabetes and dyslipidaemia, US national guidelines recommend consideration of statin therapy based on age, low-density lipoprotein cholesterol (LDL-C) level and other cardiovascular risk factors. We evaluated dyslipidaemia prevalence, statin therapy use, and associations between not meeting target LDL-C [<100 mg/dL (<5.55 mmol/L)] and other cardiovascular disease (CVD) risk factors in individuals aged 10 to <40 years in the T1D Exchange clinic registry. In 7223 participants, statin use was 2% in 10 to <18 year olds, 4% in 18 to <25 year olds, and 21% in 25 to <40 year olds. Individuals not on statin therapy with LDL-C above target were more likely to have ≥1 additional CVD risk factor(s) than those with LDL-C in the target range for all age groups (all P < 0.01). While most individuals not on statin therapy had LDL-C in the target range, those who did not were more likely to have ≥1 additional CVD risk factor(s), and therefore longitudinal study of lipid levels and statin use is needed to see if treatment of dyslipidaemia to target LDL-C levels may lower the risk of future CVD in individuals aged 10 to <40 years with type 1 diabetes.

Continuous glucose monitoring and glycemic control among youth with type 1 diabetes: International comparison from the T1D Exchange and DPV Initiative.

BACKGROUND: To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry). METHODS: Registry participants aged <18 years with T1D duration ≥1 year encompassed 29 007 individuals in 2011 and 29 150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records. RESULTS: CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic minority status or insulin delivery method. The increase in CGM use was most pronounced in the youngest patients, and usage rates remain lowest for adolescent patients in 2016. For both registries in 2016, mean HbA1c was lower among CGM users regardless of insulin delivery method compared to pump only (P < 0.001) and injection only (P < 0.001), and CGM users were more likely to achieve glycemic target of HbA1c <7.5% (56% vs 43% for DPV and 30% vs 15% for T1DX, P < 0.001). T1DX participants had a higher mean HbA1c compared with DPV despite whether they were CGM users or non-users; however, the difference was less pronounced in CGM users (P < 0.001). CONCLUSIONS: Pediatric CGM use increased in both registries and was associated with lower mean HbA1c regardless of insulin delivery modality.

Nighttime is the worst time: Parental fear of hypoglycemia in young children with type 1 diabetes.

BACKGROUND: Fear of hypoglycemia is common in parents of young children with type 1 diabetes (T1D), but little is known about the specific fears that parents most often experience. Hypoglycemia fear has been associated with poorer glycemic control in older children, though not yet studied in a large cohort of very young children. MATERIALS AND METHODS: Parents of 549 children <7 years (mean 5.2 ± 1.2 years [19% <3 years]) with a mean diabetes duration of 2.4 ± 1.0 years (range 1-6 years) and mean HbA1c 8.2% ± 1.1% (66 ± 12 mmol/mol) registered in the T1D Exchange completed the worry scale of the Hypoglycemia Fear Survey modified for parents (HFS-P). RESULTS: Mean parental fear of hypoglycemia worry score was 36.1 ± 23.1 (possible range 0-100), with most frequent worries related to the child having a low while asleep and the child not recognizing a low. The mean worry score was not associated with the child's age, glycemic control, or recent severe hypoglycemic event. Parental worries about lows while sleeping were significantly higher in pump users than non-users (61% vs. 45%; P < .001), and tended to be higher in CGM users than non-users (62% vs 51%; P = .02). CONCLUSIONS: The greatest worries of parents of young children with T1D were related to hypoglycemia during sleep and other times/circumstances during which it would be difficult to detect hypoglycemia. Using advanced diabetes technologies may be an effort to temper fears about hypoglycemia during sleep, though the directionality of this relationship is undetermined. Additional studies can clarify this association and leverage use of diabetes technologies to improve glycemic control.

Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional analysis of 3 contemporary pediatric diabetes registry databases.

OBJECTIVE: To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries. METHODS: Data for patients with type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years, were extracted from each registry for a 12-month observation period between 2011 and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia (self-reported loss of consciousness/convulsion) were estimated per 100 patient-years and analyzed by HbA1c, source registry, treatment regimen, and age group. RESULTS: Overall, the severe hypoglycemia rate per 100 patient years was 7.1, 3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not associated with an increased rate of severe hypoglycemia when examined by source registry, treatment regimen, or age group. CONCLUSION: An inverse relationship between mean HbA1c and risk of severe hypoglycemia was not observed in this study of 3, independent cohorts of children and adolescents with type 1 diabetes. Investigation in other large, longitudinal cohorts is recommended to further characterize the contemporary relationship between glycemic control and risk of severe hypoglycemia rates in pediatric patients with type 1 diabetes.

Therapeutic inertia: underdiagnosed and undertreated hypertension in children participating in the T1D Exchange Clinic Registry.

OBJECTIVES: Reduction of cardiovascular risk in children with type 1 diabetes requires aggressive management of hypertension (HTN). However, the frequency of diagnosing and effectively treating HTN in youth with type 1 diabetes has not been established. To address this question, we used the data collected in >9000 youth with type 1 diabetes who enrolled in the T1D Exchange Clinic Registry. RESEARCH DESIGN AND METHODS: This analysis included data from medical records of 9362 individuals with enrolment and 1-yr follow-up visits (age 3 to <18 yr, disease duration ≥ 1 yr at follow-up). Data included the prevalence of a documented diagnosis of HTN, elevated blood pressure (BP) (systolic or diastolic ≥95th percentile for age, gender, and height), and treatment with angiotensin converting enzyme (ACE)-receptor inhibitor (ACE-I)/angiotensin receptor blocker (ARB) therapy. RESULTS: HTN was diagnosed in only 1% (113/9362) of participants; yet, elevated BP was recorded at one of the two visits in 17% and at both visits in 4%. Among those with diagnosed HTN, only 52% (59/113) were receiving ACE-I/ARB therapy and only 32% (19 of 59) of those treated were at goal BP. Children with diagnosed HTN had higher HbA1c (adjusted p < 0.001) and higher BMI (p < 0.001) when compared with children without HTN. CONCLUSIONS: HTN is likely under diagnosed and undertreated even in pediatric diabetes clinics. The relatively low proportion of hypertensive children receiving ACE-I therapy and reaching BP goals probably identifies an important area for improving care in children with type 1 diabetes.

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

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements. RESULTS: HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p < 0.001). For the 8-18 cohort, insulin pump use, age of onset, and health insurance were significant in predicting individual HbA1c trajectory. CONCLUSIONS: Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed.

Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

IMPORTANCE: Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. OBJECTIVE: To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%). INTERVENTIONS: Randomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69). MAIN OUTCOMES AND MEASURES: Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids. RESULTS: Between October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3% [95% CI, -0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, -0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001). CONCLUSIONS AND RELEVANCE: Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control. TRIAL REGISTRATION: clinicaltrials.org Identifier: NCT01881828.

Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV registries.

AIMS/HYPOTHESIS: The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old. METHODS: Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (<7.5% [<58 mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared. RESULTS: Insulin pump use was more frequent (74% vs 50%, p < 0.001) and HbA1c levels lower in the Prospective Diabetes Follow-up Registry (DPV) than in the T1D Exchange (T1DX) (mean 7.4% vs 8.2%, p < 0.001). A lower HbA1c level was seen in the DPV compared with the T1DX for both pump users (p < 0.001) and injection users (p < 0.001). More children from DPV were meeting the recommended HbA1c goals, compared with children from T1DX (HbA1c <7.5%: 56% vs 22%, p < 0.001; HbA1c <8.5%: 90% vs 66%, p < 0.001). The adjusted odds of having an HbA1c level <7.5% or <8.5% were 4.2 (p < 0.001) and 3.6 (p < 0.001) higher for the DPV than the T1DX, respectively. The frequency of SH did not differ between registries or by HbA1c, whereas the frequency of DKA was higher for the T1DX and greater in those with higher HbA1c levels. CONCLUSIONS/INTERPRETATION: DPV data indicate that an HbA1c of <7.5% can frequently be achieved in children with type 1 diabetes who are under 6 years old. An improved metabolic control of type 1 diabetes in young patients appears to decrease the risk of DKA without increasing SH. The greater frequency of suboptimal control in young patients in the T1DX compared with the DPV is not fully explained by a less frequent use of insulin pumps and may relate to the higher HbA1c targets that are recommended for this age group in the USA.

A contrast between children and adolescents with excellent and poor control: the T1D Exchange clinic registry experience.

OBJECTIVES: Optimizing glycemic control in pediatric type 1 diabetes (T1D) is essential to minimizing long-term risk of complications. We used the T1D Exchange database from 58 US diabetes clinics to identify differences in diabetes management characteristics among children categorized as having excellent vs. poor glycemic control. METHODS: Among registry participants 6-17 yr old with diabetes duration ≥ 2 yr, those with excellent control [(A1c <7%)(53 mmol/mol) (N = 588)] were compared with those with poor control [(A1c ≥ 9% )(75 mmol/mol) (N = 2684)] using logistic regression. RESULTS: The excellent and poor control groups differed substantially in diabetes management (p < 0.001 for all) with more of the excellent control group using insulin pumps, performing blood glucose monitoring ≥ 5 ×/d, missing fewer boluses, bolusing before meals rather than at the time of or after a meal, using meal-specific insulin:carbohydrate ratios, checking their blood glucose prior to giving meal time insulin, giving insulin for daytime snacks, giving more bolus insulin, and using a lower mean total daily insulin dose than those in poor control. After adjusting for demographic and socioeconomic factors, diabetes management characteristics were still strongly associated with good vs. poor control. Notably, frequency of severe hypoglycemia was similar between the groups while DKA was more common in the poorly controlled group. CONCLUSIONS: Children with excellent glycemic control tend to exhibit markedly different diabetes self-management techniques than those with poor control. This knowledge may further inform diabetes care providers and patients about specific characteristics and behaviors that can be augmented to potentially improve glycemic control.

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.

Nocturnal hypoglycemia is associated with next day cognitive performance in adults with type 1 diabetes: Pilot data from the GluCog study.

OBJECTIVE:  Individuals with type 1 diabetes (T1D) have increased risk for cognitive dysfunction and high rates of sleep disturbance. Despite associations between glycemia and cognitive performance using cross-sectional and experimental methods few studies have evaluated this relationship in a naturalistic setting, or the impact of nocturnal versus daytime hypoglycemia. Ecological Momentary Assessment (EMA) may provide insight into the dynamic associations between cognition, affective, and physiological states. The current study couples EMA data with continuous glucose monitoring (CGM) to examine the within-person impact of nocturnal glycemia on next day cognitive performance in adults with T1D. Due to high rates of sleep disturbance and emotional distress in people with T1D, the potential impacts of sleep characteristics and negative affect were also evaluated. METHODS:  This pilot study utilized EMA in 18 adults with T1D to examine the impact of glycemic excursions, measured using CGM, on cognitive performance, measured via mobile cognitive assessment using the TestMyBrain platform. Multilevel modeling was used to test the within-person effects of nocturnal hypoglycemia and hyperglycemia on next day cognition. RESULTS:  Results indicated that increases in nocturnal hypoglycemia were associated with slower next day processing speed. This association was not significantly attenuated by negative affect, sleepiness, or sleep quality. CONCLUSIONS:  These results, while preliminary due to small sample size, showcase the power of intensive longitudinal designs using ambulatory cognitive assessment to uncover novel determinants of cognitive fluctuation in real world settings, an approach that may be utilized in other populations. Findings suggest reducing nocturnal hypoglycemia may improve cognition in adults with T1D.