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.

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.

CHEIROARTHROPATHY: A COMMON DISORDER IN PATIENTS IN THE T1D EXCHANGE.

OBJECTIVE: Diabetic cheiroarthropathy is a long-term complication of diabetes that causes significant morbidity and can impair functional abilities. It has not been well studied in individuals with type 1 diabetes (T1D). The T1D Exchange registry provided an opportunity to assess the frequency of cheiroarthropathy and related characteristics. METHODS: An internet-based survey was sent to 6,199 registry participants ≥18 years old, with 1,911 (31%) responding (62% female, 90% non-Hispanic White, mean age 40 years, median diabetes duration 20 years, mean glycated hemoglobin [HbA1c] 7.7% [61 mmol/mol]). RESULTS: A total of 586 (31%) adults reported a diagnosis of ≥1 upper extremity disorder: 293 (15%) reported frozen shoulder, 293 (15%) trigger finger, 261 (14%) carpal tunnel, and 92 (5%) Dupuytren contracture, with 281 (15%) reporting ≥2 disorders. Those with upper extremity joint disorders were more likely older ( P<.001) and had longer duration of diabetes ( P<.001) than those without. HbA1c levels at the time of survey completion were 7.6% in participants with cheiroarthropathy versus 7.8% (62 mmol/mol) in participants without cheiroarthropathy. CONCLUSION: Cheiroarthropathy is common in adults with T1D. Additional research is needed to understand the pathogenesis and risk factors for this disorder. Standards of care for early recognition and treatment of diabetic cheiroarthropathy are also needed, particularly for adults with long-term diabetes. Improved awareness of cheiroarthropathy signs and symptoms of is needed so that patients can be identified and seek treatment before the condition causes disability. ABBREVIATIONS: BMI = body mass index; CGM = continuous glucose monitor; DCCT/EDIC = Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications; HbA1C = glycated hemoglobin; T1D = type 1 diabetes; T2D = type 2 diabetes.

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.

Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries.

AIMS/HYPOTHESIS: While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries. METHODS: Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV; n = 26,198), T1D Exchange (T1DX; n = 13,755) and the National Paediatric Diabetes Audit (NPDA; n = 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA1c levels were compared. RESULTS: The overall mean HbA1c level was higher in the NPDA (8.9 ± 1.6% [74 ± 17.5 mmol/mol]) than in the DPV (8.0 ± 1.6% [64 ± 17.0 mmol/mol], p < 0.001) and T1DX (8.3 ± 1.4% [68 ± 15.4 mmol/mol], p < 0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%, p < 0.001) and T1DX (47%, p < 0.001). In a pooled analysis, pump use was associated with a lower mean HbA1c (pump: 8.0 ± 1.2% [64 ± 13.3 mmol/mol] vs injection: 8.5 ± 1.7% [69 ± 18.7 mmol/mol], p < 0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (p < 0.001) and boys were treated with a pump less often compared with girls (p < 0.001). CONCLUSIONS/INTERPRETATION: Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy.

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.

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.

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.

Incident diabetes complications among women with type 1 diabetes based on parity.

OBJECTIVES: To assess risk factors and incidence of diabetes complications in women with type 1 diabetes (T1D) based on parity. RESEARCH DESIGN/METHODS: Data were collected from women (16-40 years old) in the T1D Exchange completing pregnancy/childbirth questionnaires during 2011-2013 and 2016-2018. Incidence of risk factors and diabetes complications were compared between women with a first pregnancy at/within 1-year of enrollment (n = 28) and never pregnant women by year 5 (n = 469). RESULTS: There was a trend for lower HbA1c (adjusted p = .14) and higher rates of overweight/obesity, triglyceride/HDL > 2, log (triglyercide/HDL), and hypertension among parous women compared with nulliparous women. There were no significant differences in rates of advanced nephropathy, albuminuria or cardiovascular disease. CONCLUSIONS: Four-5 years after delivery, parous women with T1D tended to have lower HbA1c levels despite higher body mass indices and more frequent adverse lipid profiles and hypertension compared with nulliparous women. Further studies based on these trends are warranted.

Changes in Device Uptake and Glycemic Control Among Pregnant Women With Type 1 Diabetes: Data From the T1D Exchange.

OBJECTIVES: To examine changes in device use and glycemic outcomes for pregnant women from the T1D Exchange Clinic Registry between the years 2010-2013 and 2016-2018. METHODS: Participant-reported device use and glycemic outcomes were compared for women aged 16-40 years who were pregnant at the time of survey completion, comparing 2010-2013 (cohort 1) and 2016-2018 (cohort 2). Hemoglobin A1c results within 30 days prior to survey completion were obtained from medical records. RESULTS: There were 208 pregnant women out of 5,236 eligible participants completing the questionnaire in cohort 1 and 47 pregnant women out of 2,818 eligible participants completing the questionaire in cohort 2. Continuous glucose monitor (CGM) use while pregnant trended upward among cohort 2 (70% vs 37%, P = .02), while reported continuous subcutaneous insulin infusion (CSII) use while pregnant declined (76% vs 64%, P = .04). HbA1c levels trended downward (6.8% cohort 1 vs 6.5% cohort 2, P = .07). CONCLUSIONS: Self-reported CGM use while pregnant increased over the studied intervals whereas CSII use decreased. Additional evaluation of device use and the potential benefits for T1D pregnancies is needed.

HbA1c Levels in Type 1 Diabetes from Early Childhood to Older Adults: A Deeper Dive into the Influence of Technology and Socioeconomic Status on HbA1c in the T1D Exchange Clinic Registry Findings.

Objective: The T1D Exchange Clinic Registry figure of HbA1c levels according to age has become a classic picture of how average HbA1c varies from childhood to elderly. To further assess the course of HbA1c across the life span in T1D, we created similar figures stratified by device use and socioeconomic status (SES). Methods: Mean HbA1c was plotted versus age for 21,253 T1D Exchange Clinic Registry participants with an HbA1c measurement between January 1, 2016 and March 31, 2018 according to device use, race/ethnicity, and measures of SES. Results: Across the age range from childhood to elderly, continuous glucose monitoring (CGM) use without an insulin pump had better average HbA1c than pump without CGM; and among CGM users, pump and injection users had similar HbA1c levels. Any device use (pump or CGM) was associated with better HbA1c levels than no device use across the age range. Lower SES and African American race were associated with higher HbA1c across the age range. Across all device use, SES, and race/ethnicity factors, average HbA1c levels were highest in adolescents and young adults. Conclusion: Although the plot of average HbA1c from early childhood to elderly shifts according to device use and SES factors, the shape of the plots remains reasonably constant with highest HbA1c levels in adolescents and young adults. These findings emphasize the importance of targeting adolescence and early adulthood as the ages with the greatest need for improving diabetes management irrespective of device use and SES.

Cannabis Use Is Associated With Increased Risk for Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Findings From the T1D Exchange Clinic Registry.

OBJECTIVE: We examined the frequency of diabetic ketoacidosis (DKA) in cannabis users compared with nonusers in the T1D Exchange clinic registry (T1DX). RESEARCH DESIGN AND METHODS: The association between cannabis use by total substance score for cannabis (TSC) and DKA in the past 12 months was examined using a logistic regression model adjusted for potential confounders among adults in the T1DX. RESULTS: Of 932 adults with type 1 diabetes, 61 had a TSC >4, which classified them as moderate cannabis users. Adjusting for sex, age at study visit, and HbA1c, cannabis use was associated with a twofold increase in risk for DKA among adults with type 1 diabetes (odds ratio 2.5 [95% CI 1.0-5.9]). CONCLUSIONS: Cannabis use was associated with an increased risk for DKA among adults in the T1DX. Providers should inform their patients of the potential risk of DKA with cannabis use.

Alcohol Use and Clinical Outcomes in Adults in the Type 1 Diabetes Exchange.

OBJECTIVES: Alcohol consumption has serious potential consequences for persons with type 1 diabetes. This cross-sectional study examined associations between drinking status and diabetes-related outcomes. METHODS: Participants included 934 adults at Type 1 Diabetes Exchange Registry clinics who responded to an e-mail invitation to complete an electronic survey with items on alcohol consumption; glycated hemoglobin (A1C) and body mass index (BMI) were extracted from medical charts. Participants were an average 38±16 years of age, 61% were women and 90% were non-Hispanic white; A1C was 7.8%±1.5%. The sample was made up of 11% (n=103) never drinkers, 9% (n=89) former drinkers, 61% (n=567) current (past year) nonbinge drinkers and 19% (n=174) current binge drinkers. RESULTS: After controlling for covariates, diabetes distress was lower among never drinkers compared with former and nonbinge drinkers (p<0.009). Never drinkers compared with former drinkers had lower odds of past-year severe hypoglycemia (p=0.001) and lower odds of a neuropathy diagnoses (p=0.006). There were omnibus model trends toward associations between drinking status and diabetes self-care (p=0.10) and between drinking status and BMI (p=0.06). Never drinkers did not differ from other groups on daily frequency of blood glucose self-monitoring, A1C or past-year diabetic ketoacidosis (p>0.05). CONCLUSIONS: These results suggest complex relationships between drinking and diabetes-related distress, and that recent severe hypoglycemia and the presence of neuropathy may motivate some to stop drinking. Prospective studies may improve understanding of these findings.

The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange.

OBJECTIVE: To evaluate the contemporary prevalence of diabetic peripheral neuropathy (DPN) in participants with type 1 diabetes in the T1D Exchange Clinic Registry throughout the U.S. RESEARCH DESIGN AND METHODS: DPN was assessed with the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) in adults with ≥5 years of type 1 diabetes duration. A score of ≥4 defined DPN. Associations of demographic, clinical, and laboratory factors with DPN were assessed. RESULTS: Among 5,936 T1D Exchange participants (mean ± SD age 39 ± 18 years, median type 1 diabetes duration 18 years [interquartile range 11, 31], 55% female, 88% non-Hispanic white, mean glycated hemoglobin [HbA1c] 8.1 ± 1.6% [65.3 ± 17.5 mmol/mol]), DPN prevalence was 11%. Compared with those without DPN, DPN participants were older, had higher HbA1c, had longer duration of diabetes, were more likely to be female, and were less likely to have a college education and private insurance (all P < 0.001). DPN participants also were more likely to have cardiovascular disease (CVD) (P < 0.001), worse CVD risk factors of smoking (P = 0.008), hypertriglyceridemia (P = 0.002), higher BMI (P = 0.009), retinopathy (P = 0.004), reduced estimated glomerular filtration rate (P = 0.02), and Charcot neuroarthropathy (P = 0.002). There were no differences in insulin pump or continuous glucose monitor use, although DPN participants were more likely to have had severe hypoglycemia (P = 0.04) and/or diabetic ketoacidosis (P < 0.001) in the past 3 months. CONCLUSIONS: The prevalence of DPN in this national cohort with type 1 diabetes is lower than in prior published reports but is reflective of current clinical care practices. These data also highlight that nonglycemic risk factors, such as CVD risk factors, severe hypoglycemia, diabetic ketoacidosis, and lower socioeconomic status, may also play a role in DPN development.

Longitudinal trajectories of BMI z-score: an international comparison of 11,513 Australian, American and German/Austrian/Luxembourgian youth with type 1 diabetes.

BACKGROUND: BMI fluctuations during puberty are common. Data on individual change in BMI from childhood to young adulthood are limited in youth with type 1 diabetes. OBJECTIVES: To compare longitudinal trajectories of body mass index z score (BMIz) from childhood to adolescence across three registries spanning five countries. METHODS: Data sources: T1DX (USA), DPV (Germany/Austria/Luxembourg) and ADDN (Australia). The analysis included 11,513 youth with type 1 diabetes, duration >1 year, at least one BMI measure at baseline (age 8-10 years) and >5 aggregated BMI measures by year of age during follow-up until age 17 years. BMIz was calculated based on WHO charts. Latent class growth modelling was used to identify subgroups following a similar trajectory of BMIz over time. RESULTS: Five distinct trajectories of BMIz were present in the T1DX and ADDN cohorts, while six trajectories were identified in the DPV cohort. Boys followed more often a low/near-normal pattern while elevated BMIz curves were more likely in girls (ADDN; DPV). For T1DX cohort, no sex differences were observed. Comparing the reference group (BMIz ~0) with the other groups during puberty, higher BMIz was significantly associated with older age at T1D onset, racial/ethnic minority and elevated HbA1c (all p<0.05). CONCLUSION: This multinational study presents unique BMIz trajectories in youth with T1D across three continents. The prevalence of overweight and the longitudinal persistence of overweight support the need for close monitoring of weight and nutrition in this population. The international and individual differences likely result from diverse genetic, environmental and therapeutic factors.

Risk Factors for Cardiovascular Disease (CVD) in Adults with Type 1 Diabetes: Findings from Prospective Real-life T1D Exchange Registry.

CONTEXT: Cardiovascular disease (CVD) is a major cause of mortality in adults with type 1 diabetes. OBJECTIVE: We prospectively evaluated CVD risk factors in a large, contemporary cohort of adults with type 1 diabetes living in the United States. DESIGN: Observational study of CVD and CVD risk factors over a median of 5.3 years. SETTING: The T1D Exchange clinic network. PATIENTS: Adults (age ≥ 18 years) with type 1 diabetes and without known CVD diagnosed before or at enrollment. MAIN OUTCOME MEASURE: Associations between CVD risk factors and incident CVD were assessed by multivariable logistic regression. RESULTS: The study included 8,727 participants (53% female, 88% non-Hispanic white, median age 33 years [interquartile ratio {IQR} = 21, 48], type 1 diabetes duration 16 years [IQR = 9, 26]). At enrollment, median HbA1c was 7.6% (66 mmol/mol) (IQR = 6.9 [52], 8.6 [70]), 33% used a statin, and 37% used blood pressure medication. Over a mean follow-up of 4.6 years, 325 (3.7%) participants developed incident CVD. Ischemic heart disease was the most common CVD event. Increasing age, body mass index, HbA1c, presence of hypertension and dyslipidemia, increasing duration of diabetes, and diabetic nephropathy were associated with increased risk for CVD. There were no significant gender differences in CVD risk. CONCLUSION: HbA1c, hypertension, dyslipidemia and diabetic nephropathy are important risk factors for CVD in adults with type 1 diabetes. A longer follow-up is likely required to assess the impact of other traditional CVD risk factors on incident CVD in the current era.

Longitudinal Changes in Depression Symptoms and Glycemia in Adults With Type 1 Diabetes.

OBJECTIVE: This study assessed longitudinal change in depression symptoms over ≥4 years in adults with type 1 diabetes and examined the association between change in depression symptom status and glycemia. RESEARCH DESIGN AND METHODS: Adults in the T1D Exchange registry with HbA1c and Patient Health Questionnaire (PHQ-8) at 1 year (baseline) and 5 years post-enrollment (follow-up; n = 2,744, mean age, 42 years; 57% female, 92% white; mean HbA1c, 7.6% [58 mmol/mol]) were included. Depression status was defined as Persistent Elevated Depression Symptoms (EDS) (EDS at baseline and follow-up), Resolved EDS (EDS at baseline, no EDS at follow-up), New Onset EDS (no EDS at baseline, EDS at follow-up), and Not Depressed (no EDS at baseline or follow-up). RESULTS: Overall, 131 (5%) had Persistent EDS, 122 (4%) had Resolved EDS, 168 (6%) had New Onset EDS, and 2,323 (85%) were Not Depressed. Of those with EDS (PHQ ≥ 10) at baseline, 53% had EDS at follow-up; of those not depressed at baseline, 7% had EDS at follow-up. An increase in PHQ-8 was associated with an increase in HbA1c (P < 0.001). Although HbA1c increased in all groups, the increase was less in the Resolved EDS and Not Depressed groups (P = 0.001). Persistent EDS and New Onset EDS groups were more likely to experience diabetic ketoacidosis (DKA) (P < 0.001). CONCLUSIONS: T1D Exchange registry data provide evidence for relationships over time between persistently, and newly developing EDSs and worsening glycemic control, and suggest relationships between depression symptoms and the occurrence of severe hypoglycemia and DKA. Successful treatment of depression symptoms may lead to better long-term diabetes outcomes.

Biologic and social factors predict incident kidney disease in type 1 diabetes: Results from the T1D exchange clinic network.

AIMS: Diabetic kidney disease (DKD) is a major complication of type 1 diabetes (T1D). To better understand the development of DKD in modern clinical practice, we evaluated risk factors in participants from the T1D Exchange Registry who completed 5-years of longitudinal follow-up. METHODS: Participants had T1D duration ≥ 1 year, age ≥ 10 years, eGFR ≥ 60 ml/min and no albuminuria at enrollment, and at least two serum creatinine and urine albumin measurements recorded during follow-up. Adverse kidney outcomes were defined as eGFR ≪ 60 ml/min and/or albuminuria (ALB) defined by as two consecutive albumin/creatinine ratios or two out of the past three measurements ≫ 30 µg/mg at any follow-up data collection. Associations of baseline characteristics with adverse kidney outcomes were assessed. RESULTS: Among 3940 participants (mean age 41 ±â€¯15 yrs, T1D duration 21 ±â€¯13 yrs), 653 (16.6%) experienced an adverse kidney outcome: 268 (6.8%) experienced incident ALB only, 322 (8.2%) had eGFR decline to ≪60 ml/min without ALB, and 63 (1.6%) experienced eGFR ≪ 60 ml/min with ALB. In a multivariable analysis, higher HbA1c, higher SBP, lower DBP, older age and lower education level were associated with the development of adverse kidney outcomes (all p values ≤ 0.03). CONCLUSIONS: Improving modifiable risk factors, including glucose and blood pressure control, remain important to reduce the risk of DKD in T1D.

State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016-2018.

OBJECTIVE: To provide a snapshot of the profile of adults and youth with type 1 diabetes (T1D) in the United States and assessment of longitudinal changes in T1D management and clinical outcomes in the T1D Exchange registry. RESEARCH DESIGN AND METHODS: Data on diabetes management and outcomes from 22,697 registry participants (age 1-93 years) were collected between 2016 and 2018 and compared with data collected in 2010-2012 for 25,529 registry participants. RESULTS: Mean HbA1c in 2016-2018 increased from 65 mmol/mol at the age of 5 years to 78 mmol/mol between ages 15 and 18, with a decrease to 64 mmol/mol by age 28 and 58-63 mmol/mol beyond age 30. The American Diabetes Association (ADA) HbA1c goal of <58 mmol/mol for youth was achieved by only 17% and the goal of <53 mmol/mol for adults by only 21%. Mean HbA1c levels changed little between 2010-2012 and 2016-2018, except in adolescents who had a higher mean HbA1c in 2016-2018. Insulin pump use increased from 57% in 2010-2012 to 63% in 2016-2018. Continuous glucose monitoring (CGM) increased from 7% in 2010-2012 to 30% in 2016-2018, rising >10-fold in children <12 years old. HbA1c levels were lower in CGM users than nonusers. Severe hypoglycemia was most frequent in participants ≥50 years old and diabetic ketoacidosis was most common in adolescents and young adults. Racial differences were evident in use of pumps and CGM and HbA1c levels. CONCLUSIONS: Data from the T1D Exchange registry demonstrate that only a minority of adults and youth with T1D in the United States achieve ADA goals for HbA1c.