Background: To evaluate the progression of diabetic retinopathy (DR) after the initiation of automated insulin delivery (AID) systems in adults with type 1 diabetes (T1D). Methods: In this longitudinal study with 152 adults, retinal exams and clinical variables were collected before and after AID initiation up to 2.7 years. The DR worsening was defined as an increase in Early Treatment of Diabetic Retinopathy Study (ETDRS) scores or qualitative retinal exam. Results: A total of 152 adults with mean age of 42 years (57% female), 26 years of T1D duration, and mean baseline HbA 1c of 7.6% (60 mmol/mol) were included in this analysis. Of 152 adults with T1D, 42 (28%) adults had DR worsening after AID initiation. After adjusting for age, diabetes duration, and sex, baseline HbA 1c (odds ratio [OR] = 2.1 [1.34-3.04]) and low-density lipoprotein cholesterol (LDL-C) >100 mg/dL with HbA 1c >8% (OR = 3.33 [1.12-9.91]) were associated with two- and three-fold increased risk for DR worsening, respectively. The decline of HbA 1c with AID initiation between DR worsening and no-DR worsening groups was not significant (−0.38 ± 1.2% vs −0.47 ± 0.9%; P = .6). Conclusions: Higher baseline HbA 1c with LDL-C >100 mg/dL may be associated with DR worsening after initiation of AID systems in T1D. Those with elevated HbA 1c should get periodic ophthalmic examination after AID initiation to detect progression of DR. Prompt diagnosis may result in timely treatment.

Objective:To determine inequalities in access to diabetes technologies and the effect of socioeconomic factors on families with children with type 1 diabetes. Methods:In this multicenter, cross-sectional study, parents of children with type 1 diabetes completed a questionnaire about household sociodemographic characteristics, latest hemoglobin A1c (HbA1c) values, continuous glucose monitoring (CGM) and insulin pump use of children, the education and working status of parents. These characteristics were compared between technology use (only-CGM, only-pump, CGM+pump, no technology use). Results:Among 882 families, only-CGM users, only-pump users, and CGM+pump users were compared with no technology users, adjusting for age, sex, region, education levels, number of working parents, and household income. Children living in the least developed region had lower odds of having only-CGM [odds ratio (OR)=0.20, 95% confidence interval (CI): 0.12-0.34, p<0.001] and having CGM+pump (OR=0.07, 95% CI: 0.03-0.22, p<0.001) compared with those living in the most developed region. Children with parents who had not finished high school had lower odds of having only-CGM (mothers: OR=0.36, 95% CI: 0.19-0.66, p=0.001; fathers: OR=0.32, 95% CI: 0.18-0.60, p<0.001) or both CGM+pump (mothers: OR=0.27, 95% CI: 0.11-0.64, p=0.003; fathers: OR=0.34, 95% CI: 0.15-0.79, p=0.012) rather than no-technology compared to children whose parents have a university degree. Every $840 increase in the household income increased the odds by 5% for having only-CGM (OR=1.05, 95% CI: 1.02-1.09, p<0.001) or CGM+pump (OR=1.05, 95% CI: 1.01-1.08, p<0.001). Conclusion:Socioeconomic factors, such as parental education, region of residence, and income were associated with inequality in access to technologies. The inequalities are more prominent in access to CGM.

Successful management of type 1 diabetes (T1D) requires not only optimal glycemic outcomes, but also a holistic approach that encompasses all aspects of life and recommendations to address needs. Current goals include optimal glycemic values, quality of life and life expectancy similar to peers, prevention of long-term complications, prevention of severe hypoglycemia as far as possible and facilitation of glucose management. The International Society for Pediatric and Adolescent Diabetes (ISPAD) has been updating its guidelines for diabetes care every four years since 1995, covering more and more topics. For optimal metabolic outcomes, diabetes teams need to follow these current recommendations, adapt them to their clinical practice and provide guidance to people with T1D and their families. In this review, in the light of ISPAD 2018-2022 guidelines and clinical experiences, “10 Key Recommendations”, emphasizing the importance of teamwork and the use of technology, current T1D treatment is described for practical applications.

This study was aimed at investigating changes in insulin requirements and glycemic outcomes in adults with type 1 diabetes (T1D) using Control IQ (Tandem Diabetes) automated insulin delivery system (AID) over 8 months of tirzepatide treatment. In this single-center, observational study, we collected demographic, A1c, weight, sensor glucose, and insulin dose data for adults with T1D who were using AID and initiated tirzepatide adjunct therapy for clinical indications (n = 11, median age 37, 64

Aims: Time in Tight Range (TITR) is a novel glycaemic metric in monitoring type 1 diabetes (T1D) management. The aim of this study was to assess the attainability of the TITR target in children and adolescents using the advanced hybrid closed loop (AHCL). Methods: The 2128-day CGM data from 56 children and adolescents with T1D using AHCL (Minimed-780G) were analysed. Time in Range (TIR) (3.9-10 mmol/L), TITR (3.9-7.7 mmol/L), and other glycaemic parameters were separately analysed in terms of whole day, daytime (06.00-23:59), and nighttime (00.00-05.59) results. The participants were divided into two groups by autocorrection rate where Group 1 had a rate of <30% and Group 2 had a rate of >= 30. Results: All glycaemic parameters indicated a better glycaemic outcome in the nighttime with higher TIR and TITR values compared with daytime (for TIR 87.5 +/- 9.5% vs. 78.8 +/- 8%, p < 0.001, and TITR 68.2 +/- 13.5% vs. 57.5 +/- 8.8%, p < 0.001). The rates of TITR >50% and >60% were 87% and 52%, respectively. When those with TITR >60% (n: 29) and those without (n: 27) were evaluated in terms of hypoglycaemia, no statistically significant difference was found in time below range (TBR) 3-3.9 mmol/L (0.3% vs. 2.1%, p: 0.084) and TBR < 3 mmol/L (0.47% vs. 0.3%, p: 0.298). Group 1 had a significantly higher TIR and TITR compared to Group 2 (82.6 +/- 6.1% vs. 75.6 +/- 8.6%, p: 0.008 and 62.1 +/- 7.5% vs. 53.8 +/- 7.5%, p: 0.002, respectively). Conclusions: Most children and adolescents on AHCL achieved the 50% target for TITR whereas more than half achieved the >60% target. A target of >50% for TITR seems realistic in children with T1D using AHCL.

Introduction & Objective: Type 1 diabetes (T1D) incidence continues to increase in children, especially among Hispanic Whites (HW). We investigated the clinical and immunologic characteristics of HW and Non-Hispanic White (NHW) children that presented at T1D diagnosis over the last two decades to the Barbara Davis Center for Diabetes. Methods: In this single-center, observational study, children who were diagnosed with T1D (<20 years old) and tested for islet autoantibodies within 1 year of diagnosis were included and divided into two groups by ethnicity. Results: Of 1256 children, 401 HW children presented with a younger age at T1D onset, and more DKA compared to NHW children (n=855) (Table 1). There was no difference in sex, HbA1c levels, or the number and prevalence of islet autoantibodies between the two cohorts. A subset of our cohort was HLA-DR-DQ typed as specific alleles confer strong genetic risk for T1D (e.g., HLA-DR4 and DQ8). Among 556 HLA-typed children, HW children had a significantly higher prevalence of the DR4-DQ8 haplotype compared to NHW children (75.8% vs. 59.0%, p=0.002). Moreover, DR3-DQ2 was lower in HW compared to NHW T1D children (29.8% vs. 47.1%, p=0.001). Conclusion: Hispanic White children developing T1D have a strikingly high prevalence of HLA DR4-DQ8, which can be utilized in screening for T1D risk to lessen DKA and potentially prevent diabetes onset. Disclosure K.E. Karakus: None. T. Fleury: None. E.E. Baschal: None. K. McDaniel: None. H. Choi: None. V. Langarica: None. L. Yu: None. K.M. Simmons: Advisory Panel; Provention Bio, Inc. Consultant; Provention Bio, Inc. Research Support; Provention Bio, Inc., Novartis AG. Consultant; Medtronic. A.W. Michels: Stock/Shareholder; IM Therapeutics. Advisory Panel; Provention Bio, Inc.

Background: Tirzepatide is approved by the United States Food and Drug Administration (FDA) for the management of type 2 diabetes. The efficacy and safety of this drug have not been studied in people with type 1 diabetes (T1D). Methods: In this single-center, retrospective, observational study, hemoglobin A1C (HbA1c), weight, body mass index (BMI), and continuous glucose monitoring (CGM) data were collected from electronic health records of adults with T1D at initiation of tirzepatide and at subsequent clinic visits over 8 months. Primary outcomes were reduction in HbA1c and percent change in body weight and secondary outcomes were change in CGM metrics and BMI over 8 months from baseline. Results: The mean (±SD) age of the 26 adults (54% female) with T1D was 42 ± 8 years with a mean BMI of 36.7 ± 5.3 kg/m 2 . There was significant reduction in HbA1c by 0.45% at 3 months and 0.59% at 8 months, and a significant reduction in body weight by 3.4%, 10.5%, and 10.1% at 3, 6, and 8 months after starting tirzepatide. Time in target range (TIR = 70-180 mg/dL) and time in tight target range (TITR = 70-140 mg/dL) increased (+12.6%, P = .002; +10.7%, P = .0016, respectively) and time above range (TAR >180 mg/dL) decreased (−12.6%, P = .002) at 3 months, and these changes were sustained over 8 months. The drug was relatively safe and well tolerated with only 2 patients discontinuing the medication. Conclusions: Tirzepatide significantly reduced HbA1c and body weight in adults with T1D. A randomized controlled trial is needed to establish efficacy and safety of this drug in T1D.

Objective: Safety and efficacy of adjunct therapy with Tirzepatide, a dual agonist, in adults with type 1 diabetes (T1D) using Tandem Control-IQ automated insulin delivery system is unknown. This study investigates changes in insulin requirements and glycemic outcomes in adults with T1D over 8 months of Tirzepatide treatment. Methods: In this single-center, observational study, we collected demographic, A1c, weight (from electronic medical records), sensor glucose and insulin dose (from t:connect) for adults with T1D who were using Tandem Control-IQ and initiated Tirzepatide adjunct therapy for clinical indications (n=11, median age 36.2, 64% female and mean BMI of 38.6 kg/m2). Data were compared from baseline and over 8 months. Results: The insulin requirements (total, basal and bolus insulin per day) were reduced significantly within 2 months (p<0.01 for all) of Tirzepatide therapy (2.5-5 mg/week), and thereafter, there was no clinically meaningful reduction in insulin dose (Figure 1-A). The frequency of user-initiated boluses did not differ throughout the study. Despite significant reduction in insulin dose, A1c (-0.46%), weight (mean weight reduction -10 kg) and significant improvement in time in range, there was no increase in time below 70 mg/dL (Figure 1-B). Conclusion: Tirzepatide adjunct to Tandem Control-IQ improved glycemic and metabolic outcomes without increasing hypoglycemia. Disclosure K.E. Karakus: None. M.P. Klein: None. H.K. Akturk: Consultant; Medtronic. Research Support; Medtronic. Consultant; Dexcom, Inc. Research Support; MannKind Corporation, Tandem Diabetes Care, Inc. Consultant; Tandem Diabetes Care, Inc. V.N. Shah: Consultant; Dexcom, Inc., Insulet Corporation. Research Support; Insulet Corporation. Advisory Panel; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Sanofi, Medscape. Consultant; embecta, Tandem Diabetes Care, Inc.

Objective: Extended hypoglycemia (Ehypo) and extended hyperglycemia (Ehyper) are recently defined continuous glucose monitoring (CGM) metrics by the International Consensus for clinical trials as secondary endpoints for continuous outcomes. This study aims to evaluate the changes in Ehypo and Ehyper before and after automated insulin delivery (AID) initiation in adults with type 1 diabetes (T1D). Research Methods: This is a retrospective single-center study that evaluated Ehypo and Ehyper in addition to other CGM metrics in 154 adults that initiated an AID system. Metrics were compared before and after AID initiation by Wilcoxon signed-rank test. Results: Median (interquartile range) Ehypo (<70 mg/dL) events/week decreased from 0.1 (0-0.4) to 0 (0-0.1) and Ehyper (>250 mg/dL) events/week decreased from 2.2 (0.9-4.5) to 0.8 (0.3-1.7) (both P < .001) after AID initiation compared with before AID initiation. All other CGM metrics improved after AID initiation. There was a strong positive correlation between Ehyper (>250 mg/dL) and mean glucose (before AID: r = 0.947, after AID: r = 0.894), glucose management indicator (before AID: r = 0.947, after AID: r = 0.887), and time above range (TAR; >180 mg/dL) (before AID: r = 0.957, after AID: r = 0.917) and a strong positive correlation between Ehypo (<70 mg/dL) and time below range (TBR; <70 mg/dL) (before AID: r = 0.823, after AID: r = 0.608) before and after AID initiation, respectively. Conclusion: Automated insulin delivery initiation significantly improved Ehypo and Ehyper metrics. Ehypo and Ehyper had a strong positive correlation with TBR and TAR, respectively. Ehypo and Ehyper events can be used in addition to TBR and TAR metrics in clinical studies as secondary outcomes.

Objective: To compare the accuracy of commonly used continuous glucose monitoring (CGM) analysis programs with ambulatory glucose profile (AGP) and Dexcom Clarity (DC) in analyzing CGM metrics in patients with type 1 diabetes (T1D). Research Methods: CGM data up to 90 days from 152 adults using the same CGM and automated insulin delivery system with T1D were collected. Six of the 19 CGM analysis programs (CDGA, cgmanalysis, Glyculator, iglu, EasyGV, and GLU) were selected to compare with AGP and DC. Metrics were compared etween all tools with two one-sided t-tests equivalence testing. For the equivalence test, the acceptable range of deviation was set as ±2 mg/dL for mean glucose, ±2% for time in range (TIR), ±1% for time above range (TAR), time above range level 1 (TAR1), time above range level 2 (TAR2), and coefficient of variation (CV). Results: All packages were compared with each other for all CGM metrics, and most of them had statistically significant differences for at least some metrics. All tools were equivalent to AGP for mean glucose, TIR, TAR, TAR1, and TAR2 within ±2 mg/dL, ±2%, ±1%, ±1% and 1%, respectively. CDGA, Glyculator, cgmanalysis, and iglu were not equivalent to AGP for CV within ±1%. All tools were equivalent to DC for mean glucose, TIR, and TAR2 within ±2 mg/dL, ±2%, and ±1%, respectively. Glyculator was not equivalent for TAR1, TAR, and CV. CGDA, cgmanalysis, and iglu were not equivalent to DC for TAR1 and TAR. EasyGV and GLU were not equivalent for TAR within ±1%. Conclusions: CGM analysis programs reported CGM metrics statistically differently, but these differences may not be applicable in clinical practice. The equivalence test also confirmed that the differences are negligible for TIR and mean glucose, while they can be important for hyperglycemic ranges and CV. A standardization for CGM data handling and analysis is necessary for clinical studies reporting CGM-generated outcomes.

Background: We investigated the risk of incident diabetic retinopathy (DR) among high glycator compared to low glycator patients based on the hemoglobin glycation index (HGI). Visit-to-visit variations in HGI also were assessed. Methods: Glycated hemoglobin (HbA1c) and continuous glucose monitoring data were collected up to 7 years prior to the date of eye examination defining incident DR or no retinopathy (control). Hemoglobin glycation index was calculated as difference in measured HbA1c and an estimated A1c from sensor glucose (eA1c) to define high (HbA1c − eA1c >0%) or low (HbA1c − eA1c <0%) glycator. Stable glycators were defined as ≥75% of visits with same HGI category. Logistic regression was used to assess the association between glycation category and incident DR. Results: Of 119 adults with type 1 diabetes (T1D), 49 (41%) were stable low glycator (HbA1c − eA1c <0%), 36 (30%) were stable high glycator (HbA1c − eA1c >0%), and 34 (29%) were unstable glycator. Using alternate criteria to define high vs low glycator (consistent difference in HbA1c − eA1c of > 0.4% or <0.4%, respectively), 53% of the adults were characterized as unstable glycator. Compared to low glycators, high glycators did not have a significantly higher risk for incident DR over time when adjusted for age, T1D duration and continuous glucose monitoring (CGM) sensor type (odds ratio [OR] = 1.31, 95% confidence interval [CI] = 0.48-3.62, P = .15). Conclusions: The risk of diabetic retinopathy was not found to differ significantly comparing high glycators to low glycators in adults with T1D. Moreover, HbA1c − eA1c relationship was not stable in nearly 30% to 50% adults with T1D, suggesting that discordance in HbA1c and eA1c are mostly related either HbA1c measurements or estimation of A1c from sensor glucose rather than physiological reasons.

This Teachable Moment describes a 62-year-old man with thyrotoxicosis due to excess levothyroxine exposure during tirzepatide treatment that induced rapid weight loss.

Context: Type 1 diabetes incidence continues to increase in children, especially among Hispanic White (HW) children. Objective: We investigated the clinical, immunologic, and genetic characteristics of HW and non-Hispanic White (NHW) children who presented at type 1 diabetes diagnosis. Methods: In this single-center, observational study, children who were diagnosed with type 1 diabetes (<= 20 years old) and tested for islet autoantibodies within 1 year of diagnosis were included in the study and divided into 2 groups by Hispanic ethnicity. Results: Of 1297 children, 398 HW children presented with a younger age at diabetes onset (10.2 +/- 3.9 vs 11.1 +/- 4.1 years, P < .001) and more diabetic ketoacidosis (62.4% vs 51.9%, P < .001) than NHW children (n = 899). There was no difference in sex, A1c levels, or the number and prevalence of islet autoantibodies between the 2 cohorts. A subset of our cohort was human leukocyte antigen (HLA) typed as specific alleles confer strong genetic risk for type 1 diabetes (eg, HLA-DR4 and DQ8). Among 637 HLA-typed children, HW children had a significantly higher prevalence of the DR4-DQ8 haplotype than NHW children (79.1% vs 60.1%, P < .001), and this frequency was much higher than a reference Hispanic population (OR 6.5, 95% CI 4.6-9.3). Conclusion: Hispanic White children developing type 1 diabetes have a high prevalence of HLA DR4-DQ8, which can be utilized to select individuals for immune monitoring with islet autoantibodies to lessen diabetic ketoacidosis and potentially prevent diabetes onset.