Clinical Outcomes in Pediatric Patients With Type 1 Diabetes With Early Versus Late Diagnosis: Analysis From the DPV Registry.

OBJECTIVE: This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis. RESEARCH DESIGN AND METHODS: In a population-based analysis, data on 14,292 pediatric patients with type 1 diabetes diagnosed between 2015 and 2019 were retrieved from the Diabetes Prospective Documentation (DPV) registry in March 2023. Patients were divided into four groups: one with diabetic ketoacidosis (DKA) at diagnosis and three with early, intermediate, or late diagnosis based on age-dependent HbA1c terciles. Laboratory-measured HbA1c values and those estimated from continuous glucose monitoring were aggregated as a combined glucose indicator (CGI). Insulin dose-adjusted CGI values <9% were defined as partial remission. RESULTS: At diagnosis, patients had a median age of 9.8 years (IQR 6.8; 13.0). Three years later, patients with early diagnosis had lower CGI than patients with late diagnosis or DKA (mean [95% CI] 7.46% [7.40; 7.53] vs. 7.81% [7.75; 7.87] or 7.74% [7.68; 7.79], respectively; each P < 0.001). More patients experienced partial remission (12.6% [11.0; 14.4] vs. 9.1% [7.7; 10.7] or 8.6% [7.3; 10.0]; each P < 0.001), and 11.7% [10.2; 13.5] of patients with intermediate diagnosis were in partial remission. CONCLUSIONS: Early clinical diagnosis of type 1 diabetes may be beneficial for metabolic control and remission after 3 years of follow-up. Patients diagnosed early may represent a distinct group with better resources or with a different disease biology and slower ß-cell destruction, which needs further evaluation.

Demographic, Clinical, Management, and Outcome Characteristics of 8,004 Young Children With Type 1 Diabetes.

OBJECTIVE: To compare demographic, clinical, and therapeutic characteristics of children with type 1 diabetes age <6 years across three international registries: Diabetes Prospective Follow-Up Registry (DPV; Europe), T1D Exchange Quality Improvement Network (T1DX-QI; U.S.), and Australasian Diabetes Data Network (ADDN; Australasia). RESEARCH DESIGN AND METHODS: An analysis was conducted comparing 2019-2021 prospective registry data from 8,004 children. RESULTS: Mean ± SD ages at diabetes diagnosis were 3.2 ± 1.4 (DPV and ADDN) and 3.7 ± 1.8 years (T1DX-QI). Mean ± SD diabetes durations were 1.4 ± 1.3 (DPV), 1.4 ± 1.6 (T1DX-QI), and 1.5 ± 1.3 years (ADDN). BMI z scores were in the overweight range in 36.2% (DPV), 41.8% (T1DX-QI), and 50.0% (ADDN) of participants. Mean ± SD HbA1c varied among registries: DPV 7.3 ± 0.9% (56 ± 10 mmol/mol), T1DX-QI 8.0 ± 1.4% (64 ± 16 mmol/mol), and ADDN 7.7 ± 1.2% (61 ± 13 mmol/mol). Overall, 37.5% of children achieved the target HbA1c of <7.0% (53 mmol/mol): 43.6% in DPV, 25.5% in T1DX-QI, and 27.5% in ADDN. Use of diabetes technologies such as insulin pump (DPV 86.6%, T1DX 46.6%, and ADDN 39.2%) and continuous glucose monitoring (CGM; DPV 85.1%, T1DX-QI 57.6%, and ADDN 70.5%) varied among registries. Use of hybrid closed-loop (HCL) systems was uncommon (from 0.5% [ADDN] to 6.9% [DPV]). CONCLUSIONS: Across three major registries, more than half of children age <6 years did not achieve the target HbA1c of <7.0% (53 mmol/mol). CGM was used by most participants, whereas insulin pump use varied across registries, and HCL system use was rare. The differences seen in glycemia and use of diabetes technologies among registries require further investigation to determine potential contributing factors and areas to target to improve the care of this vulnerable group.

Psychosocial Burden During the COVID-19 Pandemic in Adolescents With Type 1 Diabetes in Germany and Its Association With Metabolic Control.

PURPOSE: To investigate the psychosocial burden during the COVID-19 pandemic in adolescents with type 1 diabetes and its association with metabolic control. METHODS: Prospective multicenter observational cohort study based on data from the German Diabetes Prospective Follow-up Registry. Adolescents aged 12-20 years with type 1 diabetes were asked during routine follow-up visits to complete a questionnaire on psychosocial distress and daily use of electronic media during the COVID-19 pandemic from June 2021 to November 2022. Well-being, anxiety, and depression symptoms were assessed using World Health Organization Five Well-Being Index (WHO-5), General Anxiety Disorder scale 7 (GAD-7), and Patient Health Questionnaire-9 questionnaires. The impact of mental health symptoms on metabolic control was analyzed by using multivariable linear regression models adjusted for sex, diabetes duration, treatment, socioeconomic deprivation, and immigrant background. RESULTS: Six hundred eighty eight adolescents (45.6% females) from 20 diabetes centers participated. Compared with a prepandemic cohort, WHO-5 scores were lower during the COVID-19 pandemic (estimated mean difference -9.6 [95% confidence interval -11.6; -7.6], p < .001), but GAD-7 scores were not different (estimated mean difference 0.6 [95% confidence interval -0.2; 1.5], p = .14). HbA1c was significantly positively associated with GAD-7 and Patient Health Questionnaire-9 and negatively associated with WHO-5 scores (all p < .001). Daily electronic media use was positively associated with adjusted mental health symptoms (all p < .01). DISCUSSION: Although the overall well-being of adolescents with type 1 diabetes was reduced during the later phase of the COVID-19 pandemic, the additional psychological burden was relatively low. However, mental health symptoms were associated with poorer metabolic control and higher use of electronic media.

Family structures and parents' occupational models: its impact on children's diabetes.

AIMS: This study examines how family-related factors influence the management of children and adolescents with type 1 diabetes (T1DM). We investigate the relationship between family patterns, parental work schedules and metabolic control. MATERIALS AND METHODS: We analysed data from a nationwide diabetes survey (DPV) focusing on HbA1c, severe hypoglycaemia, diabetic ketoacidosis, hospital admissions and inpatient treatment duration. We used linear regression and negative binomial regression models. Our study includes 15,340 children under the age of 18 with data on family structure and parental division of labour. RESULTS: Children from two-parent households have better HbA1c outcomes than children from single-parent, blended or no-parent households (p < .0001). Higher HbA1C levels are associated with children living with an unemployed father, as opposed to those with full-time working parents or with a full-time working father and a part-time working mother (p < .001). CONCLUSIONS: These findings emphasise the importance of carefully considering family structure and working time models in the management of paediatric T1DM. Our results highlight risk factors within the family environment and emphasise the need for family-focused counselling of high-risk patients or severe cases in clinical practice.

Outpatient screening for anxiety and depression symptoms in adolescents with type 1 diabetes - a cross-sectional survey.

BACKGROUND: The daily demands of type 1 diabetes management may jeopardize adolescents' mental health. We aimed to assess anxiety and depression symptoms by broad-scale, tablet-based outpatient screening in adolescents with type 1 diabetes in Germany. METHODS: Adolescent patients with type 1 diabetes mellitus (n = 2,394; mean age 15.4 y [SD 2.0]; 50.7% male) were screened for anxiety (GAD-7) and depression symptoms (PHQ-9) by self-report questionnaires and linked to clinical data from the DPV patient registry. Logistic regression was used to estimate the contribution of clinical parameters to positive screening results. RESULTS: Altogether, 30.2% showed a positive screening (score ≥ 7 in either test), and 11.3% reported suicidal ideations or self-harm. Patients with anxiety and depression symptoms were older (15.7 y [CI 15.5-15.8] vs. 15.3 y [CI 15.2-15.4]; p < 0.0001), had higher HbA1c levels (7.9% [CI 7.8-8.0] (63 mmol/mol) vs. 7.5% [CI 7.4-7.5] (58 mmol/mol); p < 0.0001), and had higher hospitalization rates. Females (adjusted odds ratio (aOR) 2.66 [CI 2.21-3.19]; p < 0.0001), patients > 15 years (aOR 1.40 [1.16-1.68]; p < 0.001), who were overweight (aOR 1.40 [CI 1.14-1.71]; p = 0.001), with HbA1c > 9% (> 75 mmol/mol; aOR 2.58 [1.83-3.64]; each p < 0.0001), with a migration background (aOR 1.46 [CI 1.17-1.81]; p < 0.001), or smoking (aOR 2.72 [CI 1.41-5.23]; p = 0.003) had a higher risk. Regular exercise was a significant protective factor (aOR 0.65 [CI 0.51-0.82]; p < 0.001). Advanced diabetes technologies did not influence screening outcomes. CONCLUSIONS: Electronic mental health screening was implemented in 42 centers in parallel, and outcomes showed an association with clinical parameters from sociodemographic, lifestyle, and diabetes-related data. It should be integrated into holistic patient counseling, enabling early recognition of mild mental health symptoms for preventive measures. Females were disproportionally adversely affected. The use of advanced diabetes technologies did not yet reduce the odds of anxiety and depression symptoms in this cross-sectional assessment.

Low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in type 1 diabetes and type 2 diabetes: Lipid goal attainment in a large German-Austrian diabetes registry.

AIM: To assess the implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guideline recommendations for lipid-lowering therapies among more than 30 000 patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) in a German and Austrian registry from 2020 to 2022. MATERIALS AND METHODS: Registry data from 2020 and 2021 of 32 170 adult patients (8314 patients with T1D and 23 856 with T2D) were stratified according to the 2019 ESC/EAS risk categories, and guideline-based low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment was analysed. RESULTS: In patients with T1D (median age 38.35 [20.51-57.13] years), overall statin use was 19.3%, ezetimibe use was 2.2% and the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors or fibrates was less than 1%. In patients with T2D (median age 68.76 [58.86-78.39] years), 45.7% received statins, 3.4% received ezetimibe, and fibrates and PCSK9 inhibitors were used by 1% and 0.1%, respectively. Among patients with T1D, 6.16% reached their risk-based recommended LDL-C goal of less than 55 mg/dL (very high risk), 10.97% of less than 70 mg/dL (high risk), and 69.50% of less than 100 mg/dL (moderate risk), respectively. In patients with T2D, 11.81% reached their risk-based goal of LDL-C less than 55 mg/dL, 16.25% of less than 70 mg/dL, and 51.33% of less than 100 mg/dL. Non-HDL-C goals were reached more often, with 15.3%, 25.52% and 91.61% in patients with T1D and 18.56%, 17.96% and 82.30% in patients with T2D for very high, high and moderate risk, respectively. CONCLUSION: Approximately 2 years after publication of the guidelines, LDL-C and non-HDL-C goal attainment was rarely achieved in patients with T1D and T2D with a high or very high cardiovascular risk.

Neuropathy in paediatric type 1 diabetes mellitus - clinical characterization and analysis of risk factors in the diabetes prospective follow-up registry DPV (Diabetes-Patienten-Verlaufsdokumentation)-registry.

OBJECTIVES: Data on the prevalence, clinical features and risk factors associated with paediatric diabetic neuropathy (DN) are scarce. METHODS: We retrospectively analysed data from the DPV registry, including patients under 20 years of age, treated for type 1 diabetes mellitus (T1D) between 2005 and 2021. Patients with non-diabetic neuropathy were excluded. Data came from centres in Austria, Germany, Luxembourg and Switzerland. RESULTS: 1,121 of the 84,390 patients included had been diagnosed with DN. Univariate analysis showed patients with DN to be older and predominantly female, with a longer duration of T1D, higher insulin dosages per kg and day, lower rates of insulin pump therapy, higher postprandial glucose-, higher HbA1c-and higher cholesterol levels, and higher diastolic and systolic blood pressure values. There was also a larger proportion of smokers and higher prevalence of diabetic retinopathy. Median duration of diabetes at diagnosis of DN was 8.3 years. Multivariable analysis, adjusted for demographics revealed an increased risk for DN among female patients and those who were older, underweight (BMI-SDS), smoked cigarettes or had a longer duration of T1D or higher levels of HbA1c and postprandial blood glucose. The presence of retinopathy and higher cholesterol levels were also linked to increased risk while not-using insulin pump therapy was not. CONCLUSIONS: DN can develop after just a short duration of T1D. Prevention may be achieved by a lowering of HbA1c-and postprandial glucose levels through improved glycaemic control. This warrants further investigation. The slight female predominance suggests further hormonal and genetic etiological factors.

Continuous glucose monitoring versus blood glucose monitoring for risk of severe hypoglycaemia and diabetic ketoacidosis in children, adolescents, and young adults with type 1 diabetes: a population-based study.

BACKGROUND: The effect of continuous glucose monitoring on the risk of severe hypoglycaemia and ketoacidosis in patients with diabetes is unclear. We investigated whether rates of acute diabetes complications are lower with continuous glucose monitoring, compared with blood glucose monitoring, and which metrics predict its risk in young patients with type 1 diabetes. METHODS: In this population-based cohort study, patients were identified from 511 diabetes centres across Austria, Germany, Luxembourg, and Switzerland participating in the Diabetes Prospective Follow-up initiative. We included people with type 1 diabetes aged 1·5-25·0 years, with a diabetes duration of more than 1 year, who had been treated between Jan 1, 2014, and June 30, 2021, and had an observation time of longer than 120 days in the most recent treatment year. Severe hypoglycaemia and ketoacidosis rates during the most recent treatment year were examined in people using continuous glucose monitoring and in those using blood glucose monitoring. Adjustments of statistical models included age, sex, diabetes duration, migration background, insulin therapy (pump or injections), and treatment period. Rates of severe hypoglycaemia and diabetic ketoacidosis were evaluated by several continuous glucose monitoring metrics, including percentage of time below target glucose range (<3·9 mmol/L), glycaemic variability (measured as the coefficient of variation), and mean sensor glucose. FINDINGS: Of 32 117 people with type 1 diabetes (median age 16·8 years [IQR 13·3-18·1], 17 056 [53·1%] males), 10 883 used continuous glucose monitoring (median 289 days per year), and 21 234 used blood glucose monitoring. People using continuous glucose monitoring had lower rates of severe hypoglycaemia than those using blood glucose monitoring (6·74 [95% CI 5·90-7·69] per 100 patient-years vs 8·84 [8·09-9·66] per 100 patient-years; incidence rate ratio 0·76 [95% CI 0·64-0·91]; p=0·0017) and diabetic ketoacidosis (3·72 [3·32-4·18] per 100 patient-years vs 7·29 [6·83-7·78] per 100 patient-years; 0·51 [0·44-0·59]; p<0·0001). Severe hypoglycaemia rates increased with percentage of time below target glucose range (incidence rate ratio 1·69 [95% CI 1·18-2·43]; p=0·0024, for 4·0-7·9% vs <4·0% and 2·38 [1·51-3·76]; p<0·0001, for ≥8·0% vs <4·0%) and glycaemic variability (coefficient of variation ≥36% vs <36%; incidence rate ratio 1·52 [95% CI 1·06-2·17]; p=0·022). Diabetic ketoacidosis rates increased with mean sensor glucose (incidence rate ratio 1·77 [95% CI 0·89-3·51], p=0·13, for 8·3-9·9 mmol/L vs <8·3 mmol/L; 3·56 [1·83-6·93], p<0·0001, for 10·0-11·6 mmol/L vs <8·3 mmol/L; and 8·66 [4·48-16·75], p<0·0001, for ≥11·7 mmol/L vs <8·3 mmol/L). INTERPRETATION: These findings provide evidence that continuous glucose monitoring can reduce severe hypoglycaemia and ketoacidosis risk in young people with type 1 diabetes on insulin therapy. Continuous glucose monitoring metrics might help to identify those at risk for acute diabetes complications. FUNDING: German Center for Diabetes Research, German Federal Ministry of Education and Research, German Diabetes Association, and Robert Koch Institute.

Clinical characteristics, treatment patterns, and persistence in individuals with type 2 diabetes initiating a glucagon-like peptide-1 receptor agonist: A retrospective analysis of the Diabetes Prospective Follow-Up Registry.

AIMS: To describe clinical characteristics, treatment patterns and glucagon-like peptide-1 receptor agonist (GLP-1 RA) persistence in individuals with type 2 diabetes (T2D) initiating their first GLP-1 RA. MATERIALS AND METHODS: A real-world analysis of adults with T2D initiating GLP-1 RA therapy between 2007 and June 2020 from the multicentre Diabetes Prospective Follow-Up (DPV) Registry, stratified by antidiabetes therapy at the time of GLP-1 RA initiation: oral antidiabetic drugs (OAD), insulin ± OAD or lifestyle modification (LM). GLP-1 RA treatment persistence in individuals with ≥12 months follow-up was determined by Kaplan-Meier analysis. RESULTS: Overall, 15 111 individuals with T2D initiating GLP-1 RA therapy (55% men) were identified; median [interquartile range (IQR)] age [58.7 (50.6-66.7) years], diabetes duration [8.5 (3.6-14.7) years], glycated haemoglobin [HbA1c; 8.2 (7.1-9.8)%]. Median (95% confidence interval) GLP-1 RA persistence in eligible individuals (n = 5189) was 11 (10-12) months; OAD 12 (11-14) months (n = 2453); insulin ± OAD 11 (9-12) months (n = 2204); and LM 7 (5-9) months (n = 532). Median treatment persistence tended to increase from 2007-2012 to 2017-2020. Median (IQR) HbA1c decreased from baseline [8.2 (7.1-9.8)%] to discontinuation [7.5 (6.6-8.7)%], with a greater decrease observed in individuals with persistence >12 months versus ≤12 months. Individuals who discontinued GLP-1 RA therapy predominantly switched to insulin (if not already using) or dipeptidyl peptidase-4 inhibitors. CONCLUSION: Real-world registry data revealed improved outcomes with longer median GLP-1 RA persistence; ~50% of patients overall achieved HbA1c <7% at 12 months. Persistence was highest with baseline OAD and/or insulin, and tended to increase over the period 2007-2020.

Metabolic control during the first two years of the COVID-19 pandemic in pediatric patients with type 1 diabetes: results from the German DPV initiative.

AIM: To assess effects of the SARS-CoV2 pandemic on metabolic control in youth with type 1 diabetes (T1D) in Germany in a population-based analysis. METHODS: Data from 33,372 pediatric T1D patients from the Diabetes Prospective Follow-up (DPV) registry, with face-to-face visits or telemedicine contacts in the years 2019-2021, were available. Datasets from eight time periods between March 15, 2020, and December 31, 2021, according to SARS-CoV2 incidence waves, were compared to those from five control time periods. Parameters of metabolic control were assessed with adjustment for sex, age, diabetes duration, and repeated measurements. Laboratory-measured HbA1c values and those estimated from CGM were aggregated into a combined glucose indicator (CGI). RESULTS: There was no clinically relevant difference in metabolic control between pandemic and control time periods with adjusted CGI values ranging from 7.61% [7.60-7.63] (mean [95% confidence interval (CI)]) in the third quarter of 2019 to 7.83% [7.82-7.85] in the time period from January 1 to March 15 2020, in the other control periods, and during the pandemic, CGI values lay between these values. BMI-SDS rose during the pandemic from 0.29 [0.28-0.30] (mean [95% CI]) in the third quarter of 2019 to 0.40 [0.39-0.41] during the fourth wave. Adjusted insulin dose rose during the pandemic. Event rates for hypoglycemic coma and diabetic ketoacidosis remained unchanged. CONCLUSIONS: We found no clinically relevant change of glycemic control or incidence of acute diabetes complications during the pandemic. The observed BMI increase may represent an important health risk for youth with T1D.

The WHO-5 well-being questionnaire in type 1 diabetes: screening for depression in pediatric and young adult subjects.

OBJECTIVES: To evaluate the WHO-5 tool in pediatric and young adult subjects with type 1 diabetes, and to analyse associations with demographic/psychological characteristics. METHODS: We included 944 patients with type 1 diabetes 9-25 years of age, documented in the Diabetes Patient Follow-up Registry between 2018 and 2021. We used ROC curve analysis to determine optimal cut-off values for the WHO-5 scores to predict psychiatric comorbidity (ICD-10-diagnoses) and analysed associations with obesity, HbA1c, therapy regimen, and lifestyle via logistic regression. All models were adjusted for age, sex, and diabetes duration. RESULTS: In the total cohort (54.8% male), the median score was 17 [Q1-Q3: 13-20]. Adjusted for age, sex, and diabetes duration, the WHO-5 scores<13 were associated with psychiatric comorbidity, especially depression and ADHD, poor metabolic control, obesity, smoking, and less physical activity. There were no significant associations with therapy regimen, hypertension, dyslipidemia, or social deprivation. In subjects with any diagnosed psychiatric disorder (prevalence 12.2%), the odds ratio for conspicuous scores was 3.28 [2.16-4.97] compared to patients without mental disorders. Using ROC analysis, the optimal cut-off to anticipate any psychiatric comorbidity in our cohort was 15, and 14 for depression. CONCLUSIONS: The WHO-5 questionnaire is a useful tool to predict depression in adolescents with type 1 diabetes. ROC analysis suggests a slightly higher cut-off for conspicuous questionnaire results compared to previous reports. Due to the high rate of deviant results, adolescents and young adults with type-1 diabetes should be screened regularly for signs of psychiatric comorbidity.

Diabetes and gender incongruence: frequent mental health issues but comparable metabolic control - a DPV registry study.

Context: The condition when a person's gender identity does not match the sex assigned at birth is called gender incongruence (GI). Numbers of GI people seeking medical care increased tremendously over the last decade. Diabetes mellitus is a severe and lifelong disease. GI combined with diabetes may potentiate into a burdensome package for affected people. Objective: The study aimed to characterize people with GI and diabetes from an extensive standardized registry, the Prospective Diabetes Follow-up Registry (DPV), and to identify potential metabolic and psychological burdens. Methods: We compared demographic and clinical registry data of persons with type 1 or type 2 diabetes and GI to those without GI and used propensity score matching (1:4) with age, diabetes duration and treatment year as covariates. Results: 75 persons with GI, 49 with type 1 and 26 with type 2 diabetes were identified. HbA1c values were similar in matched persons with type 1 or 2 diabetes and GI compared to those without GI. Lipid profiles showed no difference, neither in type 1 nor in type 2 diabetes. Diastolic blood pressure was higher in the type 1 and GI group than in those without, whereas systolic blood pressure showed comparable results in all groups. Depression and anxiety were significantly higher in GI people (type 1 and 2). Non-suicidal self-injurious behaviour was more common in type 1 and GI, as was suicidality in type 2 with GI. Conclusion: Mental health issues are frequent in people with diabetes and GI and need to be specially addressed in this population.

Clinical characteristics and cardiovascular risk profile in children and adolescents with latent autoimmune diabetes: Results from the German/Austrian prospective diabetes follow-up registry.

AIMS: To characterize children and adolescents with latent autoimmune diabetes of the young (LADY), and to assess the utility of classifying individuals as LADYs regarding their cardiovascular (CV) risk factors. METHODS: Data from 25,520 individuals (age at diagnosis <18 years) of the Prospective Diabetes Follow-up Registry Diabetes-Patienten Verlaufsdokumentation (DPV) were analyzed. LADY was defined as positivity of ≥one islet autoantibody (iAb+) and an insulin-free interval of ≥6 months upon diabetes diagnosis. LADYs were compared to iAb+ individuals immediately requiring insulin ("immunologically confirmed" type 1 diabetes, T1DM), iAb-/Ins- individuals ("classical" T2DM) and to those clinically defined as T2DM (iAbs not measured). RESULTS: Clinical characteristics of LADYs (n = 299) fell in between those with T1DM (n = 24,932) and T2DM (iAb-/Ins-, n = 152) or suspected T2DM (iAB not measured, n = 137). Stratifying LADYs according to their clinical diagnosis however revealed two distinct populations, highly resembling either T1DM or T2DM. Particularly, CV risk profile, precisely prevalence rates of arterial hypertension and dyslipidemia, was significantly higher in LADYs clinically classified as T2DM compared to LADYs classified as T1DM, and did not differ from those with "classical" T2DM. CONCLUSIONS: In terms of CV risk, classifying children and adolescents with diabetes as LADYs provides no additional benefit. Instead, clinical diagnosis seems to better assign individuals to appropriate risk groups for increased CV risk profiles.

Type 1 diabetes mellitus and SARS-CoV-2 in pediatric and adult patients - Data from the DPV network.

BACKGROUND: Data on patients with type 1 diabetes mellitus (T1DM) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse. This study aimed to investigate the association between SARS-CoV-2 infection and T1DM. METHODS: Data from the Prospective Diabetes Follow-up (DPV) Registry were analyzed for diabetes patients tested for SARS-CoV-2 by polymerase chain reaction (PCR) in Germany, Austria, Switzerland, and Luxembourg during January 2020-June 2021, using Wilcoxon rank-sum and chi-square tests for continuous and dichotomous variables, adjusted for multiple testing. RESULTS: Data analysis of 1855 pediatric T1DM patients revealed no differences between asymptomatic/symptomatic infected and SARS-CoV-2 negative/positive patients regarding age, new-onset diabetes, diabetes duration, and body mass index. Glycated hemoglobin A1c (HbA1c) and diabetic ketoacidosis (DKA) rate were not elevated in SARS-CoV-2-positive vs. -negative patients. The COVID-19 manifestation index was 37.5% in individuals with known T1DM, but 57.1% in individuals with new-onset diabetes. 68.8% of positively tested patients were managed as outpatients/telemedically. Data analysis of 240 adult T1MD patients revealed no differences between positively and negatively tested patients except lower HbA1c. Of these patients, 83.3% had symptomatic infections; 35.7% of positively tested patients were hospitalized. CONCLUSIONS: Our results indicate low morbidity in SARS-CoV-2-infected pediatric T1DM patients. Most patients with known T1DM and SARS-CoV-2 infections could be managed as outpatients. However, SARS-CoV-2 infection was usually symptomatic if it coincided with new-onset diabetes. In adult patients, symptomatic SARS-CoV-2 infection and hospitalization were associated with age.

Increased prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes and hypertension: The SWEET international database.

AIMS: To investigate the prevalence of modifiable cardiovascular risk factors (CVRFs), including dyslipidaemia, obesity and high glycated haemoglobin (HbA1c) concentration, in patients with type 1 diabetes (T1D), and to evaluate their association with blood pressure (BP) categories. METHODS: We analysed 21 634 children and adolescents with T1D from the SWEET international database with office BP values assessed at a three or more visits within a year from 2010 to 2021. Participants were classified into a normotensive group, a group with elevated BP (90 to 94th percentile) or a hypertensive group (≥95th percentile), based on the median BP for the visits within the last treatment year. The prevalences of dyslipidaemia [cholesterol ≥ 5.18 mmol/L (200 mg/dL)  and/or HDL cholesterol ≤ 1.036 mmol/L (40 mg/dL)  and/or LDL cholesterol ≥ 2.59 mmol/L (100 mg/dL)], obesity (body mass index ≥2 standard deviation score) and elevated HbA1c [≥ 75 mmol/mol (9%)] were evaluated in patients within each BP group. RESULTS: Patients with hypertension/elevated BP had less favourable lipid profiles, and a higher prevalence of obesity and HbA1c ≥ 75 mmol/mol than normotensive patients. A total of 38.4% of hypertensive patients and 36.0% of those with elevated BP had one CVRF, 15.1% and 10.1%, respectively, had two CVRFs, and 2.3% and 0.8%, respectively, had three CVRFs. Patients with hypertension/elevated BP had a higher prevalence of one or more CVRFs versus normotensive patients (P < 0.001). Obesity was the CVRF most strongly related to hypertension. Girls had a higher prevalence of one or more CVRFs than boys. Similar results were found in patients aged ≥13 years with hypertension compared to those aged <13 years. CONCLUSIONS: The prevalence of modifiable CVRFs is higher in children and adolescents with T1D who have elevated BP/hypertension than in those with normotension, suggesting that they are more vulnerable to future morbidity and mortality requiring early detection and intervention.

A comparison of the rapid-acting insulin analogue glulisine with lispro and aspart for the pump treatment of patients with type 1 diabetes.

AIMS: (1) To describe the population of patients with type 1 diabetes (T1DM) using the rapid-acting insulin analogue glulisine versus lispro and aspart during continuous subcutaneous insulin infusion (CSII); (2) to describe insulin relative effectiveness based on hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and dose; (3) to determine rates of hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA). METHODS: The analysis used March 2021 data from the Diabetes-Patienten-Verlaufsdokumentation registry, which contains data of 618,903 patients with diabetes. Patients were propensity-matched by age, sex, and diabetes duration. RESULTS: Overall, 42,736 patients of any age were eligible for analysis based on insulin pump usage with either glulisine (N = 707) or lispro/aspart (N = 42,029) between 2004 and 2020. Patients receiving glulisine were older (median 20.0 vs. 16.2 years), equally often male (47.2% vs. 47.8%) and had a longer diabetes duration (median 9.4 vs. 7.4 years). After propensity score matching, 707 pairs remained (total N = 1414). Patient characteristics between groups were similar. Achieved HbA1c values were also comparable: 8.04%, 64 mmol/mol versus 7.96%, 63 mmol/mol for glulisine and lispro/aspart [LS mean difference 0.08 (95%CI - 0.08, 0.25)]. FBG was 9.37 mmol/L (168.9 mg/dL) and 9.58 mmol/L (172.6 mg/dL) in the glulisine and lispro/aspart groups [LS mean diff. - 0.21; (95%CI - 1.13, 0.72)]. Total daily insulin doses and prandial to total insulin ratios were also similar. Glulisine group patients had higher rates of lipodystrophy (0.85% vs. 0.71%) (LS mean diff. 0.18 [95% CI - 1.01, 1.38]) and non-severe DKA (3.11% vs. 0.57%; p = 0.002). Fewer patients in the glulisine group had severe hypoglycemic events (7.66 vs. 9.09; p = 0.333) and severe ketoacidosis events (0.57% vs. 1.56%; p = 0.082) but more had hypoglycemic coma events (p = 0.773), although the differences were not statistically significant. CONCLUSIONS: Insulin glulisine had comparable glucose control to lispro/aspart. The use of glulisine was less frequent in the present analysis compared to the previous trials.

Disease heterogeneity of adult diabetes based on routine clinical variables at diagnosis: Results from the German/Austrian Diabetes Follow-up Registry.

AIM: To cluster adults with diabetes using variables from real-world clinical care at manifestation. MATERIALS AND METHODS: We applied hierarchical clustering using Ward's method to 56 869 adults documented in the prospective Diabetes Follow-up Registry (DPV). Clustering variables included age, sex, body mass index (BMI), HbA1c, diabetic ketoacidosis (DKA), components of the metabolic syndrome (hypertension/dyslipidaemia/hyperuricaemia) and beta-cell antibody status. Time until use of oral antidiabetic drugs (OADs), use of insulin, chronic kidney disease (CKD), cardiovascular disease (CVD), retinopathy or neuropathy were assessed using Kaplan-Meier analysis and Cox regression models. RESULTS: We identified eight clusters: four clusters comprised early diabetes onset (median age 40-50 years) but differed with regard to BMI, HbA1c, DKA and antibody positivity. Two clusters included adults with diabetes onset aged in their early 60s who met target HbA1c, but differed in BMI and sex distribution. Two clusters were characterized by late diabetes onset (median age 69 and 77 years) and comparatively low BMI, but differences in HbA1c. Earlier insulin use was observed in adults with high HbA1c, and earlier OAD use was observed in those with high BMI. Time until CKD or CVD was shorter in those with late onset, whereas retinopathy occurred earlier in adults with late onset and high HbA1c, and in adults with early onset, but high HbA1c and high percentage of antibody positivity. CONCLUSIONS: Adult diabetes is heterogeneous beyond classical type 1/type 2 diabetes, based on easily available variables in clinical practice using an automated clustering algorithm that allows both continuous and binary variables.

Early vs late histological confirmation of coeliac disease in children with new-onset type 1 diabetes.

AIM: Screening for coeliac disease in asymptomatic children with new-onset type 1 diabetes is controversial. The aim of this study was to analyse whether the confirmation of coeliac disease in children with new-onset type 1 diabetes and positive screening results can be postponed. METHODS: This was a multicentre population-based cohort study based on the German/Austrian/Swiss/Luxembourgian Prospective Diabetes Follow-up Registry (Diabetes Patienten Verlaufsdokumentation [DPV]). Participants aged ≤18 years diagnosed with type 1 diabetes between 1995 and June 2021 and with elevated IgA tissue transglutaminase antibodies (anti-tTGA) at diabetes onset on screening for coeliac disease were included. We compared outcomes of participants with a diabetes duration of more than 1 year between those in whom coeliac disease was confirmed histologically within the first 6 months and those in whom coeliac disease was confirmed between 6 and 36 months after diabetes diagnosis. RESULTS: Of 92,278 children and adolescents with a diagnosis of type 1 diabetes, 26,952 (29.2%) had documented anti-tTGA data at diabetes onset. Of these, 2340 (8.7%) had an elevated anti-tTGA level. Individuals who screened positive were younger (median age 9.0 vs 9.8 years, p<0.001) and more often female (53.1% vs 44.4%, p<0.001). A total of 533 participants (22.8% of those who screened positive) had a documented biopsy, of whom 444 had documented histological confirmation of coeliac disease. Of 411 participants with biopsy-proven coeliac disease within the first 36 months of diabetes and follow-up data, histological confirmation was performed in 264 (64.2%) within the first 6 months and in 147 (35.8%) between 6 and 36 months after diabetes onset. At follow-up (median diabetes duration 5.3 years and 5.1 years, respectively), estimated median HbA1c levels (62.8 mmol/mol vs 62.2 mmol/mol [7.9% vs 7.8%]), cardiovascular risk markers (lipids, rate of microalbuminuria, blood pressure), rates of acute diabetes complications (diabetic ketoacidosis, severe hypoglycaemia) and the proportions of participants reaching anti-tTGA levels within the normal range did not differ between groups. Participants with delayed histological confirmation of coeliac disease showed no negative effects on growth or weight gain during the observation period. CONCLUSIONS: Our study suggests that the histological confirmation of coeliac disease in asymptomatic individuals with new-onset type 1 diabetes could be postponed.

The Importance of Office Blood Pressure Measurement Frequency and Methodology in Evaluating the Prevalence of Hypertension in Children and Adolescents With Type 1 Diabetes: The SWEET International Database.

OBJECTIVE: The prevalence of hypertension is higher in children and adolescents with type 1 diabetes (T1D) compared with those without. This retrospective analysis of a large cohort of children and adolescents with T1D from the SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) international consortium of pediatric diabetes centers aimed to 1) estimate the prevalence of elevated office blood pressure (BP) and hypertension and 2) investigate the influence of BP measurement methodology on the prevalence of hypertension. RESEARCH DESIGN AND METHODS: A total of 27,120 individuals with T1D, aged 5-18 years, were analyzed. Participants were grouped into those with BP measurements at three or more visits (n = 10,440) and fewer than 3 visits (n = 16,680) per year and stratified by age and sex. A subgroup analysis was performed on 15,742 individuals from centers providing a score indicating BP measurement accuracy. RESULTS: Among participants with BP measurement at three or more visits, the prevalence of hypertension was lower compared with those with fewer than three visits (10.8% vs. 17.5% P < 0.001), whereas elevated BP and normotension were higher (17.5% and 71.7% vs. 15.3% and 67.1%, respectively; both P < 0.001). The prevalence of hypertension and elevated BP was higher in individuals aged ≥13 years than in younger ones (P < 0.001) and in male than female participants (P < 0.001). In linear regression models, systolic and diastolic BP was independently determined by the BP measurement methodology. CONCLUSIONS: The estimated prevalence of elevated BP and hypertension in children and adolescents with T1D is ∼30% and depends on the BP measurement methodology. Less frequent BP evaluation may overestimate the prevalence of hypertension.