Lipoprotein-associated phospholipase A2 activity in obese adolescents with and without type 2 diabetes.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) was identified as a strong predictor for cardiovascular events. Furthermore, it is highly associated with obesity. The role of Lp-PLA2 in diabetes mellitus is controversial and analyses, especially in adolescents with type 2 diabetes (T2D), are missing. Therefore, we compared Lp-PLA2 activity between two obese age-, sex-, and BMI-matched cohorts of adolescents with and without T2D. Relationships between Lp-PLA2 activity and age, BMI, hemoglobin A1c, lipids, and adipokines were evaluated. Lp-PLA2 activity was analyzed in serum of 72 obese adolescents without T2D (mean age 15.2 ± 1.6 years) and in 65 obese adolescents with T2D (mean age 15.5 ± 1.8 years). Clinical data were obtained from the Diabetes-Patienten-Verlaufsdokumentation (DPV) registry. Surprisingly, obese adolescents with T2D had lower levels of Lp-PLA2 activity than obese children without T2D (160.2 ± 45.0 versus 180.9 ± 35.6 nmol/min/ml, p = 0.003), but this decrease could only be detected in male (158.8 ± 45.3 versus 190.8 ± 31.3 nmol/min/ml, p < 0.001) and not in female adolescents (162.1 ± 45.5 versus 167.7 ± 37.1 nmol/min/ml, p = 0.60). In multiple linear regression analysis, differences in Lp-PLA2 activity between cohorts remained large and significant (ß-coefficient: -31.60, 95% confidence interval [-49.27;-13.93], p < 0.001). Furthermore, Lp-PLA2 activity was positively associated with BMI (ß-coefficient: 2.04 [0.68;3.40], p = 0.004) and negatively associated with the adipokines leptin (ß-coefficient: -0.53 [-0.89;-0.17], p = 0.004) and adiponectin (ß-coefficient: -3.06, [-5.63;-0.48], p = 0.02). Elevated mean glucose concentrations in adolescents with T2D were not associated with an increase but with a decrease of Lp-PLA2 activity. Hence, in young patients with T2D the Lp-PLA2 activity as a risk predictor for cardiovascular events needs further investigation.

Severe hypoglycemia and diabetic ketoacidosis in young persons with preschool onset of type 1 diabetes mellitus: An analysis of three nationwide population-based surveys.

OBJECTIVES: To describe incidence rates and temporal trends of severe hypoglycemia (SH) and of hospitalizations for SH or diabetic ketoacidosis (DKA) in persons with early-onset, long-term type 1 diabetes (T1D) and associations of these short-term complications with potential risk factors. METHODS: This study includes data of 1,875 persons 11.2 to 21.9 years of age with early-onset (<5 years) and long-term (>10 years) T1D from 3 cross-sectional nationwide, population-based surveys conducted in 2009/2010, 2012/2013 and 2015/2016 using standardized questionnaires. Negative binomial regression was used to estimate incidence rates per 100 person-years (py), temporal trends and associations between potential risk factors and outcomes. RESULTS: The crude incidence rate of SH showed a decreasing trend over time (P for trend = .004), disappearing after adjustment for confounders (P for trend = .341). In contrast, adjusted rates of SH- and DKA-associated hospitalizations did not change significantly between 2009 and 2016 (P for trend = .306 and .774, respectively). Associations between sex, diabetes duration, insulin treatment regimen, hypoglycemia awareness as well as physical activity and SH were found, while family structure was associated with hospitalizations for SH. Family structure, socioeconomic status (SES), diabetes duration, and hemoglobin A1c values showed associations with DKA-related hospitalizations. CONCLUSIONS: After adjustment, rates of SH and SH- or DKA-associated hospitalization showed no significant changes in recent years. Structured education programs focusing on high-risk groups as, for example, persons with T1D living with 1 biological parent and the parents' partner or those with a low SES, should be implemented to reduce incidence rates of hospitalizations.

Association of individual and area-level socioeconomic conditions with quality of life and glycaemic control in 11- to 21-year-old adolescents with early-onset type 1 diabetes: a cross-sectional study.

PURPOSE: To analyse the association of area-level deprivation (German Index of Multiple Deprivation, GIMD 2010) with health- and disease-related quality of life (QoL) and glycaemic control (HbA1c) jointly with individual-level socioeconomic status (SES) in young patients with preschool-onset type 1 diabetes. METHODS: A total of 425 male and 414 female patients aged 11-21 years from a Germany-wide population-based survey completed the generic KINDL-R, the DISABKIDS chronic-generic module (DCGM-12), and the DISABKIDS diabetes-specific module with impact and treatment scales (QoL indicators; range 0-100 with higher scores representing better QoL). To analyse the association of area-level deprivation and SES with QoL and HbA1c, multiple linear regression models were applied adjusting for sociodemographic and health-related variables. RESULTS: Mean QoL scores (SD) were 73.2 (12.2) for the KINDL-R, 76.1 (16.1) for the DCGM-12, 66.2 (19.9) for diabetes impact, and 56.4 (27.3) for diabetes treatment (DISABKIDS). Mean HbA1c was 8.3 (1.4)%. While both QoL outcomes and HbA1c level improved with increasing individual SES, no association was observed between area-level deprivation (GIMD 2010) and either outcome. CONCLUSIONS: Compared with individual SES, area-level deprivation seems to be of minor importance for QoL and glycaemic control in young people with early-onset type 1 diabetes.

Impact of quality of life (QoL) on glycemic control (HbA1c) among adolescents and emerging adults with long-duration type 1 diabetes: A prospective cohort-study.

OBJECTIVE: To evaluate the impact of self-reported chronic-generic and condition-specific quality of life (QoL) on glycemic control among adolescents and emerging adults with long-duration type 1 diabetes (T1D) in a longitudinal design. METHODS: The database used was a nationwide cohort study of patients with ≥10 years T1D duration at baseline in Germany. The baseline questionnaire survey was conducted in 2009-2010, the follow-up survey in 2012-2013; additional clinical data of routine care procedures were linked. QoL was assessed by the DISABKIDS chronic generic module (DCGM-12) and diabetes module (DM) with treatment and impact scales. Regression analyses were conducted for the outcome hemoglobin A1c (HbA1c) at follow up with baseline DISABKIDS scores as predictors and sociodemographic and health-related covariates. RESULTS: At baseline, the included 560 patients had a mean age of 15.9 (SD 2.3) years, a diabetes duration of 13.0 (2.0) years, and an HbA1c of 67 (14.2) mmol/mol. Mean follow-up time was 3.0 (0.6) years. Univariate analyses indicated associations between baseline QoL scores and HbA1c at follow-up (ß[DCGM-12] = -0.174 (SE 0.038), ß[DM treatment] = -0.100 (0.022), ß[DM impact] = -0.177 (0.030), p < .001). The associations remained significant after adjustment for sociodemographic and illness-related factors, but dissolved (p > .60) when additionally adjusting for baseline HbA1c. In patients with poor baseline HbA1c (>75 mmol/mol), significant associations were observed between DCGM-12 and DM impact scores and follow-up HbA1c (ß[DCGM-12] = -0.144 (0.062), p = .021; ß[DM impact] = -0.139 (0.048), p = .004). CONCLUSIONS: QoL was inversely associated with HbA1c after 3 years in the course of T1D only in patients poorly controlled at baseline.

Disordered eating and insulin restriction in youths receiving intensified insulin treatment: Results from a nationwide population-based study.

OBJECTIVE: This Germany-wide population-based study sought to estimate the prevalence of disordered eating and insulin restriction (IR) among 819 youths aged 11-21 years with early-onset type 1 diabetes (T1D) and a disease duration of at least 10 years. METHODS: All respondents answered the five-item SCOFF screening questionnaire for eating disorders (EDs) and reported on the frequency of IR and clinical outcomes. Screening for disordered eating was positive when more than two SCOFF items were answered affirmatively. Frequent IR was defined as IR occurring more than five times per week. RESULTS: A total of 28.2%/9.2% of the female/male patients were SCOFF-positive without IR and 4.2%/5.3% reported frequent IR but were SCOFF-negative; 2.7%/1.9% screened positive for both disordered eating and IR. Patients with disordered eating, frequent IR, or both showed significantly worse glycemic control and partly more inpatient-treated diabetic ketoacidoses than patients who screened negative. DISCUSSION: Approximately one in three female and one in six male patients with early-onset long-duration T1D reported disordered eating and/or frequent IR. Because of their association with worse outcomes, both disordered eating and IR should be considered in T1D care irrespective of sex, age at onset, and diabetes duration.

Studies analysing the need for health-related information in Germany - a systematic review.

BACKGROUND: Exploring health-related information needs is necessary to better tailor information. However, there is a lack of systematic knowledge on how and in which groups information needs has been assessed, and which information needs have been identified. We aimed to assess the methodology of studies used to assess information needs, as well as the topics and extent of health-related information needs and associated factors in Germany. METHODS: A systematic search was performed in Medline, Embase, Psycinfo, and all databases of the Cochrane Library. All studies investigating health-related information needs in patients, relatives, and the general population in Germany that were published between 2000 and 2012 in German or English were included. Descriptive content analysis was based on predefined categories. RESULTS: We identified 19 studies. Most studies addressed cancer or rheumatic disease. Methods used were highly heterogeneous. Apart from common topics such as treatment, diagnosis, prevention and health promotion, etiology and prognosis, high interest ratings were also found in more specific topics such as complementary and alternative medicine or nutrition. Information needs were notable in all surveyed patient groups, relatives, and samples of the general population. Younger age, shorter duration of illness, poorer health status and higher anxiety and depression scores appeared to be associated with higher information needs. CONCLUSION: Knowledge about information needs is still scarce. Assuming the importance of comprehensive information to enable people to participate in health-related decisions, further systematic research is required.

Quality of life in intensively treated youths with early-onset type 1 diabetes: a population-based survey.

OBJECTIVE: To evaluate factors associated with self-reported generic, chronic-generic, and condition-specific quality of life (QoL) impairments in intensively treated patients with early-onset and long-duration type 1 diabetes. STUDY DESIGN: A total of 840 11- to 21-year-olds with type 1 diabetes onset before 5 years of age and at least 10 years diabetes duration completed questionnaires including the generic Revised Children's Quality of Life Questionnaire (KINDL-R), the DISABKIDS chronic-generic module (DCGM-12), and the DISABKIDS diabetes-specific module with impact and treatment scales to assess QoL. Regression analyses were conducted using sociodemographic, health-related, and diabetes-related independent variables. RESULTS: The strongest associations were observed between QoL scores and diabetes-specific factors, especially glycemic control and treatment satisfaction. The adjusted mean differences [regression coefficients ß (standard error)] between patient groups with high risk vs. optimal glycemic control were ß = -4.6 (1.1) for the KINDL-R total score, ß = -8.6 (1.5) for the DCGM-12, ß = -14.4 (1.9) for the diabetes impact score, and ß = -21.1 (2.7) for the diabetes treatment score (all p < 0.001). The mean differences between patient groups with poor vs. very good treatment satisfaction were ß = -5.9 (1.3) for the KINDL-R total score, ß = -8.5 (1.7) for the DCGM-12, ß = -9.4 (2.0) for the diabetes impact score, and ß = -15.0 (2.9) for the diabetes treatment score (all p < 0.001). In addition, recent severe hypoglycemia and an insulin regimen without an insulin pump were negatively associated with the QoL scores. CONCLUSION: Good glycemic control and a high level of treatment satisfaction are associated with a positive QoL in youths with early-onset type 1 diabetes.

Efficacy of automated insulin delivery (AID) systems in type 1 diabetes: protocol of a systematic review and network meta-analysis of outpatient randomised controlled trials.

INTRODUCTION: Automated insulin delivery (AID), also known as artificial pancreas system or 'closed-loop system', represents a novel option for current treatments for type 1 diabetes (T1D). The objective of this systematic review and meta-analysis is to assess the efficacy of AID systems in comparison with current intensified insulin therapy for glycaemic control and patient-reported outcomes in individuals with T1D. METHODS AND ANALYSIS: Studies will be eligible if they are randomised controlled trials (RCTs) in people with T1D of all ages, and if they compare an AID system for self-administration during the day and night period with any other type of insulin therapy for at least 3 weeks. The primary outcome will be time in the glucose target range of 70-180 mg/dL. A systematic review will be conducted in the MEDLINE, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov registries from their inception dates. Two authors will independently screen all references based on titles and abstracts against the eligibility criteria. For data extraction, standard forms will be developed and tested before extraction. All information will be assessed independently by at least two reviewers. The risk of bias of the included studies will be assessed using the Cochrane Risk of Bias 2 tool. The data synthesis will include a random-effects pairwise and network meta-analysis (NMA) in a frequentist framework. Where applicable and if sufficient RCTs are available, sensitivity analyses will be performed, and heterogeneity and publication bias will be assessed. The certainty of evidence from the NMA will be evaluated following the Grading of Recommendations Assessment, Development, and Evaluation working group guidance. ETHICS AND DISSEMINATION: No ethical approval is needed. The results will be reported to the funder, presented in a peer-reviewed scientific journal and at conferences, and disseminated via press release, social media and public events. PROSPERO REGISTRATION NUMBER: CRD42023395492.

Comparison of diabetes distress and depression screening results of emerging adults with type 1 diabetes onset at different ages: findings from the German early-onset T1D study and the German Diabetes Study (GDS).

BACKGROUND: Diabetes distress is increasingly considered one of the most important psychosocial issues in the care of people with type 1 diabetes (T1D). We analyse whether diabetes distress and depression screening results of emerging adults are associated with the age at T1D onset. METHODS: Data were taken from two cohort studies conducted at the German Diabetes Center, Düsseldorf, Germany. The 18-30-year-old participants had an age at onset either before the age of 5 years (childhood-onset long-term T1D study group, N = 749) or during adulthood (adult-onset short-term T1D study group from the German Diabetes Study (GDS), N = 163). Diabetes distress and depression screening were analysed by means of the 20-item Problem Areas in Diabetes (PAID-20) scale and the nine-item depression module from the Patient Health Questionnaire (PHQ-9). The average causal effect of age at onset was estimated by a doubly robust causal inference method. RESULTS: The PAID-20 total scores were increased in the adult-onset study group [potential outcome mean (POM) 32.1 (95% confidence interval 28.0; 36.1) points] compared to the childhood-onset study group [POM 21.0 (19.6; 22.4) points, difference 11.1 (6.9; 15.3) points, p<0.001] adjusted for age, sex and haemoglobin A1c (HbA1c) levels. Moreover, more participants in the adult-onset group [POM 34.5 (24.9; 44.2) %] than in the childhood-onset group [POM 16.3 (13.3; 19.2) %] screened positive for diabetes distress [adjusted difference 18.3 (8.3; 28.2) %, p<0.001]. The PHQ-9 total score [difference 0.3 (-1.1; 1.7) points, p=0.660] and the proportion of participants with a positive screening result for depression [difference 0.0 (-12.7; 12.8) %, p=0.994] did not differ between the groups in the adjusted analyses. CONCLUSIONS: Emerging adults with short-term type 1 diabetes screened positive for diabetes distress more often than adults with type 1 diabetes onset during early childhood when age, sex and HbA1c values were considered confounding factors. Accounting for age at onset or the duration of diabetes may help explain the heterogeneity in the data when psychological factors are examined.

Screening for generalized anxiety disorder (GAD) and associated factors in adolescents and young adults with type 1 diabetes: Cross-sectional results of a Germany-wide population-based study.

AIMS: The aims of this study were to screen 14- to 30-year-olds with early-onset type 1 diabetes for generalized anxiety disorder (GAD) and to compare the characteristics of the study participants who had a positive result for GAD with those who had a negative result. METHODS: This study used data from a questionnaire survey conducted from 2018 to 2019. The GAD-7 questionnaire was used to screen for GAD (positive: GAD-7 score ≥ 10). All regression analyses were adjusted for age, sex, depression diagnosis and considered multiple testing. RESULTS: The 713 participants had a mean GAD-7 score of 4.32 (SD 4.18). A total of 12% of the study population (10% of adolescents, 13% of adults) was screened positive for GAD. Positive screening results were associated with impairments in various domains, such as self-assessed physical performance (RR poor versus good 3.03 [95% CI 1.85-4.96]), difficulty falling asleep (RR ≥3 times/week versus not during the last 4 weeks 5.36 [2.86-10.07]), glycemic control (RR HbA1c per 1% 1.16 [1.03-1.31]), and diabetes treatment satisfaction (RR poor versus good 2.67 [1.43-5.00]). CONCLUSIONS: Diabetologists should be aware that adolescents and young adults with GAD symptoms might experience extensive impairments in their daily lives.

Overestimation and underestimation of youths' health-related quality of life are associated with youth and caregiver positive screens for depression: results of a population-based study among youths with longstanding type 1 diabetes.

BACKGROUND: This study aimed to analyze the extent and direction of disagreement between self- and proxy-reported quality of life (QoL) and the factors associated with QoL overestimation and underestimation by caregivers compared with self-reports. METHODS: This study used data from population-based questionnaire surveys conducted in 2012-2013 and 2015-2016 with 11- to 17-year-olds with a duration of type 1 diabetes of 10 years or longer and their caregivers (n = 1058). QoL in youth was assessed via 10-item KIDSCREEN (KIDSCREEN-10) self- and proxy-reported questionnaires. The scores ranged from 0 to 100, with higher scores indicating better QoL. Depression screening was performed via the Center for Epidemiological Studies Depression Scale for Children for youths (CES-DC screen positive: score > 15) and WHO-5 Well-being Index for parents/caregivers (WHO-5 screen positive: score ≤ 50). RESULTS: The mean self- and proxy-reported normalized KIDSCREEN-10 scores were 64.2 (standard deviation [SD] 11.4) and 66.1 (11.5), respectively. More caregivers overestimated (self-reported minus proxy-reported score < - 0.5*SD self-reported score) than underestimated (self-reported minus proxy-reported score > 0.5*SD self-reported score) youths' QoL (37% versus 23%, p < 0.001). Youths who screened positive for depression (18%) were at higher risk of their QoL being overestimated and lower risk of their QoL being underestimated by caregivers than youths who screened negative for depression (RROverestimation 1.30 [95% CI 1.10-1.52], RRUnderestimation 0.27 [0.15-0.50]). Caregivers who screened positive for depression (28%) overestimated the QoL of their children less often and underestimated the QoL of their children more often than caregivers who screened negative for depression (RROverestimation 0.73 [0.60-0.89], RRUnderestimation 1.41 [1.14-1.75]). CONCLUSIONS: Caregivers often over- or underestimated their children's QoL. Positive screens for depression among both youths and caregivers contributed to the observed differences between self- and caregiver-reported QoL.

The bias from heaping on risk estimation: effect of age at diagnosis of hypertension on risk of subsequent cardiovascular comorbidities.

PURPOSE: To investigate (1) the bias in effect estimation due to heaping or digit preference, (2) the association between age at hypertension diagnosis and risk of cardiovascular comorbidities, and (3) the influence of heaping on risk estimates. METHODS: We performed a simulation study with various scenarios, binary outcome, and normal or lognormal distributed covariables. We calculated mean logistic coefficients under the original and heaped data and their relative deviation. The association of age at hypertension diagnosis and risk of ≥1 cardiovascular comorbidity was investigated using logistic regression among 50,858 participants in the NAKO Gesundheitsstudie (German National Cohort) who reported such diagnosis. We assessed the proportion of heaped observations and to what extent heaping may have influenced risk estimates. RESULTS: Based on the simulation study and assuming 50% of observations in the variable of interest to be heaped, relative bias was <6%. In NAKO, a 5-year younger age at hypertension diagnosis was associated with a 15% increased risk of having ≥1 cardiovascular comorbidity. Observed heaping in age at hypertension diagnosis was 12.6%, and bias of the risk estimate was 0.14%. CONCLUSIONS: Bias in effect estimation due to heaping is low in most common scenarios. Younger age at hypertension diagnosis is associated with a higher risk of cardiovascular comorbidities.

Increased risk of impaired treatment satisfaction among girls/women and young people with suboptimal HbA1c: Results of a nationwide type 1 diabetes study.

BACKGROUND: This study aims to analyze the patient-reported outcome (PRO) of treatment satisfaction in a sample of children, adolescents and young adults with long-duration type 1 diabetes and to determine potential risk factors for poor treatment satisfaction and the intraindividual changes over a 3-year period. METHODS: This study used data from two population-based questionnaire surveys conducted in 2015-2016 and 2018-2019. The participants were 11 to 27 years old and had a type 1 diabetes duration of 10 years or longer in 2015-2016 (n = 575). Factors that were potentially associated with poor treatment satisfaction (moderate, poor or very poor) compared to the reference group (very good or good treatment satisfaction) were analyzed by log binomial regression adjusted for sex and age group. RESULTS: In 2015-2016 (2018-2019), 26% (33%) of the respondents rated their diabetes treatment/consultation as "very good", 53% (46%) as "good", and 20% (21%) as "poor". Based on the 2018-2019 data, girls/women had an increased risk of poor treatment satisfaction (RRgirls/women: 1.64 (1.10; 2.44), p = 0.016). In addition, people with hemoglobin A1c (HbA1c) values ≥ 7.5% had a more than twice the risk of poor treatment satisfaction than people with HbA1c values < 7.5% (RRHbA1c ≥7.5%: 2.43 (1.63; 3.63), p < 0.001). A total of 42% of people with poor treatment satisfaction in 2015-2016 also reported poor treatment satisfaction at follow-up. CONCLUSIONS: Most study participants were satisfied with their diabetes treatment. However, we identified risk groups that would benefit from targeted interventions to improve this important PRO.

Correction to: Information needs in people with diabetes mellitus: a systematic review.

Following publication of the original article [1], the authors opted to revise Table 1. Below is the updated version of the table.

Information needs in people with diabetes mellitus: a systematic review.

BACKGROUND: The purpose of this study was to identify and analyse currently available knowledge on information needs of people with diabetes mellitus, also considering possible differences between subgroups and associated factors. METHODS: Twelve databases including MEDLINE, EMBASE and the Cochrane Library were searched up until June 2015. Publications that addressed self-reported information needs of people with diabetes mellitus were included. Each study was assessed by using critical appraisal tools, e.g. from the UK National Institute for Health and Care Excellence. Extraction and content analysis were performed systematically. RESULTS: In total, 1993 publications were identified and 26 were finally included. Nine main categories of information needs were identified, including 'treatment-process', 'course of disease', 'abnormalities of glucose metabolism' and 'diabetes through the life cycle'. Differences between patient subgroups, such as type of diabetes or age, were sparsely analysed. Some studies analysed associations between information needs and factors such as participation preferences or information seeking. They found, for example, that information needs on social support or life tasks were associated with information seeking in Internet forums. CONCLUSION: Information needs in people with diabetes mellitus, appear to be high, yet poorly investigated. Research is needed regarding differences between diverse diabetes populations, including gender aspects or changes in information needs during the disease course. SYSTEMATIC REVIEW REGISTRATION: The review protocol has been registered at Prospero ( CRD42015029610 ).

Correction: Reinauer et al., The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype. Genes 2017, 8, 146.

The article entitled "The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes is Independent of the HLA DR-DQ Genotype" contained a calculation error in Table 2 and the statistical methods used were not completely described.[...].

Regional differences in antihyperglycemic medication are not explained by individual socioeconomic status, regional deprivation, and regional health care services. Observational results from the German DIAB-CORE consortium.

AIMS: This population-based study sought to extend knowledge on factors explaining regional differences in type 2 diabetes mellitus medication patterns in Germany. METHODS: Individual baseline and follow-up data from four regional population-based German cohort studies (SHIP [northeast], CARLA [east], HNR [west], KORA [south]) conducted between 1997 and 2010 were pooled and merged with both data on regional deprivation and regional health care services. To analyze regional differences in any or newer anti-hyperglycemic medication, medication prevalence ratios (PRs) were estimated using multivariable Poisson regression models with a robust error variance adjusted gradually for individual and regional variables. RESULTS: The study population consisted of 1,437 people aged 45 to 74 years at baseline, (corresponding to 49 to 83 years at follow-up) with self-reported type 2 diabetes. The prevalence of receiving any anti-hyperglycemic medication was 16% higher in KORA (PR 1.16 [1.08-1.25]), 10% higher in CARLA (1.10 [1.01-1.18]), and 7% higher in SHIP (PR 1.07 [1.00-1.15]) than in HNR. The prevalence of receiving newer anti-hyperglycemic medication was 49% higher in KORA (1.49 [1.09-2.05]), 41% higher in CARLA (1.41 [1.02-1.96]) and 1% higher in SHIP (1.01 [0.72-1.41]) than in HNR, respectively. After gradual adjustment for individual variables, regional deprivation and health care services, the effects only changed slightly. CONCLUSIONS: Neither comprehensive individual factors including socioeconomic status nor regional deprivation or indicators of regional health care services were able to sufficiently explain regional differences in anti-hyperglycemic treatment in Germany. To understand the underlying causes, further research is needed.

The Clinical Course of Patients with Preschool Manifestation of Type 1 Diabetes Is Independent of the HLA DR-DQ Genotype.

INTRODUCTION: Major histocompatibility complex class II genes are considered major genetic risk factors for autoimmune diabetes. We analysed Human Leukocyte Antigen (HLA) DR and DQ haplotypes in a cohort with early-onset (age < 5 years), long term type 1 diabetes (T1D) and explored their influence on clinical and laboratory parameters. METHODS: Intermediate resolution HLA-DRB1, DQA1 and DQB1 typing was performed in 233 samples from the German Paediatric Diabetes Biobank and compared with a local control cohort of 19,544 cases. Clinical follow-up data of 195 patients (diabetes duration 14.2 ± 2.9 years) and residual C-peptide levels were compared between three HLA risk groups using multiple linear regression analysis. RESULTS: Genetic variability was low, 44.6% (104/233) of early-onset T1D patients carried the highest-risk genotype HLA-DRB1*03:01-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03:02 (HLA-DRB1*04 denoting 04:01/02/04/05), and 231 of 233 individuals carried at least one of six risk haplotypes. Comparing clinical data between the highest (n = 83), moderate (n = 106) and low risk (n = 6) genotypes, we found no difference in age at diagnosis (mean age 2.8 ± 1.1 vs. 2.8 ± 1.2 vs. 3.2 ± 1.5 years), metabolic control, or frequency of associated autoimmune diseases between HLA risk groups (each p > 0.05). Residual C-peptide was detectable in 23.5% and C-peptide levels in the highest-risk group were comparable to levels in moderate to high risk genotypes. CONCLUSION: In this study, we saw no evidence for a different clinical course of early-onset T1D based on the HLA genotype within the first ten years after manifestation.