Association of a lifestyle score with cardiometabolic markers among individuals with diabetes: a cross-sectional study.

INTRODUCTION: To investigate the associations of a lifestyle score with various cardiovascular risk markers, indicators for fatty liver disease as well as MRI-determined total, subcutaneous and visceral adipose tissue mass in adults with new-onset diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional analysis included 196 individuals with type 1 (median age: 35 years; median body mass index (BMI): 24 kg/m²) and 272 with type 2 diabetes (median age: 53 years; median BMI: 31 kg/m²) from the German Diabetes Study. A healthy lifestyle score was generated based on healthy diet, moderate alcohol consumption, recreational activity, non-smoking and non-obese BMI. These factors were summed to form a score ranging from 0 to 5. Multivariable linear and non-linear regression models were used. RESULTS: In total, 8.1% of the individuals adhered to none or one, 17.7% to two, 29.7% to three, 26.7% to four, and 17.7% to all five favorable lifestyle factors. High compared with low adherence to the lifestyle score was associated with more favorable outcome measures, including triglycerides (ß (95% CI) -49.1 mg/dL (-76.7; -21.4)), low-density lipoprotein (-16.7 mg/dL (-31.3; -2.0)), and high-density lipoprotein cholesterol (13.5 mg/dL (7.6; 19.4)), glycated hemoglobin (-0.5% (-0.8%; -0.1%)), high-sensitivity C reactive protein (-0.4 mg/dL (-0.6; -0.2)), as well as lower hepatic fat content (-8.3% (-11.9%; -4.7%)), and visceral adipose tissue mass (-1.8 dm³ (-2.9; -0.7)). The dose-response analyses showed that adherence to every additional healthy lifestyle factor was associated with more beneficial risk profiles. CONCLUSIONS: Adherence to each additional healthy lifestyle factor was beneficially associated with cardiovascular risk markers, indicators of fatty liver disease and adipose tissue mass. Strongest associations were observed for adherence to all healthy lifestyle factors in combination. TRIAL REGISTRATION NUMBER: NCT01055093.

Is COVID-19 to Blame? Trends of Incidence and Sex Ratio in Youth-Onset Type 2 Diabetes in Germany.

OBJECTIVE: We investigated the incidence of pediatric type 2 diabetes (T2D) in Germany during 2 years of the coronavirus disease 2019 (COVID-19) pandemic (2020-2021) compared with the control period 2011-2019. RESEARCH DESIGN AND METHODS: Data on T2D in children (aged 6 to <18 years) were obtained from the DPV (German Diabetes Prospective Follow-up) Registry. Poisson regression was used to estimate incidences for 2020 and 2021 based on data from 2011 to 2019, and these were compared with observed incidences in 2020 and 2021 by estimating incidence rate ratios (IRRs) with 95% CIs. RESULTS: Incidence of youth-onset T2D increased from 0.75 per 100,000 patient-years (PYs) in 2011 (95% CI 0.58, 0.93) to 1.25 per 100,000 PYs in 2019 (95% CI 1.02, 1.48), an annual increase of 6.8% (95% CI 4.1, 9.6). In 2020, T2D incidence increased to 1.49 per 100,000 PYs (95% CI 1.23, 1.81), which was not significantly higher than predicted (IRR 1.15; 95% CI 0.90, 1.48). In 2021, the observed incidence was significantly higher than expected (1.95; 95% CI 1.65, 2.31 vs. 1.38; 95% CI 1.13, 1.69 per 100,000 PYs; IRR 1.41; 95% CI 1.12, 1.77). Although there was no significant increase in incidence in girls in 2021, the observed incidence in boys (2.16; 95% CI 1.73, 2.70 per 100,000 PYs) significantly exceeded the predicted rate (IRR 1.55; 95% CI 1.14, 2.12), leading to a reversal of the sex ratio of pediatric T2D incidence. CONCLUSIONS: In Germany, incidence of pediatric T2D increased significantly in 2021. Adolescent boys were more affected by this increase, resulting in a reversal of the sex ratio of youth-onset T2D.

Dietary Factors and All-Cause Mortality in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Prospective Observational Studies.

BACKGROUND: Type 2 diabetes is a major health concern associated with mortality. Diet may influence the progression of diabetes; however, systematic reviews are lacking. PURPOSE: This study systematically summarized the evidence on diet and all-cause mortality in individuals with type 2 diabetes. DATA SOURCES: PubMed and Web of Science were searched until June 2022. STUDY SELECTION: Prospective observational studies investigating dietary factors in association with all-cause mortality in individuals with type 2 diabetes were selected. DATA SYNTHESIS: We identified 107 studies. Moderate certainty of evidence was found for inverse associations of higher intakes of fish (summary risk ratios per serving/week: 0.95; 95% CI 0.92, 0.99; n = 6 studies), whole grain (per 20 g/day: 0.84; 95% CI 0.71, 0.99; n = 2), fiber (per 5 g/day: 0.86; 95% CI 0.81, 0.91; n = 3), and n-3 polyunsaturated fatty acids (per 0.1 g/day: 0.87; 95% CI 0.82, 0.92; n = 2) and mortality. There was low certainty of evidence for inverse associations of vegetable consumption (per 100 g/day: 0.88; 95% CI 0.82, 0.94; n = 2), plant protein (per 10 g/day: 0.91; 95% CI 0.87, 0.96; n = 3), and for positive associations of egg consumption (per 10 g/day: 1.05; 95% CI 1.03, 1.08; n = 7) and cholesterol intake (per 300 mg/day: 1.19; 95% CI 1.13, 1.26; n = 2). For other dietary factors, evidence was uncertain or no association was observed. CONCLUSIONS: Higher intake of fish, whole grain, fiber, and n-3 polyunsaturated fatty acids were inversely associated with all-cause mortality in individuals with type 2 diabetes. There is limited evidence for other dietary factors, and, thus, more research is needed.

Spatiotemporal association between COVID-19 incidence and type 1 diabetes incidence among children and adolescents: a register-based ecological study in Germany.

Objective: Studies have shown an increased incidence of pediatric type 1 diabetes during the COVID-19 pandemic, but the detailed role of SARS-CoV-2 infection in the incidence increase in type 1 diabetes remains unclear. We investigated the spatiotemporal association of pediatric type 1 diabetes and COVID-19 incidence at the district level in Germany. Methods: For the period from March 2020 to June 2022, nationwide data on incident type 1 diabetes among children and adolescents aged <20 years and daily documented COVID-19 infections in the total population were obtained from the German Diabetes Prospective Follow-up Registry and the Robert Koch Institute, respectively. Data were aggregated at district level and seven time periods related to COVID-19 pandemic waves. Spatiotemporal associations between indirectly standardized incidence rates of type 1 diabetes and COVID-19 were analyzed by Spearman correlation and Bayesian spatiotemporal conditional autoregressive Poisson models. Results: Standardized incidence ratios of type 1 diabetes and COVID-19 in the pandemic period were not significantly correlated across districts and time periods. A doubling of the COVID-19 incidence rate was not associated with a significant increase in the incidence rate of type 1 diabetes (relative risk 1.006, 95% CI 0.987; 1.019). Conclusion: Our findings based on data from the pandemic period indirectly indicate that a causal relationship between SARS-COV-2 infection and type 1 diabetes among children and adolescents is unlikely.

Birth Order, Caesarean Section, or Daycare Attendance in Relation to Child- and Adult-Onset Type 1 Diabetes: Results from the German National Cohort.

(1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to "only-children", HRs for second- or later-born individuals were 0.70 (95% CI = 0.50-0.96) and 0.65 (95% CI = 0.45-0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults' T1D risk assessment for early detection.

Is HbA1c a valid surrogate for mortality in type 2 diabetes? Evidence from a meta-analysis of randomized trials.

AIMS: Hemoglobin A1c (HbA1c) has been repeatedly questioned as a valid surrogate marker, especially for patient-relevant outcomes. The aim of this study was to validate the HbA1c value as a surrogate for all-cause mortality in people with type 2 diabetes. METHODS: The effect estimates for HbA1c lowering after treatment as well as reductions in all-cause mortality of randomized trials were extracted from a systematic review and updated. For the measurement of actual surrogacy, weighted linear regression models with a random intercept for the study effect were used with the all-cause mortality estimate (risk difference and log relative risk) as the outcome and the estimate for HbA1c difference as the covariate. Surrogacy was assessed according to the criteria of Daniels and Hughes. RESULTS: A total of 346 HbA1c-mortality-pairs from 205 single randomized trials were included in the analysis. Regarding the risk difference of all-cause mortality, there was no evidence for surrogacy of the HbA1c value. For the log relative risk, a small positive association between HbA1c and the all-cause mortality estimate (slope 0.129 [95% confidence interval -0.043; 0.302]) was observed. However, there was no sign of valid surrogacy. CONCLUSIONS: Based on the results of more than 200 randomized trials, HbA1c is not a valid surrogate marker for all-cause mortality in people with type 2 diabetes.

Family Structure is Associated with Mental Health and Attention Deficit (Hyperactivity) Disorders in Adolescents with Type 1 Diabetes.

OBJECTIVE: To analyze the cross-sectional associations of family structure with mental health and attention deficit (hyperactivity) disorders (AD(H)D) in 11- to 17-year-old adolescents with early-onset type 1 diabetes participating in one of three baseline surveys as part of an ongoing cohort study. METHODS: Parents (n=1,631) completed the Strengths and Difficulties Questionnaire to screen for their child's mental health and answered questions about their child's diagnosis of AD(H)D. Associations between mental health or AD(H)D and family structure were analyzed using multivariable logistic regression analyses adjusted for various personal and diabetes-related variables. RESULTS: Compared to adolescents living with both parents, adolescents living with one parent and his/her partner had 2.35 (95% confidence interval 1.32; 4.21) higher odds of abnormal screening result and 2.08 (1.09; 3.95) higher odds of a borderline screening result while adolescents living with a single parent had 1.84 (1.07; 3.17)/1.08 (0.53; 2.21) higher odds of abnormal/borderline screening results. The odds ratios for diagnosed attention deficit (hyperactivity) disorder were 2.17 (0.98; 4.84) for adolescents living with one parent and his/her partner and 1.27 (0.54; 3.01) for those living with a single parent vs. both parents. CONCLUSIONS: Our results indicate higher odds of mental health problems and AD(H)D in adolescents with type 1 diabetes who do not live with both parents; this finding was most pronounced in individuals living with one parent and his/her partner vs. both parents. Longitudinal studies are needed to verify our results and elucidate the underlying mechanisms.

Course of screening-based depression in young adults with a long type 1 diabetes duration: Prevalence and transition probabilities - A cohort study.

AIMS: To extend the current knowledge of the prevalence and course of screening-based depression (SBD) and its predictors in emerging adults with a long type 1 diabetes duration. METHODS: A total of 487 young adults (64.7% women, mean age 24.0 years) who participated in a nationwide cohort study provided data on SBD (Patient Health Questionnaire (PHQ-9) score ≥ 10). We estimated the overall and age- and sex-specific prevalence of SBD, identified the associated covariates, and determined the transition probabilities between SBD states using adjusted first-order Markov transition models. RESULTS: The prevalence of SBD was 17.7% in women and 7.0% in men. A total of 70.4% (95%-CI 57.4%; 80.8%) of the participants with SBD at the first screening still had SBD at the three-year follow-up. Of the subjects without SBD at baseline, 6.9% (4.9%; 9.8%) had SBD at follow-up. The main predictor of current SBD was previous SBD (OR 39.0 (15.4; 98.6)), followed by living in one's own or in a shared apartment vs. living with both parents (OR: 2.75 (1.03; 7.36)). CONCLUSIONS: Using an innovative analytical approach, emerging adults with a long diabetes duration demonstrated a moderate rate of incident SBD but a high rate of persistent SBD.

Association of family structure with type 1 diabetes management and outcomes in adolescents: A population-based cross-sectional survey.

BACKGROUND: Diabetes therapies have enormously changed during past decades, but only few studies have analyzed the association between family structure and diabetes management and outcomes. OBJECTIVE: To analyze cross-sectionally the associations of family structure with type 1 diabetes (T1D) management and various diabetes outcomes. METHODS: A total of 1635 11- to 17-year-old participants and their parents completed one of three baseline surveys as part of a nationwide, population-based cohort study on early-onset, long-standing T1D. Associations between family structure and outcome variables were analyzed by multivariable linear/logistic regression. RESULTS: Compared to adolescents living with both parents (reference), HbA1c was 0.48% (95% confidence interval 0.24; 0.71) / 5.2 (2.6; 7.8) mmol/mol higher in adolescents living with one parent and 0.34% (0.08; 0.59) / 3.7 (0.9; 6.5) mmol/mol higher in those living with one parent and her/his partner. The blood glucose self-monitoring (SMBG) frequency was lower (single parent: -0.6 (-1.1; -0.2), parent and partner:-0.5 (-1.0; 0.0)) and parents reported more long-term consequences related to school or work (ORsingle-parent 1.52 (0.90; 2.57), ORparent + partner 1.50 (0.86; 2.60)). While living with one parent was associated with increased odds of insulin injection vs. insulin pump therapy (OR 1.61 [1.13; 2.29]), the odds of low hypoglycemia awareness (OR 1.75 [1.00; 3.08]) and diabetes complications (1.32 [0.78; 2.22]) were higher in people living with a parent and her/his partner. CONCLUSIONS: Living with only one parent with or without a new partner was associated with less SMBG and pump use and poor diabetes outcomes. Future studies to explore the underlying mechanisms are required.

Course of Disordered Eating Behavior in Young People With Early-Onset Type I Diabetes: Prevalence, Symptoms, and Transition Probabilities.

PURPOSE: The aims of this study were to analyze the prevalence and course of disordered eating behavior (DEB) in adolescents with intensively treated type I diabetes, describe differences in age-specific DEB symptoms, and identify predictors of current DEB. METHODS: Data were taken from 332/218 11- to 27-year-old participants (55.7% girls/women, mean age [SD] 17.8 [3.4] years, mean diabetes duration 14.9 [3.0] years) of two/three surveys of a Germany-wide longitudinal study on early-onset and long duration diabetes, respectively. A diabetes-adapted version of the SCOFF questionnaire was used to assess DEB. Both screening-based overall and age- and sex-specific prevalence of DEB and its symptoms were determined. To estimate transition probabilities between DEB states, first-order Markov transition models were implemented adjusting for previous sociodemographic, socioeconomic, and diabetes-specific covariates. RESULTS: The overall screening-based DEB prevalence among all 1,318 observations was 10.8% (95% confidence interval [CI]: 9.2%, 12.6%) with age-specific differences in symptom prevalence. Transition probabilities for developing/persistent DEB were twofold higher among female than male participants (risk ratio [RR] 2.3 [1.4, 3.9]/2.1 [1.3, 3.4]). In multiple adjusted regression, previous DEB (odds ratio [OR] 2.8 [95% CI 1.4, 5.6]), follow-up time (ORper 1-year increase 3.4 [1.4, 8.0]), and sex (ORgirls/women 2.1 [1.1, 3.9]) were the most important predictors of current DEB with further weaker associations for previous age and HbA1c. CONCLUSIONS: Our results contribute to better understanding the course of DEB in patients with early-onset diabetes and emphasize the relevance of regular DEB screenings including the age group of young adults.

Diabetic nephropathy and quality of life among youths with long-duration type 1 diabetes: A population-based cross-sectional study.

OBJECTIVE: To investigate whether diabetic nephropathy (DN) is associated with lower quality of life (QOL) in youths with long-duration type 1 diabetes and whether associations differ by diabetes duration. METHODS: Overall, 1,462 youths aged 11 to 17 years with diabetes onset between 0 and 4 years of age and at least 10 years diabetes duration completed questionnaires on QOL between 2009 and 2016. Chronic generic and diabetes-specific QOL (diabetes impact and treatment scale) were assessed with three scales of the DISABKIDS instruments. Information on DN was obtained from the diabetes patient follow-up registry ("Diabetes-Patienten-Verlaufsdokumentation") with DN defined as micro- or macroalbuminuria. Linear regression analyses were used to evaluate the association between QOL and DN. To adjust for potential confounders, we applied inverse probability of treatment weighting for the linear regression. RESULTS: In adjusted analysis, DN was associated with lower QOL in the chronic generic and the two diabetes-specific DISABKIDS scales. Overall, the observed effects were not clinically relevant but increased consistently with longer diabetes duration. Among those with at least 16 years diabetes duration, differences in QOL between patients with vs without DN were clinically relevant on the chronic generic scale (ß = -10.3 [-21.0;0.7]). CONCLUSION: The results suggest that long-term microvascular complications can impair chronic generic QOL already in youths with type 1 diabetes. Differences in QOL between patients with and without DN seem to increase with diabetes duration.

Autoimmunity risk- and protection-associated IL7RA genetic variants differentially affect soluble and membrane IL-7Rα expression.

Interleukin-7 receptor α-chain (IL7RA) haplotypes are associated with susceptibility to autoimmune diseases including type 1 diabetes (T1D). Previous studies found lower soluble IL-7Rα (sIL-7Rα) serum levels of the protection-associated IL7RA haplotype assumed to reduce IL-7 availability for self-reactive T cells. Also, a risk-associated IL7RA haplotype is accompanied by lower sIL-7Rα serum concentrations but no underlying mechanisms have been described and the causative polymorphism remains unknown. Here, we characterized functional implications of the nonsynonymous rs1494558 (Thr66Ile), which tags the protection-associated IL7RA haplotype, in HEK293T cells and serum samples of T1D patients with different haplotype carriers. Influence of risk- and protection-associated haplotypes on IL-7Rα was analyzed. The risk-associated Ile66 variant affected gel mobility and impaired secretion of the sIL-7Rα as well as expression of the membrane-associated (m)IL-7Rα in HEK293T cells. Serum sIL-7Rα analyses confirmed differential gel mobility of the Ile66 variant and found decreased sIL-7Rα serum levels of T1D patients carrying the Ile66-tagged haplotype. Differences in glycosylation were not causative for differential mobility but enhanced the effects on impaired secretion. Comparison of protection- and risk-associated haplotypes in a cell line-based in vitro model identified dominant effects of the protective haplotype tagged by rs6897932 (Ile244) on mIL-7Rα expression, whereas the risk haplotype mainly affected the sIL-7Rα. This study identified novel functional effects of the Ile66 IL7RA variant and characterized features of autoimmunity risk- and protection-associated haplotypes. The findings add to our understanding of how these haplotypes regulate sIL-7Rα and mIL-7Rα expression in T cells causing differential susceptibility to autoimmune diseases.

Risk of Microvascular Complications and Macrovascular Risk Factors in Early-Onset Type 1 Diabetes after at Least 10 Years Duration: An Analysis of Three Population-Based Cross-Sectional Surveys in Germany between 2009 and 2016.

AIMS: To estimate the risk of microvascular complications and macrovascular risk factors among persons with early-onset (diagnosed at ages 0 to <5 years) and long-duration type 1 diabetes and determine temporal trends and associations with potential predictors. METHODS: We conducted three population-based cross-sectional surveys in Germany (N = 1789) to obtain information on exposures and five outcomes (retinopathy, nephropathy, dyslipidemia, hypertension, and a composite endpoint combining all four outcomes). For each outcome, log-binomial spline regression was applied to estimate the risk and dose-response relationship with diabetes duration and exposures. RESULTS: The risk for microvascular complications increased after 14 years since diabetes diagnosis whereas dyslipidemia and hypertension were already prevalent at 10 years. The 15-year risk (95% confidence interval) of the composite endpoint for female and male patients was 22.9% (18.8%-27.9%) and 19.2% (15.5%-23.8%), respectively. Temporal trends suggested a decreasing risk between 2009 and 2016. Glycemic control, lifestyle-related factors, and SES, but not health care-related factors, were associated with the risk of the composite endpoint. CONCLUSIONS: In early-onset type 1 diabetes, there exists a considerable risk of complications and comorbidities already in young ages. Future research should focus on prevention of diabetic complications in young patients and clarification of pathways of the associations found.

Interleukin-7 receptor α-chain haplotypes differentially affect soluble IL-7 receptor and IL-7 serum concentrations in children with type 1 diabetes.

BACKGROUND: Interleukin-7 receptor α-chain (IL7RA) haplotypes are associated with susceptibility for development of autoimmune diseases, including type 1 diabetes (T1D). A protective IL7RA haplotype which causes lower soluble IL-7R (sIL-7R) serum levels is hypothesized to restrict IL-7-availability for self-reactive T cells. Functional mechanisms affected by a risk-associated IL7RA haplotype are unknown. METHODS: We investigated the influence of IL7RA haplotypes (tagged by rs6897932T for the protective or by rs1494555G for the risk haplotype) on sIL-7R and IL-7 serum concentrations as well as disease manifestation of children with T1D (n = 259). Possible effects of differential IL-7 serum concentrations on IL-7-mediated in vitro T cell functions (i.e. IL-7R regulation and cytokine expression) were measured in a second study group of children with T1D (n = 42). RESULTS: We detected lower sIL-7R serum concentrations in children with T1D carrying protective or risk haplotypes as compared to reference haplotypes. sIL-7R levels were lowest in T1D children with the protective haplotype and lower IL-7 serum levels were exclusively detected in this study group. We found no evidence for dependency between IL-7 and sIL-7R serum concentrations and no association with T1D manifestation. Neither IL-7 nor sIL-7R serum levels were associated with mIL-7R regulation or IL-7-promoted T cell cytokine expression. CONCLUSIONS: Children with T1D carrying autoimmunity risk- or protection-associated IL7RA haplotypes had both lower sIL-7R serum concentrations as compared to the reference haplotype, but only T1D children with the protective haplotype had lower IL-7 serum levels. Our results suggest additional functional mechanisms of autoimmunity-associated IL7RA variants independent from sIL-7R mediated regulation of IL-7 availability for T cells.

CISH promoter polymorphism effects on T cell cytokine receptor signaling and type 1 diabetes susceptibility.

BACKGROUND: Impaired regulatory T cell immunity plays a central role in the development of type 1 diabetes (T1D). Interleukin-2 receptor (IL-2R) signaling is essential for regulatory T cells (TREG), and cytokine-inducible SH2-containing protein (CIS) regulates IL-2R signaling as a feedback inhibitor. Previous studies identified association of CISH promoter region single nucleotide polymorphisms (SNPs) with susceptibility to infectious diseases. METHODS: Here we analyzed allele frequencies of three CISH SNPs (i.e., rs809451, rs414171, rs2239751) in a study of T1D patients (n = 260, onset age < 5 years, duration > 10 years). Minor allele frequencies were compared to a control cohort of the 1000 Genomes Project. Assigned haplotypes were determined for effects on T1D manifestation and severity. Finally, the CISH haplotype influence on cytokine signaling and function was explored in T cells from healthy donors. RESULTS: We detected similar minor allele frequencies between T1D patients and the control cohort. T1D onset age, residual serum C-peptide level, and insulin requirement were comparable between different haplotypes. Only minor differences between the haplotypes were found for in vitro cytokine (i.e., IL-2, IL-7)-induced CIS mRNA expression. STAT5 phosphorylation was induced by IL-2 or IL-7, but no differences were found between the haplotypes. TREG purified from healthy donors with the two most common haplotypes showed similar capacity to inhibit heterologous effector T cells. CONCLUSIONS: This study provides no evidence for an association of CISH promoter SNPs with susceptibility to T1D or severity of disease. In contrast to previous studies, no influence of different haplotypes on CIS mRNA expression or T cell-mediated functions was found.

Eating Frequency and Carbohydrate Intake in Adolescents with Type 1 Diabetes Differ from Those in Their Peers and are Associated with Glycemic Control.

AIM: The diet of people with type 1 diabetes may differ from that of healthy peers due to disease-related factors that may affect the course of diabetes. This cross-sectional study sought to compare meal and snacking frequency and corresponding carbohydrate intake among adolescents with intensively-treated type 1 diabetes and healthy peers and to analyze their association with glycemic control among diabetes patients. METHODS: Nutritional data of 712 11- to <19-year-olds from a nationwide population-based survey on early-onset type 1 diabetes (52.7% boys/men, mean age 15.6 years) were compared with 949 food records of 296 healthy participants in the DONALD cohort study (49.7% boys, mean age 14.4 years) using linear mixed models. Furthermore, the association between eating frequency and/or carbohydrate intake with glycemic control (HbA1c) was analyzed with multiple linear regression models. RESULTS: After comprehensive adjustment, diabetes patients had, on average, 4.6 [95% confidence interval 3.6, 5.5] more meals or snacks/week but consumed 75.9 [64.5, 87.3] fewer grams of carbohydrates/day than the comparison group. Diabetes subjects also consumed breakfast, lunch, dinner, and snacks more frequently but ate fewer carbohydrates at all eating occasions. Total carbohydrate intake and carbohydrate intake at breakfast were associated with higher HbA1c levels, while increased breakfast frequency was associated with lower HbA1c levels. CONCLUSION: Eating frequency and carbohydrate intake differed between adolescents with early-onset type 1 diabetes and non-diabetic peers. The observed associations with glycemic control challenge the concept of a completely unregulated eating frequency and carbohydrate intake for people on intensified insulin therapy.

Relationship of Serum Fetuin A with Metabolic and Clinical Parameters in German Children and Adolescents with Type 1 Diabetes.

BACKGROUND AND AIM: The hepatokine fetuin A is upregulated in the metabolic syndrome and in type 2 diabetes (T2D), while its role in adolescent type 1 diabetes (T1D) is unclear. We assessed the relationship between circulating fetuin A levels and metabolic control, comorbidities, and complications in adolescent T1D patients. METHODS: We studied the relationship between serum fetuin A and clinical diabetes-related data from the DPV registry (Diabetes-Pa-tienten-Verlaufsdokumentation) in 172 adolescent T1D patients with early-onset (<5 years) long-standing (>10 years) T1D. Fetuin A levels were further compared between adolescent T1D and T2D patients. RESULTS: Serum fetuin A levels in T1D patients (mean 0.267 ± 0.043 g/L) did not correlate with age, diabetes duration, gender, body mass index (BMI), glycated hemoglobin, serum lipid levels, blood pressure, celiac or thyroid disease, nephropathy, or retinopathy. An association of fetuin A levels with insulin requirements was only evident within the subgroup of overweight T1D patients (rs = 0.439, p = 0.028, n = 25, BMI >90th percentile), disappearing after adjustment for multiple testing. Adolescent T1D patients showed distinctly lower fetuin A levels than patients with T2D (p ≤ 0.001). CONCLUSION: Overall, we did not observe a clinically relevant association of fetuin A levels with surrogate parameters for insulin sensitivity in our juvenile T1D cohort. A correlation with insulin requirements was detectable in overweight patients only. We hypothesize that multiple factors, such as obesity, puberty, inadequate metabolic control, and hepatic steatosis, have to add up before a clinically relevant effect of fetuin A on insulin sensitivity becomes evident.

Economic evaluation of brief psychodynamic interpersonal therapy in patients with multisomatoform disorder.

BACKGROUND: A brief psychodynamic interpersonal therapy (PIT) in patients with multisomatoform disorder has been recently shown to improve health-related quality of life. AIMS: To assess cost-effectiveness of PIT compared to enhanced medical care in patients with multisomatoform disorder. METHOD: An economic evaluation alongside a randomised controlled trial (International Standard Randomised Controlled Trial Number ISRCTN23215121) conducted in 6 German academic outpatient centres was performed. Incremental cost-effectiveness ratio (ICER) was calculated from the statutory health insurance perspective on the basis of quality adjusted life years (QALYs) gained at 12 months. Uncertainty surrounding the cost-effectiveness of PIT was presented by means of a cost-effectiveness acceptability curve. RESULTS: Based on the complete-case analysis ICER was 41840 Euro per QALY. The results did not change greatly with the use of multiple imputation (ICER = 44222) and last observation carried forward (LOCF) approach to missing data (ICER = 46663). The probability of PIT being cost-effective exceeded 50% for thresholds of willingness to pay over 35 thousand Euros per QALY. CONCLUSIONS: Cost-effectiveness of PIT is highly uncertain for thresholds of willingness to pay under 35 thousand Euros per QALY.

Is disordered eating behavior more prevalent in adolescents with early-onset type 1 diabetes than in their representative peers?

OBJECTIVE: Despite modern therapeutic regimens, youths with Type 1 diabetes may be at increased risk of mental and behavioral disorders. In this study, the prevalence of disordered eating behavior (DEB) in intensely treated children and adolescents with early-onset Type 1 diabetes and peers from the general population was compared. METHOD: Data from 629 patients from a population-based, nationwide survey (54.1% male, mean age 15.3 years) with early-onset Type 1 diabetes of at least 10 years duration were compared with data from 6,813 participants of the German KiGGS study (51.3% male, mean age 14.6 years). The generic SCOFF questionnaire was used as screening instrument to identify participants with symptoms of DEB. Both groups were compared with multivariable regression analysis adjusting for sociodemographic covariates. RESULTS: 31.2% of the female and 11.7% of the male diabetic patients and 28.9% of the females and 15.2% of the males in the comparison group were SCOFF-positive (SCOFF score ≥2; p > .05). The odds for symptoms of eating disorders were 3.7% higher in female and 4.3% lower in male patients with diabetes than in the comparison group, but the differences were not significant. 20.5% of the female and 18.5% of the male diabetic patients reported insulin restriction at least three times per week. DISCUSSION: Children and adolescents with early-onset Type 1 diabetes of long duration do not seem to be more frequently SCOFF-positive than peers. However, as insulin restriction is practiced in a substantial portion of patients, attention for insulin restriction in diabetes care is essential.