Search

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.

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 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.

Objective: We investigated the incidence of pediatric type 2 diabetes (T2D) in Germany during two years of the COVID-19 pandemic (2020-2021), compared with the control period 2011-2019. Study design and methods: Data on T2D in children (6 to Results: The incidence of youth-onset T2D increased from 0.75 per 100,000 patient-years [PY] in 2011 (95% CI 0.58; 0.93) to 1.25 per 100,000 PY 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 PY (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 [1.13; 1.69] per 100,000 PY; IRR 1.41 [1.12; 1.77]). While there was no significant increase in incidence in girls in 2021, the observed incidence in boys (2.16 [1.73; 2.70] per 100,000 PY) significantly exceeded the predicted rate (IRR 1.55 [1.14; 2.12]), leading to a reversal of the sex ratio of pediatric T2D incidence. Conclusions: In Germany, incidence of pediatric type 2 diabetes increased significantly in 2021. Adolescent males were more affected by this increase, resulting in a reversal of the sex ratio of youth-onset T2D.

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.

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 1,635 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. This article is protected by copyright. All rights reserved.

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., acceptedVersion

(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.

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.

Aim To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. Methods We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. Results Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. Conclusions Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

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.

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.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.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)).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.

Aim To examine the association of family/household structure with short-term diabetes complications in adolescents and emerging adults with early-onset type 1 diabetes in more detail. Methods Data on 1690 11-21-year-olds with type 1 diabetes were used to estimate associations of family/household structure with self-reported severe hypoglycaemia, hospitalizations for severe hypoglycaemia or diabetic ketoacidosis, applying multiple negative binomial regression. Results Compared with living with both biological parents living with a single mother was associated with an increased rate of hospitalizations for ketoacidosis (incidence rate ratio 1.71, 95% CI 1.00-2.82). Incidence rate ratio of hospitalizations for ketoacidosis was similar (1.67, 95% CI 0.91-3.07) if the mother lived with a partner, however, hypoglycaemia-related hospitalizations increased (3.66, 95% CI 1.54-8.71). Participants living with a single father had 4.43 (95% CI 1.30-15.05) /10.42 (95% CI 1.55-70.22) times higher rates of severe hypoglycaemia and related hospitalizations, while living with a father and his partner was associated with an increased incidence rate ratio of hospitalizations for ketoacidosis (3.48, 95% CI 0.96-12.63) compared with living with both biological parents. Conclusions Findings of our exploratory analyses point to different self-reported diabetes outcomes depending on the family/household structure. If confirmed in future studies, they may help to identify young people with diabetes at risk of short-term diabetes complications.

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.

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-Pa­tienten-Verlaufsdokumentation) in 172 adolescent T1D patients with early-onset (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.

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 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.

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 (β = -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.

Aims. To estimate the risk of microvascular complications and macrovascular risk factors among persons with early-onset (diagnosed at ages 0 to 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.

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 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. Electronic supplementary material The online version of this article (10.1186/s40348-018-0080-7) contains supplementary material, which is available to authorized users.

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. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:342–352)

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.

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.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.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.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.

Undetected diabetes and prediabetes are common (1–3). In decision analytic models of diabetes prevention and screening in particular, the differentiation in costs of detected, undetected, and prediabetic cases are important (4). To the best of our knowledge, no study has determined costs using population-based data with oral glucose tolerance test (OGTT)–based diabetes diagnosis. We used the population-based Cooperative Health Research in the Region of Augsburg (KORA) follow-up survey, conducted in 2006–2008 in southern Germany (2,3) ( n = 2,611, aged 40–82 years). By means of participants’ self report and an OGTT, we identified individuals with previously diagnosed diabetes ( n = 233, 57.9% male, mean age 67.8 ± 8.7), undetected diabetes ( n = 109, 56.9% male, mean age 65.3 ± 10.4), and prediabetes (i.e., impaired glucose tolerance and/or impaired fasting glucose) ( n = 489, 53.2% male, mean age 63.7 ± 10.4), and those with normal …

Recently, medical expenditures were found to be 2-fold increased in paediatric patients with diabetic ketoacidotic events (DKA) in the U.S., in particular due to hospitalization. Aim of our study was to analyse DKAs and associated costs in Germany, where structured diabetes care including education is available for all patients. For all 12 001 diabetic patients 0–19 years of age (52.6% male, mean age (SD) 12.6 (3.9) years) documented in a German-wide database, all DKAs were assessed, as well as costs for diabetes-related treatment. Associations between costs and DKA were estimated using log-linear models. 457 (3.8%) patients had at least 1 DKA during 2007. Total annual costs for patients without, with 1, or ≥ 2 DKAs were € 3 330 (95%-CI 3 292–3 368), € 6 935 (CI 6 627–7 244), and € 10 728 (CI 9 813–11 644), respectively, with largest differences for hospitalization costs (€ 693, € 4 145, € 8 092). Age-sex-diabetes duration-adjusted cost ratios for patients with 1, or ≥ 2 DKAs compared to patients without DKA were 2.2 (CI 2.1–2.3) and 3.6 (CI 3.1–4.1), respectively. In Germany, paediatric diabetic patients with DKA had up to 3.6-fold higher diabetes-related costs compared to those without DKA. This cost excess was higher compared to a U.S. study, however, the proportion of patients with DKA was much lower (3.8% versus 14.9%). The lower frequency of DKA in Germany may be due to a higher access to and utilization of diabetes education. Interventions should reduce DKA and resulting hospital admission in pediatric patients in order to reduce costs and improve quality of life.