Physical activity is associated with lower insulin and C-peptide during glucose challenge in children and adolescents with family background of diabetes.

AIMS: Children and adolescents with a family history of diabetes are at increased risk of overweight, but little is known about the potentially beneficial effects of physical activity on these children. The objective of this study was to investigate the association between moderate to vigorous physical activity (MVPA) and metabolic and inflammatory risks in children and adolescents with a family background of Type 1 diabetes or gestational diabetes. METHODS: Valid MVPA measurements, made with accelerometers, were available from 234 participants (median age, 10.2 years) who had a first-degree relative with either Type 1 or gestational diabetes. Anthropometric and metabolic measurements were made and cytokines measured, and were correlated with MVPA measurements, with stepwise adjustment for confounding factors, in a cross-sectional analysis. RESULTS: MVPA was negatively associated with insulin and C-peptide during challenge with an oral glucose tolerance test. MVPA was also significantly positively associated with the insulin sensitivity index, whereas no consistently significant associations were found between MVPA and BMI, blood pressure or cytokine levels. DISCUSSION: Our findings indicate that physical activity may have beneficial effects on insulin and C-peptide metabolism in children and adolescents with a family background of diabetes, but show no evidence of a protective association with other health-related outcomes.

No further improvement in pregnancy-related outcomes in the offspring of mothers with pre-gestational diabetes in Bavaria, Germany, between 2001 and 2016.

AIMS: To investigate whether there has been further improvement in the risk of adverse outcomes in pregnancies in women with diabetes during 2008-2016 in Bavaria, Germany. METHODS: Using cross-sectional data on all 1716 170 deliveries in Bavarian hospitals between 2001 and 2016, we assessed the risks of stillbirth, early neonatal death, preterm delivery, large for gestational age, malformations, low Apgar score and low umbilical cord pH by maternal group with diabetes (gestational, pre-gestational, or none) separately for 2001-2007 and 2008-2016. We also investigated the associations of specific risk factors such as maternal smoking with respect to early mortality and malformations in each group with diabetes during 2008-2016. RESULTS: No further reduction in the risk for any adverse outcome in mothers with pre-gestational diabetes and their offspring during 2008-2016 was observed. Maternal smoking, multiple delivery and substandard antenatal care were the strongest additional predictors of both early perinatal mortality and malformations for mothers with pre-gestational diabetes. The respective risks were lower and also decreased over time for mothers with gestational diabetes. CONCLUSIONS: No significant improvement has been achieved in the management of pregnancies affected by pre-gestational diabetes during the last decade. The apparent risk reductions in women with gestational diabetes may partly be due to a change in diagnostic criteria over time. Women with pre-gestational diabetes who smoke, carry more than one child, or are not regularly seen during pregnancy, may need particular attention.

Risk Stratification in Women with Gestational Diabetes According to and Beyond Current WHO Criteria.

The pregnancy outcomes in women with gestational diabetes mellitus (GDM) and 'overt diabetes in pregnancy' were compared and the need for further subclassification was investigated with respect to postpartum outcome risk. Data from 944 women who had been uniformly diagnosed as having GDM in Munich, Germany, between 1998 and 2010, were re-classified into GDM and 'overt diabetes in pregnancy'. Pregnancy related outcomes in the offspring were derived from Bavarian birth registry data. Classification and regression trees were used to identify further GDM sub-phenotypes. In total, 88 women (9.3%) were re-classified as having 'overt diabetes in pregnancy'. Compared to women with GDM, women with 'overt diabetes in pregnancy' used insulin more frequently, and were at increased risk for large for gestational age infants [odds ratio 2.50 (95% confidence interval 1.02, 6.13)], preterm delivery [odds ratio 3.28 (1.02, 10.50)], and low APGAR-score at 5 min [odds ratio 12.70 (1.58, 102.2)]. In the 856 women with GDM, classification and regression tree analyses provided further risk stratification in that a combination of fasting glucose>5.3 mmol/l and 1-h glucose>11.1 mmol/l at GDM diagnosis predicted insulin requirement [OR 5.57 (3.75, 8.27) compared to the rest], and maternal body mass index (BMI)≥35 kg/m(2) predicted large for gestational age status. The new differentiation between GDM and 'overt diabetes in pregnancy' is a first step towards refining classification relevant to fetal and maternal postpartum risk. A combination of glucose levels and maternal BMI at diagnosis of GDM may provide further improvement.

Compromised immune response in infants at risk for type 1 diabetes born by Caesarean Section.

Children born by Caesarean Section have a higher risk for type 1 diabetes. We aimed to investigate whether Caesarean Section leads to alterations of the immune response in children with familial risk for type 1 diabetes. We examined measures of innate and adaptive immune responses in 94 prospectively followed children, including 40 born by Caesarean Section. Proinflammatory serum cytokine concentrations were determined at age 6 months. As a measure of vaccine response, IgG1, IgG2, and IgG4 tetanus antibody titers and CD4(+) T cell proliferation against tetanus toxoid were quantified. Compared to infants born by vaginal delivery, infants born by Caesarean Section had lower concentrations of the cytokines IFN-É£ (p=0.014) and IL-8 (p=0.005), and weaker CD4(+) T cell responses to tetanus measured in the first (p=0.007) and second year (p=0.047) of life. Overall, our findings provide evidence that the mode of delivery influences the immune status and responsiveness during childhood.

Reduced blood leukocyte and neutrophil numbers in the pathogenesis of type 1 diabetes.

Very little is known about the role of the innate immune system in the course of human type 1 diabetes. Here we investigated neutrophil numbers along with other leukocyte populations in patients at diagnosis of type 1 diabetes and during prediabetes. Complete and differential blood counts were analyzed from 107 adult patients with newly diagnosed type 1 diabetes, 21 children with persistent islet autoantibodies and a family history of type 1 diabetes, and 1 238 age and gender matched control subjects, all individuals without any signs of acute infection.Adult patients with newly diagnosed type 1 diabetes had significantly lower total WBC (p<1×10⁻6), neutrophil (p<1×10⁻6), basophil (p<1×10⁻6), monocyte (p=4×10⁻6) and lymphocyte (p<1×10⁻6) counts compared to control subjects. Erythrocyte, eosinophil and platelet counts did not differ between groups. Similarly, children with persistent islet autoantibodies had decreased WBC (p=0.001), neutrophils (p=0.003), and lymphocytes (p=0.006) in comparison to control children. Our findings demonstrate a perturbation of leukocyte homeostasis at and prior to onset of type 1 diabetes suggesting a general involvement of the innate immune system in the pathogenesis of type 1 diabetes.

[What are the effects of different places of death of old people?] / Welche Auswirkungen zeigen unterschiedliche Sterbeorte betagter Menschen?: Eine Analyse Münchner Todesbescheinigungen.

Background: Inadequate quality of medical postmortem examinations has been discussed in the forensic medical literature for many years. It is known that older deceased persons are less likely to have a non-natural cause of death certified and autopsies are performed less frequently compared to younger deceased persons. Methods: Death certificates of all deaths that occurred in Munich with an age of ≥ 75 years during the death period 01/01/2013-31/12/2014 were analyzed. Standardized, anonymized data entry was performed. The collected data were analyzed descriptively. Results: A total of 26,303 persons died during the study period. Of these deaths, 16,146 (60.7%) were ≥ 75 years. Most common places of death for the aged were hospital (56.1%), private address (21.8%), and nursing home (20.0%). A natural mode of death was reported in 88.5%, unexplained in 8.8%, and non-natural in 2.7%. Most common immediate causes of death were diseases of the circulatory system (23.5%), inaccurately designated or unknown causes of death (20.0%), and diseases of the respiratory system (16.3%). Autopsies were performed on 4.9%, largely judicial. The parameters studied showed large differences in the analyses depending on the place of death. Discussion: This study again shows considerable quality deficiencies in the issuance of death certificates. Despite the dual approach of the Munich health authority (control, training), the quality of death certificates could not be sustainably improved in recent years. Types and causes of death showed partly considerable differences depending on the place of death and the doctor who issued the certificate. The deficits identified in the information provided under the heading "Causes of death" are also likely to have a negative impact on the cause of death statistics.

Different age-specific incidence and remission rates in pre-school and primary school suggest need for targeted obesity prevention in childhood.

BACKGROUND: School entry marks a tremendous change in the children's life style, which might well be relevant for the emergence of overweight. Previous studies suggested a dramatic increase in the prevalence of overweight during this age. OBJECTIVE: To compare the age-specific balance between the incidence and remission of overweight between pre-school and primary school age children. DESIGN: We combined the data of three studies that had been conducted within the setting of the compulsory school entry health examination in different parts of Germany: one covering retrospective cohort data from age 2 to school entry (n=5045), one prospective data from school entry to fourth grade (n=1235) and one comprising both (n=1194). We assessed the rates of incidence and remission of overweight and obesity from age 2 to school entry and from school entry to fourth grade. RESULTS: In pre-school age, the pooled incidence for overweight was 8.2% (95% confidence interval: 7.5, 8.9) compared with a remission rate of 62.6% (58.4, 66.7), yielding a prevalence at school entry of 10.7% (9.9, 11.5). In primary school age, the pooled incidence for overweight increased to 14.6% (13.1, 16.1), whereas the remission rate was reduced to 17.7% (13.8, 22.3), yielding a prevalence of 23.7% (22.0, 25.4) in fourth grade. A similar pattern was observed for obesity. CONCLUSIONS: While high remission rates balance incident overweight in pre-school years, the dramatic increase in the prevalence of overweight and obesity in primary school years reflects a higher incidence and even more a lower remission rate. Obesity prevention programs in primary school age are mandatory and need to address primary and secondary prevention elements.

Gestational diabetes and cardiovascular risk factors in the offspring: results from a cross-sectional study.

BACKGROUND: While the association of gestational diabetes mellitus and abnormal glucose tolerance is beyond doubt, its associations with other cardiovascular disease risk factors in the offspring are less clearly established. Some of these associations, in particular overweight in the offspring, might be confounded by maternal overweight. METHODS: Data on 12,542 children in the age of 3-17 years with full information about gestational diabetes mellitus and maternal BMI were available from the German nationwide KiGGS study. We calculated linear and logistic regression models for measurements of body composition, blood pressure, HbA(1c) and cholesterol values in the offspring with gestational diabetes mellitus as the explanatory variable, with and without adjustment for maternal BMI. RESULTS: The prevalence of gestational diabetes mellitus in the dataset was 2.2%. Unadjusted regression analyses suggested weak positive effects of gestational diabetes mellitus on body composition measurements [e.g. a mean increase in BMI standard deviation scores (SDS) of 0.17 units (95% confidence interval: 0.03, 0.30)]. After adjustment for maternal BMI, the observed associations almost disappeared [e.g. BMI SDS: 0.07 (-0.06, 0.20)]. With respect to blood pressure and cholesterol, no potential effects of gestational diabetes mellitus were observed in both unadjusted and adjusted models. CONCLUSION: Gestational diabetes mellitus does not appear to have a relevant effect on cardiovascular disease correlates such as blood pressure or cholesterol levels in children, and the potential effect of gestational diabetes mellitus on body composition seems to be widely explainable by maternal BMI.

Associations of gestational weight loss with birth-related outcome: a retrospective cohort study.

OBJECTIVE: Although the prevention of gestational weight loss (GWL) has become a priority for clinicians in the past few decades, recent work has suggested that GWL may be beneficial for obese mothers. We aimed to identify the potential beneficial or adverse associations of GWL with pregnancy outcome stratified by maternal body mass index (BMI) category. DESIGN: Retrospective cohort study. SETTING AND POPULATION: Data on 709 575 singleton deliveries in Bavarian obstetric units from 2000-2007 were extracted from a standard dataset for which data are regularly collected for the national benchmarking of obstetric units. METHODS: We calculated the odds ratios (ORs) for adverse pregnancy outcome by GWL (explanatory variable) compared with nonexcessive weight gain with adjustment for confounders and stratification by BMI category (underweight, BMI < 18.5 kg/m²; normal weight, BMI = 18.5-24.9 kg/m²; overweight, BMI = 25-29.9 kg/m²; obese class I, BMI = 30-34.9 kg/m²; obese class II, BMI = 35-39.9 kg/m²; obese class III, BMI ≥ 40 kg/m²). MAIN OUTCOME MEASURES: Pre-eclampsia, nonelective caesarean section, preterm delivery, small or large for gestational age (SGA/LGA) birth and perinatal mortality. RESULTS: GWL was associated with a decreased risk of pregnancy complications, such as pre-eclampsia and nonelective caesarean section, in overweight and obese women [e.g. OR = 0.65 (95% confidence interval: 0.51, 0.83) for nonelective caesarean section in obese class I women]. The risks of preterm delivery and SGA births, by contrast, were significantly higher in overweight and obese class I/II mothers [e.g. OR = 1.68 (95% confidence interval: 1.37, 2.06) for SGA in obese class I women]. In obese class III women, no significantly increased risks of poor outcomes for infants were observed. CONCLUSIONS: The association of GWL with a decreased risk of pregnancy complications appears to be outweighed by increased risks of prematurity and SGA in all but obese class III mothers.

Physical activity and gestational weight gain: a meta-analysis of intervention trials.

BACKGROUND: high gestational weight gain (GWG) has been found to be associated with a number of adverse perinatal and long-term outcomes. OBJECTIVES: we aimed to perform a systematic review and meta-analysis to find out whether physical activity in pregnancy might help avoid high GWG. SEARCH STRATEGY: a literature search in relevant databases and an additional search by hand through bibliographies of various publications were performed. SELECTION CRITERIA: we included randomised controlled trials on healthy women, with increased physical activity as the only intervention. GWG had to be documented for the intervention and control group separately. DATA COLLECTION AND ANALYSIS: two reviewers independently extracted data and performed quality assessment. Data from the included trials were combined using a random-effects model. The effect size was expressed as mean difference (MD). MAIN RESULTS: of 1380 studies identified, 12 trials met the inclusion criteria. In seven trials, GWG was lower in the exercise group compared with the control group, whereas five trials showed a lower GWG in the control groups. The meta-analysis resulted in an MD of GWG of -0.61 (95% CI: -1.17, -0.06), suggesting less GWG in the intervention groups compared with the control groups. We found no indication for publication bias or dose effects. AUTHOR'S CONCLUSIONS: in summary, our analyses suggest that physical activity during pregnancy might be successful in restricting GWG.

Risk factors for childhood overweight: shift of the mean body mass index and shift of the upper percentiles: results from a cross-sectional study.

BACKGROUND: The worldwide increasing prevalence of childhood overweight seems to be due to an increasing proportion of extremely high body mass index (BMI) values rather than to a shift of the entire BMI distribution. These findings might be attributed to incremental exposure to risk factors particularly affecting overweight children. OBJECTIVE: To assess the possible differences in associations of several risk factors by subgroups of children's BMI distribution. METHODS: We applied quantile regression to cross-sectional data on 9698 German preschoolers (5-6 years) collected in 1999 and 2002. Sex- and age-specific BMI standard deviation scores (BMI-SDSs) were used as the outcome variable, and maternal BMI, maternal smoking during pregnancy, exclusive formula feeding, child's weight gain from birth to 2 years of life and low parental education as explanatory variables. RESULTS: All risk factors except formula feeding contributed to a positive shift in mean BMI-SDS. The estimated effects of all risk factors on BMI-SDS were greatest for children with the highest BMI-SDS value. For example, high television (TV) viewing (>2 h day(-1)) had an effect of 0.46 (95% confidence interval (CI): 0.46, 0.46) SDS units on overweight children (90th percentile), but only a 0.22 (95% CI: 0.11, 0.33) SDS effect on normal-weight children (50th percentile). CONCLUSIONS: For well-known risk factors of childhood overweight, stronger associations in children with higher BMI values were observed. These findings might possibly help to explain the secular shift in the upper BMI percentiles in children.

Improvement in pregnancy-related outcomes in the offspring of diabetic mothers in Bavaria, Germany, during 1987-2007.

AIMS: Reducing the risk of adverse outcomes in diabetic pregnancies to the level of risk in non-diabetic pregnancies is a major goal in diabetes care. So far there have not been any data to show whether progress is being made towards this goal. METHODS: We used population-based data on 2,292,053 deliveries between 1987 and 2007 in Bavaria, Germany, to assess temporal trends for stillbirths, early neonatal mortality, preterm delivery, macrosomia and malformations in consecutive 7 year intervals. We estimated prevalences and prevalence odds ratios for these outcomes. For stillbirth, as the most severe adverse outcome, we assessed the contributions of several predictors using multiple regression models. RESULTS: With the exception of early neonatal deaths, the risks for all outcomes were significantly increased in the offspring of mothers with pregestational diabetes in all three time periods (e.g. odds ratio for stillbirths in diabetic compared with non-diabetic mothers in 2001-2007, 1.89; 95% confidence interval 1.24, 2.87). However, the prevalence of stillbirths, premature delivery and macrosomia decreased over time in diabetic mothers (e.g. 1.71% for stillbirths in 1987-1993 and 0.66% in 2001-2007), as did the respective odds ratios. Maternal smoking, hypertension and substandard utilization of antenatal care were significantly associated with stillbirths in diabetic women. CONCLUSIONS: Although the risk of adverse pregnancy outcomes is still increased in diabetic mothers, considerable improvement has been achieved. We hypothesize that this improvement is possibly due to improved diabetes care.

Development of a simple tool to predict the risk of postpartum diabetes in women with gestational diabetes mellitus.

AIMS: Women with gestational diabetes mellitus (GDM) have an increased risk of diabetes postpartum. We developed a score to predict the long-term risk of postpartum diabetes using clinical and anamnestic variables recorded during or shortly after delivery. METHODS: Data from 257 GDM women who were prospectively followed for diabetes outcome over 20 years of follow-up were used to develop and validate the risk score. Participants were divided into training and test sets. The risk score was calculated using Lasso Cox regression and divided into four risk categories, and its prediction performance was assessed in the test set. RESULTS: Postpartum diabetes developed in 110 women. The computed training set risk score of 5 × body mass index in early pregnancy (per kg/m(2)) + 132 if GDM was treated with insulin (otherwise 0) + 44 if the woman had a family history of diabetes (otherwise 0) - 35 if the woman lactated (otherwise 0) had R (2) values of 0.23, 0.25, and 0.33 at 5, 10, and 15 years postpartum, respectively, and a C-Index of 0.75. Application of the risk score in the test set resulted in observed risk of postpartum diabetes at 5 years of 11 % for low risk scores ≤140, 29 % for scores 141-220, 64 % for scores 221-300, and 80 % for scores >300. CONCLUSIONS: The derived risk score is easy to calculate, allows accurate prediction of GDM-related postpartum diabetes, and may thus be a useful prediction tool for clinicians and general practitioners.

Total pubertal growth in patients with juvenile idiopathic arthritis treated with growth hormone: analysis of a single center.

OBJECTIVES: Growth failure is a permanent sequelae in juvenile idiopathic arthritis (JIA). The aim of the study was to compare pubertal growth in control and growth hormone (GH) treated JIA subjects. DESIGN: 64 children with JIA at a mean age of 10.38 ± 2.80 years were enrolled and followed until final height (measured in standard deviation (SD) scores). 39 children (20 m) received GH therapy and 24 (9 m) served as controls. GH dose was 0.33 mg/kg/week. Linear regression analysis was performed to identify factors influencing total pubertal growth. RESULTS: Mean total pubertal growth was 21.1 ± 1.3 cm (mean ± SD) in GH treated JIA patients and 13.8 ± 1.5 cm in controls. Final height was significantly higher with GH treatment (-1.67 ± 1.20 SD) compared to controls (-3.20 ± 1.84 SD). Linear regression model identified age at onset of puberty (ß=-4.2,CI: -5.9, -2.6 in controls and ß=-2.3,CI: -3.6, -1.1 in GH treated) as the main factor for total pubertal growth. Final height SDS was determined by the difference to target height at onset of puberty (ß=-0.59;CI: -0.80, -0.37 in controls and ß=-0.30,CI: -0.52, -0.08 in GH treated), age at onset of puberty (ß=0.47;CI:0.02,0.93 in controls and 0.23;CI: -0.00,0.46 in GH treated) and height gain during puberty (ß=0.13;CI:0.05,0.21 in controls and ß=0.11;CI:0.07,0.16 in GH treated). CONCLUSION: Total pubertal growth in JIA patients treated with GH was increased by a factor of 1.5 greater in comparison to controls leading to a significantly better final height. To maximize final height GH treatment should be initiated early to reduce the height deficit at onset of puberty.