TY  - JOUR
AB  - In this article, the author names Jerzy Adamski and Cornelia Prehn were missing from the author list. The original article has been corrected.
AU  - Trischitta, V.*
AU  - Antonucci, A.*
AU  - Adamski, J.
AU  - Prehn, C.
AU  - Menzaghi, C.*
AU  - Marucci, A.*
AU  - Paola, R.D.*
C1  - 71436
C2  - 56094
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 1015-1015
TI  - Correction: GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes.
JO  - Acta Diabetol.
VL  - 61
IS  - 8
PB  - Springer-verlag Italia Srl
PY  - 2024
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims Aim of this study was to investigate in type 2 diabetes whether expression level of GALNT2, a positive modulator of insulin sensitivity, is associated with a metabolic signature. Methods Five different metabolite families, including acylcarnitines, aminoacids, biogenic amines, phospholipids and sphingolipids were investigated in fasting serum of 70 patients with type 2 diabetes, by targeted metabolomics. GALNT2 expression levels were measured in peripheral white blood cells by RT-PCR. The association between GALNT2 expression and serum metabolites was assessed using false discovery rate followed by stepwise selection and, finally, multivariate model including several clinical parameters as confounders. The association between GALNT2 expression and the same clinical parameters was also investigated. Results GALNT2 expression was independently correlated with HbA1c levels (P value = 0.0052), a finding that is the likely consequence of the role of GALNT2 on insulin sensitivity. GALNT2 expression was also independently associated with serum levels of the aminoacid glycine (P value = 0.014) and two biogenic amines phenylethylamine (P value = 0.0065) and taurine (P value = 0.0011). The association of GALNT2 expression with HbA1c was not mediated by these three metabolites. Conclusions Our data indicate that in type 2 diabetes the expression of GALNT2 is associated with several serum metabolites. This association needs to be further investigated to understand in depth its role in mediating the effect of GALNT2 on insulin sensitivity, glucose control and other clinical features in people with diabetes.
AU  - Trischitta, V.*
AU  - Antonucci, A.*
AU  - Adamski, J.
AU  - Prehn, C.
AU  - Menzaghi, C.*
AU  - Marucci, A.*
AU  - Di Paola, R.*
C1  - 71574
C2  - 56093
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 1007-1013
TI  - GALNT2 expression is associated with glucose control and serum metabolites in patients with type 2 diabetes.
JO  - Acta Diabetol.
VL  - 61
IS  - 8
PB  - Springer-verlag Italia Srl
PY  - 2024
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aim: To evaluate the long-term effect of intra-lymphatic administration of GAD-alum and a booster dose 2.5 years after the first intervention (DIAGNODE Extension study) in patients with recent-onset type 1 diabetes. Methods: DIAGNODE-1: Samples were collected from 12 patients after 30 months who had received 3 injections of 4 μg GAD-alum into a lymph node with one-month interval. DIAGNODE Extension study: First in human, a fourth booster dose of autoantigen (GAD-alum) was given to 3 patients at 31.5 months, who were followed for another 12 months. C-peptide was measured during mixed meal tolerance tests (MMTTs). GADA, IA-2A, GADA subclasses, GAD65-induced cytokines, PBMCs proliferation and T cells markers were analyzed. Results: After 30-month treatment, efficacy was still seen in 8/12 patients (good responders, GR). Partial remission (IDAA1c < 9) had decreased compared to 15 months, but did not differ from baseline, and HbA1c remained stable. GAD65-specific immune responses induced by the treatment started to wane after 30 months, and most changes observed at 15 months were undetectable. GADA subclasses IgG2, IgG3 and IgG4 were predominant in the GR along with IgG1. A fourth intra-lymphatic GAD-alum dose to three patients after 31.5 months gave no adverse events. In all three patients, C-peptide seemed to increase the first 6 months, and thereafter, C-peptide, HbA1c, insulin requirement and IDAA1c remained stable. Conclusion: The effect of intra-lymphatic injections of GAD-alum had decreased after 30 months. Good responders showed a specific immune response. Administration of a fourth booster dose after 31.5 months was safe, and there was no decline in C-peptide observed during the 12-month follow-up.
AU  - Casas, R.*
AU  - Dietrich, F.*
AU  - Puente-Marin, S.*
AU  - Barcenilla, H.*
AU  - Tavira, B.*
AU  - Wahlberg, J.*
AU  - Achenbach, P.
AU  - Ludvigsson, J.*
C1  - 64221
C2  - 52112
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 687-696
TI  - Intra-lymphatic administration of GAD-alum in type 1 diabetes: Long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial).
JO  - Acta Diabetol.
VL  - 59
IS  - 5
PB  - Springer-verlag Italia Srl
PY  - 2022
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims: Prior studies demonstrated an association between hospital admission blood glucose and mortality in acute myocardial infarction (AMI). Because stress hyperglycemia ratio (SHR) has been suggested as a more reliable marker of stress hyperglycemia this study investigated to what extent SHR in comparison with admission blood glucose is associated with short- and long-term mortality in diabetic and non-diabetic AMI patients. Methods: The analysis was based on 2,311 AMI patients aged 25–84 years from the population-based Myocardial Infarction Registry Augsburg (median follow-up time 6.5 years [IQR: 4.9–8.1]). The SHR was calculated as admission glucose (mg/dl)/(28.7 × HbA1c (%)—46.7). Using logistic and COX regression analyses the associations between SHR and admission glucose and mortality were investigated. Result: Higher admission glucose and higher SHR were significantly and nonlinearly associated with higher 28-day mortality in AMI patients with and without diabetes. In patients without diabetes, the AUC for SHR was significantly lower than for admission glucose (SHR: 0.6912 [95%CI 0.6317–0.7496], admission glucose: 0.716 [95%CI 0.6572–0.7736], p-value: 0.0351). In patients with diabetes the AUCs were similar for SHR and admission glucose. Increasing admission glucose and SHR were significantly nonlinearly associated with higher 5-year all-cause mortality in AMI patients with diabetes but not in non-diabetic patients. AUC values indicated a comparable prediction of 5-year mortality for both measures in diabetic and non-diabetic patients. Conclusions: Stress hyperglycemia in AMI patients plays a significant role mainly with regard to short-term prognosis, but barely so for long-term prognosis, underlining the assumption that it is a transient dynamic disorder that occurs to varying degrees during the acute event, thereby affecting prognosis.
AU  - Schmitz, T.*
AU  - Freuer, D.*
AU  - Harmel, E.*
AU  - Heier, M.
AU  - Peters, A.
AU  - Linseisen, J.
AU  - Meisinger, C.*
C1  - 64981
C2  - 52544
SP  - 1019-1029
TI  - Prognostic value of stress hyperglycemia ratio on short- and long-term mortality after acute myocardial infarction.
JO  - Acta Diabetol.
VL  - 59
IS  - 8
PY  - 2022
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - AIMS: As the first long-term RCT on insoluble cereal fibre, the optimal fibre trial demonstrated glycometabolic benefits, confirming cohort studies. The combined study intervention of lifestyle recommendations and supplementation with insoluble oat hulls fibre allows to clarify, which amount of fibre is required for a beneficial effect. METHODS: One hundred and eighty participants with impaired glucose tolerance underwent the one-year PREDIAS lifestyle programme and received a blinded, randomized fibre or placebo supplement for two years. We conducted a regression analyses and cut-off-based tertile comparisons in subjects with full data on dietary compliance (food records and accounted supplement; n = 120) after one year, investigating effects on fasting blood parameters, oral glucose tolerance test and anthropometry. RESULTS: We found a nonlinear inverse relation between fibre intake and change in postprandial 2-h glucose levels, showing a metabolic benefit beyond 14 g and a plateau beyond 25 g of total insoluble fibre per day. 2-h glucose levels improved significantly stronger in both upper tertiles (-0.9 [-1.6;-0.2] mmol/l, p = 0.047, and -0.6 [-1.6;0.3] mmol/l, p = 0.010) compared to the lowest tertile (0.1 [-1.2;1.1] mmol/l), also when adjusted for changes in bodyweight. Subjects with the highest fibre intake showed superior effects on fasting and postprandial insulin resistance, hepatic insulin clearance, leucocyte count and fatty liver index. CONCLUSIONS: Extending the knowledge on the benefits of insoluble oat hulls fibre, our post hoc analysis demonstrates a dose effect for glycaemia and associated metabolic markers. Further research is needed in order to replicate our findings in larger trials.
AU  - Kabisch, S.*
AU  - Honsek, C.*
AU  - Kemper, M.*
AU  - Gerbracht, C.*
AU  - Arafat, A.M.*
AU  - Birkenfeld, A.L.
AU  - Dambeck, U.*
AU  - Osterhoff, M.A.*
AU  - Weickert, M.O.*
AU  - Pfeiffer, A.F.H.*
C1  - 62585
C2  - 50961
CY  - Via Decembrio, 28, Milan, 20137, Italy
TI  - Dose-dependent effects of insoluble fibre on glucose metabolism: A stratified post hoc analysis of the Optimal Fibre Trial (OptiFiT).
JO  - Acta Diabetol.
PB  - Springer-verlag Italia Srl
PY  - 2021
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims: The aim of the current study was to investigate the association of type 2 diabetes (T2D) and insulin treatment with changes in muscle mass, muscle strength, and physical performance in older adults. Methods: In 731 participants of the population-based KORA-Age study aged 74.6 ± 6.2 years (T2D: n = 118; insulin treatment: n = 20), skeletal muscle index (SMI [kg/m2]), hand grip strength (GS [kg]), and a timed up and go test (TUG [s]) were performed at baseline and after a follow-up time of 3 years. The association of T2D and insulin therapy with changes in muscle parameters was analyzed using linear regression models. Results: After adjustment for sex, age, BMI, physical activity, smoking, and multimorbidity, T2D was associated with the change in SMI during follow-up (β − 0.1 (95% CI − 0.3 to − 0.02) kg/m2; p = 0.02), but not with a change in GS (β − 0.9 (95% CI − 1.9 to 0.04) kg) or TUG (β − 0.1 (95% CI − 0.7 to 0.5) s). Insulin therapy was positively associated with change in SMI (β 0.6 (95% CI 0.3–0.9) kg/m2; p = 0.001), but not in GS (β − 1.6 (95% CI − 4.1 to 0.8) kg) or TUG (β 1.6 (95% CI − 0.2–3.4) s) in comparison with treatment with oral anti-diabetic medication alone. Conclusions: Participants with T2D showed an accelerated decline in muscle mass compared to non-diabetic participants. Insulin therapy was associated with preserved muscle mass, but not muscle function parameters, indicating a discrepancy between muscle mass and function in this high-risk population.
AU  - Ferrari, U.*
AU  - Then, C.*
AU  - Rottenkolber, M.*
AU  - Selte, C.*
AU  - Seissler, J.*
AU  - Conzade, R.
AU  - Linkohr, B.*
AU  - Peters, A.
AU  - Drey, M.*
AU  - Thorand, B.
C1  - 58772
C2  - 48379
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 1057-1063
TI  - Longitudinal association of type 2 diabetes and insulin therapy with muscle parameters in the KORA-Age study.
JO  - Acta Diabetol.
VL  - 57
IS  - 9
PB  - Springer-verlag Italia Srl
PY  - 2020
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims To identify socioeconomic, behavioral and clinical factors that are associated with prediabetes according to different prediabetes definition criteria. Methods Analyses use pooled data of the population-based Cooperative Health Research in the Region of Augsburg (KORA) studies (n = 5312 observations aged >= 38 years without diabetes). Prediabetes was defined through either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or elevated HbA1c according to thresholds of the American Diabetes Association. Explanatory variables were regressed on prediabetes using generalized estimating equations. Results Mean age was 58.4 years; 50% had prediabetes (33% had IFG, 16% IGT, and 26% elevated HbA1c, 10% fulfilled all three criteria). Age, obesity, hypertension, low education, unemployment, statutory health insurance, urban residence and physical inactivity were associated with prediabetes. Male sex was a stronger risk factor for IFG (OR = 2.5; 95%-CI: 2.2-2.9) than for IGT or elevated HbA1c, and being unemployed was a stronger risk factor for IGT (OR = 3.2 95%-CI: 2.6-4.0) than for IFG or elevated HbA1c. Conclusions The overlap of people with IFG, IGT and elevated HbA1c is small, and some factors are associated with only one criterion. Knowledge on sociodemographic and socioeconomic risk factors can be used to effectively target interventions to people at high risk for type 2 diabetes.
AU  - Greiner, G.
AU  - Emmert-Fees, K.
AU  - Becker, J.
AU  - Rathmann, W.*
AU  - Thorand, B.
AU  - Peters, A.
AU  - Quante, A.S.
AU  - Schwettmann, L.
AU  - Laxy, M.
C1  - 59840
C2  - 49066
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 1481-1491 
TI  - Toward targeted prevention: Risk factors for prediabetes defined by impaired fasting glucose, impaired glucose tolerance and increased HbA1c in the population-based KORA study from Germany.
JO  - Acta Diabetol.
VL  - 57
PB  - Springer-verlag Italia Srl
PY  - 2020
SN  - 0940-5429
ER  - 

TY  - JOUR
AU  - Klöting, N.
AU  - Kern, M.*
AU  - Moruzzi, M.*
AU  - Stumvoll, M.
AU  - Blüher, M.
C1  - 57765
C2  - 48123
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 495-498
TI  - Tamoxifen treatment causes early hepatic insulin resistance.
JO  - Acta Diabetol.
VL  - 57
IS  - 4
PB  - Springer-verlag Italia Srl
PY  - 2020
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. Methods We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). Results In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs >= 5% were below $50,000/QALY gained. Conclusions Intervening in those with >= 7% diabetes risk based on the GDRS or >= 9% on the ARIC 2009 score would be cost-effective. A risk score threshold >= 5% together with elevated FPG would also allow targeting interventions cost-effectively.
AU  - Mühlenbruch, K.*
AU  - Zhuo, X.*
AU  - Bardenheier, B.*
AU  - Shao, H.*
AU  - Laxy, M.
AU  - Icks, A.*
AU  - Zhang, P.*
AU  - Gregg, E.W.*
AU  - Schulze, M.B.*
C1  - 57370
C2  - 47770
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 447-454
TI  - Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: A cost-effectiveness analysis.
JO  - Acta Diabetol.
VL  - 57
IS  - 4
PB  - Springer-verlag Italia Srl
PY  - 2020
SN  - 0940-5429
ER  - 

TY  - JOUR
AU  - Hippich, M.
AU  - Oleynik, A.*
AU  - Jain, K.*
AU  - Winkler, C.
AU  - Ferreira, R.C.*
AU  - Bonifacio, E.*
AU  - Ziegler, A.-G.
AU  - Briese, T.*
C1  - 53449
C2  - 44864
CY  - Via Decembrio, 28, Milan, 20137, Italy
SP  - 881-884
TI  - Searching peripheral blood mononuclear cells of children with viral respiratory tract infections preceding islet autoimmunity for viruses by high-throughput sequencing.
JO  - Acta Diabetol.
VL  - 55
IS  - 8
PB  - Springer-verlag Italia Srl
PY  - 2018
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Insulin autoantibodies (IAA) are often the first marker of autoimmunity detected in children in the preclinical phase of type 1 diabetes (T1D). Currently, the vast majority of laboratories adopt the radiobinding micro-assay (RBA) for measuring IAA. Our aim was to replace RBA with a novel non-radioactive IAA Luciferase Immuno Precipitation System (LIPS) assay with improved performance. We developed (pro)insulin antigens with alternative placements of a NanoLuc (TM) luciferase reporter (NLuc). Performance in LIPS was evaluated by testing sera from new onset T1D (n = 80), blood donors (n = 123), schoolchildren (n = 186), first-degree relatives (FDRs) from the Bart's Oxford family study (n = 53) and from the Belgian Diabetes Registry (n = 136), coded sera from the Islet Autoantibody Standardization Program (IASP) (T1D n = 50, blood donors n = 90). IAA LIPS based on B chain-NLuc proinsulin or B chain-NLuc insulin, in which NLuc was fused at the C-terminus of the insulin B chain, required only 2 mu L of serum and a short incubation time, showed high concordance with RBA (Spearman r = 0.866 and 0.833, respectively), high assay performance (B chain-NLuc proinsulin ROC-AUC = 0.894 and B chain-NLuc insulin ROC-AUC = 0.916), and an adjusted sensitivity at 95% specificity ranking on par with the best assays submitted to the two most recent IASP workshops. In FDRs, the IAA LIPS showed improved discrimination of progressors to T1D compared to RBA. We established a novel high-performance non-radioactive IAA LIPS that might replace the current gold standard RBA and find wide application in the study of the IAA response in T1D.
AU  - Liberati, D.*
AU  - Wyatt, R.C.*
AU  - Brigatti, C.*
AU  - Marzinotto, I.*
AU  - Ferrari, M.*
AU  - Bazzigaluppi, E.*
AU  - Bosi, E.*
AU  - Gillard, B.T.*
AU  - Gillespie, K.M.*
AU  - Gorus, F.*
AU  - Weets, I.*
AU  - Balti, E.*
AU  - Piemonti, L.*
AU  - Achenbach, P.
AU  - Williams, A.J.K.*
AU  - Lampasona, V.*
C1  - 52681
C2  - 44108
CY  - Milan
SP  - 263–270
TI  - A novel LIPS assay for insulin autoantibodies.
JO  - Acta Diabetol.
VL  - 55
IS  - 3
PB  - Springer-verlag Italia Srl
PY  - 2018
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aromatic hydrocarbons belong to the most abundant contaminants in groundwater systems. They can serve as carbon and energy source for a multitude of indigenous microorganisms. Predictions of contaminant biodegradation and microbial growth in contaminated aquifers are often vague because the parameters of microbial activity in the mathematical models used for predictions are typically derived from batch experiments, which don't represent conditions in the field. In order to improve our understanding of key drivers of natural attenuation and the accuracy of predictive models, we conducted comparative experiments in batch and sediment flow-through systems with varying concentrations of contaminant in the inflow and flow velocities applying the aerobic Pseudomonas putida strain F1 and the denitrifying Aromatoleum aromaticum strain EbN1. We followed toluene degradation and bacterial growth by measuring toluene and oxygen concentrations and by direct cell counts. In the sediment columns, the total amount of toluene degraded by P. putida F1 increased with increasing source concentration and flow velocity, while toluene removal efficiency gradually decreased. Results point at mass transfer limitation being an important process controlling toluene biodegradation that cannot be assessed with batch experiments. We also observed a decrease in the maximum specific growth rate with increasing source concentration and flow velocity. At low toluene concentrations, the efficiencies in carbon assimilation within the flow-through systems exceeded those in the batch systems. In all column experiments the number of attached cells plateaued after an initial growth phase indicating a specific "carrying capacity" depending on contaminant concentration and flow velocity. Moreover, in all cases, cells attached to the sediment dominated over those in suspension, and toluene degradation was performed practically by attached cells only. The observed effects of varying contaminant inflow concentration and flow velocity on biodegradation could be captured by a reactive-transport model. By monitoring both attached and suspended cells we could quantify the release of new-grown cells from the sediments to the mobile aqueous phase. Studying flow velocity and contaminant concentrations as key drivers of contaminant transformation in sediment flow-through microcosms improves our system understanding and eventually the prediction of microbial biodegradation at contaminated sites.
AU  - Mendler, M.*
AU  - Kopf, S.*
AU  - Groener, J.B.*
AU  - Riedinger, C.*
AU  - Fleming, T.H.*
AU  - Nawroth, P.P.
AU  - Okun, J.G.*
C1  - 53333
C2  - 44601
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - 585-592
TI  - Urine levels of 5-aminoimidazole-4-carboxamide riboside (AICAR) in patients with type 2 diabetes.
JO  - Acta Diabetol.
VL  - 55
IS  - 6
PB  - Springer
PY  - 2018
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims: The onset of clinical type 1 diabetes (T1D) is preceded by the occurrence of disease-specific autoantibodies. The level of autoantibody titers is known to be associated with progression time from the first emergence of autoantibodies to the onset of clinical symptoms, but detailed analyses of this complex relationship are lacking. We aimed to fill this gap by applying advanced statistical models. Methods: We investigated data of 613 children from the prospective TEDDY study who were persistent positive for IAA, GADA and/or IA2A autoantibodies. We used a novel approach of Bayesian joint modeling of longitudinal and survival data to assess the potentially time- and covariate-dependent association between the longitudinal autoantibody titers and progression time to T1D. Results: For all autoantibodies we observed a positive association between the titers and the T1D progression risk. This association was estimated as time-constant for IA2A, but decreased over time for IAA and GADA. For example the hazard ratio [95% credibility interval] for IAA (per transformed unit) was 3.38 [2.66, 4.38] at 6 months after seroconversion, and 2.02 [1.55, 2.68] at 36 months after seroconversion. Conclusions: These findings indicate that T1D progression risk stratification based on autoantibody titers should focus on time points early after seroconversion. Joint modeling techniques allow for new insights into these associations.
AU  - Köhler, M.
AU  - TEDDY Study Group (Beyerlein, A.
AU  - Ziegler, A.-G.
AU  - Hummel, M.
AU  - Hummel, S.
AU  - Janz, N.
AU  - Knopff, A.
AU  - Peplow, C.
AU  - Roth, R.
AU  - Scholz, M.
AU  - Stock, J.
AU  - Warncke, K.
AU  - Wendel, L.
AU  - Winkler, C.)
AU  - Vehik, K.*
AU  - Greven, S.*
AU  - Umlauf, N.*
AU  - Lernmark, Å.*
AU  - Hagopian, W.A.*
AU  - Rewers, M.*
AU  - She, J.X.*
AU  - Toppari, J.*
AU  - Akolkar, B.*
AU  - Krischer, J.P.*
AU  - Bonifacio, E.*
C1  - 51854
C2  - 43529
CY  - Milan
SP  - 1009–1017 
TI  - Joint modeling of longitudinal autoantibody patterns and progression to type 1 diabetes: Results from the TEDDY study.
JO  - Acta Diabetol.
VL  - 54
IS  - 11
PB  - Springer-verlag Italia Srl
PY  - 2017
SN  - 0940-5429
ER  - 

TY  - JOUR
AU  - Wagner, R.
AU  - Fritsche, L.
AU  - Heni, M.
AU  - Fehlert, E.
AU  - Stefan, N.
AU  - Staiger, H.
AU  - Häring, H.-U.
AU  - Fritsche, A.
C1  - 51284
C2  - 43119
CY  - Milan
SP  - 713-714
TI  - Erratum to: A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation.
JO  - Acta Diabetol.
VL  - 54
IS  - 7
PB  - Springer-verlag Italia Srl
PY  - 2017
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - 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/m2) + 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 R2 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.
AU  - Köhler, M.
AU  - Ziegler, A.-G.
AU  - Beyerlein, A.
C1  - 47142
C2  - 40521
CY  - Milan
SP  - 433-437
TI  - Development of a simple tool to predict the risk of postpartum diabetes in women with gestational diabetes mellitus.
JO  - Acta Diabetol.
VL  - 53
IS  - 3
PB  - Springer-verlag Italia Srl
PY  - 2016
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Aims: Insulin resistance underlies the etiology of both type 2 diabetes and gestational diabetes. In pregnancy, insulin resistance is also associated with an unfavorable metabolic programming of the fetus, potentially contributing to a higher risk of obesity and type 2 diabetes in the offspring. To assess insulin sensitivity, several methods based on glucose and insulin levels during a 75-g oral glucose tolerance test (OGTT) exist. It is unclear how they perform during pregnancy, where physiologically altered metabolism could introduce a bias. Methods: In a cohort comprising 476 non-diabetic subjects undergoing OGTT and hyperinsulinemic-euglycemic clamp (HEC), we used cross-validation to develop an insulin sensitivity index also based on non-esterified fatty acids (NEFA) that could be more robust during pregnancy (NEFA-index). We tested commonly used OGTT-based indexes and the NEFA-index in a different cohort of 42 women during pregnancy and 1 year after delivery. Results: The Matsuda and OGIS index failed to detect lower insulin sensitivity during pregnancy as compared to the follow-up OGTT 1 year after delivery (p > 0.09). The new NEFA-index incorporating BMI, plasma insulin and NEFA, but not glucose, clearly indicated lower insulin sensitivity during pregnancy (p < 0.0001). In the non-pregnant cohort, this NEFA-index correlated well with the gold-standard HEC-based insulin sensitivity index, and outperformed other tested indexes for the prediction of HEC-measured insulin resistance. Conclusions: This insulin/NEFA-based approach is feasible, robust, and could be consistently used to estimate insulin sensitivity also during pregnancy.
AU  - Wagner, R.
AU  - Fritsche, L.
AU  - Heni, M.
AU  - Fehlert, E.
AU  - Stefan, N.
AU  - Staiger, H.
AU  - Häring, H.U.
AU  - Fritsche, A.
C1  - 49856
C2  - 40994
CY  - Milan
SP  - 1037-1044
TI  - A novel insulin sensitivity index particularly suitable to measure insulin sensitivity during gestation.
JO  - Acta Diabetol.
VL  - 53
IS  - 6
PB  - Springer-verlag Italia Srl
PY  - 2016
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - We investigated whether food supplementation within the first year life or age at introduction of gluten-containing foods influenced the risk of developing islet autoimmunity and type 1 diabetes. A total of 2,291 children with a family history of type 1 diabetes were prospectively followed from birth for 28,983 patient years (median 13.1 years). Dietary exposure data were collected by questionnaires, food records and by family interview. Exposure to gluten-containing foods before age 3 months, which occurred in 19 children, increased the risk of developing islet autoantibodies (n = 4), multiple islet autoantibodies (n = 4), and type 1 diabetes (n = 3) compared to exclusive breastfeeding within the first 3 months [adjusted hazard ratio (HR) 3.97 (95 % confidence interval 1.41-11.17), 5.39 (1.89-15.35), and 3.45 (1.04-11.48), respectively] and also compared to first exposure to gluten between 3.1 and 6.0 months of age [adjusted HR 3.40 (1.19-9.70), 4.25 (1.47-12.26), and 3.43 (1.01-11.66), respectively]. Children who received infant formula or other solid food within the first 3 months and children who received gluten-containing foods after age 6 months did not have an increased risk of islet autoantibodies, multiple islet autoantibodies or type 1 diabetes. Our present data affirm that compliance to infant feeding guidelines is a possible way to reduce type 1 diabetes risk in genetically susceptible children.
AU  - Chmiel, R.
AU  - Beyerlein, A.
AU  - Knopff, A.
AU  - Hummel, S.
AU  - Ziegler, A.-G.
AU  - Winkler, C.
C1  - 31796
C2  - 34761
CY  - Milan
SP  - 621-624
TI  - Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes.
JO  - Acta Diabetol.
VL  - 52
IS  - 3
PB  - Springer-verlag Italia Srl
PY  - 2015
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Elevated plasma CT-pro-vasopressin (copeptin) has been described as biomarkers for type 2 diabetes (T2D) and the metabolic syndrome (MetS), which, however, was not confirmed by all studies. Here, we analyzed the association of copeptin with T2D, MetS and MetS components in the population-based KORA F4 study. Plasma copeptin concentrations were analyzed in 1,554 study participants. We used fractional polynomial selection procedures to check for nonlinearity of the associations between copeptin and T2D and HbA1c, respectively. In logistic regression models, we investigated associations between copeptin and T2D, MetS and its components according to IDF criteria. In the fractional polynomial approach, linear models fitted best for copeptin. In multivariable adjusted models, copeptin as a continuous variable was associated with T2D and HbA1c only in men (OR = 1.38 per standard deviation, 95 % CI 1.13-1.70 for T2D). Comparing the top quartile Q4 versus Q1-3, elevated copeptin was associated with T2D (OR 2.70, 95 % CI 1.60-4.59) in men but not in women (OR 0.98, 95 % CI 0.52-1.83). Copeptin was not significantly associated with MetS, central obesity, triglycerides and reduced HDL cholesterol. A significant association with copeptin was observed for hypertension in women (OR 1.59, 95 % CI 1.08-2.33) and glucose dysfunction according to IDF criteria in men (OR 1.63, 95 % CI 1.14-2.34). In the KORA F4 study, copeptin was significantly associated with T2D only in men, whereas hypertension was associated with copeptin in women. No other components of the MetS were related to elevated copeptin.
AU  - Then, C.
AU  - Kowall, B.*
AU  - Lechner, A.
AU  - Meisinger, C.
AU  - Heier, M.
AU  - Koenig, W.*
AU  - Peters, A.
AU  - Rathmann, W.*
AU  - Seissler, J.
C1  - 31797
C2  - 34788
CY  - Milan
SP  - 103-112
TI  - Plasma copeptin is associated with type 2 diabetes in men but not in women in the population-based KORA F4 study.
JO  - Acta Diabetol.
VL  - 52
IS  - 1
PB  - Springer-verlag Italia Srl
PY  - 2015
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - We recently developed a novel approach capable of identifying gene combinations to obtain maximal disease risk stratification. Type 1 diabetes has a preclinical phase including seroconversion to autoimmunity and subsequent progression to diabetes. Here, we applied our gene combination approach to identify combinations that contribute either to islet autoimmunity or to the progression from islet autoantibodies to diabetes onset. We examined 12 type 1 diabetes susceptibility genes (INS, ERBB3, PTPN2, IFIH1, PTPN22, KIAA0350, CD25, CTLA4, SH2B3, IL2, IL18RAP, IL10) in a cohort of children of parents with type 1 diabetes and prospectively followed from birth. The most predictive combination was subsequently applied to a smaller validation cohort. The combinations of genes only marginally contributed to the risk of developing islet autoimmunity, but could substantially modify risk of progression to diabetes in islet autoantibody-positive children. The greatest discrimination was provided by risk allele scores of five genes, INS, IFIH1, IL18RAP, CD25, and IL2 genes, which could identify 80 % of islet autoantibody-positive children who progressed to diabetes within 6 years of seroconversion and discriminate high risk (63 % within 6 years; 95 % CI 45-81 %) and low risk (11 % within 6 years; 95 % CI 0.1-22 %; p = 4 × 10(-5)) antibody-positive children. Risk stratification by these five genes was confirmed in a second cohort of islet autoantibody children. These findings highlight genes that may affect the rate of the beta-cell destruction process once autoimmunity has initiated and may help to identify islet autoantibody-positive subjects with rapid progression to diabetes.
AU  - Bonifacio, E.*
AU  - Krumsiek, J.
AU  - Winkler, C.
AU  - Theis, F.J.
AU  - Ziegler, A.-G.
C1  - 28392
C2  - 33354
CY  - Milan
SP  - 403-411
TI  - A strategy to find gene combinations that identify children who progress rapidly to type 1 diabetes after islet autoantibody seroconversion.
JO  - Acta Diabetol.
VL  - 51
IS  - 3
PB  - Springer
PY  - 2014
SN  - 0940-5429
ER  - 

TY  - JOUR
AU  - Krause, S.
AU  - Beyerlein, A.
AU  - Winkler, C.
AU  - Gavrisan, A.*
AU  - Kayser, C.
AU  - Puff, R.*
AU  - Bonifacio, E.*
AU  - Ziegler, A.-G.
AU  - Achenbach, P.
C1  - 31645
C2  - 34616
CY  - Milan
SP  - 517-518
TI  - Soluble interleukin-2 receptor alpha in preclinical type 1 diabetes.
JO  - Acta Diabetol.
VL  - 51
IS  - 3
PB  - Springer-verlag Italia Srl
PY  - 2014
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - The dopamine agonist bromocriptine has been approved for the treatment of type 2 diabetes in the United States. Bromocriptine inhibits prolactin secretion, and patients with hyperprolactinaemia display impaired insulin sensitivity. We therefore hypothesized that low prolactin levels are associated with lower glycaemia and higher insulin sensitivity in healthy subjects. Prolactin levels were determined from fasting serum in participants without diabetes from the cross-sectional Tübingen family study for type 2 diabetes (m/f = 562/1,121, age = 40 ± 13 years, BMI = 30 ± 9 kg/m(2)). A 75 g oral glucose tolerance test was performed, and the area under the glucose curve (AUC0-120Glucose) and insulin sensitivity index were calculated. A subgroup (n = 494) underwent hyperinsulinaemic-euglycaemic clamp tests. Prolactin associated positively with insulin sensitivity (p = 0.001, adjusted for gender, age, and BMI). Age strongly interacted (p < 0.0001) with the effect of prolactin on insulin sensitivity, inverting the positive relationship to a negative one in younger participants. Glycated haemoglobin (HbA1c) and AUC0-120Glucose correlated negatively with prolactin, and an interaction with age was found as well. Higher prolactin levels are associated with improved insulin sensitivity and lower glucose in individuals without diabetes. This relationship turns to its opposite in younger persons. As prolactin is a proxy for the dopaminergic tone in the central nervous system, these associations may indicate an age-dependent influence of the brain on peripheral insulin sensitivity.
AU  - Wagner, R.*
AU  - Heni, M.*
AU  - Linder, K.*
AU  - Ketterer, C.*
AU  - Peter, A.*
AU  - Böhm, A.*
AU  - Hatziagelaki, E.*
AU  - Stefan, N.
AU  - Staiger, H.
AU  - Häring, H.-U.
AU  - Fritsche, A.
C1  - 28730
C2  - 33529
CY  - Milan
SP  - 71-78
TI  - Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans.
JO  - Acta Diabetol.
VL  - 51
IS  - 1
PB  - Springer
PY  - 2014
SN  - 0940-5429
ER  - 

TY  - JOUR
AB  - Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.
AU  - Heni, M.
AU  - Schöpfer, P.
AU  - Peter, A.
AU  - Sartorius, T.
AU  - Fritsche, A.
AU  - Synofzik, M.*
AU  - Häring, H.-U.
AU  - Maetzler, W.*
AU  - Hennige, A.M.
C1  - 29088
C2  - 33631
CY  - Milan
SP  - 679-681
TI  - Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.
JO  - Acta Diabetol.
VL  - 51
IS  - 4
PB  - Springer-verlag Italia Srl
PY  - 2013
SN  - 0940-5429
ER  -