TY  - JOUR
AB  - BACKGROUND AND AIMS: Obesity has reached epidemic proportions, emphasizing the importance of reliable biomarkers for detecting early metabolic alterations and enabling early preventative interventions. However, our understanding of the molecular mechanisms and specific lipid species associated with childhood obesity remains limited. Therefore, the aim of this study was to investigate plasma lipidomic signatures as potential biomarkers for adolescent obesity. METHODS AND RESULTS: A total of 103 individuals comprising overweight/obese (n = 46) and normal weight (n = 57) were randomly chosen from the baseline ORANGE (Obesity Reduction and Noncommunicable Disease Awareness through Group Education) cohort, having been followed up for a median of 7.1 years. Plasma lipidomic profiling was performed using the UHPLC-HRMS method. We used three different models adjusted for clinical covariates to analyze the data. Clustering methods were used to define metabotypes, which allowed for the stratification of subjects into subgroups with similar clinical and metabolic profiles. We observed that lysophosphatidylcholine (LPC) species like LPC.16.0, LPC.18.3, LPC.18.1, and LPC.20.3 were significantly (p < 0.05) associated with baseline and follow-up BMI in adolescent obesity. The association of LPC species with BMI remained consistently significant even after adjusting for potential confounders. Moreover, applying metabotyping using hierarchical clustering provided insights into the metabolic heterogeneity within the normal and obese groups, distinguishing metabolically healthy individuals from those with unhealthy metabolic profiles. CONCLUSION: The specific LPC levels were found to be altered and increased in childhood obesity, particularly during the follow-up. These findings suggest that LPC species hold promise as potential biomarkers of obesity in adolescents, including healthy and unhealthy metabolic profiles.
AU  - Sharma, S.
AU  - Subrahmanyam, Y.V.*
AU  - Ranjani, H.*
AU  - Sidra, S.
AU  - Parmar, D.*
AU  - Vadivel, S.*
AU  - Kannan, S.*
AU  - Grallert, H.
AU  - Usharani, D.*
AU  - Anjana, R.M.*
AU  - Balasubramanyam, M.*
AU  - Mohan, V.*
AU  - Adamski, J.
AU  - Panchagnula, V.*
AU  - Gokulakrishnan, K.*
C1  - 70312
C2  - 55507
CY  - 125 London Wall, London, England
SP  - 1807-1816
TI  - Circulatory levels of lysophosphatidylcholine species in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses.
JO  - Nutr. Metab. Cardiovasc. Dis.
VL  - 34
IS  - 7
PB  - Elsevier Sci Ltd
PY  - 2024
SN  - 0939-4753
ER  - 

TY  - JOUR
AB  - BACKGROUND AND AIMS: Evidence suggests that people react differently to the same diet due to inter-individual differences. However, few studies have investigated variation in response to dietary interventions based on individuals' baseline metabolic characteristics. This study aims to examine the differential reaction of metabotype subgroups to an OGTT and a dietary fiber intervention. METHODS AND RESULTS: We assigned 356 healthy participants of an OGTT sub-study and a 12-week dietary fiber intervention sub-study within the enable cluster to three metabotype subgroups previously identified in the KORA F4 study population. To explore the association between plasma glucose level and metabotype subgroups, we used linear mixed models adjusted for age, sex, and physical activity. Individuals in different metabotype subgroups showed differential responses to OGTT. Compared to the healthy metabotype (metabotype 1), participants in intermediate metabotype (metabotype 2) and unfavorable metabotype (metabotype 3) had significantly higher plasma glucose concentrations at 120 min after glucose bolus (β = 7.881, p = 0.005; β = 32.79, p < 0.001, respectively). Additionally, the linear regression model showed that the Area under the curve (AUC) of plasma glucose concentrations was significantly different across the metabotype subgroups. The associations between metabotype subgroups and metabolic parameters among fiber intervention participants remained insignificant in the multivariate-adjusted linear model. However, the metabotype 3 had the highest mean reduction in insulin, cholesterol parameters (TC, LDLc, and non-HDLc), and systolic and diastolic blood pressure at the end of the intervention period. CONCLUSION: This study supports the use of the metabotype concept to identify metabolically similar subgroups and to develop targeted dietary interventions at the metabotype subgroup level for the primary prevention of diet-related diseases.
AU  - Dahal, C.
AU  - Wawro, N.
AU  - Meisinger, C.
AU  - Brandl, B.*
AU  - Skurk, T.*
AU  - Volkert, D.*
AU  - Hauner, H.*
AU  - Linseisen, J.
C1  - 65770
C2  - 52909
SP  - 2399-2409
TI  - Evaluation of the metabotype concept after intervention with oral glucose tolerance test and dietary fiber-enriched food: An enable study.
JO  - Nutr. Metab. Cardiovasc. Dis.
VL  - 32
IS  - 10
PY  - 2022
SN  - 0939-4753
ER  - 

TY  - JOUR
AB  - Background and aims: In a non-interventional study of older persons, we assessed the impact of changes in BMI and waist circumference (WC) on reversion from glucose- and HbA1c-defined prediabetes to normoglycaemia (in short: reversion) and on persistence of normoglycaemia. Moreover, we studied whether reversion reduced cardiovascular risk. Methods and results: From the population-based KORA S4/F4/FF4 cohort study conducted in Southern Germany, we utilized data from the second and third visit to the study center (median follow-up 6.5 years). We used two overlapping data sets, one with 563 persons with HbA1c<6.5% (mean age 69 years, 51.5% men), one with 510 persons with glucose-based prediabetes or normal glucose tolerance. We calculated proportions of reversion, and estimated adjusted relative risks for the association between initial BMI/WC and change of BMI/WC, respectively, and reversion (and persistence of normoglycaemia, respectively). We estimated 10-year cardiovascular risks using the Framingham 2008 score. Overall, 27.3% of persons with HbA1c-defined prediabetes and 9.2% of persons with glucose-based prediabetes returned to normoglycaemia during follow-up. Lower initial BMI/WC and reduction of BMI/WC were associated with larger probabilities of returning to normoglycaemia (e.g., for HbA1c 5.7–6.4%, RR = 1.24 (95% CI: 1.09–1.41) per 1 kg/m2 decline of BMI). Moreover, reduction of BMI/WC increased probabilities of maintaining normoglycaemia (e.g., for glucose-based prediabetes, RR = 1.09 (1.02–1.16) per 1 kg/m2 decline of BMI). 10-year cardiovascular risk was 5.6 (1.7–9.6) percentage points lower after reversion from glucose-based prediabetes to normoglycaemia. Conclusion: In older adults, even moderate weight reduction contributes to reversion from prediabetes to normoglycaemia and to maintaining normoglycaemia.
AU  - Kowall, B.*
AU  - Rathmann, W.*
AU  - Kuss, O.*
AU  - Herder, C.*
AU  - Roden, M.*
AU  - Stang, A.*
AU  - Huth, C.
AU  - Thorand, B.
AU  - Meisinger, C.
AU  - Peters, A.
C1  - 60411
C2  - 49434
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - 429-438
TI  - Reversion from prediabetes to normoglycaemia after weight change in older persons: The KORA F4/FF4 study.
JO  - Nutr. Metab. Cardiovasc. Dis.
VL  - 31
IS  - 2
PB  - Elsevier Sci Ltd
PY  - 2021
SN  - 0939-4753
ER  - 

TY  - JOUR
AB  - Background and Aims: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Methods and Results: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. Conclusion: Our findings suggest that prediabetes might have harmful effects on the kidney.
AU  - Markus, M.R.P.*
AU  - Ittermann, T.*
AU  - Baumeister, S.E.*
AU  - Huth, C.
AU  - Thorand, B.
AU  - Herder, C.*
AU  - Roden, M.*
AU  - Siewert-Markus, U.*
AU  - Rathmann, W.*
AU  - Koenig, W.*
AU  - Dörr, M.*
AU  - Völzke, H.*
AU  - Schipf, S.*
AU  - Meisinger, C.*
C1  - 52736
C2  - 44224
CY  - Oxford
SP  - 234-242
TI  - Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.
JO  - Nutr. Metab. Cardiovasc. Dis.
VL  - 28
IS  - 3
PB  - Elsevier Sci Ltd
PY  - 2018
SN  - 0939-4753
ER  - 

TY  - JOUR
AB  - BACKGROUND/AIMS: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D. Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. METHODS: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448). RESULTS: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89-1.04) or in the meta-analysis (OR = 1.01; 0.98-1.05). CONCLUSION: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.
AU  - Prudente, S.*
AU  - Copetti, M.*
AU  - Morini, E.*
AU  - Mendonca, C.*
AU  - Andreozzi, F.*
AU  - Chandalia, M.*
AU  - Baratta, R.*
AU  - DIAGRAM Consortium (Huth, C.
AU  - Grallert, H.
AU  - Gieger, C.
AU  - Klopp, N.
AU  - Meitinger, T.
AU  - Petersen, A.-K.
AU  - Thorand, B.
AU  - Wichmann, H.-E.
AU  - Illig, T.)
AU  - Pellegrini, F.*
AU  - Mercuri, L.*
AU  - Bailetti, D.*
AU  - Abate, N.*
AU  - Frittitta, L.*
AU  - Sesti, G.*
AU  - Florez, J.C*
AU  - Doria, A.*
AU  - Trischitta, V.*
C1  - 28111
C2  - 32944
SP  - 1043-1049
TI  - The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry.
JO  - Nutr. Metab. Cardiovasc. Dis.
VL  - 23
IS  - 11
PB  - Elsevier Science
PY  - 2013
SN  - 0939-4753
ER  - 

TY  - JOUR
AB  - It is unclear to what extent diabetes modulates the ageing-related adaptations of cardiac geometry and function. METHODS AND RESULTS: We examined 1005 adults, aged 25-74 years, from a population-based survey at baseline in 1994/5 and at follow-up in 2004/5. We compared persistently non-diabetic individuals (ND; no diabetes at baseline and at follow-up, n=833) with incident (ID; non-diabetic at baseline and diabetic at follow-up, n=36) and with prevalent diabetics (PD; diabetes at baseline and follow-up examination, n=21). Left ventricular (LV) geometry and function were evaluated by echocardiography. Statistical analyses were performed with multivariate linear regression models. Over ten years the PD group displayed a significantly stronger relative increase of LV mass (+9.34% vs. +23.7%) that was mediated by a more pronounced increase of LV end-diastolic diameter (+0% vs. +6.95%) compared to the ND group. In parallel, LA diameter increased (+4.50% vs. +12.7%), whereas ejection fraction decreased (+3.02% vs. -4.92%) more significantly in the PD group. Moreover, at the follow-up examination the PD and ID groups showed a significantly worse diastolic function, indicated by a higher E/EM ratio compared with the ND group (11.6 and 11.8 vs. 9.79, respectively). CONCLUSIONS: Long-standing diabetes was associated with an acceleration of age-related changes of left ventricular geometry accumulating in an eccentric remodelling of the left ventricle. Likewise, echocardiographic measures of systolic and diastolic ventricular function deteriorated more rapidly in individuals with diabetes.
AU  - Markus, M.R.*
AU  - Stritzke, J.*
AU  - Wellmann, J.*
AU  - Duderstadt, S.*
AU  - Siewert, U.*
AU  - Lieb, W.*
AU  - Luchner, A.*
AU  - Döring, A.
AU  - Keil, U.*
AU  - Schunkert, H.*
AU  - Hense, H.W.*
C1  - 6478
C2  - 28776
SP  - 189-196
TI  - Implications of prevalent and incident diabetes mellitus on left ventricular geometry and function in the ageing heart: The MONICA/KORA Augsburg cohort study.
JO  - Nutr. Metab. Cardiovasc. Dis.
VL  - 21
IS  - 3
PB  - Elsevier
PY  - 2011
SN  - 0939-4753
ER  -