Non-targeted urine metabolomics and associations with prevalent and incident type 2 diabetes
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ABSTRACT:
SUBMITTER: Salihovic S
PROVIDER: S-EPMC7536211 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Identification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction.In this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n?=?1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n?=?970; TwinGene, n?=?1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n?=?855). Assessment of the association of metabolite-regulating genetic variants with type 2 diabetes was done using data from a meta-analysis of genome-wide association studies.Out of 5961 investigated metabolic features, 1120 were associated with prevalent type 2 diabetes and IFG and 70 were annotated to metabolites and replicated in the three cohorts. Fifteen metabolites were associated with incident type 2 diabetes in the four cohorts combined (358 events) following adjustment for age, sex, BMI, waist circumference and fasting glucose. Novel findings included associations of higher values of the bile acid deoxycholic acid and monoacylglyceride 18:2 and lower concentrations of cortisol with type 2 diabetes risk. However, adding metabolites to an existing risk score improved model fit only marginally. A genetic variant within the CYP7A1 locus, encoding the rate-limiting enzyme in bile acid synthesis, was found to be associated with lower concentrations of deoxycholic acid, higher concentrations of LDL-cholesterol and lower type 2 diabetes risk. Variants in or near SGPP1, GCKR and FADS1/2 were associated with diabetes-associated phospholipids and type 2 diabetes.We found evidence that the metabolism of bile acids and phospholipids shares some common genetic origin with type 2 diabetes.Metabolomics data have been deposited in the Metabolights database, with accession numbers MTBLS93 (TwinGene), MTBLS124 (ULSAM) and MTBLS90 (PIVUS).
| S-EPMC5451119 | biostudies-literature
Project description:ObjectiveCharacterizing specific metabolites in sub-clinical phases preceding the onset of type 2 diabetes to enable efficient preventive and personalized interventions.Research design and methodsWe developed predictive models of type 2 diabetes using two strategies. One strategy focused on the probability of incidence only and was based on logistic regression (MRS1); the other strategy accounted for the age at diagnosis of diabetes and was based on Cox regression (MRS2). We assessed 293 metabolites using non-targeted metabolomics in fasting plasma samples of 1,044 participants (including 231 incident cases over 9 years) used as training population; and fasting serum samples of 128 participants (64 incident cases versus 64 controls) used as validation population. We applied a LASSO-based variable selection aiming at maximizing the out-of-sample area under the receiver operating characteristic curve (AROC) and integrated AROC.ResultsSixteen and 17 metabolites were selected for MRS1 and MRS2, respectively, with AROC = 90% and 73% in the training and validation populations, respectively for MRS1. MRS2 had a similar performance and was significantly associated with a younger age of onset of type 2 diabetes (? = -3.44 years per MRS2 SD in the training population, p = 1.56 × 10(-7); ? = -4.73 years per MRS2 SD in the validation population, p = 4.04 × 10(-3)).ConclusionsOverall, this study illustrates that metabolomics improves prediction of type 2 diabetes incidence of 4.5% on top of known clinical and biological markers, reaching 90% in total AROC, which is considered the threshold for clinical validity, suggesting it may be used in targeting interventions to prevent type 2 diabetes.
| S-EPMC5034686 | biostudies-literature
Project description:Despite multiple examples of glucose-lowering therapies affecting heart failure (HF) risk, ascertainment of HF data in cardiovascular outcome trials of these medications has not been systematically characterized. In this review, large (n >1,000) published phase III and IV cardiovascular outcome trials evaluating glucose-lowering therapies through June 2017 were identified. Data were abstracted from publications, U.S. Food and Drug Administration advisory committee records, and U.S. Food and Drug Administration labeling documents. Overall, 21 trials including 152,737 patients were evaluated. Rates and definitions of baseline HF and incident HF were inconsistently provided. Baseline ejection fraction data were provided in 3 studies but not specific to patients with HF. No trial reported functional class, ejection fraction, or HF therapy at the time of incident HF diagnosis. HF hospitalization data were available in 15 trials, but only 2 included HF-related events within the primary composite endpoint. This systematic review highlights gaps in HF data capture within cardiovascular outcome trials of glucose-lowering therapies and outlines rationale and strategies for improving HF characterization.
| S-EPMC5832063 | biostudies-literature
Project description:Our objective was to identify metabolites associated with fetal growth restriction (FGR) by examining early and late pregnancy differences in non-targeted urinary metabolites among FGR cases and non-FGR controls. An exploratory case-control study within LIFECODES birth cohort was performed. FGR cases (N?=?30), defined as birthweight below the 10th percentile, were matched with controls (N?=?30) based on maternal age, race, pre-pregnancy body mass index, and gestational age at delivery. Gas chromatography/electron-ionization mass spectrometry was performed on urine samples collected at 10 and 26 weeks of gestation. Differences in urinary metabolite levels in cases and controls at each time point and between the two time points were calculated and then changes compared across pregnancy. 137 unique urinary metabolites were annotated, and several identified that were higher in cases compared to controls. For example, urinary concentrations of benzoic acid were higher in cases compared to controls at both study visits (3.01-fold higher in cases at visit 1, p?<?0.01; 3.10-fold higher in cases at visit 3, p?=?0.05). However, these findings from our exploratory analysis were not robust to false-discovery-rate adjustment. In conclusion, using a high-resolution, non-targeted approach, we found specific urinary organic acids differed over pregnancy by FGR case status.
| S-EPMC7093500 | biostudies-literature
Project description:We aimed to simultaneously examine the associations of both essential and non-essential amino acids with both prevalent and incident type 2 diabetes in a Chinese population. A case-control study was nested within the Singapore Chinese Health Study. Participants included 144 cases with prevalent and 160 cases with incident type 2 diabetes and 304 controls. Cases and controls were individually matched on age, sex, and date of blood collection. Baseline serum levels of 9 essential and 10 non-essential amino acids were measured using liquid chromatography tandem mass spectrometry. We identified that five essential (isoleucine, leucine, lysine, phenylalanine, and valine) and five non-essential (alanine, glutamic acid, glutamine, glycine, and tyrosine) amino acids were associated with the prevalence of type 2 diabetes; four essential (isoleucine, leucine, tryptophan, and valine) and two non-essential (glutamine and tyrosine) amino acids were associated with the incidence of type 2 diabetes. Of these, valine and tyrosine independently led to a significant improvement in risk prediction of incident type 2 diabetes. This study demonstrates that both essential and non-essential amino acids were associated with the risk for prevalent and incident type 2 diabetes, and the findings could aid in diabetes risk assessment in this Chinese population.
| S-EPMC6359471 | biostudies-literature
Project description:Aims/hypothesisData on type 1 diabetes incidence and prevalence are limited, particularly for adults. This study aims to estimate global numbers of incident and prevalent cases of type 1 diabetes in 2017 for all age groups, by country and areas defined by income and region.MethodsIncidence rates of type 1 diabetes in children (available from 94 countries) from the IDF Atlas were used and extrapolated to countries without data. Age-specific incidence rates in adults (only known across full age range for fewer than ten countries) were obtained by applying scaling ratios for each adult age group relative to the incidence rate in children. Age-specific incidence rates were applied to population estimates to obtain incident case numbers. Duration of diabetes was estimated from available data and adjusted using differences in childhood mortality rate between countries from United Nations demographic data. Prevalent case numbers were derived by modelling the relationship between prevalence, incidence and disease duration. Sensitivity analyses were performed to quantify the impact of alternative assumptions and model inputs.ResultsGlobal numbers of incident and prevalent cases of type 1 diabetes were estimated to be 234,710 and 9,004,610, respectively, in 2017. High-income countries, with 17% of the global population, accounted for 49% of global incident cases and 52% of prevalent cases. Asia, which has the largest proportion of the world's population (60%), had the largest number of incident (32%) and prevalent (31%) cases of type 1 diabetes. Globally, 6%, 35%, 43% and 16% of prevalent cases were in the age groups 0-14, 15-39, 40-64 and 65+ years, respectively. Based on sensitivity analyses, the estimates could deviate by ±15%.Conclusions/interpretationGlobally, type 1 diabetes represents about 2% of the estimated total cases of diabetes, ranging from less than 1% in certain Pacific countries to more than 15% in Northern European populations in 2017. This study provides information for the development of healthcare and policy approaches to manage type 1 diabetes. The estimates need further validation due to limitations and assumptions related to data availability and estimation methods.
| S-EPMC8563635 | biostudies-literature
Project description:AimsThere are several epidemiological studies on the association between statins and incident diabetes, but most of them lack details. In this study, we aimed to investigate the association of statin use with glycaemic traits and incident type 2 diabetes.MethodsUsing the prospective population-based Rotterdam Study, we included 9535 individuals free from diabetes at baseline (>45 years) during the study period between 1997 and 2012. Linear regression analysis was applied to examine the cross-sectional associations between statin use and glycaemic traits including fasting blood serum of glucose and insulin concentrations, and insulin resistance. In a longitudinal follow-up study, we applied a Cox regression analysis to determine adjusted hazard ratios (HR) for incident type 2 diabetes in new users of statins.ResultsThe mean age at baseline was 64.3 ± 10.1 years and 41.7% were men. In the fully adjusted model, compared to never users of statins, baseline use of statins was associated with higher concentrations of serum fasting insulin (β = 0.07; 95% CI: 0.02-0.13) and insulin resistance (β = 0.09; 95% CI: 0.03-0.14). Ever use of statins was associated with a 38% higher risk of incident type 2 diabetes (HR = 1.38; 95% CI: 1.09-1.74). This risk was more prominent in subjects with impaired glucose homeostasis and in overweight/obese individuals.ConclusionsIndividuals using statins may be at higher risk for hyperglycaemia, insulin resistance and eventually type 2 diabetes. Rigorous preventive strategies such as glucose control and weight reduction in patients when initiating statin therapy might help minimize the risk of diabetes.
| S-EPMC6475692 | biostudies-literature
Project description:BackgroundDiabetes is especially prevalent among African Americans. Prior studies suggest that long-term exposure to ambient air pollution may be associated with greater incidence of diabetes, but results remain heterogeneous. Few studies have included large numbers of African Americans.MethodsWe assessed diabetes status and concentrations of 1- and 3-year fine particulate matter (PM2.5) and ozone (O3) among African American participants of the Jackson Heart Study at visits 1 (2000-2004, N = 5128) and 2 (2005-2008, N = 2839). We used mixed-effect modified Poisson regression to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of incidence of diabetes by visit 2 and prevalence ratios (PRs) of the association between air pollution exposure and prevalent diabetes at visits 1 and 2. We adjusted for potential confounding by patient characteristics, as well as inverse probability weights of diabetes at visit 2, accounting for clustering by census tract.ResultsWe observed associations between incident diabetes and interquartile range increase in 1-year O3 (RR 1.34, 95% CI = 1.11, 1.61) and 3-year O3 (RR 0.88, 95% CI = 0.76, 1.02). We observed associations between prevalent diabetes and 1-year PM2.5 (PR 1.08, 95% CI = 1.00, 1.17), 1-year O3 (PR 1.18, 95% CI = 1.10, 1.27), and 3-year O3 (PR 0.95, 95% CI = 0.90, 1.01) at visit 2.ConclusionsOur results provide some evidence of positive associations between indicators of long-term PM2.5 and O3 exposure and diabetes. This study is particularly relevant to African Americans, who have higher prevalence of diabetes but relatively few studies of environmental pollution risk factors.
| S-EPMC8078431 | biostudies-literature
Project description:ObjectiveThe objective of this analysis is to compare people with prevalent type 2 diabetes, incident type 2 diabetes and without diabetes with respect to longitudinal change in health-related quality of life (HRQOL) when adjusting for baseline determinants of HRQOL.Research design and methodsPrimary baseline and follow-up data from three regional and one national population-based cohort studies in Germany were pooled for analysis. HRQOL was measured using physical and mental health summary scores (PCS and MCS) from the German version of the Short Form Health Survey with 36 or 12 items. Mean score change per observation year was compared between the three groups (prevalent diabetes, incident diabetes, no diabetes) based on linear regression models.ResultsThe analysis included pooled data from 5367 people aged 45-74 years at baseline. Of these, 85.5% reported no diabetes at baseline and follow-up, 6.3% reported diabetes at both baseline and follow-up (prevalent diabetes), and 8.2% reported diabetes only at follow-up (incident diabetes). Over a mean observation period of 8.7 years, annual decline in HRQOL scores is pronounced at 0.27-0.32 (PCS) and 0.34-0.38 (MCS) in the group with prevalent diabetes compared with people without diabetes. Those with incident diabetes showed intermediate values but did not differ significantly from people without diabetes after adjustment for covariates in the full model.ConclusionCompared with data from cross-sectional analysis, the HRQOL loss associated with prevalent diabetes appears to be much larger than previously assumed.
| S-EPMC5415190 | biostudies-literature
Project description:ObjectiveTo investigate the association between intakes of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk in three prospective cohort studies of U.S. men and women.Research design and methodsWe followed 83,648 women from the Nurses' Health Study (NHS) (1980-2012), 88,610 women from NHSII (1991-2013), and 41,771 men from the Health Professionals Follow-Up Study (HPFS) (1986-2012). Dietary data were collected every 2-4 years by using validated food-frequency questionnaires. Self-reported incident diabetes, identified biennially, was confirmed by using a validated supplementary questionnaire.ResultsDuring 4.93 million person-years of follow-up, 18,442 type 2 diabetes cases were documented. Dietary n-6 PUFAs accounted for 4.4-6.8% of total energy, on average, and consisted primarily of linoleic acid (LA) (≥98%). In multivariate-adjusted models, hazard ratios (95% CIs) of type 2 diabetes risk comparing extreme n-6 PUFA quintiles (highest vs. lowest) were 0.91 (0.85, 0.96) (P trend = 0.002) for total n-6 PUFAs and 0.92 (0.87, 0.98) (P trend = 0.01) for LA. In an isocaloric substitution model, diabetes risk was 14% (95% CI 5%, 21%) (P = 0.002) lower when LA isocalorically replaced saturated fats (5% of energy), 17% (95% CI 9%, 24%) (P < 0.001) lower for trans fats (2% of energy), or 9% (95% CI 17%, 0.1%) (P = 0.047) lower for carbohydrates (5% of energy). Replacing n-3 PUFAs or monounsaturated fats with LA was not significantly associated with type 2 diabetes risk.ConclusionsOur study provides additional evidence that LA intake is inversely associated with risk of type 2 diabetes, especially when replacing saturated fatty acids, trans fats, or carbohydrates.
| S-EPMC6647042 | biostudies-literature