Dataset Information

Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort.

ABSTRACT: OBJECTIVE:Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA). RESEARCH DESIGN AND METHODS:Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who developed prediabetes (progressors) and 70 matched participants who maintained normoglycemia (nonprogressors) during 5.5?years of follow-up in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included plasma amino acid levels, insulin sensitivity, and beta-cell function. RESULTS:The total level of all 18 amino acid assayed was significantly associated with lean mass (r?=?0.36, P?

SUBMITTER: Owei I

PROVIDER: S-EPMC6690793 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort.

Owei Ibiye I Umekwe Nkiru N Stentz Frankie F Wan Jim J Dagogo-Jack Samuel S

Metabolism: clinical and experimental 20190619

<h4>Objective</h4>Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA).<h4>Research design and methods</h4>Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who develop ...[more]

PMID: 31228482

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Project description:Intensive lifestyle intervention (ILI) prevents progression from prediabetes to type 2 diabetes (T2D) but reversal of prediabetes is less well studied. The overall objectives of the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) Study (ClinicalTrials.gov ID: NCT02027571) are to determine the natural history and reversibility of prediabetes. The study tests specific hypotheses on the patterns of progression to prediabetes among normoglycemic African-American (AA) and European-American (EA) offspring of parents with T2D; emergence of microvascular and macrovascular complications during transition from normal to impaired glucose regulation; significance of the 'metabolically healthy' obese phenotype; and effect of duration of the prediabetic state on its reversibility with lifestyle intervention. Participants who developed incident prediabetes were offered ILI and evaluated quarterly for 5 years. The primary outcome was restoration of normal glucose regulation (fasting plasma glucose <100 mg/dL and two-hour plasma glucose (2hrPG)<140 mg/dL). Of the 223 subjects enrolled in the PROP-ABC Study, 158 participants with incident prediabetes started ILI. The mean age was 53.3±9.28 years; body mass index 30.6±6.70 kg/m2; 70% were female, 52.4% AA and 47.6% EA. The ILI program used goal setting, weight-based calorie restriction, physical activity (180 min/week), self-monitoring, and meal replacement. Monthly face-to-face (F2F) counseling sessions during the initial 6 months, and quarterly visits thereafter, were supplemented with electronic and postal contacts. Attendance at F2F sessions was highly correlated with weight loss (r=0.98, p<0.0001). Meal replacement induced ~5 kg weight loss within 3 months in participants with recrudescent weight pattern. Self-reported exercise minutes correlated with pedometer step counts (r=0.47, p<0.0001). The PROP-ABC Study has demonstrated the feasibility of executing an ILI program designed to test reversibility of incident prediabetes in a biracial cohort.

Project description:Dietary and exercise data are frequently recorded in clinical research, but their correlation with metabolic measures needs further evaluation.We examined the association of food and exercise habits with body size, lipid profile, and glycemia in a prospective biracial cohort.The Pathobiology of Prediabetes in A Biracial Cohort study followed initially normoglycemic offspring of parents with type 2 diabetes (T2DM) for the occurrence of incident prediabetes, defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). At enrollment, participants underwent a 75-gram OGTT, anthropometry, measurement of fasting lipids, insulin, and body fat (DEXA), and completed the Food Habits Questionnaire (FHQ), and Modifiable Activity Questionnaire (MAQ). We assessed the relationship between FHQ and MAQ scores and adiposity, cardiometabolic measures, and incident dysglycemia.Among our cohort of 338 subjects (188 black, 150 white; mean age {±SD} 45.2±10.2 years, BMI 30.3±7.2 kg/m(2)), FHQ and MAQ scores were individually correlated with BMI (r=0.14, -0.12; P=0.01, 0.03) and waist circumference (r=0.19, -0.11; P=0.004, 0.05). Diet-adjusted leisure activity (MAQ/FHQ) was significantly correlated with total body fat (r=-0.20, P=0.0007), trunk fat (r=-0.20, P=0.0006), and serum triglycerides (r=-0.17, P=0.003) and HDL cholesterol (r=0.11, P=0.04) levels. During 5.5 years of follow-up, 111 subjects (Progressors) developed prediabetes (n=101) or diabetes (n=10) and 227 remained normoglycemic (Non-progressors). Age, BMI, MAQ and MAQ/FHQ values were significant predictors of incident prediabetes/diabetes. Progressors reported similar dietary habits (FHQ score 2.57±0.49 vs. 2.57±0.53) but 30% lower physical activity (MAQ score 15.2±20.5 vs. 22.3±30.5 MET-hr/wk, P=0.015) compared with non-progressors.Among African-American and Caucasian offspring of parents with T2DM, self-reported dietary and exercise habits correlated with measures of adiposity and dyslipidemia; however, physical activity, but not dietary recall, significantly predicted incident dysglycemia during 5.5 years of follow-up.

Project description:BackgroundExcess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findingsWe assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.ConclusionsThis study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer.

Project description:BackgroundThe identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up.MethodsIn the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110-125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman's coefficients. Kaplan-Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models.ResultsDuring a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan-Meier survival curves also showed that the lower third of plasma apoE levels (< 5.97 mg/dL) was significantly associated with a lower risk of conversion to T2D (log-rank test, p = 0.002) compared to the middle and upper thirds.ConclusionsThe plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509.

Dataset Information

Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort.

Publications

Amino acid signature predictive of incident prediabetes: A case-control study nested within the longitudinal pathobiology of prediabetes in a biracial cohort.

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