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 < 0.0001), waist circumference (r = 0.27, P = 0.001), fasting plasma glucose (r = 0.24, P = 0.005), HOMA-IR (r = 0.22, P = 0.01) and HDL cholesterol (r = -0.18, P = 0.03). Individual amino acid levels were significantly associated with insulin sensitivity and insulin secretion. Compared with nonprogressors, progressors had higher baseline levels of asparagine and aspartic acid (P <0.0001), glutamine/glutamic acid (P = 0.005) and phenylalanine (P = 0.02), and lower histidine (P = 0.02) levels. In fully-adjusted logistic regression models, aspartic acid/asparagine (OR 2.72 [95% CI 1.91-3.87]) and histidine (OR 0.90 [95% CI 0.85-0.96]) were the only amino acids that significantly predicted incident prediabetes.

Conclusions

Baseline plasma aspartic acid and asparagine levels predicted progression to prediabetes, whereas histidine levels were protective of prediabetes risk. Thus, the amino acid signature associated with prediabetes in a diverse population may be distinct from that previously linked to T2DM in Caucasians.

SUBMITTER: Owei I

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

REPOSITORIES: biostudies-literature

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Publications

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:BackgroundDietary and exercise data are frequently recorded in clinical research, but their correlation with metabolic measures needs further evaluation.ObjectiveWe examined the association of food and exercise habits with body size, lipid profile, and glycemia in a prospective biracial cohort.MethodsThe 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.ResultsAmong 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.ConclusionsAmong 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: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:IntroductionIn studies that enrolled people with prevalent pre-diabetes of unknown duration, lifestyle intervention (LI) delayed progression to type 2 diabetes (T2D) but did not reverse pre-diabetes in most participants. Here, we assessed the effects of LI among individuals with pre-diabetes of known duration to determine whether outcomes are related to duration of pre-diabetes.Research design and methodsThe Pathobiology and Reversibility of Prediabetes in a Biracial Cohort study initiated LI in subjects with incident pre-diabetes during follow-up of initially normoglycemic African Americans and European Americans with parental T2D. Participants were stratified into those initiating LI after <3, 3-5, or >5 years of pre-diabetes diagnosis. Assessments included anthropometry, body fat, fasting and 2-hour plasma glucose (FPG, 2hPG), and insulin sensitivity and secretion. The outcomes were normal glucose regulation (NGR; ie, normal FPG and 2hPG), persistent pre-diabetes, or T2D. Participants who maintained normal FPG and normal 2hPG levels during follow-up served as the control. The control subjects did not receive lifestyle or other intervention to alter the course of glycemia or body weight.ResultsOf 223 participants (age 53.3±9.28 years, body mass index 30.6±6.70 kg/m2), 72 (control) maintained normoglycemia during follow-up and 138 subjects with incident pre-diabetes initiated LI after 4.08±2.02 years (range 3 months-8.3 years) of diagnosis. Compared with control, LI participants showed decrease in glucose, weight, and body fat; 42.8% reverted to NGR, 50% had persistent pre-diabetes, and 7.2% developed T2D after 5 years. These outcomes were similar across race and pre-diabetes duration strata, but greater glycemic decrease occurred when LI was initiated within 5 years of pre-diabetes diagnosis.ConclusionsNinety-three per cent of adults with parental T2D who initiated LI within 3 months to 8.3 years of developing pre-diabetes did not progress to T2D; nearly half reverted to NGR.Trial registration number NCT02027571.

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Project description:The ability to predict prediabetes, which affects ∼90 million adults in the US and ∼400 million adults worldwide, would be valuable to public health. Acylcarnitines, fatty acid metabolites, have been associated with type 2 diabetes risk in cross-sectional studies of mostly Caucasian subjects, but prospective studies on their link to prediabetes in diverse populations are lacking. Here, we determined the association of plasma acylcarnitines with incident prediabetes in African Americans and European Americans enrolled in a prospective study. We analyzed 45 acylcarnitines in baseline plasma samples from 70 adults (35 African-American, 35 European-American) with incident prediabetes (progressors) and 70 matched controls (non-progressors) during 5.5-year (mean 2.6 years) follow-up in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. Incident prediabetes (impaired fasting glucose/impaired glucose tolerance) was confirmed with OGTT. We measured acylcarnitines using tandem mass spectrometry, insulin sensitivity by hyperinsulinemic euglycemic clamp, and insulin secretion using intravenous glucose tolerance test. The results showed that progressors and non-progressors during POP-ABC study follow-up were concordant for 36 acylcarnitines and discordant for nine others. In logistic regression models, beta-hydroxy butyryl carnitine (C4-OH), 3-hydroxy-isovaleryl carnitine/malonyl carnitine (C5-OH/C3-DC), and octenoyl carnitine (C8:1) were the only significant predictors of incident prediabetes. The combined cut-off plasma levels of <0.03 micromol/L for C4-OH, <0.03 micromol/L for C5-OH/C3-DC, and >0.25 micromol/L for C8:1 acylcarnitines predicted incident prediabetes with 81.9% sensitivity and 65.2% specificity. Thus, circulating levels of one medium-chain and two short-chain acylcarnitines may be sensitive biomarkers for the risk of incident prediabetes among initially normoglycemic individuals with parental history of type 2 diabetes.

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Dataset Information

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

Objective

Research design and methods

Results

Conclusions

Publications

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

Similar Datasets

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