Dataset Information

Is diabetes mellitus-linked amino acid signature associated with ?-blocker-induced impaired fasting glucose?

ABSTRACT: The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment.Among 234 European American participants enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study and treated with atenolol for 9 weeks, we prospectively followed a nested cohort that had both metabolomics profiling and genotype data available for the development of IFG. We assessed the association between baseline circulating levels of isoleucine, leucine, valine, tyrosine, and phenylalanine, as well as single-nucleotide polymorphisms in branched-chain amino-acid transaminase 1 (BCAT1) and phenylalanine hydroxylase (PAH) with development of IFG. All baseline AA levels were strongly associated with IFG development. Each increment in standard deviation of the 5 AAs was associated with the following odds ratio and 95% confidence interval for IFG based on a fully adjusted model: isoleucine 2.29 (1.31-4.01), leucine 1.80 (1.10-2.96), valine 1.77 (1.07-2.92), tyrosine 2.13 (1.20-3.78), and phenylalanine 2.04 (1.16-3.59). The composite P value was 2×10(-5). Those with PAH (rs2245360) AA genotype had the highest incidence of IFG (P for trend=0.0003).Our data provide important insight into the metabolic and genetic mechanisms underlying atenolol-associated adverse metabolic effects. Clinical Trial Registration- http://www.clinicaltrials.gov; Unique Identifier: NCT00246519.

SUBMITTER: Cooper-Dehoff RM

PROVIDER: S-EPMC4050976 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Is diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose?

Cooper-Dehoff Rhonda M RM Hou Wei W Weng Liming L Baillie Rebecca A RA Beitelshees Amber L AL Gong Yan Y Shahin Mohamed H A MH Turner Stephen T ST Chapman Arlene A Gums John G JG Boyle Stephen H SH Zhu Hongjie H Wikoff William R WR Boerwinkle Eric E Fiehn Oliver O Frye Reginald F RF Kaddurah-Daouk Rima R Johnson Julie A JA

Circulation. Cardiovascular genetics 20140313 2

<h4>Background</h4>The 5-amino acid (AA) signature, including isoleucine, leucine, valine, tyrosine, and phenylalanine, has been associated with incident diabetes mellitus and insulin resistance. We investigated whether this same AA signature, single-nucleotide polymorphisms in genes in their catabolic pathway, was associated with development of impaired fasting glucose (IFG) after atenolol treatment.<h4>Methods and results</h4>Among 234 European American participants enrolled in the Pharmacogen ...[more]

PMID: 24627569

Similar Datasets

Project description:BACKGROUND:The extent to which diabetes mellitus or hyperglycemia is related to risk of death from cancer or other nonvascular conditions is uncertain. METHODS:We calculated hazard ratios for cause-specific death, according to baseline diabetes status or fasting glucose level, from individual-participant data on 123,205 deaths among 820,900 people in 97 prospective studies. RESULTS:After adjustment for age, sex, smoking status, and body-mass index, hazard ratios among persons with diabetes as compared with persons without diabetes were as follows: 1.80 (95% confidence interval [CI], 1.71 to 1.90) for death from any cause, 1.25 (95% CI, 1.19 to 1.31) for death from cancer, 2.32 (95% CI, 2.11 to 2.56) for death from vascular causes, and 1.73 (95% CI, 1.62 to 1.85) for death from other causes. Diabetes (vs. no diabetes) was moderately associated with death from cancers of the liver, pancreas, ovary, colorectum, lung, bladder, and breast. Aside from cancer and vascular disease, diabetes (vs. no diabetes) was also associated with death from renal disease, liver disease, pneumonia and other infectious diseases, mental disorders, nonhepatic digestive diseases, external causes, intentional self-harm, nervous-system disorders, and chronic obstructive pulmonary disease. Hazard ratios were appreciably reduced after further adjustment for glycemia measures, but not after adjustment for systolic blood pressure, lipid levels, inflammation or renal markers. Fasting glucose levels exceeding 100 mg per deciliter (5.6 mmol per liter), but not levels of 70 to 100 mg per deciliter (3.9 to 5.6 mmol per liter), were associated with death. A 50-year-old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. CONCLUSIONS:In addition to vascular disease, diabetes is associated with substantial premature death from several cancers, infectious diseases, external causes, intentional self-harm, and degenerative disorders, independent of several major risk factors. (Funded by the British Heart Foundation and others.).

Project description:BackgroundDiabetes is associated with higher fracture risk despite higher bone mineral density (BMD), with FRAX® underestimating risk. This study aimed to investigate FRAX score with and without BMD for women with normoglycaemia, impaired fasting glucose (IFG) and diabetes.MethodsAmong 566 women, aged 40-90?years, enrolled in the Geelong Osteoporosis Study, IFG was defined as fasting plasma glucose (FPG) ?5.5?mmol/L and diabetes as FPG???7.0?mmol/L, use of antihyperglycaemic medication and/or self-report. FRAX (Australia) 10-year probabilities of major osteoporotic (MOF) and hip fracture were calculated, with and without BMD, producing four FRAX scores per participant. Kruskal-Wallis test for non-parametric data was used to examine differences between the three glycaemia groups. Fractures over 10?years were ascertained using radiological reports. The number of fractures predicted by FRAX was compared with the number of fractures observed using Chi-square tests.ResultsFor MOF FRAX calculated without BMD, women with diabetes (n?=?67) tended to have a higher median score 7.1 (IQR 2.7-12.0) than normoglycaemia (n?=?252) (4.3 (IQR 1.9-9.9) and IFG (n?=?247) (5.1 (IQR 2.2-9.6)). For hip FRAX without BMD, diabetes tended to have a higher score (2.5 (IQR 06-4.3)) than normoglycaemia (1.2 (IQR 0.3-4.1)) and IFG (1.3 (IQR 0.3-4.1)). In the normoglycaemia and IFG groups, MOFs were underestimated; 15 predicted vs 28 observed, p?=?0.038; and 16 predicted vs 31 observed, p?=?0.021, respectively. Fractures were accurately estimated in all other groups.When including BMD, the association with diabetes was non-significant for both MOF FRAX (normoglycaemia 3.7 (IQR 1.9-8.0), IFG 4.3 (IQR 2.2-8.1) and diabetes 5.3 (IQR 2.7-9.4)) and hip FRAX scores (normoglycaemia 0.6 (IQR 0.2-2.5), IFG 0.8 (IQR 0.2-2.7) and diabetes 1.0 (IQR 0.3-3.0)). For normoglycaemia and IFG, MOFs were underestimated (normoglycaemia: 13 predicted vs 28 observed and IFG: 13 vs 31). For diabetes, both MOFs and hip fractures tended to be underestimated by FRAX with BMD (MOF: 4 predicted vs 11 observed, p?=?0.055, hip: 1 predicted vs 6 observed, p?=?0.052). Hip fractures were accurately estimated in the normoglycaemia and IFG groups.ConclusionsCompared with women who had normoglycaemia or IFG, women with diabetes tended to have a higher FRAX score for both MOF and hip fractures when BMD was not included. When BMD was included, there was no difference. Fractures in diabetes tended to be underestimated by FRAX with BMD. This suggests that FRAX calculations including BMD may not be accurate for estimating fractures in those with diabetes.

Dataset Information

Is diabetes mellitus-linked amino acid signature associated with ?-blocker-induced impaired fasting glucose?

Publications

Is diabetes mellitus-linked amino acid signature associated with β-blocker-induced impaired fasting glucose?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure