Dataset Information

Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin.

ABSTRACT: Sodium glucose co-transporter 2 (SGLT2) inhibitors have been associated with increased serum ketone body levels in patients with type 2 diabetes mellitus (T2DM). In the present analysis we evaluated serum ketone body levels and variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen with both canagliflozin doses. The median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for ?-hydroxybutyrate. Approximately two-thirds of the variability in each ketone measure was attributed to intra-subject variability. Intra-subject variability was higher for serum ketones than other metabolites. Patients in the lowest response tertile exhibited no increase in ketones. Those in the highest response tertile tended to be male and have higher fasting plasma glucose levels, lower insulin levels, and longer T2DM duration at baseline. Moreover, changes in serum ketones were not fully explained by changes in plasma fatty acids, suggesting downstream effects of SGLT2 inhibition on hepatic metabolism that favour ketogenesis. In summary, increases in serum ketone bodies with canagliflozin were greater and more variable than changes in other metabolic measures in Japanese patients with T2DM.

SUBMITTER: Polidori D

PROVIDER: S-EPMC5947648 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin.

Polidori David D Iijima Hiroaki H Goda Maki M Maruyama Nobuko N Inagaki Nobuya N Crawford Peter A PA

Diabetes, obesity & metabolism 20180214 5

Sodium glucose co-transporter 2 (SGLT2) inhibitors have been associated with increased serum ketone body levels in patients with type 2 diabetes mellitus (T2DM). In the present analysis we evaluated serum ketone body levels and variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen with both canagliflozin doses. The median (interquartile range) percent change from baseline was 62% (0;180) ...[more]

PMID: 29341404

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Project description:The stop signal task has been used to quantify the human inhibitory control. The inter-subject and intra-subject variability was investigated under the inhibition of human response with a realistic environmental scenario. In present study, we used a battleground scenario where a sniper-scope picture was the background, a target picture was a go signal, and a nontarget picture was a stop signal. The task instructions were to respond on the target image and inhibit the response if a nontarget image appeared. This scenario produced a threatening situation and endorsed the evaluation of how subject's response inhibition manifests in a real situation. In this study, 32 channels of electroencephalography (EEG) signals were collected from 20 participants during successful stop (response inhibition) and failed stop (response) trials. These EEG signals were used to predict two possible outcomes: successful stop or failed stop. The inter-subject variability (between-subjects) and intra-subject variability (within-subjects) affect the performance of participants in the classification system. The EEG signals of successful stop versus failed stop trials were classified using quadratic discriminant analysis (QDA) and linear discriminant analysis (LDA) (i.e., parametric) and K-nearest neighbor classifier (KNNC) and Parzen density-based (PARZEN) (i.e., nonparametric) under inter- and intra-subject variability. The EEG activities were found to increase during response inhibition in the frontal cortex (F3 and F4), presupplementary motor area (C3 and C4), parietal lobe (P3 and P4), and occipital (O1 and O2) lobe. Therefore, power spectral density (PSD) of EEG signals (1-50Hz) in F3, F4, C3, C4, P3, P4, O1, and O2 electrodes were measured in successful stop and failed stop trials. The PSD of the EEG signals was used as the feature input for the classifiers. Our proposed method shows an intra-subject classification accuracy of 97.61% for subject 15 with QDA classifier in C3 (left motor cortex) and an overall inter-subject classification accuracy of 71.66% ± 9.81% with the KNNC classifier in F3 (left frontal lobe). These results display how inter-subject and intra-subject variability affects the performance of the classification system. These findings can be used effectively to improve the psychopathology of attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), schizophrenia, and suicidality.

Dataset Information

Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin.

Publications

Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin.

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