Dataset Information

Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance.

ABSTRACT:

Introduction

Rosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity.

Methods

Patients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; < 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; < 800 kcal/day).

Results

A total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant.

Conclusions

Neither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance.

SUBMITTER: Hovd M

PROVIDER: S-EPMC10181972 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance.

Hovd Markus M Robertsen Ida I Johnson Line Kristin LK Krogstad Veronica V Wegler Christine C Kvitne Kine Eide KE Kringen Marianne Kristiansen MK Skovlund Eva E Karlsson Cecilia C Andersson Shalini S Artursson Per P Sandbu Rune R Hjelmesæth Jøran J Åsberg Anders A Jansson-Löfmark Rasmus R Christensen Hege H

Clinical pharmacokinetics 20230329 5

<h4>Introduction</h4>Rosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity.<h4>Methods</h4>Patients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic ...[more]

PMID: 36988826

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Project description:BackgroundFew long-term or controlled studies of bariatric surgery have been conducted to date. We report the 12-year follow-up results of an observational, prospective study of Roux-en-Y gastric bypass that was conducted in the United States.MethodsA total of 1156 patients with severe obesity comprised three groups: 418 patients who sought and underwent Roux-en-Y gastric bypass (surgery group), 417 patients who sought but did not undergo surgery (primarily for insurance reasons) (nonsurgery group 1), and 321 patients who did not seek surgery (nonsurgery group 2). We performed clinical examinations at baseline and at 2 years, 6 years, and 12 years to ascertain the presence of type 2 diabetes, hypertension, and dyslipidemia.ResultsThe follow-up rate exceeded 90% at 12 years. The adjusted mean change from baseline in body weight in the surgery group was -45.0 kg (95% confidence interval [CI], -47.2 to -42.9; mean percent change, -35.0) at 2 years, -36.3 kg (95% CI, -39.0 to -33.5; mean percent change, -28.0) at 6 years, and -35.0 kg (95% CI, -38.4 to -31.7; mean percent change, -26.9) at 12 years; the mean change at 12 years in nonsurgery group 1 was -2.9 kg (95% CI, -6.9 to 1.0; mean percent change, -2.0), and the mean change at 12 years in nonsurgery group 2 was 0 kg (95% CI, -3.5 to 3.5; mean percent change, -0.9). Among the patients in the surgery group who had type 2 diabetes at baseline, type 2 diabetes remitted in 66 of 88 patients (75%) at 2 years, in 54 of 87 patients (62%) at 6 years, and in 43 of 84 patients (51%) at 12 years. The odds ratio for the incidence of type 2 diabetes at 12 years was 0.08 (95% CI, 0.03 to 0.24) for the surgery group versus nonsurgery group 1 and 0.09 (95% CI, 0.03 to 0.29) for the surgery group versus nonsurgery group 2 (P<0.001 for both comparisons). The surgery group had higher remission rates and lower incidence rates of hypertension and dyslipidemia than did nonsurgery group 1 (P<0.05 for all comparisons).ConclusionsThis study showed long-term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux-en-Y gastric bypass. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.).

Project description:ImportancePregnancy weight gain may affect the association of bariatric surgery with postsurgery pregnancy outcomes. However, the association of pregnancy weight gain with bariatric surgery is unclear.ObjectiveTo compare pregnancy weight gain among women with a history of bariatric surgery vs those without and to investigate whether pregnancy weight gain differs by surgical procedure, surgery-to-conception interval, and/or surgery-to-conception weight loss.Design, setting, and participantsThis nationwide, population-based matched cohort study was conducted in Sweden from 2014 to 2021. Singleton pregnancies with a history of bariatric surgery were propensity score matched (1:1) to pregnancies without such a history according to early-pregnancy body mass index (BMI), prepregnancy diabetes, prepregnancy hypertension, maternal age, smoking status, education level, height, country of birth, and delivery year. In addition, post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy. Data analysis was performed from November 2022 to May 2023.ExposureHistory of bariatric surgery.Main outcomes and measuresPregnancy weight gain was standardized by gestational age into early-pregnancy BMI-specific z scores.ResultsThis study included 12 776 pregnancies, of which 6388 had a history of bariatric surgery and 6388 were matched controls. The mean (SD) age was 31.6 (4.9) years for the surgery group and 31.4 (5.2) for the matched controls, with an early-pregnancy mean (SD) BMI of 29.4 (5.2) in both groups. Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls. The differences in pregnancy weight gain z score values between the 2 groups were -0.33 (95% CI, -0.43 to -0.23) for normal weight, -0.33 (95% CI, -0.40 to -0.27) for overweight, -0.21 (95% CI, -0.29 to -0.13) for obese class I, -0.16 (95% CI, -0.29 to -0.03) for obese class II, and -0.08 (95% CI, -0.28 to 0.13) for obese class III. Pregnancy weight gain did not differ by surgical procedure. A shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss was associated with lower pregnancy weight gain.Conclusions and relevanceIn this nationwide matched cohort study, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls with similar early-pregnancy characteristics. Pregnancy weight gain was lower in those with a shorter surgery-to-conception interval or lower surgery-to-conception weight loss, but did not differ by surgical procedure.

Dataset Information

Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance.

Introduction

Methods

Results

Conclusions

Publications

Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance.

Similar Datasets

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