Bariatric Surgery Improves the Atherogenic Profile of Circulating Methylarginines in Obese Patients: Results from a Pilot Study

Q: What are the key findings of this study?

Bariatric surgery reduced serum monomethylarginine by 12% (95% CI 6-17) and asymmetric-dimethylarginine by 36% (95% CI 27-45; p=0.003) at 12 months in severely obese patients.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Severe obesity (n=62). Intervention: Bariatric surgery (gastric bypass or sleeve gastrectomy) vs. Baseline pre-surgery status and age- and sex-matched healthy individuals. Primary outcome: Percentage reduction in serum asymmetric-dimethylarginine (ADMA) concentration at 12 months after bariatric surgery (36% reduction, 95% CI 27-45, p=0.003).

Q: What does this research mean for the field?

Bariatric surgery significantly reduces serum concentrations of atherogenic monomethylarginine and asymmetric-dimethylarginine at 12 months in obese patients. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

J L Poirier; Chloé Cloteau; Audrey Aguesse; Xavier Billot; Etienne Thévenot; Michel Krempf; René Valéro; Marie Maraninchi; Mikaël Croyal

doi:10.3390/metabo11110759

November 4, 2021MetabolitesOpen Access

Bariatric Surgery Improves the Atherogenic Profile of Circulating Methylarginines in Obese Patients: Results from a Pilot Study

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Key result

Bariatric surgery reduces serum asymmetric-dimethylarginine by ~36% at 12 months in severe obesity.

36% reduction
95% CI 27-45
P=0.003
n=62

Figures

Why the study?

Methylarginines are biomarkers of cardiometabolic risk, liver steatosis, and insulin resistance, but their profiles in obese patients undergoing bariatric surgery compared to healthy controls required investigation.

Does bariatric surgery reduce circulating atherogenic methylarginine concentrations in severely obese patients over 12 months of follow-up?

Key Points

To investigate circulating methylarginine concentrations in obese patients before and after bariatric surgery compared to age- and sex-matched healthy individuals.
Retrospective pilot study evaluating 31 obese patients undergoing bariatric surgery and 31 age- and sex-matched healthy individuals.
Serum concentrations of methylarginines were quantified at baseline in healthy controls, and at baseline, 6 months, and 12 months post-surgery in obese patients using mass spectrometry.
At baseline, obese patients exhibited higher concentrations of monomethylarginine (+95%, p < 0.001), asymmetric-dimethylarginine (+105%, p < 0.001), symmetric-dimethylarginine (+25%, p = 0.003), and dimethylguanidino valerate (+32%, p = 0.008) than healthy controls.
At 12 months, bariatric surgery reduced BMI by 28% (95% CI: 24–33, p = 0.002) and decreased monomethylarginine by 12% (95% CI: 6–17) and asymmetric-dimethylarginine by 36% (95% CI: 27–45) (p = 0.003).
Symmetric-dimethylarginine and dimethylguanidino valerate did not change significantly following surgery, with symmetric-dimethylarginine correlating almost exclusively with renal function.

Study Design

Type

Cohort (n=62)

Multicenter

No

Structured PICO

Does bariatric surgery reduce circulating atherogenic methylarginine concentrations in severely obese patients over 12 months of follow-up?

P

Population

62 adults in France (31 severely obese patients with BMI >=40 kg/m2 or >=35 kg/m2 with comorbidities undergoing bariatric surgery followed for 12 months, and 31 age- and sex-matched healthy controls).

E

Exposure

Bariatric surgery: gastric bypass (n=16) or sleeve gastrectomy (n=15) performed by a single surgeon, with 12-month follow-up.

C

Comparator

Pre-surgical baseline values (paired longitudinal comparison at 6 and 12 months) and 31 age- and sex-matched healthy controls at baseline.

O

Outcome

Serum concentrations of methylarginine metabolites—arginine (ARG), citrulline (CIT), monomethylarginine (NMMA), asymmetric-dimethylarginine (ADMA), symmetric-dimethylarginine (SDMA), and dimethylguanidino valerate (DMGV)—quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) before surgery and at 6 and 12 months post-surgery.surrogate

Main Result

Effect estimate: 36% reduction (95% CI 27-45)

p-value: p=0.003

Bariatric surgery significantly lowers circulating atherogenic methylarginines (ADMA and NMMA) alongside improvements in BMI, insulin resistance, and lipid profiles in severely obese patients, while leaving SDMA and DMGV unchanged.

Limitations

Retrospective and observational pilot study design with small sample size (n=31 obese patients)
Healthy control individuals were recruited a posteriori, had no 12-month follow-up, and had different sample storage durations
Number of subjects with NAFLD was too small to clearly determine the relationship between DMGV and liver fat, and NAFLD was assessed by fibrosis score rather than CT scan
Drastic post-surgical reductions in total energy intake and baseline differences in medications and comorbidities may have confounded biomarker levels
Retrospective observational pilot design with a small sample size not powered to adjust for covariates
Healthy controls were recruited a posteriori without 12-month follow-up or dietary assessment, resulting in differing sample storage durations
Small number of NAFLD patients and reliance on NAFLD fibrosis score rather than CT imaging
Potential confounding from drastic post-surgical dietary changes and baseline medications/comorbidities

Implication

Suggests potential vascular benefits from bariatric surgery; hypothesis-generating for cardiovascular event reduction in severe obesity.

Abstract

Bariatric surgery improves obesity-related comorbidities. Methylarginines are biomarkers of cardiometabolic risk, liver steatosis, and insulin resistance. Here, we aimed to investigate methylarginines in obese patients undergoing bariatric surgery and compared them to age- and sex-matched healthy subjects. Thirty-one obese patients who underwent bariatric surgery and 31 healthy individuals were used for this retrospective study. The basal serum methylarginine levels were determined in the healthy individuals and the obese patients, before surgery and 6 and 12 months after surgery, by mass spectrometry. Compared with the healthy individuals, the obese patients displayed elevated monomethylarginine (mean change: +95%, p < 0.001), asymmetric-dimethylarginine (+105%, p < 0.001), symmetric-dimethylarginine (+25%, p = 0.003), and dimethylguanidino valerate (+32%, p = 0.008) concentrations. Bariatric surgery durably reduced the body mass index by 28% (12 months, 95%CI: 24–33, p = 0.002) and improved plasma lipids, insulin resistance, and liver function. Bariatric surgery reduced the serum levels of monomethylarginine and asymmetric-dimethylarginine by 12% (95%CI: 6–17) and 36% (95%CI: 27–45) (12 months, p = 0.003), respectively, but not symmetric-dimethylarginine or dimethylguanidino valerate. The monomethylarginine and asymmetric-dimethylarginine concentrations were strongly correlated with markers of dyslipidemia, insulin resistance, and a fatty liver. Serum dimethylguanidino valerate was primarily correlated with glycemia and renal function, whereas serum symmetric-dimethylarginine was almost exclusively associated with renal function. In conclusion, the monomethylarginine and asymmetric-dimethylarginine levels are efficiently decreased by bariatric surgery, leading to a reduced atherogenic profile in obese patients. Methylarginines follow different metabolic patterns, which could help for the stratification of cardiometabolic disorders in obese patients.

Discussion

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Cite This Study

Poirier et al. (2021) conducted a cohort in Severe obesity (n=62). Bariatric surgery (gastric bypass or sleeve gastrectomy) vs. Baseline pre-surgery status and age- and sex-matched healthy individuals was evaluated on Percentage reduction in serum asymmetric-dimethylarginine (ADMA) concentration at 12 months after bariatric surgery (36% reduction, 95% CI 27-45, p=0.003). Bariatric surgery reduced serum monomethylarginine by 12% (95% CI 6-17) and asymmetric-dimethylarginine by 36% (95% CI 27-45; p=0.003) at 12 months in severely obese patients.

synapsesocial.com/papers/6a74a64a8d2049c8dd033205 https://doi.org/10.3390/metabo11110759

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Bariatric Surgery Improves the Atherogenic Profile of Circulating Methylarginines in Obese Patients: Results from a Pilot Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Bariatric Surgery Improves the Atherogenic Profile of Circulating Methylarginines in Obese Patients: Results from a Pilot Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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